Abstract: Fibrosis, caused by excessive production and deposition as well as reduction of the extracellular matrix, is a common occurrence during aging of many substantial organs. Under a pathological state, fibrosis can cause damage to organ structure and function, thereby resulting in organ failure in severe cases. Since 2012, advancement of high-throughput technology has led to exploration of many circular RNAs (circRNAs). These competitive endogenous RNAs play a complicated but crucial role in various processes of cell signal transduction and human diseases. To date, numerous researches have shown that circRNAs can either inhibit or promote fibrosis in many organs, including the heart, kidney, lung, and liver. In this review, we systematically review the current progress for the role of circRNA in fibrosis, with the aim of providing a theoretical basis for future development of targeted therapies against the disease.

Aim The study was planned to assess the acceptance of the COVID-19 vaccine in pregnant and lactating women and identify the significant hurdles in vaccine acceptance. Material and Method It was a prospective observational, cross-sectional study conducted at the Department of Gynecology and Obstetrics, Kasturba Medical College, Manipal, Karnataka, in April 2021. A self-made questionnaire was prepared to gauge the acceptance and major hurdles of COVID- 19 vaccination among pregnant and lactating women. Upon receiving the subject’s consent to participate in the study, they were then required to respond to the questionnaire. Results: Among 281 participants, 159 (56.6%) women were pregnant, and 122 (43.4%) were lactating. In the study population, 66% (n, 105) of pregnant women and 68% (n, 83) of lactating women were unwilling to take the vaccine. The risk of adverse events with COVID-19 vaccination, chances of pregnancy loss, doctor’s recommendation, and vaccine convenience were significant factors that impacted the acceptance rate of COVID-19 vaccination. Conclusion Most women were concerned about the risk of COVID-19 vaccination, and only 34.0% were ready to take the vaccine during pregnancy and lactation. Government and health centers should promote awareness regarding the safety and use of the vaccine to avoid unfounded fear and encourage joint decision-making in pregnant and lactating women.

Objectives: The aim of current study was to appraise the relationship between women body image perception and depression in case and controls Methods: In this case-control study 60 polycystic ovarian syndrome patients established agreeing to Rotterdam criteria and 20 healthy controls of reproductive age group were enrolled. The PCOS patients and healthy controls were evaluated on questionnaire for physical appearance and depression. Body image perception was accessed using the validated Body Esteem Scale (Franzoi et al., 1984).The symptoms of Depression were evaluated with the Quick Inventory of Depressive Symptomatology-Self Report (Rush et al., 2003). Results: The groups were age matched therefore no significant disparities were detected (p>0.05). Additionally, significant change (p<0.05) was found of body image perception between cases and controls with vast majority of females declared that they have perceived a positive body image for themselves in both groups which depict a healthy mind frame. However, it was found that controls (those without PCO) were 96% less likely to have negative body image perception as compared to cases (those with PCO). Furthermore, 55% women in PCO group admitted of being depressed as compared to controls as insignificant (p>0.05) association was seen between depression and PCO status of the study subjects. Though PCOS (cases) have 2.27 times more odds to develop depression as compared to those without PCOS Conclusion: There was significant difference found of body image perception between case and controls. In addition, insignificant association was seen between depression and PCO status of study subjects. In addition, the probabilities of negative body image perception and depression were more present in PCOS than normal females. Therefore, health of the patients with the set of symptoms is essential to be acknowledged more fully, predominantly in relation to the despair and poor body image.

Integration of community ecology with disease biology is viewed as a promising avenue for uncovering determinants of pathogen diversity, and for predicting disease risks. Plant-infecting viruses represent a vastly underestimated component of biodiversity with potentially important ecological and evolutionary roles. We performed hierarchal spatial analysis of wild plant populations to characterise the diversity and coexistence structure of within-host virus communities, and their predictors. Our results show that these virus communities are characterised by single infections of few, dominating virus taxa as well as diverse, non-random coinfections. Using a novel graphical modelling framework we demonstrate that after accounting for environmental heterogeneity at the level of both individual host plants and populations, most virus co-occurrence patterns can be attributed to virus-virus associations. Moreover, we show that conditioning variables changed virus association networks especially through their indirect effects. This highlights a previously underestimated mechanism of how human-driven environmental change can influence disease risks.

Desert Locust is an important pest to agriculture. In 2019-2020, a major upsurge originated in the southern Arabian Peninsula gradually spread to East Africa, then to South-West Asia, as far as Pakistan and India, even reaching Nepal, resulting in major agricultural losses. For the first time, a few swarms have entered southern Tibet. Using field observations and experiments, we studied their path to the Tibetan plateau and their behaviour at these very high altitudes. The locusts have moved up the Tibetan valleys from low-lying areas (1700 m) to much higher elevations (5400 m). The low temperatures and high humidity put them under severe stress; their activities were limited, and they did not survive long or produce local offspring. It is clear that the high-altitude environmental conditions in the Himalayan mountains provided an important natural barrier that limited the northward expansion of the desert locust populations.

Nitrogen deposition and land use are known to influence various ecosystems, but how these anthropogenic activities influence community and ecosystem responses to disturbance remains poorly understood. Here we investigated the effects of increased nitrogen deposition and mowing on the resistance and recovery of a temperate semiarid grassland experiencing a three-year drought. Nitrogen addition reduced grassland biomass resistance and increased biomass recovery, whereas annual mowing reduced grassland structural resistance and increased structural recovery. The treatment effects on community biomass resistance and recovery were largely modulated by the stability of the most dominant species, whereas the treatment effects on community structural resistance and recovery were largely modulated by the structural stability of dominant species assemblages. The discrepancy in the response of biomass and structural stability emphasizes the need to study changes across levels of ecological organization for a more complete understanding of ecosystem responses to disturbances under widespread environmental changes.

Introduction: Pneumopericardium is a rare complication of epicardial ablation after dry pericardiocentesis to treat ventricular arrhythmia (VA); its exact clinical effects on patients are still unclear. The purpose of this study was to evaluate the clinical effects of pneumopericardium during epicardial ablation on patients with VA. Methods and Results: A total of 86 patients with VA who underwent epicardial catheter ablation under local anesthesia at West China Hospital of Sichuan University from August 2012 to March 2021 were enrolled in this study. 22 cases had pneumopericardium, with an incidence rate of 25.6%. and 12 (54.55%) patients complained of dyspnea during the procedure with an average occurrence time of 5.4±3.2 minutes after pericardiocentesis. The blood pressure (BP) decreased significantly, with the mean BP dropping from 119.8/73.2 mmHg to 103.5/64.9 mmHg (p<0.001). None of the cases progressed to tension pneumopericardium. Postoperative follow-up with a median period of 496 days showed that the incidence rate of major adverse cardiovascular events (MACEs), including the composite endpoints of all-cause death, rehospitalization for heart failure, and tachyarrhythmia events, was 65% (n=13) in the pneumopericardium group and 43.4% (n=23) in the non-pneumopericardium group. The Kaplan-Meier survival analysis showed that there was no statistically significant difference in the incidence of MACEs between the two groups (p=0.80). Conclusion: The incidence of pneumopericardium during epicardial ablation was relatively high. However, it can barely progress to tension pneumopericardium and further lead to serious consequences. The occurrence of pneumoperitoneum during the procedure may not significantly affect the long-term prognosis of patients.

Abstract Objective: Evaluation of COVID-19 during pregnancy and the pregnancy outcomes. Design: A prospective cohort study. Setting: Central First Health Care Cluster (multicentric), Riyadh. Population or Sample: Pregnant women with a singleton pregnancy diagnosed with COVID-19 . Methods: Parameters included: the age of the patient, gestational age at diagnosis, symptoms at presentation (cough, fever), presence of congenital anomalies, IUFD, mode of delivery, presence of PPH, admission to ICU, newborn Apgar s.core, cord PH, need for NICU admission, and the newborn becoming infected with COVID-19. Main Outcome Measures: COVID-19 positive women and adverse maternal and fetal outcome Results: One hundred pregnant, COVID-19-positive women met the inclusion criteria; the average age of participants was 31.2 years (SD ± 6.4). Asymptomatic patients represented 54% of participants. Most of the deliveries occurred at 36 weeks or less as preterm delivery. Cesarean sections represented 55% of our population. The average weight of the newborn was 2.86 ± 0.65SD); however, 23 (26.4 %) of the newborns delivered to a COVID-positive mother became COVID-19 positive. Conclusion: A high rate of preterm labor, miscarriage, cesarean section, and newborn testing positive for COVID-19 were observed among our population. No congenital anomalies related to COVID-19 were observed. Keywords: Pregnancy, COVID 19, Preterm labor, Miscarriage, Saudi Arabia

Objectives Whole exome sequencing technology can identify the undiscovered genetic etiology of product of concepts(POC) and improve the diagnosis rate of abortion.This study examines the value of a combined trio-WES strategy in identifying the etiology of abortion in the case of negative karyotype and chromosomal microarray sequencing. Design: A retrospective study Setting: Center of Prenatal Diagnosis Sample: Fourteen abortion samples with normal karyotype analysis and CMA Methods: In this study, Trio-WES was used to sequence 14 POC with normal CMA and karyotype analysis, and to evaluate the detection rate of abnormal abnormalities and the diagnostic value of variation. Main outcome measures: The detection rate of gene mutation sequence in flow products, the definite diagnosis rate of single gene disease and its relationship with clinical phenotype Results A total of 10 variants of 7 genes were detected, including 2 pathogenicity variant, 4 likely pathogenicity variant and 4 uncertain significance variant. Four families were accepted as positive results, with a definite diagnosis rate of 28.6% (4/14). Case 1 was type 4 of autosomal dominant polycystic kidney disease caused by complex heterozygous variation of PKHD1 gene, Case 2 was Alagille syndrome caused by heterozygous variation of JAG1 gene, Case 5 and Case7 were type 3 of short rib dysplasia caused by complex heterozygous variation of DYNC2HI gene. Conclusions These data support the application value of whole exome sequencing technology in the detection of abortion etiology and enhance the understanding of pathogenicity variation. Funding: National Key Research and Development Program (2018YFC1002203-2);

Botnets, especially peer-to-peer (P2P) botnets have become the root because of many Internet attacks recently. A novel dynamical model is presented to describe the propagation of P2P botnets which is called SIIR model. To effectively suppress P2P botnets, quarantine and virtual patching strategy are proposed and two dynamical models are given based on the SIIR model (SIIQR model and SIIQPR model). The two models can examine the impact of different containment strategies on the growth of the P2P botnets. In addition, the stability of equilibrium is investigated and the basic reproduction number is obtained which governs whether or not P2P botnets are extinct. The virtual patching strategy and quarantine strategy can effectively contain the propagation of the P2P botnets. Numerical and simulation results show the effectiveness of our models, larger infected rate and larger deploying rate of virtual patching can control the number of infected hosts more effectively.

Background and purpose Monoamine-based antidepressants can protect from stress-induced gastric ulcer. Central nucleus of amygdala (CeA) has been shown to modulate the severity of stress ulcers in rats. Proton magnetic resonance spectroscopy (1H-MRS) provided a non-invasive tool to identify the duration-related neurometabolites of CeA in the process of gastroprotective of antidepressants. Experimental Approach We used 1H-MRS to explore the specific neurometabolite in CeA which was correlated with severity of gastric ulcer induced by water immersion restraint stress (WIRS) in rats, and further determined which kinds of enzymes modulating this molecule were involved in the gastroprotective effect of antidepressants. We started with SNRI duloxetine and then extended to the other three types of monoamine-based antidepressants to probe the potential generalized molecular mechanisms. Key Results Duloxetine decreased NAA/creatine in CeA after 6 h of WIRS, whereas vehicle had no effect. Gastric ulcer index was negatively correlated with reduced NAA/creatine. Furthermore, intra-CeA infusion of NAA aggravated WIRS-induced gastric mucosa damage. NAA catabolizing enzyme aspartoacylase (ASPA) was the only enzyme downregulated by 0.5-h WIRS and upregulated by duloxetine. Overexpressing ASPA in CeA alleviated the gastric ulcer caused by WIRS. Pretreatment with other monoamine-based antidepressants including fluoxetine, amitriptyline and moclobemide all increased ASPA expression in the CeA in the same model. Conclusion and Implications Collectively, monoamine-based antidepressants exerted gastroprotective effects against stress by increasing ASPA to hydrolyze NAA in CeA. Our work demonstrated ASPA as a joint target more than monoamine regulation for this kind of drugs.

INTRODUCTION: The aim of this study investigated the effect of eosinophil and basophil counts on mortality in patients with COVID-19 infection. METHODS: Blood tests of 582 patients with RT-PCR test in an oropharyngeal swab sample who were admitted to Diyarbakır Gazi Yaşargil Training and Research Hospital between March 2020 and December 2020 were retrospectively analysed. The patients were divided into two groups: those who recovered and discharged and those who had a mortal course. Demographic data, comorbid diseases, routine blood tests, and haematological parameters were compared between both groups. RESULTS: An eosinophil count of 0.01 ± 0.04 and basophil count of 0.0261 ± 0.026 was observed in the patient group who had a mortal course at first admission to the hospital, while the eosinophil count was 0.06 ± 0.12 and basophil count was 0.020 ± 0.017 in the recovered patient group. On the fifth day after admission, the eosinophil count was 0.02 ± 0.07 and basophil count was 0.043 ± 0.042 in the patient group with a mortal course, while the count of eosinophils was 0.13 ± 0.14 and basophils was 0.023 ± 0.016 in the recovered patient group. In both groups, the eosinophil and basophil counts on the fifth day increased compared to the first day, and the eosinophil and basophil counts were lower in those who had a mortal course on both the first and fifth day (p < 0.05). CONCLUSIONS: In our study, a significant decrease was observed in the count of eosinophils and basophils in the mortal group of COVID-19 patients. Eosinopenia and basopenia may be parameters that can be used to facilitate the diagnosis of COVID-19, and the depth of both eosinopenia and basopenia is positively correlated with COVID-19 mortality.

Through the detection of changes in serum CCL28 content in Sjögren’s syndrome (SS), we explored the significance of CCL28 in disease diagnosis and evaluation. Serum samples were collected from patients with SS, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Serum levels of CCL28 were measured using enzyme-linked immunosorbent assay and compared to healthy controls (HC). We also detected serum IgA levels and the focus score of labial salivary gland (LSG) in patients with SS, and explored the correlation with serum CCL28. In addition, patients with SS were divided into two groups based on clinical symptoms and laboratory tests. The level of serum CCL28 was then compared. Serum levels of CCL28 in both primary and secondary SS patients were significantly lower than those in the HC group, whereas, serum levels of CCL28 in patients with RA and SLE were not significantly different from those in the HC group. Comparing with RA and SLE patients alone, serum levels of CCL28 were dramatically lower in patients with SS secondary to RA or SLE. No remarkable correlation between serum IgA and CCL28 levels was observed, while focus score of LSG negatively correlated with serum CCL28 levels. Serum levels of CCL28 were lower in patients with SS who suffered from dental carries and thrombocytopenia. Low serum levels of CCL28 should be considered in the diagnosis of SS. Serum CCL28 levels reflect the degree of salivary gland injury. In summary, we concluded that serum CCL28 levels are invaluable in the diagnosis and evaluation of SS.

Background: Many studies done during this pandemic revealed several neurological manifestations related to coronavirus disease 2019 or COVID 19 infection. The aim of this narrative review is to discuss the neurological manifestations and complications of COVID-19 disease. Methods: Data were retrieved from: PubMed, Scopus, Science direct in addition to manual search using Google scholar from December 2019–May 2020.Keywords were used in the search such as COVID-19; Neurological manifestations; Cranial nerves; Motor system. Results: Neurological manifestations and complications are common and increase with the severity of the respiratory involvement . It ranges from 34% to reach 80% in some studies. It involves the central and peripheral nervous system leading to cranial nerves palsies and limbs paralysis. Conclusion: Neurological complications of COVID-19 is an important determinant for the severity and mortality of patients .The virus can lead to Headache, Convulsion, Mental and Psychic changes , Delirium and Insomnia (the most affected cranial nerve is the olfactory nerve leading to anosmia), Stroke (mainly infarction), Encephalitis, Meningitis , Guillain-Barre Syndrome ,Relapse of Multiple Sclerosis and Transverse Myelitis.

Triterpenoids are plant specialized metabolites with various pharmacological activities. They are widely distributed in higher plants, such as legumes. Due to its low accumulation in plants, there is a need for improving triterpenoid production. Cytochrome P450 monooxygenases (CYPs) play critical roles in the structural diversification of triterpenoids. To perform site-specific oxidations, CYPs require the electrons that are transferred by NADPH-cytochrome P450 reductase (CPR). Plants possess two main CPR classes, class I and class II. CPR classes I and II have been reported to be responsible for primary and specialized (secondary) metabolism, respectively. First, we compared expression levels from three legume species, showing that the expression level of CPR class I was lower and more stable, while that of CPR class II was higher in almost all the samples. By expressing different combinations of CYP families and CPR classes from these three legumes in transgenic yeast, we found that generally CYP716As worked better with CPR-I, while CYP72As worked better with CPR-II. Using engineered yeast strains, CYP88D6 paired with class II GuCPR produced the highest 11-oxo-β-amyrin level. This study provides insight into co-expressing genes from legumes for heterologous production of triterpenoids in yeast.

Background: As increasing evidence showed the efficacy of percutaneous left atrial appendage (LAA) occlusion in reducing the stroke risks in patients with non-valvular atrial fibrillation(AF), we design this study to quantify the effect of surgical LAA occlusion (SLAAO) for patients with valvular diseases and with or without AF. Methods: The current study will be implemented in two parts: Part 1 (AF study) is a prospective longitudinal study with a plan to consecutively register 2032 patients diagnosed with valvular diseases and AF and receiving cardiovascular surgeries. SLAAO will be performed at the individual surgeon’s preference. We centrally conducted a one-year follow-up on stroke, systemic arterial embolism, and all-cause mortality. Part 2 (non AF study) is a single-blinded, multicenter, randomized controlled trial with the purpose to evaluate the efficacy of SLAAO to reduce one-year embolism events in patients with valvular diseases, without AF, and receiving cardiovascular surgeries. 2118 patients will be randomized 1:1 to the intervention or control arm using a central randomization system. Results: The primary outcome is a composition of newly occurred ischemic stroke/transient ischemic attack (TIA) with positive neuroimaging or systemic arterial embolism, and cardiovascular mortality during one-year follow-up. Conclusion: The trial is designed to evaluate the efficacy of SLAAO to reduce embolism events one year after mitral or aortic surgeries, and this paper presents the prospective study protocol. It provides details of patient randomization, follow-up, methods of analysis of the material, and publication plan.

We present a 22-year-old male patient, a history of a right bidirectional Glenn procedure (BDG), with dyspnea, cyanosis, palpitations and chest pain. Transthoracic echocardiography and computed tomography showed aneurysmal dilation of the right superior venous system. BDG takedown was performed with resection of the aneurysmal superior vena cava and reconnection of the superior vena cava to the right atrium and the creation of a central systemic-to-pulmonary shunt. The patient died from complications derived from a massive collateral circulation.

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by severely reduced activity of the von Willebrand factor-cleaving protease ADAMTS13. Over 95% are acquired autoimmune TTP. In children, acquired TTP is a very rare, life-threatening disease. To date, no consensus exists on the treatment strategy of pediatric TTP. In our experience, the combined use of PEX, Caplacizumab and immunosuppressive therapy during the acute phase of the disease results in a prompt and persistent normalization of laboratory findings and successful clinical outcome.

Children with COVID-19 have milder disease with better outcomes as compared to adults. Whilst adults especially with hematological malignancies have a more severe illness with high mortality, data on children with cancer is still evolving. We aim to describe the clinical profile and outcome of pediatric oncology patients with COVID-19 infection over the last 14 months. Fifty out of 252 patients on active treatment in the unit had documented COVID-19 infection. Severe disease was seen in 4% cases with one mortality. Children with cancer appear to be at higher risk of severe disease as compared to general pediatric population.

The clinical course of COVID-19 in pediatric patients with aplastic anemia (AA) have not been thoroughly investigated. We report a case of COVID-19 in a 15-year-old male with AA treated via immunosuppressive therapy. The patient initially presented with a fever and mild sore throat. He continued cyclosporine treatment, and his symptoms improved with a single dose of hydrocortisone. Antibody testing showed increased anti-S1 and anti-RBD IgA levels, followed by elevation of anti-S1 and anti-N IgM/IgG levels. Our results suggest that AA is not necessarily associated with a higher risk of severe COVID-19.

Acute Disseminated Encephalomyelitis (ADEM) is a monophasic demyelinating disease most often triggered by infection or immunization, though associations with malignancy and stem cell transplant have been described. We describe the case of a four-year old male with new onset neurological symptoms associated with ADEM, acute leukemia, and equivocal evidence of Mycoplasma pneumoniae infection. He responded to a short course of antibiotics and chemotherapy for B cell acute lymphoblastic leukemia (B-ALL) that included a prolonged course of high dose steroids with immunosuppressive therapy. This case illustrates a possible association between paraneoplastic ADEM and leukemia in pediatric patients.

Premature centromere division (PCD) and C-anaphase are well known phenomena in leukemias. However, their biological significance is not well understood. We describe the relationship of levels of PCD and C-anaphase with leukemic phase, blasts, aneuploidy and polyploidy in children with acute lymphoblastic leukemia (ALL). Methods Cytogenetic preparations of bone marrow (BM) and peripheral blood (PB) cells from 57 children with ALL and 15 healthy children were evaluated. For children with ALL, cells were examined prior to treatment in the acute phase and during remission. PCD and C-anaphase designations were assigned to chromosomal preparations and analyzed. Results The PCD and C-anaphase levels in BM and PB cells were significantly higher in the acute phase of ALL and decreased, approaching normal during remission. Strong correlations were found between PCD levels in PB (r = 0.890) and BM (r = 0.896) cells compared with blast levels in PB cells. Strong correlations were observed between PB levels of aneuploid (r = 0.832) and polyploid (r = 0.955) cells compared with PCD levels in PB cells. The C-anaphase levels in PB (r = 0.139) and BM (r = 0.171) compared with blasts in PB did not demonstrate a positive correlation. Conclusions Our data demonstrates that PCD is a cause of genome instability associated with ALL and that the phenomenon of PCD and C-anaphase provide additional criteria for diagnosis of ALL and its remission.

Background: There is an urgent need for risk assessment and mechanism exploration of fish allergens to provide a theoretical basis and methodological reference for food safety. PV is a major marine food allergen that can cause allergic reactions in fish allergic patients. This study aims to break through the previous model of evaluating the sensitivity of food allergens on single effector cells but to construct a coupling cell co-culture system for the process of dendritic cell maturation and T cell differentiation during sensitization. Methods: A new type of highly effective allergen sensitization evaluation model was proposed based on the effect of PV-induced differentiation of dendritic cells and T cells on the sensitization process. Results: Flow cytometry, ELISA, proteomics and transcriptomics approaches revealed that PV could promote the maturation of dendritic cells, mainly by inducing BMDC to express MHC Ⅱ, CD86, and other phenotypic molecules, while promoting cytokines/chemokines IL-6, IFN-γ, IL-23, and IL-12p70, whereas inhibiting TNF-α expression. It could strengthen the synthesis process of biological protein of DC cells and improve the expression level of genes such as the migration ability of DC cells in vivo. Finally, PV could induce T cells to shift to Th2 differentiation by inducing the increase of IL-4 level, which leads to allergic behavior. Conclusions: Therefore, the new allergen sensitization evaluation coupled with the cell co-culture system, in combination with the changes of the above markers could be used for quick and efficient determination of the potential sensitization possibility and sensitization intensity of fish allergens.

Like most areas worldwide, there is a shortage of pediatric drugs in mainland China to provide prescriptions. The Chinese government recently launched policies and incentives to encourage pediatric drug development and clinical trials. However, few data are available on the characteristics or development trends of these trials. We extracted source data from the Chinese Clinical Trials Registry and Information Transparency Platform and systematically reviewed the pediatric clinical trials conducted in mainland China from 2009–2020, providing data support to policy makers and industry stakeholders. This study includes 487 pediatric clinical trials.Over the past decade, the number of pediatric trials has increased annually, especially since 2016.The most common therapeutic areas were infectious diseases (n=108, 22.2%),agents for preventive purpose (n=99,20.3%), and neurological and psychiatric diseases (n=71,14.6%). The number of clinical trials involving epilepsy (39,10.1%), asthma (33,8.5%), and influenza (24,6.2%) were the highest. The distribution of leading institutions is unbalanced in mainland China, with most units in East China (34.0%) and few in Southwest China (6.9%). China has made constant progress in improving the R&D environment of pediatric drugs and increasing pediatric trials. However, a wide gap in pediatric drug development remains between China and developed countries. The pharmaceutical industry in China still faces grim setbacks, including study duplication, a lack of innovation, and poor research design. Thus, the Chinese government should adjust their policies to improve innovation and clinical design capacity, and to optimize resource allocation between regions.