Objective To investigate the perioperative safety of patients with myasthenia gravis who take high doses of oral glucocorticoids. Methods A retrospective analysis was conducted on the clinical data of patients with myasthenia gravis who received oral glucocorticoids and underwent thoracoscopic thymectomy at the Department of Thoracic Surgery, the University of Hong Kong-Shenzhen Hospital from April 2013 to October 2019. Patients were divided into a high-dose steroid group and a medium-to-low dose steroid group based on the dosage of oral steroids, and the clinical data of the two groups were compared. Results A total of 102 patients were included, including 19 (18.62%) males and 83 (81.37%) females, with an average age of (32.25±9.83) years. There were 75 patients in the medium-to-low dose steroid group and 27 patients in the high-dose steroid group. All patients in both groups successfully completed the surgery without major intraoperative bleeding, conversion to open chest surgery, delayed extubation, severe infection, or perioperative death. The daily oral steroid dose for the high-dose steroid group was (35.81±4.29) mg, and for the medium-to-low dose steroid group it was (15.29±2.17) mg. There was no statistical difference in the operation time [(124.69±23.51) min vs. (117.89±21.46) min, P=0.172] and intraoperative blood loss [(21.19±3.48) mL vs. (20.56±3.41) mL, P=0.419] between the two groups. Postoperatively, 12 (11.76%) patients developed complications: one patient of myasthenic crisis (the medium-to-low dose steroid group), which was improved after short-term respiratory support and intravenous immunoglobulin treatment; 11 patients of respiratory/swallowing difficulties (9 in the medium-to-low dose steroid group and 2 in the high-dose steroid group), which were improved after anticholinergic treatment to reduce oral secretions and sputum suction, and the patients were discharged smoothly. There was no statistical difference in the incidence of postoperative complications between the two groups (P=0.637). Conclusion On the basis of good perioperative management, it is safe and feasible for patients with myasthenia gravis who take high dose of oral steroids to undergo thymectomy, and they have the same perioperative safety as patients with medium-to-low dose steroids.

ObjectiveTo analyze the safety of simultaneous vaccination of 13-valent pneumococcal conjugate vaccine (PCV13) and oral pentavalent human rotavirus live attenuated vaccine (RV5) in age-eligible children in Changning District, Shanghai. MethodsAdverse events following immunization (AEFI) and vaccination information after PCV13 and RV5 vaccination from Jan.1, 2022 to Dec.31, 2023 were collected through the National Immunization Program Information Management System and the Shanghai Immunization Information System in Changning District. We compared the incidence rates of AEFI reports after PCV13 and RV5 standalone and simultaneous vaccination. ResultsPCV13 was administered standalone in 7 654 doses, with 107 AEFI reports and an AEFI reporting rate of 1 397.96/100 000, including 1 371.83/100 000 for general reactions (105 cases) and 26.13/100 000 for abnormal reactions (2 cases). RV5 was administered standalone in 8 114 doses, with 30 AEFI reports and an AEFI reporting rate of 369.73/100 000, all of which were general reactions. PCV13 and RV5 were administered simultaneously in 6 731 doses, with 56 AEFI reports and an AEFI reporting rate of 831.97/100 000, including 802.26/100 000 for general reactions (54 cases), 14.86/100 000 for abnormal reactions (1 case), and 14.86/100 000 for coupling symptoms (1 case). ConclusionThe incidence rates of AEFI reports after PCV13 and RV5 vaccination standalone or simultaneous among age-eligible children in Changning District are within an acceptable range, primarily consisting of general reactions. PCV13 and RV5 simultaneous vaccination did not increase the risk of AEFI incidence.

BACKGROUND: Pre-transplant exposure to immune checkpoint inhibitors (ICIs) significantly increases the risk of allograft rejection after liver transplantation (LT); however, whether ICI-related rejection leads to increased graft loss remains controversial. Therefore, this study aimed to investigate the association between ICI-related allograft rejection and perioperative graft loss. METHODS: This was a retrospective analysis of adult liver transplant recipients with early biopsy-proven T-cell-mediated rejection (TCMR) at Liver Transplantation Center of Sun Yat-sen Memorial Hospital from June 2019 to September 2024. The pathological features, clinical characteristics, and perioperative graft survival were analyzed. RESULTS: Twenty-eight patients who underwent early TCMR between June 2019 and September 2024 were included. Based on pre-LT ICI exposure, recipients were categorized into ICI-related TCMR (irTCMR, n = 12) and conventional TCMR (cTCMR, n = 16) groups. Recipients with irTCMR had a higher median Banff rejection activity index (RAI) (6 vs . 5, P = 0.012) and more aggressive tissue damage and inflammation. Recipients with irTCMR showed higher proportion of treatment resistance, achieving a complete resolution rate of only 8/12 compared to 16/16 for cTCMR. Graft loss occurred in 5/12 of irTCMR recipients within 90 days after LT, with no graft loss in cTCMRs recipients. Cox analysis demonstrated that irTCMR with an ICI washout period of <30 days was an independent risk factor for perioperative graft loss (hazard ratio [HR], 6.540; 95% confidence interval [CI], 1.067-40.067, P = 0.042). CONCLUSION IrTCMR is associated with severe pathological features, increased resistance to treatment, and higher graft loss in adult liver transplant recipients.
Humans ; Liver Transplantation/adverse effects* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Graft Rejection/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; T-Lymphocytes/drug effects* ; Graft Survival/immunology* ; Aged

Baihuasheshecao(Hedyotis diffusa) is a commonly used traditional Chinese medicine derived from the whole herb of H. diffusa and has been widely utilized in folk medicine. It possesses anti-tumor, antibacterial, and anti-inflammatory properties, making it one of the frequently used herbs in TCM clinical practice. However, Shuixiancao(H. corymbosa) and Xianhuaercao(H. tenelliflora), species of the same genus, are often used as substitutes for Baihuasheshecao. To substantiate the medicinal basis of Baihuasheshecao, this study systematically reviewed classical herbal texts and modern literature, examining its nomenclature, botanical origin, harvesting, processing, properties, meridian tropism, pharmacological effects, and clinical applications. The results indicate that Baihuasheshecao was initially recorded as "Shuixiancao" in Preface to the Indexes to the Great Chinese Botany(Zhi Wu Ming Shi Tu Kao). Based on its morphological characteristics and habitat description, it was identified as H. diffusa in the Rubiaceae family. Subsequent records predominantly refer to it as Baihuasheshecao as its official name. In most regions, Baihuasheshecao is recognized as the authentic medicinal material, distinct from Shuixiancao and Xianhuaercao. Baihuasheshecao is harvested in late summer and early autumn, and the dried whole plant, including its roots, is used medicinally. The standard processing method involves cutting. It is known for its effects in clearing heat, removing toxins, reducing swelling and pain, and promoting diuresis to resolve abscesses. Initially, it was mainly used for treating appendicitis, intestinal abscesses, and venomous snake bites, and later, it became a treatment for cancer. The excavation of its clinical value followed a process in which overseas Chinese introduced the herb from Chinese folk medicine to other countries. After its unique anti-cancer effects were recognized abroad, it was reintroduced to China and gradually became a crucial TCM for cancer treatment. The findings of this study help clarify the historical and contemporary uses of Baihuasheshecao, providing literature support and a scientific basis for its rational development and precise clinical application.
Humans ; China ; Drugs, Chinese Herbal/chemistry* ; Hedyotis/classification* ; Medicine, Chinese Traditional/history*

PURPOSE: This study aims to identify the prevalence and risk factors of military training-related abdominal injuries and help plan and conduct training properly. METHODS: This questionnaire survey study was conducted from October 2021 to May 2022 among military personnel from 6 military units and 8 military medical centers and participants' medical records were consulted to identify the training-related abdominal injuries. All the military personnel who ever participated in military training were included. Those who refused to participate in this study or provided an incomplete questionnaire were excluded. The questionnaire collected demographic information, type of abdominal injury, frequency, training subjects, triggers, treatment, and training disturbance. Chi-square test and t-test were used to compare baseline information. Univariate and multivariate regression analyses were used to explore the risk factors associated with military training-related abdominal injuries. RESULTS: A total of 3058 participants were involved in this study, among which 1797 (58.8%) had suffered training-related abdominal injuries (the mean age was 24.3 years and the service time was 5.6 years), while 1261 (41.2%) had no training-related abdominal injuries (the mean age was 23.1 years and the service time was 4.3 years). There were 546 injured patients (30.4%) suspended the training and 84 (4.6%) needed to be referred to higher-level hospitals. The most common triggers included inadequate warm-up, fatigue, and intense training. The training subjects with the most abdominal injuries were long-distance running (589, 32.8%). Civil servants had the highest rate of abdominal trauma (17.1%). Age ≥ 25 years, military service ≥ 3 years, poor sleep status, and previous abdominal history were independent risk factors for training-related abdominal injury. CONCLUSION More than half of the military personnel have suffered military training-related abdominal injuries. Inadequate warm-up, fatigue, and high training intensity are the most common inducing factors. Scientific and proper training should be conducted according to the factors causing abdominal injuries.
Humans ; Military Personnel ; Risk Factors ; Prevalence ; Male ; Abdominal Injuries/etiology* ; Female ; Adult ; Surveys and Questionnaires ; Young Adult

OBJECTIVE: To evaluate the therapeutic effect of Yu Melody relaxation training (YMRT) combined with Jianpi Jieyu Decoction (JJD) in treating patients with insomnia disorders (ID). METHODS: In this randomized controlled study, 94 ID patients were included from Xiyuan Hospital, China Academy of Chinese Medical Sciences from September 2022 to January 2024. They were randomly assigned to the YMRT group (47 cases, YMRT plus JJD) and the control group (47 cases, oral JJD) using a random number table. Both treatment administrations lasted for 4 weeks, with a 2-week follow-up. The primary outcome was change in Insomnia Severity Index (ISI) scores from baseline to 4 weeks of intervention. Secondary outcomes included ISI response at week 4, as well as ISI, Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder 7-item (GAD-7) scores at baseline and weeks 1, 2, 3, 4, and 6. Additionally, Pittsburgh Sleep Quality Index (PSQI) scores were evaluated at baseline and weeks 4 and 6. Adverse events (AEs) were recorded and compared between groups. RESULTS: Five patients in each group did not complete the protocol requirements. The overall dropout rate was 10.64%. The full analysis set included all 47 cases in each group. The ISI score decreased significantly at week 4 from baseline in the YMRT group compared with the control group, with a between-group difference of -3.2 points [95% confidence interval (CI): -5.08 to -1.34; P<0.05]. The ISI response at week 4 in the YMRT group was significantly higher than that in the control group (85.11% vs. 51.06%), with a between-group difference of 34.05% (95% CI: 13.77% to 50.97%; P<0.05). At week 6, the YMRT group demonstrated greater reductions from baseline than the control group, with between-group differences of -2.1 points (-95% CI: -3.49 to -0.64; P<0.05) for PHQ-9 scores, -3.5 points (95% CI: -5.21 to -1.85; P<0.05) for PSQI scores, and -1.9 points (95% CI: -3.47 to -0.28; P<0.05) for GAD-7 scores. Moreover, at weeks 4 and 6, the ISI and PSQI scores in the YMRT group were significantly lower than those in the control group (P<0.05); and at week 6, the PHQ-9 score in the YMRT group was significantly lower (P<0.05). There was no significant difference in the incidence rates of AEs between the two groups (8.51% vs. 4.26%, P>0.05). CONCLUSIONS YMRT combined with oral JJD could improve sleep quality and alleviate depressive and anxiety symptoms in patients with ID. This combined therapy was effective and safe, and its effect was superior to oral JJD alone. (Registration No. ChiCTR2200063884).
Humans ; Sleep Initiation and Maintenance Disorders/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Relaxation Therapy/methods* ; Middle Aged ; Adult ; Treatment Outcome ; Combined Modality Therapy

In protein engineering, while computational models are increasingly used to predict mutation effects, their evaluations primarily rely on high-throughput deep mutational scanning (DMS) experiments that use surrogate readouts, which may not adequately capture the complex biochemical properties of interest. Many proteins and their functions cannot be assessed through high-throughput methods due to technical limitations or the nature of the desired properties, and this is particularly true for the real industrial application scenario. Therefore, the desired testing datasets, will be small-size (∼10-100) experimental data for each protein, and involve as many proteins as possible and as many properties as possible, which is, however, lacking. Here, we present VenusMutHub, a comprehensive benchmark study using 905 small-scale experimental datasets curated from published literature and public databases, spanning 527 proteins across diverse functional properties including stability, activity, binding affinity, and selectivity. These datasets feature direct biochemical measurements rather than surrogate readouts, providing a more rigorous assessment of model performance in predicting mutations that affect specific molecular functions. We evaluate 23 computational models across various methodological paradigms, such as sequence-based, structure-informed and evolutionary approaches. This benchmark provides practical guidance for selecting appropriate prediction methods in protein engineering applications where accurate prediction of specific functional properties is crucial.

The PA-PB1 interface of the influenza polymerase is an attractive site for antiviral drug design. In this study, we designed and synthesized a mini-library of indazole-containing compounds based on rational structure-based design to target the PB1-binding interface on PA. Biological evaluation of these compounds through a viral yield reduction assay revealed that compounds 27 and 31 both had a low micromolar range of the half maximal effective concentration (EC₅₀) values against A/WSN/33 (H1N1) (8.03 μmol/L for 27; 14.6 μmol/L for 31), while the most potent candidate 24 had an EC₅₀ value of 690 nM. Compound 24 was effective against different influenza strains including a pandemic H1N1 strain and an influenza B strain. Mechanistic studies confirmed that compound 24 bound PA with a K _d which equals to 1.88 μmol/L and disrupted the binding of PB1 to PA. The compound also decreased the lung viral titre in mice. In summary, we have identified a potent anti-influenza candidate with potency comparable to existing drugs and is effective against different viral strains. The therapeutic options for influenza infection have been limited by the occurrence of antiviral resistance, owing to the high mutation rate of viral proteins targeted by available drugs. To alleviate the public health burden of this issue, novel anti-influenza drugs are desired. In this study, we present our discovery of a novel class of indazole-containing compounds which exhibited favourable potency against both influenza A and B viruses. The EC₅₀ of the most potent compounds were within low micromolar to nanomolar concentrations. Furthermore, we show that the mouse lung viral titre decreased due to treatment with compound 24. Thus our findings identify promising candidates for further development of anti-influenza drugs suitable for clinical use.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Aim To investigate the effects of Ixerin Z,a sesquiterpene lactone from Ixeris sonchifolia,on bone-lipid metabolic imbalance in ApoE-/-mice and to elu-cidate its molecular mechanisms.Methods A mouse model of ApoE-/-was induced using a high-fat diet,followed by eight weeks of Ixerin Z administration at doses of 1 and 10 mg·kg-1.Serum markers related to bone-lipid metabolism and inflammatory cytokines were quantified.Bone mineral density,biomechanical prop-erties,bone tissue morphology,and bone microstructure changes were analyzed.Computational molecular doc-king was performed to identify potential target proteins of Ixerin Z,and its regulatory effects on bone-lipid me-tabolism were investigated.Results Treatment with Ixerin Z markedly decreased the serum levels of total cholesterol,triglycerides,TNF-α,and IL-1β in ApoE-/-mice.It significantly improved bone mineral density,enhanced biomechanical strength,restored tra-becular structure,and reduced fat accumulation in bone tissue.Investigations revealed that Ixerin Z activated PPARα,thereby promoting fatty acid β-oxidation in bone tissue,and stimulating the Wnt/β-Catenin signa-ling pathway to facilitate bone formation.Furthermore,Ixerin Z suppressed the OPG/RANKL/NF-κB signaling pathway,leading to reduced bone resorption,independ-ent of PPARα activation.Conclusions Ixerin Z dem-onstrates potent therapeutic effects on bone-lipid meta-bolic imbalance in ApoE-/-mice.The mechanism in-volves activating PPARα to promote fatty acid β-oxida-tion in bone tissue,activating PPARα/Wnt/β-Catenin signaling pathway to promote bone formation,and in-hibiting OPG/RANKL/NF-κB signaling pathway to re-duce bone resorption.