Yuejuwan is a classic formula widely used by doctors to relieve liver and depression， with precise clinical efficacy in traditional Chinese medicine （TCM）. The authors used bibliometric methods to collect and collate 495 ancient data related to Yuejuwan， and 105 valid data were screened out， involving 68 ancient Chinese medical books. After systematic verification of the origin of the formula of Yuejuwan， the main treatment symptoms， the principle of the formula， the composition of the drug， the dosage， the preparation method， the decoction method， and other information， the results showed that Yuejuwan originated from the Danxi Xinfa （《丹溪心法》） of the Yuan Dynasty by ZHU Zhenheng， and it is composed of five medicines， namely Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， Massa Medicata Fermentata， and Gardeniae Fructus. In terms of drug base， Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， and Gardeniae Fructus are in line with the records in the 2020 edition of Chinese Pharmacopoeia， and Massa Medicata Fermentata is used. The preparation method is as follows： Massa Medicata Fermentata and Gardeniae Fructus are fried， and Cyperi Rhizoma is roasted in vinegar. Chuanxiong Rhizoma is used in the raw form， and Atractylodis Rhizoma is prepared with rice swill. The formula can regulate Qi and relieve depression and broaden the middle and remove fullness. It is clinically used for the treatment of six types of depression syndromes， chest and diaphragm plumpness， abdominal distension and leg acid， acid swallowing and vomiting， eating and drinking disharmony， toothache， mouth and tongue sores， and other diseases. The most used dosage of the formula in the ancient records through the ages is converted into the modern dosage， namely 3.05 g Atractylodis Rhizoma， 3.05 g Cyperi Rhizoma， 3.05 g Chuanxiong Rhizoma， 3.05 g Massa Medicata Fermentata， and 3.05 g Gardeniae Fructus， and the daily dosage is 15.25 g. The converted dosage is similar to that recorded in the 2020 edition of the Chinese Pharmacopoeia. The formula is in pill form， and medicine should be taken with lukewarm boiled water after the meal. Through the excavation of the ancient literature related to Yuejuwan， the key information of the formula is identified， with a view to providing a more accurate reference for the clinical application of Yuejuwan and subsequent in-depth investigation.

Yuejuwan is a classic formula widely used by doctors to relieve liver and depression， with precise clinical efficacy in traditional Chinese medicine （TCM）. The authors used bibliometric methods to collect and collate 495 ancient data related to Yuejuwan， and 105 valid data were screened out， involving 68 ancient Chinese medical books. After systematic verification of the origin of the formula of Yuejuwan， the main treatment symptoms， the principle of the formula， the composition of the drug， the dosage， the preparation method， the decoction method， and other information， the results showed that Yuejuwan originated from the Danxi Xinfa （《丹溪心法》） of the Yuan Dynasty by ZHU Zhenheng， and it is composed of five medicines， namely Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， Massa Medicata Fermentata， and Gardeniae Fructus. In terms of drug base， Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， and Gardeniae Fructus are in line with the records in the 2020 edition of Chinese Pharmacopoeia， and Massa Medicata Fermentata is used. The preparation method is as follows： Massa Medicata Fermentata and Gardeniae Fructus are fried， and Cyperi Rhizoma is roasted in vinegar. Chuanxiong Rhizoma is used in the raw form， and Atractylodis Rhizoma is prepared with rice swill. The formula can regulate Qi and relieve depression and broaden the middle and remove fullness. It is clinically used for the treatment of six types of depression syndromes， chest and diaphragm plumpness， abdominal distension and leg acid， acid swallowing and vomiting， eating and drinking disharmony， toothache， mouth and tongue sores， and other diseases. The most used dosage of the formula in the ancient records through the ages is converted into the modern dosage， namely 3.05 g Atractylodis Rhizoma， 3.05 g Cyperi Rhizoma， 3.05 g Chuanxiong Rhizoma， 3.05 g Massa Medicata Fermentata， and 3.05 g Gardeniae Fructus， and the daily dosage is 15.25 g. The converted dosage is similar to that recorded in the 2020 edition of the Chinese Pharmacopoeia. The formula is in pill form， and medicine should be taken with lukewarm boiled water after the meal. Through the excavation of the ancient literature related to Yuejuwan， the key information of the formula is identified， with a view to providing a more accurate reference for the clinical application of Yuejuwan and subsequent in-depth investigation.

Objective To analyze the proportion and clinicopathological characteristics of HER2-positive breast cancer patients with BRCA1/2 pathogenic variants, and their response to neoadjuvant anti-HER2 targeted therapy. Methods The clinicopathological data of 531 breast cancer patients with germline BRCA1/2 pathogenic variants (201 with BRCA1 variants and 330 with BRCA2 variants) were analyzed. Results Among the 201 BRCA1 and 330 BRCA2 variants, 17 (8.5%) and 42 (12.7%) HER2-positive breast cancer cases were identified, respectively, accounting for 11.1% of all BRCA1/2-mutated breast cancers. Compared with BRCA1/2-mutated HR-positive/HER2-negative patients, HER2-positive patients did not present any significant differences in clinicopathological features; however, compared with triple-negative breast cancer patients, HER2-positive patients had a later onset age and lower tumor grade. Among the 17 patients who received neoadjuvant anti-HER2 targeted therapy, 10 cases achieved pCR (58.8%), whereas 7 cases did not (41.2%). Conclusion HER2-positive breast cancer accounts for more than 10% of BRCA1/2-mutated patients. Approximately 40% of these patients fail to achieve pCR after neoadjuvant targeted therapy. This phenomenon highlights the possibility of combining anti-HER2 targeted agents with poly (adenosine diphosphate-ribose) polymerase inhibitors.

The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.

Alzheimer’s disease (AD) is a neurodegenerative disorder involving multiple pathological processes, clinically characterized by memory loss and cognitive impairment. The pathological processes of AD are complex, and the etiology remains unclear. Currently, there are various hypotheses including β-amyloid (Aβ) deposition, tau protein hyperphosphorylation, neuroinflammation, and synaptic loss, upon which researchers base their drug development efforts. Prior to 2021, drugs approved by the U.S. Food and Drug Administration (FDA) had targeted neurotransmitter modulation, but their efficacy was limited. In recent years, the approval of two anti-Aβ monoclonal antibody drugs has brought some clinical benefits to patients, yet they have not fully met clinical needs, which had highlighted the urgent necessity for exploration of new mechanisms and targets in AD drug development. Presently, research on novel mechanisms and targets for AD drug development focuses primarily on several directions: anti-Aβ drugs, anti-Tau protein drugs, anti-neuroinflammation immunotherapies, mitochondrial function-improving drugs, neurogenesis-promoting drugs, and synapse-protective drugs. This paper provides an overview of AD drugs entering clinical trials in the past decade in these directions, details some representative drugs, and concludes with prospects, integrating findings from our research group.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective:To evaluate the healthcare accessibility and quality of diagnosis and treatment services of Internet hospitals in China.Methods:One hundred and eighty Internet hospitals in 60 cities were seleted based on the sampling of development levels in the eastern, central and western regions of China. From April to May 2023, standardized patients methodology was applied to evaluate the accessibility(including the number of Internet hospitals, functional settings, online doctor status, the doctor′s attending rate and consultation fees) and diagnosis and treatment service quality(including the diagnosis and treatment services quality, response speed and patient′s evaluation) of Internet hospitals.Results:The average opening rate of Internet hospitals in China was 52.9% (560/1 058), the average online rate of doctors was 64.2% (1 099/1 713), the average doctor′s attending rate was 33.6% (112/333), the average consultation fee was 4.85 yuan, the average score of consultation was 1.92 out of 9, the average score of diagnosis and treatment was 1.12 out of 4, the average score of the response speed was 1.70 out of 3, and patient satisfaction was 2.73 out of 3.Conclusions:The Internet hospital accessibility in China is unevenly developed, and the overall quality of diagnosis and treatment is low. It is recommended to accurately position and optimize the function of Internet hospital, establish the incentive mechanism for online consultation doctors, construct and improve the regulatory system of Internet hospital diagnosis and treatment, so as to improve the accessibility and quality of diagnosis and treatment of Internet hospitals.

Objective:To examine the potential of combining the blood urea nitrogen(BUN)/albumin(ALB)ratio(BAR)with soluble growth stimulation expressed gene 2(sST2)as an early warning indicator for myocardial injury in elderly patients with sepsis in the emergency intensive care unit(EICU).Methods:The clinical data of elderly patients with sepsis admitted to the EICU of the Emergency Medicine Department at Harrison International Peace Hospital of Hebei Medical University from August 2018 to August 2022 were prospectively analyzed.The patients were divided into two groups based on the presence or absence of myocardial injury: the myocardial injury group and the non-myocardial injury group.The general clinical data and laboratory indexes of the two groups were compared, and the BAR was calculated.The correlation between BAR and myocardial injury in elderly patients with sepsis was analyzed.Binary Logistic regression analysis was used to identify the risk factors for myocardial injury in elderly patients with sepsis in the EICU.MedCalc software was employed to determine the early warning value of the combined sST2 and BAR for myocardial injury in elderly patients with sepsis in the EICU.Results:A total of 165 cases were analyzed, with 106 cases(64.24%)showing myocardial injury.It was found that elderly sepsis patients with lung and abdominal infection were more likely to experience myocardial injury( P<0.05 for all).In comparison to the group without myocardial injury, the levels of inflammatory markers such as white blood cell count(WBC), neutrophil to lymphocyte ratio(NLR), lactic acid, and procalcitonin(PCT), as well as combined markers BAR and sST2, were higher in elderly sepsis patients with myocardial injury upon admission.Correlation analysis results revealed significant positive correlations between BAR and lactic acid, PCT, and C-reactive protein(CRP)within 24 hours of admission to EICU in elderly sepsis patients with myocardial injury.Among these correlations, the strongest was observed between BAR and PCT( r=0.417, P<0.001).Additionally, BAR exhibited a positive correlation with acute physiology and chronic health evaluation scoring system(APACHEⅡ)scores( r=0.241, P=0.002).Furthermore, BAR showed positive correlations with myocardial injury markers sST2 and cTnI( r=0.327, 0.307, P<0.05 for all).Logistic regression analysis revealed that septic shock( OR=2.406, P=0.008), decreased left ventricular ejection fraction(EF)( OR=0.939, P=0.015), BAR( OR=2.205, P=0.044), lactic acid( OR=1.137, P=0.014), and sST2 elevation( OR=1.016, P=0.020)were identified as independent risk factors for predicting myocardial injury in elderly patients with sepsis.The results of ROC analysis indicated that BAR had a high early warning value for the occurrence of myocardial injury in elderly patients with EICU sepsis[area under curve(AUC)0.651, P<0.05], with an optimal cut-off value of 0.32(sensitivity 77.4%, specificity 60.2%).Furthermore, the combined detection of BAR and sST2 demonstrated a higher early warning value for the occurrence of myocardial injury in elderly patients with sepsis(AUC 0.697, P<0.05).The mortality rate of patients with myocardial injury below a cut-off value of 0.32 was 36.00%(9/25), while the mortality rate of patients with myocardial injury equal to or above 0.32 was 66.67%(54/81).The difference between the two groups was statistically significant( χ2=8.624, P=0.003). Conclusions:Both BAR and sST2 are considered independent risk factors for myocardial injury in elderly patients with sepsis.The combined detection of BAR and sST2 provides a more accurate prediction for the occurrence of myocardial injury in these patients.

Objective To retrospectively analyze the periprocedural and postprocedural antithrombotic therapy regimens for patients undergoing percutaneous left atrial appendage closure(PLAAC)at Nanjing Drum Tower Hospital(hereinafter referred to as"the hospital")and their association with prognosis,and to provide a basis for antithrombotic therapy in clinical practice for such patients.Methods We systematically collected medical records of non-valvular atrial fibrillation patients underwent PLAAC treatment from January 2018 to January 2022 at our hospital.We recorded basic patient information,preoperative left atrial appendage(LAA)thrombus screening,and antithrombotic regimens,and analyzed the incidence of bleeding and thrombotic events during the periprocedural period and up to 12 months postprocedure.Results A total of 96 patients underwent PLAAC,with 86 included in the final analysis.Eight patients had LAA thrombus detected by transesophageal echocardiography before the procedure,and all thrombi resolved after one month of extended antithrombotic therapy.There was one bleeding event in the continuous anticoagulation group during the periprocedural period,while no bleeding events occurred in the interrupted anticoagulation group.Within one year postprocedure,11 patients(18.0%)in the continuous anticoagulation group and 4 patients(16.0%)in the interrupted anticoagulation group experienced bleeding events.All patients adhered to anticoagulant therapy as prescribed for the first three months postprocedure;between three to six months postprocedure,33.7%of patients received dual antiplatelet therapy(DAPT),and 29.1%discontinued therapy;between six to twelve months,47.7%of patients received single antiplatelet therapy(SAPT)and 48.8%discontinued therapy.During the one-year follow-up,there was one case each of device-related thrombus,ischemic stroke,and cerebral hemorrhage,indicating a low overall incidence of adverse events.Conclusion In the real-world setting,the individualized antithrombotic regimens provided by physicians at the hospital,both periprocedurally and postprocedurally,were reasonable and consistent with guidelines.However,poor medication adherence was a significant issue among patients.It is recommended that clinical pharmacists actively engage in pharmacotherapy monitoring and enhance medication education to improve medication adherence.