Viruses,with high adaptability and immune evasion capabilities,are responsible for a wide spectrum of diseases from lo-calized infections to global pandemics,continuously posing threats to global public health.In recent years,traditional Chinese medi-cine(TCM)has demonstrated significant potential in antiviral therapy.With its multi-component,multi-target synergistic mechanism,TCM offers unique advantages in the intervention of viral diseases.However,progress in elucidating the active antiviral constituents of TCM and identifying their precise molecular targets remains limited,primarily due to the lack of humanized models that can faithfully recapitulate the natural course of viral infection.The emergence of organoid technology has introduced new opportunities for antiviral research in TCM.Human organoids,which recapitulate the three-dimensional architecture and physiological functions of human tis-sues,provide an advanced platform for modeling host-virus interactions in a human-relevant context.This article highlights the latest advances in applications of human tissue organoids,including lung,liver,and brain organoids,in the study of respiratory viruses(SARS-CoV-2,influenza virus,respiratory syncytial virus),hepatitis viruses(HBV,HCV,HEV),and neurotropic viruses(ZIKV,pri-ons,HCMV);illustrates how organoid models have been leveraged to evaluate both the efficacy and safety of TCM-based antiviral inter-ventions.Although human tissue organoids still face technical challenges in insufficient vascularization and incomplete immune micro-environment,they represent a powerful tool for dissecting the mechanism of TCM antiviral action and for guiding the development of personalized antiviral strategies.Looking ahead,human tissue organoid technology is expected to become key enabling platform for pro-moting the clinical transformation of TCM in the field of antiviral medicine.

To enhance the practical ability and job competency of full-time master of public health (MPH) postgraduates and explore a collaborative training mode that integrates medical education with a prevention-and-control approach, in line with standardized public health physician training, the Beijing Center for Disease Control and Prevention, in collaboration with the School of Public Health affiliated to Capital Medical University, had recruited full-time MPH postgraduates since 2015. These students were trained and assessed through a collaborative training mode based on the Beijing public health physician training mechanism. Through the introduction and analysis of the training objectives, training process, practical assessment methods, training quality, and results, this article suggests that the construction of a collaborative training mode integrating MPH postgraduate education of public health professionals and standardized public health physician training has explored a new pathway for cultivating "four-certification integration" public health professionals. This aligns with the Chinese national strategy for public health talent development and can alleviate the problems of "contradictions between work and study", including the current shortage of public health physicians at present and the difficulties in standardized training enrollment. In addition, this collaborative training mode provides valuable experience for other medical schools in training applied public health professionals who meet national public health standards and combine prevention with treatment.

Objective To analyze the research hotspots and trends of invasive fungal infections(IFIs)in China over the past 24 years,and provide references and suggestions for future research.Methods Literatures on IFIs re-search in China from 2000 to 2024 were retrieved from China National Knowledge Infrastructure(CNKI)and Web of Science(WOS).CiteSpace software was employed to conduct collaboration network analysis on authors' institu-tions,and co-occurrence,clustering,and burst analyses were conducted on key words.Results A total of 2 479 li-teratures retrieved from CNKI and 1 149 from WOS were included in the analysis,involving 295 research institu-tions,with no core research team identified having a intermediary centrality＞0.1.Institutions with intermediary centrality＞0.1 included Chinese Academy of Sciences,Peking University,Fudan University,Sun Yat-sen Univer-sity and Zhejiang University.Key words with high centrality included"diagnosis""risk factor""voriconazole"and"Candida albicans".Clustering analysis grouped the co-occurrence network of key words into 6 clusters,mainly covering fungal diagnosis,treatment,and susceptible factors.Since 2020,focuses on the safety of antifungal treat-ment agents and primary prevention have emerged,with hot topics including pharmacokinetics,children,clinical features,and risk factors.Conclusion Currently,research teams are dispersed with insufficient interdisciplinary collaboration.Research topics are relatively simple.It is necessary to strengthen research on fungal resistance and healthcare-associated infection prevention and control.Risk factors and prevention measures for IFIs may be the fo-cus of future research.

OBJECTIVE: Lipid oxidation is involved in the pathogenesis of atherosclerosis and may be contribute to the development of Ischemic stroke (IS). However, the lipid profiles associated with IS have been poorly studied. We conducted a pilot study to identify potential IS-related lipid molecules and pathways using lipidomic profiling. METHODS: Serum lipidomic profiling was performed using LC-MS in 20 patients with IS and 20 age- and sex-matched healthy controls. Univariate and multivariate analyses were simultaneously performed to identify the differential lipids. Multiple testing was controlled for using a false discovery rate (FDR) approach. Enrichment analysis was performed using MetaboAnalyst software. RESULTS: Based on the 294 lipids assayed, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were used to distinguish patients with IS from healthy controls. Fifty-six differential lipids were identified with an FDR-adjusted P less than 0.05 and variable influences in projection (VIP) greater than 1.0. These lipids were significantly enriched in glycerophospholipid metabolism (FDR-adjusted P = 0.009, impact score = 0.216). CONCLUSIONS Serum lipid profiles differed significantly between patients with IS and healthy controls. Thus, glycerophospholipid metabolism may be involved in the development of IS. These results provide initial evidence that lipid molecules and their related metabolites may serve as new biomarkers and potential therapeutic targets for IS.
Humans ; Pilot Projects ; Lipidomics ; Male ; Female ; Biomarkers/blood* ; Middle Aged ; Ischemic Stroke/blood* ; Aged ; China ; Lipids/blood* ; Adult ; Case-Control Studies ; East Asian People

BACKGROUND: Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia. We compared the effects of acarbose and sitagliptin add on to metformin on time in range (TIR) and glycemic variability (GV) in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring (CGM). METHODS: This study was a randomized, open-label, active-con-trolled, parallel-group trial conducted at 15 centers in China from January 2020 to August 2022. We recruited patients with type 2 diabetes aged 18-65 years with body mass index (BMI) within 19-40 kg/m 2 and hemoglobin A1c (HbA1c) between 6.5% and 9.0%. Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days. After the first 14-day treatment period, patients wore CGM and entered another 14-day treatment period. The primary outcome was the level of TIR after treatment between groups. We also performed time series decomposition, dimensionality reduction, and clustering using the CGM data. RESULTS: A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin. There was no statistically significant difference in TIR between the two groups. Time below range (TBR) and coefficient of variation (CV) levels in acarbose users were significantly lower than those in sitagliptin users. Median (25th percentile, 75th percentile) of TBR below target level <3.9 mmol/L (TBR 3.9 ): Acarbose: 0.45% (0, 2.13%) vs . Sitagliptin: 0.78% (0, 3.12%), P = 0.042; Median (25th percentile, 75th percentile) of TBR below target level <3.0 mmol/L (TBR 3.0 ): Acarbose: 0 (0, 0.22%) vs . Sitagliptin: 0 (0, 0.63%), P = 0.033; CV: Acarbose: 22.44 ± 5.08% vs . Sitagliptin: 23.96 ± 5.19%, P <0.001. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV (group with small wave, moderate wave and big wave). No significant difference was found in the complexity of glucose time series index (CGI) between acarbose users and sitagliptin users. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV. CONCLUSIONS: Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia. Time series analysis of CGM data may predict GV and the risk of hypoglycemia. TRIAL REGISTRATION Chinese Clinical Trial Registry: ChiCTR2000039424.
Humans ; Metformin/therapeutic use* ; Sitagliptin Phosphate/therapeutic use* ; Acarbose/therapeutic use* ; Diabetes Mellitus, Type 2/blood* ; Middle Aged ; Male ; Female ; Adult ; Blood Glucose/drug effects* ; Hypoglycemic Agents/therapeutic use* ; Aged ; Glycated Hemoglobin/metabolism* ; Adolescent ; Young Adult ; China ; East Asian People

Hematologic malignancies, including leukemia, lymphoma, and multiple myeloma, are hazardous diseases characterized by the uncontrolled proliferation of cancer cells. Dysregulated cell cycle resulting from genetic and epigenetic abnormalities constitutes one of the central events. Importantly, cyclin-dependent kinases (CDKs), complexed with their functional partner cyclins, play dominating roles in cell cycle control. Yet, efforts in translating CDK inhibitors into clinical benefits have demonstrated disappointing outcomes. Recently, mounting evidence highlights the emerging significance of WEE1 G2 checkpoint kinase (WEE1) to modulate CDK activity, and correspondingly, a variety of therapeutic inhibitors have been developed to achieve clinical benefits. Thus, WEE1 may become a promising target to modulate the abnormal cell cycle. However, its function in hematologic diseases remains poorly elucidated. In this review, focusing on hematologic malignancies, we describe the biological structure of WEE1, emphasize the latest reported function of WEE1 in the carcinogenesis, progression, as well as prognosis, and finally summarize the therapeutic strategies by targeting WEE1.
Humans ; Protein-Tyrosine Kinases/physiology* ; Hematologic Neoplasms/drug therapy* ; Cell Cycle Proteins/antagonists & inhibitors* ; Nuclear Proteins/antagonists & inhibitors* ; Cyclin-Dependent Kinases ; Molecular Targeted Therapy ; Animals

OBJECTIVE: To compare the short-term clinical efficacy and safety of closed reduction with Kirschner wire fixation versus open reduction with plate fixation for treating osteoporotic Colles' fractures in middle-aged and elderly patients. METHODS: Between January 2018 and January 2023, 119 patients with Colles fractures were retrospectively analyzed, including 39 males and 80 females, aged from 48 to 74 years old with an average of(60.58±6.71) years old. The time from injury to operation ranged 1 to 13 days with an average of (5.29±2.52) days. According to the surgical method, they were divided into Kirschner wire fixation group (Kirschner wire group) and plate internal fixation group (plate group). In Kirschner wire group, there were a total of 68 patients, comprising 21 males and 47 females. The average age was (61.15±6.24) years old, ranged from 49 to 74 years old. Among them, 41 cases involved the left side while 27 cases involved the right side. In the plate group, there were a total of 51 patients, including 18 males and 33 females. The average age was (59.78±5.71) years old ranged from 48 to 72 years old. Among them, there were 31 cases on the left side and 20 cases on the right side. The following parameters were recorded before and after the operation:operation time, intraoperative blood loss, hospitalization days, hospitalization expenses, postoperative complications, and radiographic parameters of distal radius (distal radius height, ulnar deviation angle, palmar tilt angle). The clinical efficacy was evaluated at 3 and 12 months after the operation using Gartland-Werley and disabilites of the arm shoulder and hand (DASH) scores. RESULTS: The patients in both groups were followed up for a duration from 12 to 19 months with an average of(13.32±2.02) months. The Kirschner wire group exhibited significantly shorter operation time compared to the plate group 27.91(13.00, 42.00) min vs 67.52(29.72, 105.32) min, Z=-8.74, P=0.00. Intraoperative blood loss was also significantly lower in the Kirschner wire group than in the plate group 3.24(1.08, 5.40) ml vs 21.91(17.38, 26.44) ml, Z=-9.31, P=0.00. Furthermore, patients in the Kirschner wire group had a shorter length of hospital stay compared to those in the plate group (8.38±2.63) days vs (11.40±2.78) days, t=-3.12, P=0.00. Additionally, hospitalization cost was significantly lower in the Kirschner wire group than in the plate group 10 111.29(6 738.98, 13 483.60) yuan vs 15 871.11(11 690.40, 20 051.82) yuan, Z=-5.62, P=0.00. The incidence of complications was 2 cases in the Kirschner wire group and 1 case in the plate group, with no statistically significant difference(P>0.05). At 3 months postoprative, the radial height of the Kirschner wire group was found to be significantly smaller than that of the plate group, with measurements of (11.45±1.69) mm and (12.11±1.78) mm respectively (t=-2.06, P=0.04). However, there were no statistically significant differences observed in ulnar deviation angle and palmar tilt angle between the two groups (P>0.05). The DASH score and Gartland-Werley score in the Kirschner group were significantly higher than those in the plate group at 3 months post-operation (19.10±9.89) vs (13.47±3.51), t=4.34, P=0.00;(11.15±3.61) vs (6.41±2.75), t=8.13, P=0.00). However, there was no significant difference between the two groups at 12 months post-operation (P>0.05). CONCLUSION Compared to plate internal fixation, closed reduction with Kirschner wire support fixation yields a slightly inferior recovery of radial height;however, there is no significant disparity in the functional score of the affected limb at 12 months post-operation. Nonetheless, this technique offers advantages such as shorter operation time, reduced intraoperative blood loss, decreased hospitalization duration, and lower cost.
Humans ; Female ; Male ; Middle Aged ; Aged ; Fracture Fixation, Internal/instrumentation* ; Bone Wires ; Bone Plates ; Retrospective Studies ; Colles' Fracture/surgery* ; Minimally Invasive Surgical Procedures/methods* ; Open Fracture Reduction/methods* ; Osteoporotic Fractures/surgery*

Objective To assess the exposure levels of heavy metals,including lead,arsenic,mercury,and cadmium,in the local population in Sichuan and Chongqing,China,to compare and analyze the differences in reference intervals(RIs)obtained from direct and indirect sampling methods,and to explore the interchangeability and limitations of these two sampling methods.Methods RIs were obtained by the direct sampling method and the indirect sampling method.In the direct sample method,the levels of blood arsenic,urinary cadmium,urinary mercury,and blood lead levels of 5562 healthy participants aged 22-50 years in Sichuan and Chongqing,China were measured by atomic absorption spectrometry and inductively coupled plasma-mass spectrometry.Using the human biomonitoring(HBM)data,we established RIs for the population by a nonparametric method.On the other hand,in the indirect sampling method,RIs were established via a nonparametric method based on data from the laboratory information system(LIS)of a local hospital after stratifying healthy individuals using a Gaussian mixture model(GMM).Comparative analysis of the RIs derived from the two sampling methods were then conducted.Results The RI for blood arsenic was 0.11-1.3 μmol/L.The RI for urinary cadmium was 0.51-2.80 μmol/mol creatine for adults aged 22 to under 43 years and 0.66-2.96 μmol/mol creatine for adults aged 43-50 years.The RI for urinary mercury was 0.12-1.10 μmol/mol creatine.The RI for blood lead was 14.00-47.00 pg/L for adults aged 22 to under 41 year,16.00-53.38 pg/L for males aged 41-50 year,and 15.00-51.02 pg/L for females aged 41-50 year.Most of the RIs established by the direct sampling method had a narrower range compared to those established by the indirect sampling method,and the RIs established by both sampling methods were partially biased.Conclusions The RIs for blood arsenic,urine cadmium,urine mercury,and blood lead in healthy individuals aged 22-50 years in Sichuan and Chongqing,China were established using both direct and indirect sampling methods,which contributes to a better understanding of environmental exposure to metals in the general population and provides a reference for metal poisoning.For data from the same lab,the GMM-based indirect sampling method demonstrated relatively consistent performance in establishing RIs compared with the direct sampling method.

In recent years, as societal perceptions have evolved and women's social standing has improved, the average age of childbearing for women in China has generally increased. This shift has contributed to a notable decline in fertility rates among Chinese women. The introduction of the "three-child" policy and the inclusion of assisted reproductive technology (ART) in medical insurance coverage across many regions have further fueled the rapid rise in demand for ART among older women. However, numerous high-level evidence-based medical studies have confirmed that age remains a critical factor influencing the success rates of ART treatments. Many older women seeking pregnancy assistance, particularly than aged 43 years and above, continue to experience unsatisfactory outcomes despite multiple attempts at ART. Therefore, considering the principles of beneficence, protection of offspring, and social welfare, and in light of relevant domestic and international guidelines, consensus, policies, regulations, and research data, should there be an age limit for high-aged patients undergoing ART treatments? This issue warrants a thorough ethical examination.

In recent years, as societal perceptions have evolved and women's social standing has improved, the average age of childbearing for women in China has generally increased. This shift has contributed to a notable decline in fertility rates among Chinese women. The introduction of the "three-child" policy and the inclusion of assisted reproductive technology (ART) in medical insurance coverage across many regions have further fueled the rapid rise in demand for ART among older women. However, numerous high-level evidence-based medical studies have confirmed that age remains a critical factor influencing the success rates of ART treatments. Many older women seeking pregnancy assistance, particularly than aged 43 years and above, continue to experience unsatisfactory outcomes despite multiple attempts at ART. Therefore, considering the principles of beneficence, protection of offspring, and social welfare, and in light of relevant domestic and international guidelines, consensus, policies, regulations, and research data, should there be an age limit for high-aged patients undergoing ART treatments? This issue warrants a thorough ethical examination.