Investigator-initiated clinical trials （IIT） are an important part of scientific and technological activities involving human study participants. Among them， high-quality IIT can be used to support the marketing and registration application of drugs， medical devices， and other products when conditions permit. Currently， there is a huge gap between IIT and industry-initiated clinical trials. The use of unlisted products in IIT has problems， such as lack of regulatory support， insufficient research funding support， the need to improve the ability of clinical research management departments， the weakness of professional clinical research teams， and the difficulty of ethics review to match the demands. The challenges could be addressed by improving regulations and conducting pilot trials on a small scale， guaranteeing adequate research funding， strengthening the construction of clinical research management systems， building professional clinical research teams， ensuring the quality of ethical reviews and strict follow-up reviews， shifting from ethical reviews to a system for protecting research participants， and reinforcing training for researchers. Ethics committees should strictly review key points， such as the risk-benefit ratio， informed consent， research funding， compensation for damages， qualifications and equipment of research team members， and management of conflict of interest.

BACKGROUND:Erythropoietin has anti-inflammatory,anti-apoptotic,and pro-bone defect repair effects.To date,fewer studies have been conducted on its effects and molecular mechanism underlying restorative dentin formation after pulp injury. OBJECTIVE:To explore the effect of erythropoietin on restorative dentin formation after pulp injury. METHODS:(1)Animal experiment:Thirty-two rats were randomly divided into control group(n=16)and experimental group(n=16).In the experimental group,collagen sponges containing erythropoietin were used to directly cap the pulp at the pulp injury,and in the control group,collagen sponges containing PBS were used to directly cap the pulp at the exposed pulp injury.The cavity was then closed with glass ionomer adhesive.After 2 and 4 weeks of treatment,the maxillary bones of the two groups were collected,and the expression of nestin in dentin was detected by immunohistochemistry,and the reparative dentin production was observed by hematoxylin-eosin staining.The maxillae of four Sprague-Dawley rats were taken for immunohistochemical detection of erythropoietin expression in molar and incisor teeth.(2)Cell experiment:Human dental pulp cells,human periodontal ligament cells and human gingival fibroblasts were obtained from human dental tissue,periodontal ligament,and gingival tissue.Real-time reverse transcription PCR(RT-PCR)was used to detect the mRNA expression of erythropoietin.Erythropoietin,dentin sialophosphoprotein,dentin matrix protein 1,and nestin mRNA levels in human pulp cells were detected by RT-PCR under induced or uninduced odontoblastic differentiation.After down-regulation of erythropoietin expression or exogenous administration of erythropoietin intervention under induced or uninduced differentiation odontoblastic differentiation,the relative mRNA expression of dentin sialophosphoprotein and dentin matrix protein 1 in human pulp cells was detected by RT-PCR,and the formation of mineralized nodules was detected by alizarin red S staining,and mRNA and protein expressions of bone morphogenetic protein 2 were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:(1)Animal experiment:Compared with the control group,the restorative dentin production and nestin expression were higher in the experimental group after 2 and 4 weeks of treatment.The expression of erythropoietin was weakly positive in pulp,odontoblastic cell layer and periodontal membrane of the rat's first maxillary molar,and strongly positive in odontoblasts.(2)Cell experiment:The mRNA expression of erythropoietin was higher in human dental pulp cells than in the other two types of cells.The mRNA expressions of dentin sialophosphorin,dentin matrix protein 1,nestin,erythropoietin and bone morphogenetic protein 2 in human pulp cells increased and the formation of mineralized nodules during odontoblastic differentiation under induction compared with non-induction conditions.The mRNA expression of dentin sialophosphoprotein,dentin matrix protein 1,nestin,bone morphogenetic protein 2 and the formation of mineralized nodules were decreased in human pulp cells after downregulation of erythropoietin under induced odontoblastic differentiation,and the protein expression of bone morphogenetic protein 2 was also decreased.After exogenous erythropoietin intervention,the expression of the above indexes in human dental pulp cells increased.To conclude,erythropoietin can promote the formation of dentin to some extent.

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Objective To understand the changing trend of Internet outpatient visits in public hospitals,and provide support for the development planning of Internet hospitals.Methods Using the data of Internet outpatient visits in a public hos-pital from January 2021 to June 2023,the ARIMA model and GM(1,1)model were constructed respectively.The mean absolute error(MAE)and root mean square error(RMSE)were used to evaluate the fitting effect,and the Internet outpatient visits from July to December 2023 were predicted based on the dominance model.Results ARIMA(1,2,1)model and GM(1,1)model were used to predict the number of return visits of Internet outpatient service.The average absolute errors were 369.86 and 978.84,and the root-mean-square errors were 479.49 and 1444.83,respectively.The ARIMA(0,1,0)model and GM(1,1)model were used to predict the number of Internet outpatient consultations.The average absolute errors were 297.23 and 369.62,and the root-mean-square errors were 413.61 and 496.30,respectively,indicating that the ARIMA model has a good prediction effect.The forecast results show that the predicted value of Internet outpatient visits in December 2023 is 14,831 cases,and the predicted value of consultation visits is 7461 cases.Conclusion The number of Internet outpatient visits in a public hospital will continue to rise from 2021 to 2023.Therefore,hospitals should fully realize the importance of Internet medical services,take ac-tive measures to continuously optimize the medical service model,and provide patients with high-quality,efficient and convenient Internet medical services.

Goiter is a kind of non-inflammatory and non-neoplastic hyperplasia and enlargement. Many studies have shown that substances such as thiocyanates and isothiocyanates can prevent the development of a variety of tumors. However, some studies have also found that such substances can lead to goiter. In this article, relevant information on common goitrogen in food are collected to explore their mechanism of action, laying a foundation for guiding residents to maintain a healthy and balanced diet.

Major depressive disorder(MDD)is a mental disease characterized by persistent depression,lack of interest and impaired cognitive function.Antidepressants currently availablein clinic are effective but accompanied by many adverse reactions,such as slow onset,cognitive impairment,sexual dysfunction.Therefore,novel antidepressant targets and therapeutic strategies with rapid onset of action,cognitive enhancement and low adverse effects have increasingly become a promising sphere of research.Studies have suggested that Sigma-1 receptor plays an important role in combating depression by regulating inflammatory response,excitation/inhibition balance and endoplasmic reticulum homeostasis.Moreover,Sigma-1 receptor agonists may have the advantages of rapid onset,enhanced cognition and low adverse reactions,which show good prospects for the development of new antidepressants.This article reviews the research progress related to Sigma 1 receptors in the regulatory mechanism and treatments for depression in the hopes of providing new insights into new antidepressants.

The relevant data reported by laboratories carrying out serological prenatal screening in Jiangsu Province from 2021 to 2022 were retrospectively analyzed, and the provincial inter-ventricular quality assessment was realized by comparing the internal quality control data of laboratories. The quality control analysis platform of prenatal screening in Jiangsu Province was used to collect the determination methods, quality control data results of three concentrations, instrument platform, reagents and other relevant information of maternal serological screening quality control in early and middle pregnancy in each laboratory from 2021 to 2022. Firstly, the test results of each laboratory were statistically analyzed, and the precision of each laboratory was evaluated by the variation coefficient of indoor quality control. Secondly, the consistency was evaluated by comparing laboratories with different experimental platforms. The results showed that the passing rate of PAPP-A(pregnancy-associated plasma protein-A) precision test in 2021 and 2022 was 87.5% (7/8) and 92.3% (12/13), respectively. The accuracy pass rate of the Free β-hCG (free beta-human chorionic gonadotrophin)(early pregnancy) test in 2021 and 2022 was 97.5% (39/40) and 95.5% (42/44), and the accuracy pass rate of the AFP(alpha-fetal protein) test in 2021 and 2022 was 100% (40/40) and 90.9% (40/44), respectively. The accuracy pass rate of Free β-hCG (middle pregnancy) test in 2021 and 2022 was 100% (40/40) and 95.5% (42/44), respectively. The consistency of each index was 100%. In conclusion, the relevant data reported by laboratories carrying out serological prenatal screening in Jiangsu Province has a high consistency, and for a small number of laboratories with poor stability, it is necessary to make periodic evaluation and rectification according to the data analysis results, so as to improve the quality control management of maternal serological prenatal screening.

Objective:To study the diagnostic value of artificial intelligence B-ultrasound image computer-aided diagnosis system (hereinafter referred to as intelligent ultrasound system) in adult goiter.Methods:In June 2022 and March 2023, two phases of thyroid disease survey were carried out in 4 cities in Anhui Province. One village was selected in each city, and 250 adults were selected as survey subjects in each village. Adult bilateral thyroid area was scanned by both intelligent ultrasound system and conventional ultrasound scanning equipment, and the effectiveness of intelligent ultrasound system in the diagnosis of goiter was analyzed based on the results of conventional ultrasound examination. Receiver operating characteristic (ROC) curve was drawn, and Kappa test was used to analyze the consistency between intelligent ultrasound system and conventional ultrasound examination in the diagnosis of goiter. At the same time, Spearman correlation analysis and Bland-Altman method were used to evaluate the consistency of the two methods in measuring thyroid volume.Results:After screening and removing outliers and missing values, a total of 910 adults were included, including 253 males (27.80%) and 657 females (72.20%). The age was (45.92 ± 10.20) years old, ranging from 18 to 60 years old. The sensitivity, specificity, and accuracy of the intelligent ultrasound system for diagnosing adult goiter were 80.00%, 99.67%, and 99.56%, respectively. The area under the ROC curve (AUC) was 0.996, which was consistent with the results of conventional ultrasound examination for diagnosing goiter ( κ = 0.67, P < 0.001). After controlling for variables such as gender, thyroid function, and thyroid nodules, the intelligent ultrasound system showed good consistency with conventional ultrasound examination in the diagnosis of goiter in females, adults with thyroid dysfunction, and adults without thyroid nodules ( κ = 0.66, 0.80, 0.80, P < 0.001). The consistency in the diagnosis of goiter in adults with thyroid nodules was moderate ( κ = 0.56, P < 0.001). Spearman correlation analysis showed a highly positive correlation between the measurement results of adult thyroid volume by intelligent ultrasound system and conventional ultrasound examination ( r = 0.88, P < 0.001). The Bland-Altman method results showed that only 4.62% (42/910) of points in adults were outside the 95% consistency limit, indicating good consistency between intelligent ultrasound system and conventional ultrasound examination in measuring thyroid volume (< 5%). The proportion of points outside the 95% consistency limit in males, adults with thyroid dysfunction, and adults with thyroid nodules was 6.72% (17/253), 5.83% (12/206), and 6.45% (12/186), respectively. Conclusions:The intelligent ultrasound system has certain diagnostic value for adult goiter and has good consistency with conventional ultrasound examination for thyroid volume measurement. However, the accuracy of diagnosis for males and adults with thyroid nodules still needs to be improved.

Surgical position is very important in upper urinary calculi surgery.The correct surgical position can provide a good surgical field of view,shorten the operation time,reduce the incidence of complications,and ensure the safety of patients'airway and comfort.Endoscopic surgery is the preferred treatment for kidney and ureteral stones.As the traditional position causes higher recurrence rate and more complications,more positions have been experimented.This article reviews the application and therapeutic effects of different surgical positions in percutaneous nephrolithotomy(PCNL),retrograde intrarenal flexible ureteroscopic lithotripsy(RIRS)as well as their combined use,and summarizes the advantages and disadvantages for clinical reference.

In the implementation of exemption from ethical review,medical institutions equate exemption from ethical review with no ethical review or simple review,misunderstand the scope of exemption from ethical review,confuse the concepts of de-identification and anonymization,and equate privacy with personal information.The implementation faced challenges such as the coordination of conditions for exempt review with other regulations,the lack of clear decision-making subjects for exempting from ethical review,the legality and compliance of using general informed consent for biological samples and information data,as well as non-traceability and the risk of being re-identified of anonymous information for exemption from ethical review.Measures such as improving relevant laws and regulations,perfecting the construction and management of information databases and biological sample libraries,strengthening the project management and process supervision of exemption from ethical review,and implementing scientific review can ensure the legal and compliant implementation of exemption from ethical review by medical and health institutions.