HR-positive HER2-low breast cancer is a new hotspot therapeutic subtype, accounting for approximately 53.7% of all breast cancers. Patients with this type of cancer tend to have a high rate of lymph node metastasis and poor sensitivity to neoadjuvant chemotherapy and conventional anti-HER2 therapy, and exploring therapeutic strategies for this subtype of patient is a current clinical challenge. Therapeutic strategies for HR-positive HER2-low breast cancer are constantly being updated, including CDK4/6 inhibitors across the lines of therapy, and next-generation antibody-drug conjugates such as T-DXd. With the accumulation of high-level evidence-based evidence for HR-positive HER2-low breast cancer in the future, the research data will provide more practical support for precise diagnosis and treatment, thereby improving the prognosis of patients with HR-positive HER2-low breast cancer.

Objective To explore the effective induction scheme for differentiation of adipose-derived mesenchymal stem cell (ADMSC) to insulin producing cell (IPC). Methods Different schemes of small molecule compound were used to induce the differentiation of ADMSC. The purity of cells was analyzed by flow cytometry and the morphological changes of cells were observed under the microscope. The quality, performance and insulin related indicators of cells were detected by hematoxylin-eosin and immunohistochemical staining. The maturity and activity of cells were detected by dithizone (DTZ) and diacetylfluorescein/propidium iodide staining. The induction effect of ADMSC differentiated into IPC was analyzed. Results The purity of ADMSC reached more than 99%, and the sphere forming properties of schemes Ⅰ, Ⅱ and Ⅲ were good. Cell induction mass, the expression effects of pancreatic and duodenal homeobox 1 (PDX1), musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA) and insulin and C peptide of schemes Ⅰ were both better than those of other schemes. The DTZ staining depth may be related to IPC maturity, among which the number of apoptotic cells in scheme Ⅰ was significantly less than that of scheme Ⅱ and Ⅲ. Conclusions Induction scheme Ⅰ may improve the differentiation efficiency of ADMSC to IPC and lay a certain foundation for future clinical IPC transplantation applications.

Due to its synergistic effects and reduced side effects, combination therapy has become an important strategy for treating complex diseases. In traditional Chinese medicine (TCM), the "monarch, minister, assistant, envoy" compatibilities theory provides a systematic framework for drug compatibility and has guided the formation of a large number of classic formulas. However, due to the complex compositions and diverse mechanisms of action of TCM, it is difficult to comprehensively reveal its potential synergistic patterns using traditional methods. Synergistic prediction based on molecular compatibility theory provides new ideas for identifying combinations of active compounds in TCM. Compared to resource-intensive traditional experimental methods, artificial intelligence possesses the ability to mine synergistic patterns from multi-omics and structural data, providing an efficient means for modeling and optimizing TCM combinations. This paper systematically reviews the application progress of AI in the synergistic prediction of TCM active compounds and explores the challenges and prospects of its application in modeling combination relationships, thereby contributing to the modernization of TCM theory and methodological innovation.
Artificial Intelligence ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Drug Synergism

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

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Objective To determine the rules of acupoint selection for hiccup based on data mining.Methods From the acupuncture and moxibustion sections of 53 medical books included in the 5th edition of Chinese Medical Classics,entries related to acupuncture treatment for hiccups was screened and constructed a"Classical Chinese Medicine Database for Acupuncture Treatment of Hiccups."Data mining techniques,including cluster analysis and association rule analysis,were employed to study the characteristics and patterns of acupoint selection for hiccup treatment in ancient medical texts.Results A total of 126 prescriptions were collected,involving 65 acupoints with a total application frequency of 172 times.The most frequently selected acupoints were Taiyuan(LU9),Shaoshang(LU11),Shiguan(KI18),Wenliu(LI7),Laogong(PC8),and Zusanli(ST36).The primary meridians used were the conception vessel(CV1)and the lung meridian of hand-taiyin.The most commonly stimulated body regions were the upper limbs and the chest/abdomen.Among special acupoint categories,the five-shu points and crossing points were predominantly utilized.Cluster analysis identified two significant clusters:Daling(PC7)-Ximen(PC4)-Yuji(LU10),and Qimen(LR14)-Chengjiang(CV24)-Dadun(LR1)-Guanyuan(CV4)-Juque(CV14).Association rule analysis revealed the strongest acupoint correlation between Danzhong(CV17)and Zhongwan(CV12),followed by the combination of Danzhong-Zhongwan-Zusanli.Conclusion In ancient acupuncture treatment of hiccups,particular emphasis was placed on the flexible combination of Taiyuan-Shaoshang and Danzhong-Zhongwan with other acupoints.This approach fully embodies the meridian syndrome differentiation principle of"where the meridian passes,it can treat"and"where the disease locates,it can treat."The selection follows the acupoint pairing principles of"combining distal and local points"and"coordinating upper and lower regions",while also emphasizing the application of specific acupoint categories.

Objective To analyze the differences in clinical indicators between malignant insulinoma and benign in-sulinoma,in order to provide diagnostic and therapeutic insights for the early detection and diagnosis of malignant insulinoma.Methods A retrospective analysis was conducted in patients diagnosed and treated for insulinoma at Peking Union Medical College Hospital from January 2018 to June 2022.Among them,10 cases were diagnosed as malignant insulinoma.Twenty cases of benign insulinoma patients matched for age,sex,and body mass index(BMI),were randomly selected.Statistical analysis was performed to compare the differences between malignant and benign insulinomas.Results 1)Compared to benign insulinoma,malignant insulinoma showed significantly ele-vated C-peptide(CP)and C-peptide to glucose ratio(CPGlu)during hypoglycemia(blood glucose＜3.0 mmol/L)[6.04(3.40,6.76)vs 1.68(1.39,2.47)ng/mL,P＜0.05),2.25(1.12,3.58)vs 0.74(0.54,1.54),P＜0.05].The tumor diameter(DIA)was larger(1.9±0.6 vs 1.4±0.3 cm,P＜0.05),and the insulin level at 300 minutes(INS300)during the 5-hour oral glucose tolerance test(5 h OGTT)was significantly elevated(30.47±5.67 vs 9.67±3.32)μIU/mL,P＜0.01).Levels of blood tumor markers AFP,CEA,and CA724 were also increased(P＜0.05).2)Correlation analysis indicated that CP,CPGlu,DIA,INS300,AFP,CEA,and CA724 were positively correlated with malignant insulinoma during hypoglycemia.3)The ROC curve analysis suggested that the optimal cut-off points for distinguishing malignant from benign insulinomas were CP 2.49 ng/mL,CPGlu 1.31,DIA 1.85 cm,and INS300 20.22 μIU/mL,respectively.Conclusions In clinical practice,if an insulinoma patient has a CP level higher than 2.49 ng/mL and a tumor diameter larger than 1.9 cm during hypoglycemia,the possibility of malignant insulinoma should be considered,warranting further examinations and enhanced follow-up.Persistent elevation of AFP,CEA,and CA724 may indicate malignant insulinoma.

The objective of this study is to assess the current status of vaccination against respiratory disease among the elderly aged ≥60 and analyze the factors influencing vaccination rates at both service provider and recipient levels in Zhejiang Province. Using a stratified random sampling method, a questionnaire survey was conducted from September 2022 to January 2023 among elderly people aged ≥60 in 30 townships/streets in Zhejiang Province, as well as immunization planning staff at the provincial, municipal, county/district, and township/street levels. Logistic regression models were used to analyze the factors related to vaccination among elderly people in Zhejiang Province. Based on the Zhejiang Provincial Comprehensive Management Information System for Vaccine and Vaccination, the systematic coverage rates of influenza vaccine and pneumonia vaccine for the elderly were 21.76% and 4.57%, respectively. Multivariate logistic regression analysis indicated that advanced age ( OR=1.74, 95% CI: 1.51-1.99), knowing that influenza is more severe than the common cold ( OR=1.67, 95% CI: 1.37-2.04) and having heard of the influenza vaccine ( OR=9.78, 95% CI: 7.03-13.59) were motivating factors for elderly to receive influenza vaccines. Advanced age ( OR=1.71, 95% CI: 1.43-2.06), knowing the serious consequences of pneumonia in the elderly ( OR=1.93, 95% CI: 1.47-2.55) and knowing that pneumonia vaccines can prevent pneumonia ( OR=6.36, 95% CI: 4.84-8.36) were motivating factors for elderly to receive pneumonia vaccines. Zhejiang Immunization Program staff believed that the main reasons why the elderly aged ≥60 would not be vaccinated against influenza or pneumonia were that they felt they would not get sick (55.52% and 56.35% respectively), it would not be serious if get sick (47.73% and 37.46% respectively), lacking trust in vaccine efficacy and safety (38.31% and 43.69% respectively). Vaccination rates for influenza and pneumonia vaccines among the elderly aged ≥60 in Zhejiang Province are suboptimal. Advanced age, awareness of the severity of respiratory diseases and awareness of vaccines against such diseases are related factors for elderly individuals to receive influenza and pneumonia vaccines.

Objective:To retrospectively analyze the clinical and pathologic characteristics, response to treatment, survival, and prognosis of patients with primary large B-cell lymphoma of the central nervous system (PCNSLBCL) .Methods:Clinical and pathologic data of 70 patients with PCNSLBCL admitted to Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2010 to November 2022 were collected for retrospective analysis. Survival analysis was performed using the Kaplan-Meier method and log-rank test, and prognosis analysis was conducted using the Cox proportional hazards model.Results:Among 70 patients with PCNSLBCL, complete remission (CRs) were achieved in 49 (70.0% ) and partial remission in 4 (5.7% ) after the first-line induction therapy; the overall remission rate was 75.7%. The 2-year progression-free survival (PFS) rate was 55.8% and the median progression-free survival (mPFS) time was 35.9 months, whereas the 2-year overall survival (OS) rate was 79.1% with a median OS time not reached. After CR induced by first-line therapy, cumulative incidence of relapse (CIR) was lower in patients who had received auto-HSCT than in those who had not received consolidation therapy ( P=0.032), whose 2-year PFS rate was 54.4% and mPFS time was 35.9 months; comparatively, the 2-year PFS rate in patients having received oral maintenance of small molecule drugs reached 84.4% with a mPFS time of 79.5 months ( P=0.038). Multivariant analysis demonstrated that Class 3 in the Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic model is an independent adverse prognostic factor of OS in patients with PCNSLBCL ( HR=3.127, 95% CI 1.057-9.253, P=0.039) . Conclusions:In patients with PCNSLBCL achieving CR after the first-line induction therapy, auto-HSCT as consolidation therapy would lead to a decreased CIR, and PFS time could be prolonged by oral maintenance of small molecule drugs. Class 3 MSKCC prognostic model is independently associated with poorer OS.

Objective: To analyze the prevalence and related factors of pediatric flexible flatfoot (PFF) among 7-8 year old children in Changzhou, so as to provide a feasible basis for the prevention and treatment of PFF. Methods: From December 2023 to February 2024, a total of 1 685 children aged 7-8 from 10 primary schools in Changzhou were selected by stratified cluster random sampling method, and screened for PFF by using a foot optical assessment recording device. Information including sex, body mass index (BMI), diet, exercise and shoe wearing habits were collected. The valgus angle of the hindfoot was measured on the body surface by using an orthopedic measuring ruler in the standing position. Pain levels were evaluated by using visual analogue score (VAS) for children with flatfoot syndrome. Multivariate Logistic analysis was used to analyze related factors of PFF. Results: The overall detection rate of PFF was 27.4%, and there was a significant difference in the detection rate of PFF between boys and girls, with 30.3% and 24.1% respectively ( χ 2=7.96, P < 0.01 ). Most cases of PFF were mild flatfoot (60.8%) and bilateral ( 60.4% ). Approximately 13.2% of children with PFF had flatfoot syndrome, with a mean VAS of (2.86±0.73). About 56.1% of children with PFF had a normal valgus angle of the hindfoot. Sex, high BMI and preference for shoe last with front upturned shoe shape were positively correlated with the detection of PFF ( OR= 1.74, 1.54, 1.13, P <0.05). After stratified by sex, regular exercise in boys and age in girls were negatively correlated with the detection of PFF ( OR=0.40, 0.64, P <0.05). Conclusions The detection rate of PFF in 7-8 year old children is high. Additionally, PFF combined with flatfoot syndrome or valgus hindfoot is relatively rare and is likely to be underestimated, which emphasizes the importance of early detection and intervention for PFF.