OBJECTIVE To study the improvement effect and mechanism of Tripterygium wilfordii multiglucoside （TWM） on nephrotic syndrome in rats. METHODS The nephrotic syndrome model was established by intravenous injection of adriamycin via the tail vein. The modeling rats were randomly divided into the model group （distilled water）， prednisone group （10 mg/kg）， and TWM high- and low-dose groups （10 and 5 mg/kg， respectively）. Additionally， blank group （distilled water） without model induction was established. Each group consisted of 9 rats. Rats in each group were administered the corresponding drugs or distilled water by gavage， once a day， for 6 consecutive weeks. The histopathological morphology of kidney tissues in rats was observed； the levels of 24-hour urinary protein （24 h-UTP） and serum biochemical indicators [albumin （ALB）， blood urea nitrogen （BUN）， serum creatinine （SCr）， cholesterol （CHOL）， and triglyceride （TG）] in rats were determined； the levels of oxidative stress indicators [superoxide dismutase （SOD）， malondialdehyde （MDA）] in kidney tissue of rats were determined； expressions of hypoxia-inducible factor-1α （HIF-1α）/microRNA-155-5p （miR-155-5p）/nuclear factor erythriod 2- related factor 2 （Nrf2） signaling pathway-related mRNA and protein in the renal tissues of rats were detected. RESULTS Compared with the blank group， the rats in the model group exhibited disordered renal tissue structure， with a small amount of glomerular necrosis and edema of the renal tubular epithelial cells. 24 h-UTP， serum levels of SCr， BUN， CHOL and TG， MDA content， mRNA and protein expressions of HIF-1α and Keap1 as well as the expression of miR-155-5p in renal tissues were increased significantly （ P ＜0.05）. Serum level of ALB， SOD level in renal tissue as well as mRNA and protein expressions of Nrf2 were decreased significantly （ P ＜0.05）. Compared with the model group， TWM high-dose and low-dose groups exhibited significant improvements in renal injury， with notable reversals in the levels of the above quantitative indicators （ P ＜0.05）. CONCLUSIONS TWM can alleviate oxidative stress-induced damage and thereby improve nephrotic syndrome in rats by regulating the HIF-1α/miR-155-5p/Nrf2 signaling pathway.

ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

Objective To explore the factors affecting the quality of psychological assistance hotline connections in Shaanxi Province, and to provide a basis for optimizing services. Methods A total of 149 calls with suicidal tendencies were included from January to March 2022, and data were collected by 31 trained assessors through standardized questionnaires (general information, suicide risk, emotional intensity, and wiring characteristics). Results The results showed that 56.38% of the callers were female, with age groups concentrated between ≤ 18 years old (29.53%) and 19-34 years old (43.62%). The call duration was mainly between 31 and 45 minutes (50.34%). Operators conducted a suicide risk assessment on the callers, with 38.9% having a comprehensive assessment, 38.9% having an incomplete assessment, and 22.1% having no assessment. The main mental disorders of the callers were depression (48.32%), anxiety (15.44%), and bipolar disorder (14.77%), with 25.50% having comorbidities of ≥ 2 disorders. Emotional scores were as follows: depression (4.11 ± 0.76), sadness (3.97 ± 1.03), and despair (3.78 ± 1.05). There were significant differences in depression, anger, despair, and sadness among the callers with different levels of danger (t=4.79, 3.35, 15.79, 4.24, all P<0.05). Women had higher levels of fear than men (t=3.10, P<0.01). The longer the call duration, the higher the level of despair (t=5.66, P<0.01). Multiple regression analysis showed that incomplete suicide risk assessment by operators (B=-2.36), general procedures for operators' connections (B=5.44), and technical factors (B=2.01) significantly affected the quality of psychological assistance hotlines (all P<0.05). Conclusion Callers with suicidal tendencies generally have serious mental and psychological problems and prominent negative emotions. Strengthening the suicide risk assessment ability of operators and standardizing processes and service attitudes are key to improving the quality of psychological assistance hotlines.

OBJECTIVE To explore the application effect of ticagrelor combined with aspirin antiplatelet therapy in high-risk non-disabling ischemic cerebrovascular events （HR-NICE）. METHODS A total of 232 patients with HR-NICE treated at the First Affiliated Hospital of Nanyang Medical College from January 1， 2023 to January 1， 2025 were retrospectively selected. According to different antiplatelet regimens， the patients were divided into three groups： group A （78 cases） received clopidogrel 300 mg as a loading dose on the first day， followed by clopidogrel 75 mg， qd combined with aspirin 100 mg， qd； group B （69 cases） received ticagrelor 120 mg as a loading dose on the first day， followed by ticagrelor 60 mg， bid combined with aspirin 100 mg， qd； group C （85 cases） received ticagrelor 180 mg as a loading dose on the first day， followed by ticagrelor 90 mg， bid combined with aspirin 100 mg， qd. All groups received dual-antiplatelet therapy for 21 days and were then switched to aspirin monotherapy. The primary outcome [incidence of early neurological deterioration （END）] and secondary outcomes， including incidence of ischemic events within 90 days post-discharge， favorable prognosis at 30/90 days， and incidence of bleeding events within 90 days， were compared among the three groups. Logistic regression was used to analyze the relationship between different antiplatelet regimens and END. Interaction terms between treatment regimen and demographic and clinical baseline characteristics were further included to evaluate the interaction effect between treatment regimen and END risk in different subgroups. Propensity score matching （PSM） was performed for sensitivity analysis. RESULTS For the primary outcome， the incidence of END in group C was significantly lower than that in group A （ P ＜0.05）. For secondary outcomes， there were no statistically significant differences among the three groups in the incidence of ischemic events within 90 days post-discharge， favorable prognosis at 30/90 days （ P ＞0.05）. The incidence of minor bleeding events in groups B and C was significantly higher than that in group A （ P ＜0.05）， while no significant differences were observed among the three groups in moderate or severe bleeding events （ P ＞0.05）. Interaction analysis showed that ischemic cerebrovascular disease， Age-Blood Pressure-Clinical Feature-Duration-Diabetes Score （ABCD2）， REACH risk score， and Essen Stroke Risk Score （ESSEN） had significant interactions with treatment regimen （ P ＜0.05）. Among patients with ischemic cerebrovascular disease， ABCD2≥6 points， REACH risk score≥6 points， or ESSEN≥3 points， regimens B or C were associated with a lower risk of END compared with regimen A. The PSM results were generally consistent with the analysis before matching. CONCLUSIONS Ticagrelor， especially the 90 mg bid regimen， plus aspirin， was associated with a lower risk of END in patients with HR-NICE， but increased the risk of minor bleeding events. Patients with ischemic cerebrovascular disease and higher ABCD2， REACH risk score， or ESSEN may be potential beneficiaries of this combination regimen.

The Department of Thoracic Surgery of Shanghai Chest Hospital has performed esophageal function testing for over 30 years, being the only department of its kind in China with this capability. The pressure testing and 24-hour pH/impedance monitoring of the esophagus is of great help to assist in the diagnosis and treatment of benign and malignant esophageal diseases related to it. Thanks to the esophageal function test, in addition to the routine various endoscopic anti-reflux procedures, our hospital has taken the lead in China in recent years to carry out a series of clinical and research work for benign esophageal diseases, such as the development of magnetic ring, double nedoscopic combination and new anti-reflux endoscopic techniques. In recent years, we have carried out high-resolution esophageal manometry and 24-hour pH/impedance monitoring for patients with interstitial pneumonia and pulmonary fibrosis suspected to be caused by gastroesophageal acid reflux. We can better assess the correlation between gastroesophageal reflux and pulmonary fibrosis, and to provide the different clinical treatments and even surgical interventions. The Bravo capsule is used more often in the United States, and it has obvious advantages over traditional approach for acid measurement. We strongly call for the collaboration between industry and academic institutions in this field, and the development of our own related products with independent intellectual property rights.

ObjectiveTo develop a nomogram-based risk prediction model for chronic obstructive pulmonary disease (COPD) incidence among the community-dwelling population aged 40 years old and above, so as to provide targeted references for the screening and prevention of COPD. MethodsBased on a natural population cohort in suburban Shanghai, a total of 3 381 randomly selected participants aged ≥40 years underwent pulmonary function tests between July and October 2021. Cox stepwise regression analysis was used to develop overall and gender-specific risk prediction models, along with the construction of corresponding risk nomograms. Model predictive performance was evaluated using the C-indice, area under the curve (AUC) values, and Brier score. Stability was assessed through 10-fold cross-validation and sensitivity analysis. ResultsA total of 3 019 participants were included, with a median follow-up duration of 4.6 years. The COPD incidence density was 17.22 per 1 000 person-years, significantly higher in males (32.04/1 000 person-years) than that in females (7.38/1 000 person-years) (P<0.001). The overall risk prediction model included the variables such as gender, age, education level, BMI, smoking, passive smoking, and respiratory comorbidities. The male-specific model incorporated the variables such as age, BMI, respiratory comorbidities, and smoking, while the female-specific model included age, marital status, respiratory comorbidities, and pulmonary tuberculosis history. The C-indices for the overall, male-specific, and female-specific models were 0.829, 0.749, and 0.807, respectively. The 5-year AUC values were 0.785, 0.658, and 0.811, with Brier scores of 0.103, 0.176, and 0.059, respectively. Both 10-fold cross-validated C-indices and sensitivity analysis (excluding participants with a follow-up duration of <6 months) yielded C-indices were above 0.740. ConclusionThis study developed concise and practical overall and gender-specific COPD risk prediction models and corresponding nomograms. The models demonstrated robust performance in predicting COPD incidence, providing a valuable reference for identifying high-risk populations and formulating targeted screening and personalized management strategies.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Diterpenoid ferruginol is a key intermediate in biosynthesis of active ingredients such as tanshinone and carnosic acid.However, the traditional process of obtaining ferruginol from plants is often cumbersome and inefficient. In recent years, the increasingly developing gene editing technology has been gradually applied to the heterologous production of natural products, but the production of ferruginol in microbe is still very low, which has become an obstacle to the efficient biosynthesis of downstream chemicals, such as tanshinone. In this study, miltiradiene was produced by integrating the shortened diterpene synthase fusion protein,and the key genes in the MVA pathway were overexpressed to improve the yield of miltiradiene. Under the shake flask fermentation condition, the yield of miltiradiene reached about(113. 12±17. 4)mg·L~(-1). Subsequently, this study integrated the ferruginol synthase Sm CYP76AH1 and Sm CPR1 to reconstruct the ferruginol pathway and thereby realized the heterologous synthesis of ferruginol in Saccharomyces cerevisiae. The study selected the best ferruginol synthase(Il CYP76AH46) from different plants and optimized the expression of pathway genes through redox partner engineering to increase the yield of ferruginol. By increasing the copy number of diterpene synthase, CYP450, and CPR, the yield of ferruginol reached(370. 39± 21. 65) mg·L~(-1) in the shake flask, which was increased by 21. 57-fold compared with that when the initial ferruginol strain JMLT05 was used. Finally, 1 083. 51 mg·L~(-1) ferruginol was obtained by fed-batch fermentation, which is the highest yield of ferruginol from biosynthesis so far. This study provides not only research ideas for other metabolic engineering but also a platform for the construction of cell factories for downstream products.
Saccharomyces cerevisiae/genetics* ; Diterpenes/metabolism* ; Metabolic Engineering ; Fermentation ; Abietanes

As a new type of production factor that can empower the development of new quality productivity, the data element is an important engine to promote the high quality development of the industry. Traditional Chinese medicine(TCM) dispensing is the most basic work of TCM clinical pharmacy, and its quality directly affects the clinical efficacy of TCM. The integration of data elements and TCM dispensing can stimulate the innovation and vitality of the TCM dispensing industry and promote the high-quality and sustainable development of the industry. A large-scale, detailed, and systematic study on TCM dispensing was conducted. The innovative practice path of data fusion construction in the whole process of TCM dispensing was investigated by integrating the digital resources "nine full activities" of TCM dispensing, creating the digital dictionary of "TCM clinical information data elements", and exploring innovative applications of TCM dispensing driven by data and technology, so as to promote the standardized, digital, and intelligent development of TCM dispensing in medical health services. The research content of this project was successfully selected as the second batch of "Data element×" typical cases of National Data Administration in 2024, which is the only selected case in the field of TCM.
Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal ; Humans

Triple-negative breast cancer (TNBC) represents an aggressive breast cancer subtype with poor prognosis and limited targeted treatment options. This investigation examined the anti-cancer potential of Caerulomycin A (Cae A), a natural compound derived from marine actinomycetes, against TNBC. Cae A demonstrated selective inhibition of viability and proliferation in TNBC cell lines, including 4T1, MDA-MB-231, and MDA-MB-468, through apoptosis induction. Mechanistic analyses revealed that the compound induced sustained endoplasmic reticulum (ER) stress and subsequent upregulation of C/EBP homologous protein (CHOP) expression, resulting in mitochondrial damage-mediated apoptosis. Inhibition of ER stress or CHOP expression knockdown reversed mitochondrial damage and apoptosis, highlighting the essential role of ER stress and CHOP in Cae A's anti-tumor mechanism. Both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) decreased in TNBC cells following Cae A treatment, indicating reduced mitochondrial respiratory and glycolytic capacities. This diminished energy metabolism potentially triggers ER stress and subsequent apoptosis. Furthermore, Cae A exhibited significant anti-tumor effects in the 4T1 tumor model in vivo without apparent toxicity. The compound also effectively inhibited human TNBC organoid growth. These results indicate that Cae A may serve as a potential therapeutic agent for TNBC, with its efficacy likely mediated through the disruption of glucose metabolism and the induction of ER stress-associated apoptosis.
Humans ; Endoplasmic Reticulum Stress/drug effects* ; Triple Negative Breast Neoplasms/genetics* ; Apoptosis/drug effects* ; Cell Line, Tumor ; Female ; Animals ; Glucose/metabolism* ; Mice ; Cell Proliferation/drug effects* ; Transcription Factor CHOP/genetics* ; Antineoplastic Agents/pharmacology* ; Mitochondria/metabolism* ; Mice, Inbred BALB C