OBJECTIVE To sort out the evaluation mechanism and methodology of published cases of comprehensive clinical evaluation of drugs in China， and provide a reference for promoting standardized comprehensive clinical evaluation of drugs and strengthening policy transformation in China. METHODS Clinical comprehensive evaluation cases of drugs published in China from CNKI， Wanfang Data， PubMed and Web of Science were systematically searched， and the retrieval time was from the inception to December 31st， 2023. The summary and analysis were performed from the aspects of theme selection， indicator system construction， evaluation methods， comprehensive decision-making， quality control， etc. RESULTS A total of 143 pieces of literature were ultimately included from 2014 to 2023. The number of publications has shown a rapid upward trend since 2019. The subjects of the evaluation cases were mainly pediatric drugs， Chinese patent medicines， cardiovascular drugs and anti-tumor drugs. The evaluation dimensions were between 3-8， all involving safety and effectiveness dimensions. Most cases adopted rapid evaluation methods based on literature review and expert interviews/questionnaire surveys with less emphasis on real-world research. Most cases did not involve comprehensive decision-making， quality control， or policy transformation. CONCLUSIONS The clinical comprehensive evaluation of drugs in China has made rapid progress under the guidance of national policies. However， there are still issues and challenges such as incomplete evaluation methods and standards， few cases of evaluation results being converted into decision-making， and a lack of quality control mechanisms. It is suggested that standardized evaluation paths and quality control mechanisms should be explored； when the evidence-based basis is insufficient， real-world research should be conducted as much as possible， so as to accelerate the policy transformation of evaluation results.

OBJECTIVE To sort out the evaluation mechanism and methodology of published cases of comprehensive clinical evaluation of drugs in China， and provide a reference for promoting standardized comprehensive clinical evaluation of drugs and strengthening policy transformation in China. METHODS Clinical comprehensive evaluation cases of drugs published in China from CNKI， Wanfang Data， PubMed and Web of Science were systematically searched， and the retrieval time was from the inception to December 31st， 2023. The summary and analysis were performed from the aspects of theme selection， indicator system construction， evaluation methods， comprehensive decision-making， quality control， etc. RESULTS A total of 143 pieces of literature were ultimately included from 2014 to 2023. The number of publications has shown a rapid upward trend since 2019. The subjects of the evaluation cases were mainly pediatric drugs， Chinese patent medicines， cardiovascular drugs and anti-tumor drugs. The evaluation dimensions were between 3-8， all involving safety and effectiveness dimensions. Most cases adopted rapid evaluation methods based on literature review and expert interviews/questionnaire surveys with less emphasis on real-world research. Most cases did not involve comprehensive decision-making， quality control， or policy transformation. CONCLUSIONS The clinical comprehensive evaluation of drugs in China has made rapid progress under the guidance of national policies. However， there are still issues and challenges such as incomplete evaluation methods and standards， few cases of evaluation results being converted into decision-making， and a lack of quality control mechanisms. It is suggested that standardized evaluation paths and quality control mechanisms should be explored； when the evidence-based basis is insufficient， real-world research should be conducted as much as possible， so as to accelerate the policy transformation of evaluation results.

Objective:To investigate the relationship between CBCT imaging changes of condyle and clinical features,and related risk factors in patients with temporomandibular disorders(TMD).Methods:453 patients with TMD were enrolled and underwent CBCT scan for bilateral temporomandibular joints(TMJ),3D reconstruction of the TMJs was analyzed.Logistic regression analysis was performed to investigate the relationship between condylar bone changes and TMD clinical features.Results:Patients＜18 years old were more likely to have condylar bone changes than the adults.The symptoms of pain and restricted mouth opening were more likely to be detected in the condylar bone change group(n=133)than in the normal condylar bone group(n=320).The incidence of brux-ism in the normal condylar bone group was higher than that in the condylar bone change group.Univariate logistic regression analysis showed that only bruxism(OR=0.550),pain(OR=1.844)and mouth restriction(OR=2.024)were included in the regression equa-tion.Multivariate logistic regression analysis showed that,due to the protective effect of bruxism,the OR value of pain decreased from 1.844 to 1.791,and the OR value of mouth restriction decreased from 2.024 to 1.847.Conclusion:The condylar bone change in TMD patients more likely occur in puberty or patients with pain and restricted mouth opening.Bruxism may be a protective factor in the occurrence of condylar bone changes in TMD patients.

Objective:To compare the clinical efficacy of rotator cuff repair combined with transposition of the long head of the biceps tendon in the treatment of massive rotator cuff tears with or without subscapularis injury.Methods:A total of 73 patients with massive rotator cuff tears who underwent arthroscopic rotator cuff repair combined with transposition of the long head of the biceps tendon in the Department of Upper Arm, Sichuan Orthopaedic Hospital from January 2019 to September 2022 were retrospectively analyzed, including 35 males and 38 females, aged 58.8±7.6 years (range, 46-73 years). There were 11 cases on the left side and 62 cases on the right side. Causes of injuries: 6 cases of car accidents, 13 cases of fall injuries, 54 cases of no obvious cause of injury. The patients were divided into subscapularis injury group (37 cases) and no subscapularis injury group (36 cases) according to the subscapularis injury or not. The visual analogue scale (VAS), Constant - Murley score, University of California Los Angeles (UCLA) shoulder score and range of motion were used to evaluate shoulder pain and functional improvement. MRI of the shoulder was taken at the final follow-up and the rotator cuff was assessed for retear using Sugaya grading.Results:All patients successfully completed the operation. The VAS score at 1 year postoperatively in the group without subscapularis injury was 0.58±0.87, which was less than 1.16±1.14 in the group with subscapularis injury ( t=-2.426, P=0.018). The Constant-Murley score and UCLA score at 1 year postoperatively in the group without subscapularis injury were 94.03±6.19 and 32.94±2.59, respectively, which were greater than those of the group with subscapularis injury, which were 86.51±11.96 and 30.38±3.33, and the difference was statistically significant ( P<0.05). Anterior flexion and body external rotation at 1 year postoperatively in the group without subscapularis injury were 137.22°±26.79° and 54.72°±13.20°, which were greater than those in the group with subscapularis injury of 121.08°±22.83° and 38.65°±17.19°, and the difference was statistically significant ( P<0.05), and the difference between the two groups in body internal rotation was not statistically significant ( P>0.05). The subacromial spacing at 1 year postoperatively was 9.4±1.3 mm in the group without subscapularis injury and 9.0±1.5 mm in the group with subscapularis injury, and the difference was not statistically significant ( t=1.318, P=0.192). There were 2 cases of rotator cuff retear 1 year after surgery without subscapular muscle injury and 5 cases of subscapular muscle injury. Conclusion:The clinical efficacy of arthroscopic rotator cuff repair combined with transposition of the tendon of the long head of the biceps tendon in the treatment of massive rotator cuff tears with or without subscapularis muscle injury is satisfactory, and the improvement of pain and function is more obvious in patients without subscapularis muscle injury.

The mechanistic target of rapamycin(mTOR)plays a pivotal role in various cellular processes,including growth,proliferation and differentiation.As an essential component of the human immune system,T lymphocytes are regulated by mTOR through metabolic pathways such as carbohydrate metabolism and lipid metabolism.This article summarizes the critical role of mTOR in T cell differentiation and reviews recent advances in natural compounds that modulate T cells via mTOR.These findings contribute to the development of mTOR-targeted therapies for diseases.

Objective To investigate the effect of intrarectal local anesthesia (IRLA) with heated oxybuprocaine gel on pain during transrectal ultrasound guided prostate biopsy (TRUSPB).Methods A total of 150 cases patients who underwent TRUSPB in Huzhou Central Hospital from January to June 2023 were prospectively taken into.The patients were randomly divided into group A (routine group),group B (oxybuprocaine gel for IRLA at room temperature) and group C (oxybuprocaine gel for IRLA at 40℃),with 50 cases in each group.Nurses who were unaware of the anesthesia type used visual analog scale (VAS) to score the pain level of patients at each stage (VAS Ⅰ:when the ultrasound probe was inserted into the rectum;VAS Ⅱ:during the biopsy;VAS Ⅲ:30 minutes after biopsy),and the incidence of complications after biopsy were compared.Results The VAS Ⅱ score of group C was lower than that of group A and group B,and the difference was statistically significant (P<0.05).There was no statistically significant difference (P>0.05) in the VAS Ⅰ,VAS Ⅲ scores,and incidence of complications after biopsy among the three groups.There was no allergic reaction to oxybuprocaine gel.Conclusion In TRUSPB,IRLA with heated oxybuprocaine gel can effectively control pain without increasing incidence of complications.

Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
Pregnancy ; Female ; Animals ; Mice ; Tetraploidy ; Blastocyst ; Embryo, Mammalian ; Cell Differentiation ; Embryonic Development

Cardiovascular diseases (CVDs) and metabolic disorders are major components of noncommunicable diseases, causing an enormous health and economic burden worldwide. There are common risk factors and developmental mechanisms among them, indicating the far-reaching significance in exploring the corresponding therapeutic targets. MST1/2 kinases are well-established proapoptotic effectors that also bidirectionally regulate autophagic activity. Recent studies have demonstrated that MST1/2 influence the outcome of cardiovascular and metabolic diseases by regulating immune inflammation. In addition, drug development against them is in full swing. In this review, we mainly describe the roles and mechanisms of MST1/2 in apoptosis and autophagy in cardiovascular and metabolic events as well as emphasis on the existing evidence for their involvement in immune inflammation. Moreover, we summarize the latest progress of pharmacotherapy targeting MST1/2 and propose a new mode of drug combination therapy, which may be beneficial to seek more effective strategies to prevent and treat CVDs and metabolic disorders.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Objective:To form the expert consensus on nursing care of adults with status epilepticus (SE), promote nurses to provide standardized and safe first aid, monitoring and support to SE patients, and effectively prevent and control complications, with a view to controlling seizures as soon as possible.Methods:The medical and nursing evidence on SE was retrieved, evaluated and summarized, and the retrieval time limit was from the establishment of the database to March 31, 2022. Recommendations and studies were extracted to form a first draft of consensus. A total of 31 experts were selected to conduct two rounds of Delphi expert consultation and expert demonstration meetings to analyze, revise and improve the experts' suggestions and form a consensus final draft.Results:The expert positive coefficient was 100.00% (31/31), the expert judgment coefficient was 0.93, the familiarity degree was 0.87, and the authority coefficient was 0.90. Kendall's harmony coefficient was 0.25 to 0.27 ( P<0.05). The final consensus included adult SE identification, first aid, monitoring and support, complication prevention and control, and effect evaluation of terminating SE. Conclusions:This consensus is practical and provides guidance for clinical nursing practice and quality control of SE patients.