OBJECTIVE To preliminarily investigate the antiasthmatic effect and mechanism of Ephedrae Herba-Armeniacae Semen Amarum herb pair on the respiratory center. METHODS Male SD rats were randomly divided into blank group， model group， dexamethasone group （positive control）， and Ephedrae Herba-Armeniacae Semen Amarum 2∶1， 1∶1 and 1∶2 groups. Rats in each group were administered different ratios of the herb pair decoction [all at 18 g （crude drug）/kg]， dexamethasone suspension （0.5 mg/kg）， or normal saline intragastrically twice daily for seven consecutive days. Forty minutes after the last administration， medicated cerebrospinal fluid was collected to determine the content of effective components entering the brain. One and a half hours after the last administration， the nucleus tractus solitarius （NTS） was located using a stereotaxic apparatus. Histamine phosphate （1 μL） was injected into the NTS region at a constant rate of 1 μL/min using a 10 μL microsyringe to induce excitation of the respiratory center in rats； the blank group was injected with normal saline. The contents of neurotransmitters [nerve growth factor （NGF）， substance P （SP）， norepinephrine （NA）， 5-hydroxytryptamine （5-HT） and acetylcholine （Ach）] in the medulla oblongata brain tissue were detected. The mRNA expressions of neurokinin-1 receptor （NK-1R）， p38 mitogen-activated protein kinase （MAPK）， and c-fos in the medulla oblongata， as well as the protein expressions of NK-1R， p38 MAPK， and c-fos in the NTS region， were determined. RESULTS The main active components of Ephedrae Herba-Armeniacae Semen Amarum herb pair entering the brain were ephedrine， pseudoephedrine， and methylephedrine. Compared with blank group， the contents of NGF， SP， NA， 5-HT and Ach， and the relative expression levels of NK-1R， p38 MAPK， and c-fos mRNA and protein were significantly increased in the model group （ P ＜0.01）. Compared with model group， Ephedrae Herba-Armeniacae Semen Amarum herb pair groups with different ratios significantly reduced the neurotransmitter contents and the relative expression levels of NK-1R， p38 MAPK， and c-fos mRNA and protein （ P ＜0.01）， with the 2∶1 Ephedrae Herba-Armeniacae Semen Amarum herb pair and 1∶1 mass ratios showing relatively better effects. CONCLUSIONS Ephedrae Herba alkaloids are the main active components in affecting the function of the respiratory center. The herb pair groups with a larger proportion of Ephedrae Herba exhibit stronger effects. Ephedrae Herba-Armeniacae Semen Amarum herb pair can reduce the excitability of the respiratory center by down-regulating the expression of the NK-1R/MAPK/c-fos pathway in the NTS and decreasing the abnormal release of neurotransmitters such as NGF and SP.

OBJECTIVE: To evaluate the effectiveness of correcting post-traumatic equinovarus deformity using Ilizarov external fixation technique combined with limited osteotomy. METHODS: A retrospective analysis was conducted on clinical data from 29 patients with post-traumatic equinovarus deformity treated between July 2018 and March 2023. The cohort included 18 males and 11 females, with ages ranging from 15 to 57 years (mean, 24.3 years). All patients exhibited ankylosed ankle joints with equinovarus deformity. During surgery, external fixators were installed according to Ilizarov pinning principles, and minimally invasive osteotomy was performed at the ankle joint. Concurrently, soft tissue release was achieved via minimally invasive Achilles tendon lengthening. Postoperatively, multiplanar deformity correction was accomplished through gradual adjustment of the external fixator. The fixator was removed after bony union at the osteotomy site, followed by bracing. The surgical duration, intraoperative blood loss, fixator wear time, and complications were recorded. Postoperative outcomes included assessment of deformity correction and bony union at the osteotomy site. Functional improvement and pain relief were evaluated using pre- and post-operative scores from the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score and visual analogue scale (VAS) score. RESULTS: All 29 patients were followed up 12-24 months (mean, 18 months). The mean surgical duration was 85.6 minutes, with a mean intraoperative blood loss of 110 mL. Full deformity correction was achieved within 26-80 days (mean, 40.7 days) through progressive fixator adjustments. At correction completion, all ankles restored to a neutral or 5°-10° dorsiflexed position with plantigrade foot function. Superficial pin tract infections occurred in 3 patients (10.3%), resolved with local wound care, enhanced nursing, and oral antibiotics. No deep or systemic infections was observed. One patient sustained a calcaneal half-pin fracture due to a fall during fixator wear, but no bone fragment displacement occurred. No vascular or neurological complication was reported. Complete bony union was achieved at all osteotomy sites without nonunion. At last follow-up, the AOFAS ankle-hindfoot score improved from preoperative 42.7±8.7 to postoperative 65.7±9.3, and the VAS score decreased from preoperative 4.5±1.3 to postoperative 2.5±1.1, with significant differences ( P<0.05). Functional outcomes were rated as excellent in 14 cases, good in 13 cases, fair in 1 case, and poor in 1 case, with an excellent and good rate of 93.1%. CONCLUSION The progressive correction strategy combining Ilizarov external fixation technique with limited foot osteotomy effectively corrects post-traumatic equinovarus deformity while preserving soft tissue integrity. This method is associated with minimal, largely controllable complications and achieves alignment stability and fusion outcomes comparable to traditional open surgery, making it an effective treatment for complex foot and ankle deformities.
Humans ; Male ; Female ; Osteotomy/methods* ; Adult ; Retrospective Studies ; Ilizarov Technique ; Middle Aged ; Adolescent ; External Fixators ; Young Adult ; Treatment Outcome ; Ankle Joint/surgery* ; Clubfoot/etiology* ; Minimally Invasive Surgical Procedures/methods*

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.

Objective:To analyze the comorbidity patterns between thyroid dysfunction and other common cardiometabolic diseases.Methods:In this cross-sectional study, 93 967 participants aged 18 years or older who underwent thyroid function tests at the Health Checkup Center of China-Japan Friendship Hospital between 2017 and 2024 were included. The comorbidity patterns between thyroid dysfunction and six common cardiometabolic diseases of obesity, diabetes, hypertension, dyslipidemia, hyperuricemia, and non-alcoholic fatty liver disease (NAFLD) were described systematicly. The logistic regression models was used to analyze the association between thyroid dysfunction and these cardiometabolic diseases.Results:The detection rates of subclinical hyperthyroidism, overt hyperthyroidism, subclinical hypothyroidism, and overt hypothyroidism in those participants was 1.9%, 0.9%, 3.7% and 1.1%, respectively. The proportion of the paticipants with subclinical hyperthyroidism, overt hyperthyroidism, subclinical hypothyroidism, and overt hypothyroidism who had at least one comorbid cardiometabolic disease was 67.5%, 64.8%, 73.5%, and 77.6%, respectively; the proportion of those participants with two or more concurrent cardiometabolic diseases was 38.6%, 36.7%, 42.8%, and 47.5%, respectively; and the proportion with three or more concurrent cardiometabolic diseases was 19.0%, 18.1%, 22.9%, and 27.5%, respectively. After adjusting for age and gender, the participants with overt hypothyroidism (≥2 comorbidities: OR=1.7, 95% CI: 1.5-1.9;≥3 comorbidities: OR=1.8, 95% CI: 1.5-2.1) or subclinical hypothyroidism (≥2 comorbidities: OR=1.3, 95% CI: 1.2-1.4;≥3 comorbidities: OR=1.3, 95% CI: 1.2-1.4) had a significantly higher risk of multiple cardiometabolic diseases when compared with euthyroid individuals. Analysis of comorbidity patterns revealed that individuals with overt hyperthyroidism ( OR=1.8, 95% CI: 1.0-3.1) and subclinical hyperthyroidism ( OR=1.5, 95% CI=1.0-2.2) had a significantly higher risk of the “NAFLD+hypertension” comorbidity complex when compared with euthyroid individuals. Similarly, individuals with overt hypothyroidism ( OR=1.7, 95% CI: 1.2-2.3) and subclinical hypothyroidism ( OR=1.3, 95% CI: 1.1-1.5) had a significantly higher risk of the “dyslipidemia+NAFLD+hyperuricemia” comorbidity complex when compared with euthyroid individuals. Conclusion:Individuals with thyroid dysfunction exhibit a high prevalence of comorbid cardiometabolic diseases, highlighting the need for future research on integrated management strategies for multimorbidity in this population.

Objective:To analyze serum inflammatory factors associated with antihistamine resistance in patients with chronic spontaneous urticaria (CSU) .Methods:A total of 88 CSU patients were enrolled from Guangzhou Dermatology Hospital from January 2022 to December 2024. All patients received antihistamine treatment according to the "Guideline for diagnosis and treatment of urticaria in China (2022) " . Based on the 7-day urticaria activity score (UAS7) after 4-week treatment, these patients were divided into an antihistamine-sensitive group and an antihistamine-resistant group. Serum levels of inflammatory factors at the initial visit were analyzed using the Olink-targeted proteomics technology. Specific biomarkers associated with antihistamine resistance were identified, and Spearman correlation analysis was carried out to analyze correlations among differentially expressed proteins. A logistic regression model was constructed based on the Olink proteomics data, and the predictive performance of the model was evaluated using receiver operating characteristic (ROC) curve analysis. Measurement data were expressed as mean ± standard deviation or median (lower quartile, upper quartile) .Results:The 88 CSU patients aged 12 to 81 (38.78 ± 13.89) years, with the disease duration being 18 (7.00, 60.00) months. There were 32 patients in the antihistamine-sensitive group and 56 in the antihistamine-resistant group. No significant differences were found between the two groups in terms of age, disease duration, gender, or history of allergic diseases (all P > 0.05) . After 4 weeks of antihistamine treatment, the UAS7 score was significantly higher in the antihistamine-resistant group (25.00 [15.25, 31.00] points) than in the antihistamine-sensitive group (0.50 [0.00, 4.00] points; Z = -7.08, P < 0.001) . The Olink-targeted proteomics identified 5 differentially expressed proteins between the two groups: compared with the antihistamine-sensitive group, the antihistamine-resistant group showed > 2-fold higher expression of fibroblast growth factor 19 (FGF19) , interleukin-15 receptor subunit alpha (IL-15RA) , eotaxin (CCL11) , and monocyte chemoattractant protein-1 (MCP-1) ; in contrast, the expression of sulfotransferase 1A1 (ST1A1) in the antihistamine-sensitive group was 2.54 times that in the antihistamine-resistant group. Among the differentially expressed proteins, MCP-1 showed the highest specificity (1.00) for predicting antihistamine resistance, followed by CCL11 (0.97) . Correlation analysis revealed a significant positive correlation between MCP-1 and CCL11, and a significant negative correlation between IL-15RA and ST1A1. ROC curve analysis showed that MCP-1 and CCL11 had area under the curve values of 0.603 and 0.630, respectively, in predicting antihistamine resistance. Conclusion:MCP-1 and CCL11 may be potential biomarkers for predicting antihistamine resistance in CSU patients.

Objective:To evaluate the stability of percutaneous screw fixation for minimally invasive treatment of intra-articular calcaneal fractures using three-dimensional finite element analysis.Methods:CT scan was performed on the calcaneus of a normal adult for three-dimensional reconstruction. The DICOM data were imported into Mimics software to establish a model of a Sanders type IIB intra-articular calcaneal fracture. Based on the Essex-Lopresti classification of posterior facet morphology, the model was subdivided into two subtypes: tongue-type and depression-type. The calcaneus was divided into four fragments: sustentaculum tali, posterior tuberosity, anterior process (three points), and posterior articular surface (one surface). Two types of fixation methods, classical lateral anatomical plates and combinations of percutaneous screws, were simulated and performed. A three-dimensional finite element analysis was conducted by applying a stress combination of 420 N on the posterior subtalar articular surface, 200 N on the middle subtalar articular surface, and 300 N at the Achilles tendon insertion point. The maximum displacement and von Mises stress values of each bone fragment and implant were recorded to evaluate the biomechanical stability. For clinical validation, 34 patients with Sanders type IIB calcaneal fractures from Orthopedics Department of the Sixth Affiliated People's Hospital of Shanghai Jiao Tong University were treated with percutaneous reduction and screw fixation using the following configurations.Results:Under simulated stress, the A4 group with medial support screws in the tongue-type fracture subgroup demonstrated minimal overall calcaneal displacement (0.22 mm) and internal fixation displacement (0.14 mm). For the depression-type, the B2 group with medial support screws showed lower maximum stress in the calcaneus and internal fixation, at 22.04 MPa and 41.14 MPa, respectively, along with the lowest overall displacement (0.14 mm). The peak stress of all groups of implants remained below the material yield strength. The A4 and B2 protocols were applied to 15 cases of tongue-type calcaneal fractures and 19 cases of collapse-type calcaneal fractures. At the final follow-up The American Orthopaedic Foot & Ankle Society ankle-hindfoot score scale was 86.1±5.82 and 87.2±5.18, respectively, while the visual analog scale for pain was 1.60±1.24 and 1.58±1.02, respectively.Conclusions:Percutaneous screw fixation provided reliable stability for Sanders type IIB calcaneal fractures. The fixation configuration incorporating a medial support screw offers superior biomechanical performance in both tongue-type and depression-type fractures, representing an optimized minimally invasive technique with strong clinical applicability.

Objective:To explore the construction and validation of a nomogram model for predicting poor survival prognosis in patients with clear cell renal cell carcinoma（ccRCC）based on deep learning of pathological images.Methods:This study was an observational cohort study. The original pathological images and clinicopathological data（TCGA cohort）of 378 patients with ccRCC were obtained from the Cancer Genome Atlas Database（TCGA）for model training. A total of 301 patients with ccRCC who underwent surgical treatment at Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2010 to December 2020（Renji cohort）and 214 patients with ccRCC who underwent surgical treatment at the First People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2012 to December 2018（General cohort）were included for model validation. Their original pathological images and clinical pathological data were collected. A clustering-constrained attention and multi-instance learning method was used to accurately identify sub-regions of the images to classify and extract features of the pathological images. A deep learning-based disease-free survival prognosis prediction model（DL-DFS）was constructed through a weakly supervised learning strategy. The clinical pathological features and DL-DFS were further combined to construct a nomogram model for the clinical prognosis of ccRCC patients. Univariate and multivariate Cox regression analyses were employed to evaluate the independent risk factors for disease-free survival（DFS）. The efficacy of the predictive model were evaluated by the receiver operating characteristic curve（ROC）with area under the curve（AUC），respectively. Survival analysis was conducted using the Kaplan-Meier curve.Results:DL-DFS could accurately predict the DFS status of ccRCC patients in 5 years after surgery. Through ROC analysis in the training cohort，the AUC value reached 0.75（ P < 0.001）. In the Renji cohort and the General cohort，the AUC values were 0.65（ P < 0.001）and 0.81（ P < 0.001），respectively. Through Kaplan-Meier survival analysis，we found that DL-DFS could identify ccRCC patients with high survival risks. The hazard ratio in the training cohort was 3.86（95% CI 2.36-6.30， P < 0.001）. The hazard ratio in the Renji cohort and General cohort were 1.97（95% CI 1.03-3.80， P = 0.009）and 4.66（95% CI 1.80-12.06， P = 0.008），respectively. Univariate and multivariate Cox regression analyses indicated that DL-DFS risk score，tumor grade，and tumor stage could act as prognostic risk factors for patients with ccRCC（ P < 0.05）. Considering that age was a common prognostic risk factor for patients with renal cancer，a nomogram model was constructed by combining the DL-DFS risk score with patient age，tumor grade，and tumor stage. The AUC of this model for predicting the 5-year DFS of ccRCC patients after surgery was 0.87，which was significantly higher than that of DL-DFS（AUC = 0.74），tumor stage（AUC = 0.84），tumor grade（AUC = 0.72），and patient age（AUC = 0.56）in the TCGA cohort（all P<0.05）. In the Renji cohort and the General cohort，the AUC of the nomogram model were 0.78 and 0.86 respectively，which was significantly higher than that of DL-DFS（0.65 and 0.81），tumor stage（0.72 and 0.69），tumor grade（0.64 and 0.77），and patient age（0.56 and 0.63）. Conclusions:In this study a DL-DFS for ccRCC patients was constructed. Then a nomogram model was constructed by combining the DL-DFS risk value with patient age，tumor grade，and tumor stage. This nomogram model demonstrated superior predictive performance compared to DL-DFS alone in evaluating the DFS prognosis of ccRCC patients，which still needs to be further verified in prospective clinical studies.

[Purpose]To analyze the trends of disease burden for lung cancer worldwide and in China from 1990 to 2021.[Methods]Data of the disease burden of lung cancer and population demographics in 1990 and 2021 stratified by sex and age groups for global,five SDI quintiles re-gions,and eight countries including China,Japan,Republic of Korea,United Kingdom,France,United States,Canada,and Australia were extracted from the Global Burden of Disease Study 2021(GBD 2021)database.The age-standardized mortality rate(ASMR)and age-standard-ized disability-adjusted life year rate(ASDR)of lung cancer attributable to 7 level-3 risk factors in China for 1990 and 2021 were also extracted.Counterfactual analysis was used to decompose changes in lung cancer deaths and DALY from 1990 to 2021 into four contributing factors:popu-lation size,population structure,age-standardized incidence or prevalence,and lung cancer case fatality or disease severity.The percentage changes in lung cancer deaths and DALY attributed to these four factors were calculated respectively.[Results]In 2021,there were 934 704 new cases and 814 364 deaths of lung cancer in China.From 1990 to 2021,the incidence,preva-lence,mortality,and DALY rates of lung cancer in China increased faster than those worldwide and in high-middle SDI regions,which was similar to Japan and Republic of Korea.In contrast,the mortality rates of lung cancer decreased in United States and United Kingdom;and the DALY rates of lung cancer decreased in United States,United Kingdom,Canada and Australia.From 1990 to 2021,the age-related lung cancer deaths and DALY in China increased by 193.91％and 146.20％,respectively.The primary contributor to the increase in lung cancer deaths was population aging(102.82％)among men and rising age-standardized incidence(119.00％)among women,while the primary contributor to the increase in DALY was rising age-standardized prevalence for both men(153.12％)and women(218.77％).In 2021,the top three risk factors contributing to lung cancer ASMR and ASDR in China were smoking,particulate matter pollution and occupational carcinogen exposure.Compared with 1990,the ASMR of lung cancer and its proportion at-tributable to particulate matter pollution and low dietary fruits were decreased,while the propor-tions in ASDR of lung cancer attributable to smoking and secondhand smoke increased.[Conclu-sion]Lung cancer is a major public health challenge in China.Compared with worldwide,high-middle SDI regions and certain developed countries,China has experienced faster growth in the incidence,prevalence,mortality and DALY of lung cancer,especially among women.To reduce disease burden,sustained efforts on lung cancer prevention and control are urgently required in China.

Objective:To evaluate the clinical value of multi-disciplinary treatment (MDT) combined with enhanced recovery after surgery (ERAS) for the elderly patients with osteoporotic ankle fracture.Methods:A retrospective analysis was conducted to analyze the 88 elderly patients with osteoporotic ankle fracture who had been treated with MDT combined with ERAS or non-MDT at Department of Foot and Ankle Surgery, Shanghai Sixth People's Hospital from January 2021 to January 2024. According to whether MDT was adopted or not, this cohort was assigned into 2 groups using the propensity score matching method: a MDT group and a non-MDT group with a matching ratio of 1∶1 (44 cases per group). The 2 groups were compared in terms of choice of intraoperative fixation, hospital stay, time for return to work/daily life, patient satisfaction questionnaire (PSQ-18) during hospitalization, ankle range of motion at 1 and 3 months after surgery, ankle-hindfoot score of American Orthopaedic Foot and Ankle Society (AOFAS), visual analogue scale (VAS) for pain, gait, and incidence of complications.Results:There were no significant differences in the preoperative general data between the 2 groups, indicating comparability ( P<0.05). The choice of intraoperative fixation, PSQ-18 [(78.4±8.5) points], AOFAS ankle-hindfoot score at 3 months after operation [(75.4±8.2) points], and gait in the MDT group were significantly better than those in the non-MDT group [(74.2±9.6) points and (70.9±9.4) points] ( P<0.05). There was no significant difference in the hospital stay or time for return to work/daily life between the 2 groups ( P>0.05). There was no statistically significant difference either in ankle dorsiflexion or plantarflexion, VAS for pain, or incidence of complications between the 2 groups at 1 or 3 months after surgery, as well as in AOFAS ankle-hindfoot score or gait at 1 month after surgery ( P>0.05). Conclusion:MDT combined with ERAS can effectively increase the therapeutic efficacy for the elderly patients with osteoporotic ankle fracture, improve their function of affected limbs, and enhance their patient satisfaction.