Background While A few studies have suggested associations between ambient temperature and cardiac autonomic function, the relationship between hourly temperature variations and heart rate variability (HRV) remains unclear. Objective To examine the acute effects and lag patterns of short-term ambient temperature exposure on HRV at an hourly temporal resolution during cold and warm seasons, and to further characterize the exposure-response relationships. Methods We conducted a longitudinal panel study involving 1047 eligible participants who ordered repeated 24 h ambulatory electrocardiogram monitoring at the First Affiliated Hospital of Xinjiang Medical University in Urumqi, Xinjiang Uygur Autonomous Region, China, between March 2020 and March 2022. Twelve HRV parameters were extracted, including standard deviation of all NN intervals (SDNN), standard deviation of the 5 min averages of NN intervals (SDANN), standard deviation of NN intervals index (SDNNIDX), root mean square of successive differences of adjacent NN intervals (rMSSD), triangle index (TI), percent of NN50 in the total number of NN intervals (pNN50), total power (TP), ultralow frequency (ULF), very low frequency (VLF), low frequency (LF), high frequency (HF), and ratio of low frequency to high frequency (LF/HF). Hourly meteorological data (mean temperature and relative humidity) were obtained from the nearest monitoring stations to participants' residences. Linear mixed effects models (LME) and generalized additive mixed effects models (GAMM) were employed to assess temperature-HRV associations and lag patterns during cold (from October to March next year) and warm (from April to September) seasons, with stratification by sex and age. Results A total of 1047 Urumqi residents who had repeated 24 h ambulatory electrocardiograms were included in this study. In both cold and warm seasons, the exposure-response relationship between ambient temperature and HRV showed an approximately linear negative correlation with no threshold effect; HRV parameters decreased as ambient temperature increased. The correlation between ambient temperature and HRV usually began at a lag of 6 h and disappeared around 24 h lag. The cold season induced a stronger effect on HRV decline, and for every 1 °C increase in ambient temperature during the cold season from lag 0 to 6 h, SDNN decreased by 0.72%, SDNNIDX decreased by 1.46%, TI decreased by 0.07%, SDANN decreased by 1.23%, rMSSD decreased by 1.00%, pNN50 decreased by 2.74%, TP decreased by 3.30%, ULF decreased by 3.74%, VLF decreased by 3.76%, LF decreased by 2.75%, HF decreased by 2.49%, and LF/HF decreased by 0.74%; for every 1 °C increase in ambient temperature during the warm season, SDNN decreased by 0.56%, SDNNIDX decreased by 1.08%, TI decreased by 0.29%, SDANN decreased by 0.56%, rMSSD decreased by 0.68%, pNN50 decreased by 2.11%, TP decreased by 2.64%, ULF decreased by 3.14%, VLF decreased by 2.74%, LF decreased by 1.85%, HF decreased by 1.68%, and LF/HF decreased by 0.47%. Conclusion Elevated ambient temperatures in Urumqi are significantly associated with decreased HRV in the residents, affecting cardiac autonomic function.

Objective:To explore the efficacy of immune checkpoint inhibitors combined with adjuvant chemotherapy in patients with phase III gastric cancer and esophagogastric junction cancer.Methods:This study used a retrospective cohort study method based on real-world data. Clinical data of 403 patients with stage III gastric/esophagogastric junction cancer who underwent gastrectomy followed by adjuvant therapy in the Department of Gastric Surgery at Sun Yat-sen University Cancer Center from January 2020 to December 2023 were retrospectively collected. The study cohort comprised 147 (36.5%) patients with stage IIIA, 130 (32.3%) with stage IIIB, and 126 (31.3%) with stage IIIC gastric/esophagogastric junction cancer. Of them, 15 (3.7%) were HER-2 positive, 25 (6.2%) dMMR, and 22 (5.5%) patients Epstein-Barr virus encoding RNA (EBER) positive. Based on treatment plans, the patients were divided into immune checkpoint inhibitor combined with chemotherapy group (immune therapy group, n=110, 71 males and 39 females, median age 59 years old) and chemotherapy alone group (chemotherapy group, n=293, 186 males and 107 females, median age 60 years old). All patients in the immunotherapy group received immune checkpoint inhibitors targeting the programmed cell death protein-1 (PD-1) and its ligand (PD-L1). Of them, 85 received pembrolizumab, 10 received sintilimab, 8 received tislelizumab, 4 received camrelizumab, 2 received toripalimab, and 1 received pabocizumab. The adjuvant chemotherapy regimens used among the chemotherapy alone group includes SOX regimen (132 cases), XELOX (102 cases), S-1 monotherapy (44 cases), and other regimens (15 cases). The 3-year DFS rate of the two groups was compared, and subgroup analysis was conducted based on different ages, molecular phenotypes, pTNM staging, extranodal infiltration, and tumor length. Results:The median follow-up was 20.5 months (range 3.1~46.3), with a 3-year overall DFS rate of 61.4% for the entire 403 patients. The 3-year DFS rate for the immunotherapy group was 82.7%, higher than the chemotherapy alone group (58.8%), with a statistically significant difference ( P=0.021). Multivariate analysis showed that postoperative immunotherapy was a protective factor for DFS (HR=0.352, 95%CI: 0.180~0.685). Subgroup analysis showed that stage IIIC (HR=0.416, 95%CI: 0.184~0.940), aged ≥60 years (HR=0.336, 95%CI: 0.121~0.934) and extranodal invasion (HR=0.378, 95%CI: 0.170~0.839) were associated with benefit from the combined immune adjuvant chemotherapy, while no association was observed for MMR, HER-2 or EBER status. Conclusion:Stage III gastric/esophagogastric junction cancer patients may benefite from postoperative immune checkpoint inhibitor combined with adjuvant chemotherapy in real-world settings.

Objective:To explore the efficacy of immune checkpoint inhibitors combined with adjuvant chemotherapy in patients with phase III gastric cancer and esophagogastric junction cancer.Methods:This study used a retrospective cohort study method based on real-world data. Clinical data of 403 patients with stage III gastric/esophagogastric junction cancer who underwent gastrectomy followed by adjuvant therapy in the Department of Gastric Surgery at Sun Yat-sen University Cancer Center from January 2020 to December 2023 were retrospectively collected. The study cohort comprised 147 (36.5%) patients with stage IIIA, 130 (32.3%) with stage IIIB, and 126 (31.3%) with stage IIIC gastric/esophagogastric junction cancer. Of them, 15 (3.7%) were HER-2 positive, 25 (6.2%) dMMR, and 22 (5.5%) patients Epstein-Barr virus encoding RNA (EBER) positive. Based on treatment plans, the patients were divided into immune checkpoint inhibitor combined with chemotherapy group (immune therapy group, n=110, 71 males and 39 females, median age 59 years old) and chemotherapy alone group (chemotherapy group, n=293, 186 males and 107 females, median age 60 years old). All patients in the immunotherapy group received immune checkpoint inhibitors targeting the programmed cell death protein-1 (PD-1) and its ligand (PD-L1). Of them, 85 received pembrolizumab, 10 received sintilimab, 8 received tislelizumab, 4 received camrelizumab, 2 received toripalimab, and 1 received pabocizumab. The adjuvant chemotherapy regimens used among the chemotherapy alone group includes SOX regimen (132 cases), XELOX (102 cases), S-1 monotherapy (44 cases), and other regimens (15 cases). The 3-year DFS rate of the two groups was compared, and subgroup analysis was conducted based on different ages, molecular phenotypes, pTNM staging, extranodal infiltration, and tumor length. Results:The median follow-up was 20.5 months (range 3.1~46.3), with a 3-year overall DFS rate of 61.4% for the entire 403 patients. The 3-year DFS rate for the immunotherapy group was 82.7%, higher than the chemotherapy alone group (58.8%), with a statistically significant difference ( P=0.021). Multivariate analysis showed that postoperative immunotherapy was a protective factor for DFS (HR=0.352, 95%CI: 0.180~0.685). Subgroup analysis showed that stage IIIC (HR=0.416, 95%CI: 0.184~0.940), aged ≥60 years (HR=0.336, 95%CI: 0.121~0.934) and extranodal invasion (HR=0.378, 95%CI: 0.170~0.839) were associated with benefit from the combined immune adjuvant chemotherapy, while no association was observed for MMR, HER-2 or EBER status. Conclusion:Stage III gastric/esophagogastric junction cancer patients may benefite from postoperative immune checkpoint inhibitor combined with adjuvant chemotherapy in real-world settings.

As the foremost among the four examinations in traditional Chinese medicine （TCM）， inspection and related equipment research face challenges in landing and transformation due to variations in evidence quality， lack of standardization， insufficient algorithm transparency， and poor reliability and stability of decision-making. Against the backdrop of rapid development of emerging technologies such as big data， the internet of things， and artificial intelligence， coupled with macro policy support from the government， digital and intelligent generalized inspection in TCM has emerged， with the aim of utilizing digital technologies to overcome the limitations of naked-eye inspection and comprehensively perceive and analyze facial and bodily expressions. The research in this field intelligently correlates Zang-fu organ functions with health conditions and disease progression and establishes a technical system for digital and intelligent inspection， multi-dimensional and multimodal perception， fusion analysis， and decision-making. This system aims to enhance the accuracy of disease risk warning and diagnosis， bridging the gap between inspection equipment and assistance in clinical decision-making. From an evidence-based perspective， this paper systematically examines the research ideas of digital and intelligent inspection and the development of related equipment， deeply explores how to propose clinical practice-oriented key scientific issues， comprehensively acquire and co-apply multi-dimensional data， establish precise inspection models driven by digital intelligence， optimize standards to enhance equipment interoperability and reliability， construct post-effect evaluation mechanisms to promote improvement， and actively address potential risks such as the black box nature and information security in the application of intelligent technology. This paper not only demonstrates the tremendous potential of digital technologies in improving the accuracy and clinical application efficiency of inspection but also provides new perspectives and ideas for the modernization of inspection in TCM， paving the way for the application of inspection in the global medical and health field.

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD⁺), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD⁺ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
Humans ; NAD/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Nicotinamide Phosphoribosyltransferase/metabolism* ; Cytokines/metabolism* ; Quinones ; Oxidoreductases

Purpose To observe the clinicopathological changes of gastric adenocarcinoma of fundic-gland mucosa type(GA-FGM).Methods The clinicopathological data of 4 cases of GA-FGM was analyzed retrospectively.The expression of MUC5AC and MUC6 was detected by immunohistochemical method,and review relevant literature.Results The tumor dif-ferentiated into gastric foveal epithelium and gastric fundus gland.The differentiated part of the pits consists of high colum-nar neoplastic epithelium with low atypia,which can be papilla-ry,villous or tubular morphology.Immunohistochemical staining showed MUC5AC expression.The gastric fundus gland differen-tiated into cervical mucous cells,main cells and parietal cells,and was positive for MUC6 immunohistochemistry.Conclusion Gastric adenocarcinoma of fundic-gland mucosa type has u-nique pathologic characteristics,which is very difficult to diag-nose in biopsy,and the morphology of GA-FGM overlaps with that of gastric fundus adenocarcinoma,so we need to strengthen our understanding.Immunohistochemistry plays an important role in differential diagnosis.

BACKGROUND:Lower limb peri-knee muscle strength training and neuromuscular electrical stimulation are generally safe and effective rehabilitation methods for patellofemoral joint pain,but the mechanism of their intervention is still unclear. OBJECTIVE:To determine the effect of muscle strength training combined with neuromuscular electrical stimulation on pain,lower extremity function and biomechanical characteristics in patients with patellofemoral pain. METHODS:Thirty-seven patients with patellofemoral pain were randomly divided into muscle strength training combined with electrical stimulation group(trial group,n=19)and muscle strength training group(control group,n=18).Both groups underwent intervention training for 6 weeks,three times a week.The visual analog scale and anterior knee pain scale were used to evaluate the pain level and functional level of the knee.Kinematic and kinetics data during running were collected by using an infrared motion capture system and a three-dimensional force platform simultaneously.A two-way analysis of variance with repeated measures(group*time)was applied to analyze the data. RESULTS AND CONCLUSION:(1)After the intervention,the visual analog scale scores of the trial group and the control group were significantly decreased(P<0.001),and the anterior knee pain scale scores were significantly increased(Ptrial group<0.001,Pcontrol group=0.001)in the trial group and control group.The anterior knee pain scale scores of the trial group were significantly higher compared to the control group after the intervention(P=0.001).(2)The peak knee flexion angle(P=0.011),peak knee extension moment(P<0.001),the peak knee internal rotation moment(P=0.008),the peak patellofemoral stress(P<0.001)and the peak patellofemoral contact force(P<0.001)were significantly decreased in the trial and control groups during running after the intervention compared with those before the intervention.(3)In conclusion,both muscle strength training and muscle strength training combined with electrical stimulation training are helpful to improve the subjective pain and lower limb function of patellofemoral pain patients,enhance the movement pattern during running and reduce the stress of the patellofemoral joint.Compared with muscle strength training alone,muscle strength training combined with electrical stimulation can improve lower limb function more significantly.

Objective:To investigate the effect and mechanism of Grifola frondosa extract on inflammatory response of colon tissue in rats with ulcerative colitis(UC)by regulating interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods:Forty SD rats were randomly divided into blank control group,UC model group,Grifola frondosa treatment group,western medicine treatment group and combined treatment group,with 8 rats in each group.After UC rats were established by free drinking 3%DSS for 7 days,the treatment group were given Grifola frondosa extract 10 mg/(kg·d),sulfasalazine 0.3 g/(kg·d),and the same amount of two drugs,for 14 consecutive days.During the experiment,general state of rats were observed,and the disease activity index(DAI)score was calculated;pathological changes of rats colon tissue were observed by HE staining;protein expression levels of IL-6,JAK2,STAT3 and p-STAT3 in rats colon tissue were detected by Western blot;content of IL-6 in rats serum was detected by ELISA;protein contents and expressions of IL-6R and MPO in rats colon tissue were determined by immunohistochemistry.Results:Compared with blank control group,general state of rats in UC model group was poor,DAI score was increased,obvious tissue mucosal defects and inflammatory cell infiltration were observed by HE staining;protein expression levels of IL-6,JAK2,STAT3 and p-STAT3 in rats colon tissue and contents of IL-6R and MPO were significantly increased(P<0.01);content of IL-6 in rats serum was significantly increased(P<0.01),the difference was statistically significant.Compared with UC model group,general condition of rats in each treatment group was improved,DAI score was decreased,HE staining showed that mucosal defects were improved to varying degrees,and occasionally inflammatory cell infiltration was observed;protein expression levels of IL-6,JAK2,STAT3 and p-STAT3 in colon tissue were significantly decreased(P<0.01),contents of IL-6R and MPO in colon tissue and content of IL-6 in serum were significantly decreased(P<0.01 or P<0.05),the differences were statistically significant.Conclusion:Grifola frondosa extract can reduce the inflammatory response in colon tissue of UC rats by regulating expressions of IL-6/JAK2/STAT3 signaling pathway related factors.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Pelvic floor muscle training (PFMT) is the first-line intervention for non-surgical treatment of female patients with stress urinary incontinence (SUI). However, due to the particularity of the physiological position of the pelvic floor muscles, 13% to 53% of patients are unable to perform PFMT correctly after the initial visit. In view of this, scholars at China and abroad put forward some other sports rehabilitation methods and achieve good clinical results. In this paper, exercise rehabilitation methods for female SUI patients were reviewed, including PFMT, core muscle training, Pilates, yoga, physical activities, etc., in order to provide reference for medical personnel to formulate scientific and feasible exercise rehabilitation programs for female SUI patients.