Objective:To evaluate the survival benefit of surgical treatment for intrahepatic cholangiocarcinoma.Methods:This study is conducted based on the hepatobiliary tumor registry database. From May 2009 to December 2022,a total of 704 patients who were initially diagnosed with intrahepatic cholangiocarcinoma and underwent liver resection were consecutively enrolled at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University. Among them,there were 380 males and 324 females,aged ( M(IQR)) 61(15) years(range:27 to 88 years). Twenty-six (3.7%) patients received neoadjuvant therapy before surgery. The overall survival(OS) and disease-free survival(DFS) rates were estimated by life table method, and Kaplan-Meier survival curves were plotted. Log-rank test was used to compare the survival difference among tumor-node-metastasis(TNM) staging or three periods. The OS and DFS differences among lymph node groups or adjuvant treatment groups were quantified as HR with 95% CI estimated using Cox proportional-hazards model with adjustment for prognostic factors. Results:Among the 704 patients,349 cases(49.6%) underwent major hepatectomy (≥3 segments),331(47.0%) had lymph node resection during surgery,and 524 cases(74.4%) achieved R0 resection. The morbidity of Clavien-Dindo grade Ⅲ or higher complications was 16.5%(116/704),with a mortality rate of 3.0%(21/704) within 30 days post-surgery. The median OS time was 27.1 months, and the OS rates at 1-,3-,5- and 10-year were 69.1%, 42.4%,34.1% and 24.5%,respectively. The median DFS time was 10.5 months,and the corresponding DFS rates were 46.0%,25.4%,21.9% and 16.9%,respectively. According to the 8 th edition of AJCC staging system, the 5-year survival rates for ⅠA,ⅠB,Ⅱ,ⅢA,ⅢB and Ⅳ were 68.4%, 43.2%, 30.3%,32.2%,14.0% and 0,respectively. The corresponding DFS rates were 55.8%, 28.1%,13.8%,21.2%,3.3% and 0,respectively. There were no statistically significant differences of OS or DFS between stage ⅠB and Ⅱ, stage ⅠB and ⅢA, or between stage Ⅱ and ⅢA(Log-rank test:all P>0.05),while there were significant differences of OS and DFS among other stages(Log-rank test:all P<0.05). Using Cox model with adjustment for prognostic factors, there were no statistically significant differences of OS and DFS between non-lymphadenectomy group or the biopsy-N0 group and dissection-N0 group(both P>0.05). However,the overall and disease-free survival of the biopsy-N1 group or dissection-N1 group were worse than those of dissection-N0 group(both P<0.05),with overall survival being better in dissection-N1 group than biopsy-N1 group( P=0.017). Overall survival in the period from 2019 to 2022 were significantly superior to that during the periods from 2009 to 2013 and 2014 to 2018(both P<0.01). Adjusting for prognostic factors, the disease-free and overall survival of the postoperative adjuvant therapy group were significantly better than those of the observation group in the period 2019 to 2022(both P<0.01). Conclusions:Surgery remains a milestone for achieving long-term survival for patients with intrahepatic cholangiocarcinoma. Regional lymph node dissection is required for patients with lymph node metastasis. Adjuvant therapy can significantly reduce tumor recurrence and prolong overall survival.

In recent years,the incidence of heat-related diseases has been on a steady upward trend,which is closely associated with environmental factors such as climate change and air pollution.Exposure to a hot environment and/or strenuous physical activities can progress to heat stroke(HS),an acute disease that can lead to death.Current research indicates that gut injury occupies the most crucial initiating position in the pathophysiological changes and pathogenesis of HS.Probiotics can reduce the incidence and mortality of HS through maintaining the health of the gut microbiota,regulating the intestinal immune system,and other effects.In addition,the gut microbiota can construct axis systems to interact with multiple organs such as the liver,lungs,and brain,which is of great significance for alleviating the damage to distant organs caused by HS.This paper reviews the regulation of the gut microbiota by probiotics to improve the intestinal heat tolerance ability and barrier function,aiming to provide references for the prevention and treatment of heat stroke in clinical practice.

Artificial intelligence-based medical decision-making systems can significantly accelerate decision processes and enhance accuracy.However,challenges persist in achieving personalized care and in the compre-hensive collection of medical data.This paper explores potential solutions to these issues by examining AI ap-plications in diagnostic omics and multi-dimensional data acquisition,providing an overview of current pro-gress and limitations in developing intelligent medical decision systems through these approaches.Additional-ly,the paper also discusses the broad potential for artificial intelligence applications in medical education and their possible contributions to advancing overall decision-making standards in healthcare.

With the rapid development of artificial intelligence and machine learning algorithms in the med-ical field,as well as the high-quality development requirements put forward by the state for hospitals and vari-ous departments,the development of laboratory medicine shows a new trend.The development of clinical labo-ratory has evolved from the initial test suite to the test pathway based on clinical pathway and diagnosis-relat-ed groups payment,and then to clinical laboratory omics.Clinical laboratory omics refers to the use of high-throughput methods to obtain a large number of laboratory project results data.Combined with the clinical characteristics of patients,statistical methods and machine learning algorithms are commonly used to reveal the information behind a large number of medical data to assist clinicians in diagnosis and treatment.Clinical laboratory omics may be a new trend in the future development of laboratory medicine,and it is likely to play an important role in the field of laboratory medicine.

Objective:To investigate the feasibility of the bortezomib, lenalidomide, and dexamethasone (VRD) regimen combined with autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with multiple myeloma (MM) and renal impairment, analyze treatment efficacy and renal responses stratified based on renal dysfunction severity, and explore the prognostic significance of early renal response and its affecting factors.Methods:This retrospective study, conducted at the First Affiliated Hospital of Soochow University, categorized 316 patients with newly diagnosed MM (NDMM) from August 2018 to October 2022 based on renal function for analysis of clinical characteristics, treatment response, and prognosis. Continuous variables were compared using t-tests or Mann-Whitney U tests, categorical variables utilizing Chi-square tests, survival outcomes employing Kaplan-Meier and Log-rank tests, and renal response predictors with logistic regression.Results:Patients were stratified based on baseline estimated glomerular filtration rate (eGFR) : normal [≥90 ml·min -1· (1.73 m 2) -1, n=160], mild [≥60 ml·min -1· (1.73 m 2) -1 to <90 ml·min -1· (1.73 m 2) -1, n=55], moderate [≥30 ml·min -1· (1.73 m 2) -1 to <60 ml·min -1· (1.73 m 2) -1, n=39], and severe impairment [<30 ml·min -1· (1.73 m 2) -1, n=62]. Moderate and severe renal impairment correlated with advanced International Staging System/Revised International Staging System classification, lower hemoglobin levels, frailty, and higher light-chain/IgD subtype prevalence ( P<0.05). Despite younger age ( P=0.001) and higher transplant rates ( P=0.041) in severe cases, overall response rates ( ORR: 93.7% ; ≥VGPR: 82.9% ) were comparable across groups ( P>0.05). Among 24 dialysis-dependent patients at diagnosis, 11 (45.8% ) achieved dialysis independence after induction [median: 3.0 (0.5–4.0) months], including 10 undergoing auto-HSCT. In 89 evaluable patients [baseline eGFR <50 ml·min -1· (1.73 m 2) -1], renal ORR (RORR) was 70.8% [rapid complete response: 31.5% ; rapid partial response: 11.2% ; rapid minimal response (RMR) : 28.1% ]. Renal response predicted better survival (overall survival: HR=0.36, 95% CI: 0.13–0.99, P=0.049). Moderate-to-severe renal impairment was associated with increased transplant-related adverse events and delayed engraftment ( P<0.05) ; however, auto-HSCT significantly improved outcomes after 33.5-month median follow-up (range: 2–65 months). Multivariate analysis identified 1q21+ ( OR=3.58, 95% CI: 1.17–11.02, P=0.026) and light-chain subtype ( OR=2.86, 95% CI: 1.08–7.69, P=0.036) as independent predictors of poor renal response. Conclusion:VRD regimen plus auto-HSCT demonstrates robust efficacy in NDMM, including patients with renal impairment, with a 70.8% RORR and manageable toxicity. Achieving ≥RMR correlates with superior prognosis, whereas 1q21+ and light-chain subtype independently predict inferior renal response.

Objective:To investigate the epidemiological and genetic characteristics of hand, foot and mouth disease (HFMD) caused by coxsackievirus A6 (CVA6) in Xi′an city from 2021 to 2023.Methods:Collected clinical cases of HFMD, epidemiological information and samples were obtained. The specimens were tested by the real-time RT-PCR for enterovirus A71(EVA71), CVA16, CVA6 and CVA10, respectively. The VP1 regions of CVA6 were amplified and sequenced, MEGA X was used for phylogenetic analysis.Results:From 2021 to 2023, a total of 1 393 HFMD samples were collected, 1 106 (79.40%, 1 106/1 393) of which were positive for enteroviruses. The proportions of EVA71, CVA16, CVA6 and CVA10 were 0.45% (5/1 106), 16.64% (184/1 106), 72.42% (801/1 106) and 2.17% (24/1 106). A total of 801 HFMD cases tested positive for CAV6, including 783 mild cases and 18 severe cases, mainly in children aged ≤5 years (86.02%, 689/801), with a male/female ratio of 1.49∶1. The composition ratio of CVA6 infection differed with year(χ 2=332.62, P<0.01), and the highest composition ratio of CVA6 was in 2023 (91.01%, 638/701). The nucleotide and amino acid similarities in the VP1 region of Xi′an strains of CVA6 were 92.4%-99.8% and 98.3%-100.0%, respectively. Compared with the CVA6 prototype strain(Gdula), the nucleotide and amino acid similarities in the VP1 region of Xi′an strains were 82.2%-84.0% and 95.4%-96.0%, respectively, and there were 18 amino acid mutations in different degrees. Based on the phylogenetic analysis of VP1 region sequences, the CVA6 strains in Xi′an city from 2021 to 2023 belonged to D3a subtype, and could be divided into two clusters with 18 strains in cluster 1 while two strain in cluster 2. Conclusions:The sub-genotype D3a of CVA6 is the predominant virus causing HFMD in Xi′an city from 2021 to 2023, and there are two transmission chains. The monitoring and prevention of CVA6 should be strengthened.

T7 RNA polymerase (T7 RNAP) is one of the simplest known RNA polymerases. Its unique structural features make it a critical model for studying the mechanisms of RNA synthesis. This review systematically examines the static crystal structure of T7 RNAP, beginning with an in-depth examination of its characteristic “thumb”, “palm”, and “finger” domains, which form the classic “right-hand-like” architecture. By detailing these structural elements, this review establishes a foundation for understanding the overall organization of T7 RNAP. This review systematically maps the functional roles of secondary structural elements and their subdomains in transcriptional catalysis, progressively elucidating the fundamental relationships between structure and function. Further, the intrinsic flexibility of T7 RNAP and its applications in research are also discussed. Additionally, the review presents the structural diagrams of the enzyme at different stages of the transcription process, and through these diagrams, it provides a detailed description of the complete transcription process of T7 RNAP. By integrating structural dynamics and kinetics analyses, the review constructs a comprehensive framework that bridges static structure to dynamic processes. Despite its advantages, T7 RNAP has a notable limitation: it generates double-stranded RNA (dsRNA) as a byproduct. The presence of dsRNA not only compromises the purity of mRNA products but also elicits nonspecific immune responses, which pose significant challenges for biotechnological and therapeutic applications. The review provides a detailed exploration of the mechanisms underlying dsRNA formation during T7 RNAP catalysis, reviews current strategies to mitigate this issue, and highlights recent progress in the field. A key focus is the semi-rational design of T7 RNAP mutants engineered to minimize dsRNA generation and enhance catalytic performance. Beyond its role in transcription, T7 RNAP exhibits rapid development and extensive application in fields, including gene editing, biosensing, and mRNA vaccines. This review systematically examines the structure-function relationships of T7 RNAP, elucidates the mechanisms of dsRNA formation, and discusses engineering strategies to optimize its performance. It further explores the engineering optimization and functional expansion of T7 RNAP. Furthermore, this review also addresses the pressing issues that currently need resolution, discusses the major challenges in the practical application of T7 RNAP, and provides an outlook on potential future research directions. In summary, this review provides a comprehensive analysis of T7 RNAP, ranging from its structural architecture to cutting-edge applications. We systematically examine: (1) the characteristic right-hand domains (thumb, palm, fingers) that define its minimalistic structure; (2) the structure-function relationships underlying transcriptional catalysis; and (3) the dynamic transitions during the complete transcription cycle. While highlighting T7 RNAP’s versatility in gene editing, biosensing, and mRNA vaccine production, we critically address its major limitation—dsRNA byproduct formation—and evaluate engineering solutions including semi-rationally designed mutants. By synthesizing current knowledge and identifying key challenges, this work aims to provide novel insights for the development and application of T7 RNAP and to foster further thought and progress in related fields.

Objective:To evaluate the epidemiological characteristics and influencing factors of out-of-hospital sudden cardiac death (SCD) in Hangzhou from 2016 to 2019.Methods:SCD events recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019 were reviewed. Demographic and mortality data were recorded, and the distribution patterns of SCD events in terms of date, time, and population with different characteristics were observed. Time series analysis method and a distributed lag nonlinear model based on quasi-Poisson distribution were used to explore the possible nonlinear association between ambient temperature and SCD incidence.Results:A total of 4 744 out-of-hospital sudden death events were recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019. After excluding non-SCD events and observed events with missing items, 3 743 SCD events were finally included in the study. The survey results showed that the incidence of out-of-hospital SCD in Hangzhou was 96.5 cases per 100 000 person-years. Most of the people who experienced SCD were aged ≥60 years. The incidence in males (2 462 cases, 66%) was significantly higher than that in females (1 281 cases, 34%), and the proportion of events occurring during the day (2 737 cases, 73%) was significantly higher than that at night (1 006 cases, 27%), mainly occurring between 7: 00 and 9: 00. High temperature was associated with an increased risk of SCD. When the average daily temperature was higher than 25.5 ℃, the risk of SCD increased with the further increase of average daily temperature.Conclusions:SCD events mainly occur in the elderly population aged ≥60 years, with a significantly higher incidence in males than in females, and more frequently during the day than at night, mainly between 7: 00 and 9: 00 in the morning. High temperature is closely related to the risk of SCD. It is particularly important to carry out targeted SCD screening and prevention for different populations and implement appropriate prevention strategies for high-risk groups of SCD in high-temperature weather.

In recent years, the reform of the registration, evaluation, and approval system for traditional Chinese medicine(TCM) has been promoted at the national level, with establishment of an evaluation evidence system for TCM registration that combines TCM theory, human use experience, and clinical trials(known as the "three-combined" evaluation evidence system). This system, which aligns with the characteristics of TCM clinical practice and the laws of TCM research and development, recognizes the unique value of human use experience in medicine and returns to the essence of medicine as an applied science, thus receiving widespread recognition from both academia and industry. However, it meanwhile poses new and higher challenges. This article delves into the value and challenges faced by the "three-combined" evaluation evidence system from three perspectives: registration management, medical institutions, and the TCM industry. Furthermore, it discusses how the China Association of Chinese Medicine, leveraging its academic platform advantages and leading roles, has made exploratory and practical efforts to facilitate the research and development of new TCM drugs and the implementation of the "three-combined" evaluation evidence system.
Drugs, Chinese Herbal/standards* ; Humans ; Medicine, Chinese Traditional/standards* ; China ; Drug Development

In this study, we explored the pharmacological effects of Siwu Decoction in treating premature ovarian insufficiency(POI) and its molecular mechanism based on the mitophagy pathway modulated and mediated by estrogen receptor(ER) subtypes. Female Balb/c mice were divided into a control group, model group, as well as high-dose and low-dose groups of Siwu Decoction. The POI mice model was constructed by intraperitoneal injection of cisplatin. The high-dose and low-dose groups of Siwu Decoction were administered intragastrically with Siwu Decoction each day for 14 days. During this period, we monitored the estrous cycle and body weight of the mice and calculated the ovarian index. The morphology of the ovaries was detected by hematoxylin-eosin(HE) staining, and the number of primordial follicles was counted. The apoptosis of the ovarian tissue was detected by TUNEL staining. The expression levels of anti-Müllerian hormone(AMH), apoptosis-associated and mitophagy-associated proteins, ER subtypes, and the expression levels of key proteins of its mediated molecular pathways were detected by Western blot and immunohistochemistry. KGN cells were divided into a control group, model group, Siwu Decoction group, and gene silencing group. The apoptosis model was induced by H_2O_2, and PTEN-induced putative kinase 1(PINK1) gene silencing was induced by siRNA transfection. The Siwu Decoction group and gene silencing group were added to the medium containing Siwu Decoction. Cell viability was detected by CCK-8 assay. Cell senescence was detected by senescence-associated-β-galactosidase. The expression levels of apoptosis-associated and mitophagy-associated proteins were detected by Western blot. The results of in vivo experiments showed that compared with the model group, the mice in the high-dose and low-dose groups of Siwu Decoction significantly recovered the rhythm of the estrous cycle, and the levels of ovarian index, number of primordial follicles, and expression of AMH, representative indexes of ovarian function, were significantly higher, suggesting that the level of ovarian function was significantly improved. The expression levels of the apoptosis-related proteins, cytochrome C(Cyt C), cysteinyl aspartate specific proteinase 3(caspase 3), B-cell lymphoma-2(Bcl-2)-associated X(Bax), and mitophagy-associated indicator(Beclin 1) were significantly decreased, and the expression levels of Bcl-2 was significantly elevated. The positive area of TUNEL was significantly reduced, suggesting that the apoptosis level of the ovaries was significantly reduced. The expression levels of PINK1, Parkin, and sequestosome 1(p62) were significantly reduced, suggesting that the level of ovarian mitophagy was significantly down-regulated. The expression levels of ERα and ERβ were significantly elevated, and the ratio of ERα/ERβ was significantly reduced. The expression levels of key proteins in the pathway, phosphoinositide 3-kinase(PI3K) and protein kinase B(Akt), were significantly reduced, suggesting that the regulation of ER subtypes and the mediation of PI3K/Akt pathway were the key mechanisms. In vitro experiments showed that compared with the model group, the proportion of senescent cells in the Siwu Decoction group was significantly reduced. Cyt C, caspase 3, Beclin 1, Parkin, and p62 were significantly reduced, which was in line with in vivo experimental results. The proportion of senescent cells and the expression level of the above proteins were further significantly reduced after PINK1 silencing. It can be seen that Siwu Decoction can regulate the expression level and proportion of ER subtypes in KGN cells, then mediate the PI3K/Akt pathway to inhibit excessive mitophagy and apoptosis, and exert therapeutic effects of POI.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Mitophagy/drug effects* ; Primary Ovarian Insufficiency/physiopathology* ; Mice ; Mice, Inbred BALB C ; Humans ; Receptors, Estrogen/genetics* ; Apoptosis/drug effects* ; Ovary/metabolism* ; Signal Transduction/drug effects* ; Anti-Mullerian Hormone/genetics*