ObjectiveTo investigate the effect of Tougu Xiaotong capsules （TGXTC） on the regulation of chondrocyte PANoptosis， delay of chondrocyte degeneration， and improvement of the symptoms in knee osteoarthritis （KOA）. MethodsIn vivo experiments： 50 male C57BL/6 mice were randomly assigned into five groups （n=10 per group）： sham operation group， model group， low-dose TGXTC group （7.2 g·kg^-1）， high-dose TGXTC group （14.4 g·kg^-1）， and diclofenac sodium group （0.05 g·kg^-1）. Except for the sham group， KOA models were established in all other groups using the modified Hulth method. Following successful model induction， the TGXTC groups received daily oral gavage of 7.2 or 14.4 g·kg^-1 for 6 weeks， while the diclofenac sodium group received 0.05 g·kg^-1 solution daily over the same duration. Model evaluation was performed using Lequesne MG score； micro-computed tomography （micro-CT） was used to scan the knee， hematoxylin-eosin （HE） staining and safranin O-fast green staining were used to observe the morphology of cartilage， transmission electron microscopy （TEM） was used to determine ultrastructural changes of PANoptosis. Multiple immunofluorescence （IF） co-localization assays was performed to detect the co-localization of cleaved Caspase-3， receptor-interacting protein 3 （RlPK3）， and the N-terminal domain of gasdermin D （GSDMD-N） in cartilage tissue， while western blot was employed to detect the expression levels of cleaved Caspase-3， RIPK3， and GSDMD-N. In vitro experiments： The knee cartilages of 4-week-old SD rats were isolated， and a chondrocyte in vitro culture system was established through mechanical digestion with 0.2% type Ⅱ collagenase. Second-generation chondrocytes were divided into three groups： the control group， the model group （pretreated with 10 mg·L^-1 lipopolysaccharide （LPS） for 24 h followed by treatment with 1 μmol·L^-1 nigericin for 4 h）， and the TGXTC treatment group （pretreated with 10 mg·L^-1 LPS for 24 h， followed by exposure to 1 μmol·L^-1 nigericin for 4 h and subsequently treated with 100 mg·L^-1 TGXTC for an additional 24 h）. The levels of reactive oxygen species （ROS）， apoptosis， necroptosis， and pyroptosis of chondrocytes were evaluated via fluorescence microscopy following staining with ROS detection， AO/EB and YO-PRO-1/PI staining kits. Transmission electron microscopy was utilized to investigate the ultrastructural changes associated with PANoptosis in cartilage tissue of KOA mice. Inflammatory cytokine levels （IL-1β and IL-18） were measured using ELISA. Western blot was conducted to assess protein expressions related to PANoptosis， including cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3. ResultsCompared with the sham group， the Lequesne MG scores were significantly up-regulated（P<0.01） in the model group， and the pathological changes of cartilage were significantly， with joint spaces narrower， osteophyte formation increased， secere abrasion of cartilage surface. Ultrastructural analysis revealed pronounced chondrocyte apoptosis， necroptosis， and pyroptosis， along with markedly elevated expression of cleaved Caspase-3， RlPK3， and GSDMD-N in cartilage tissue （P<0.01）. In addition， The mean fluorescence intensities of ROS， orange-red fluorescence in AO/EB staining， green fluorescence and red fluorescence in YO-PRO-1/PI staining were increased of chondrocyte in the model group （P<0.01） . The levels of inflammatory factors IL-1β and IL-18 in the supernatant were increased （P<0.01）. The expression of PANoptosis related proteins （cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3） were also significantly upregulated（P<0.05）. Compared to the model group， the TGXTC group demonstrated a significant improvement in various parameters of mice. These included a reduction in the Lequesne MG score， an increase in joint space， a decrease in osteophyte formation， diminished cartilage damage， reduced release of ROS， and alleviation of apoptotic， necroptotic， and pyroptotic processes in chondrocytes. Additionally， mitochondrial swelling and endoplasmic reticulum dilation were also mitigated. The levels of ROS as well as IL-1β and IL-18 were significantly decreased （P<0.05）. Furthermore， the expression levels of proteins associated with PANoptosis in cartilage tissue showed marked reductions （P<0.05）. Similar results were observed in chondrocytes： cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3 exhibited significant decreases as well （P<0.05）. ConclusionTGXTC may mitigate chondrocytes degeneration and alleviate KOA symptoms by reducing oxidative stress and suppressing the activation of PANoptosis pathways.

ObjectiveTo investigate the effect of Tougu Xiaotong capsules （TGXTC） on the regulation of chondrocyte PANoptosis， delay of chondrocyte degeneration， and improvement of the symptoms in knee osteoarthritis （KOA）. MethodsIn vivo experiments： 50 male C57BL/6 mice were randomly assigned into five groups （n=10 per group）： sham operation group， model group， low-dose TGXTC group （7.2 g·kg^-1）， high-dose TGXTC group （14.4 g·kg^-1）， and diclofenac sodium group （0.05 g·kg^-1）. Except for the sham group， KOA models were established in all other groups using the modified Hulth method. Following successful model induction， the TGXTC groups received daily oral gavage of 7.2 or 14.4 g·kg^-1 for 6 weeks， while the diclofenac sodium group received 0.05 g·kg^-1 solution daily over the same duration. Model evaluation was performed using Lequesne MG score； micro-computed tomography （micro-CT） was used to scan the knee， hematoxylin-eosin （HE） staining and safranin O-fast green staining were used to observe the morphology of cartilage， transmission electron microscopy （TEM） was used to determine ultrastructural changes of PANoptosis. Multiple immunofluorescence （IF） co-localization assays was performed to detect the co-localization of cleaved Caspase-3， receptor-interacting protein 3 （RlPK3）， and the N-terminal domain of gasdermin D （GSDMD-N） in cartilage tissue， while western blot was employed to detect the expression levels of cleaved Caspase-3， RIPK3， and GSDMD-N. In vitro experiments： The knee cartilages of 4-week-old SD rats were isolated， and a chondrocyte in vitro culture system was established through mechanical digestion with 0.2% type Ⅱ collagenase. Second-generation chondrocytes were divided into three groups： the control group， the model group （pretreated with 10 mg·L^-1 lipopolysaccharide （LPS） for 24 h followed by treatment with 1 μmol·L^-1 nigericin for 4 h）， and the TGXTC treatment group （pretreated with 10 mg·L^-1 LPS for 24 h， followed by exposure to 1 μmol·L^-1 nigericin for 4 h and subsequently treated with 100 mg·L^-1 TGXTC for an additional 24 h）. The levels of reactive oxygen species （ROS）， apoptosis， necroptosis， and pyroptosis of chondrocytes were evaluated via fluorescence microscopy following staining with ROS detection， AO/EB and YO-PRO-1/PI staining kits. Transmission electron microscopy was utilized to investigate the ultrastructural changes associated with PANoptosis in cartilage tissue of KOA mice. Inflammatory cytokine levels （IL-1β and IL-18） were measured using ELISA. Western blot was conducted to assess protein expressions related to PANoptosis， including cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3. ResultsCompared with the sham group， the Lequesne MG scores were significantly up-regulated（P<0.01） in the model group， and the pathological changes of cartilage were significantly， with joint spaces narrower， osteophyte formation increased， secere abrasion of cartilage surface. Ultrastructural analysis revealed pronounced chondrocyte apoptosis， necroptosis， and pyroptosis， along with markedly elevated expression of cleaved Caspase-3， RlPK3， and GSDMD-N in cartilage tissue （P<0.01）. In addition， The mean fluorescence intensities of ROS， orange-red fluorescence in AO/EB staining， green fluorescence and red fluorescence in YO-PRO-1/PI staining were increased of chondrocyte in the model group （P<0.01） . The levels of inflammatory factors IL-1β and IL-18 in the supernatant were increased （P<0.01）. The expression of PANoptosis related proteins （cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3） were also significantly upregulated（P<0.05）. Compared to the model group， the TGXTC group demonstrated a significant improvement in various parameters of mice. These included a reduction in the Lequesne MG score， an increase in joint space， a decrease in osteophyte formation， diminished cartilage damage， reduced release of ROS， and alleviation of apoptotic， necroptotic， and pyroptotic processes in chondrocytes. Additionally， mitochondrial swelling and endoplasmic reticulum dilation were also mitigated. The levels of ROS as well as IL-1β and IL-18 were significantly decreased （P<0.05）. Furthermore， the expression levels of proteins associated with PANoptosis in cartilage tissue showed marked reductions （P<0.05）. Similar results were observed in chondrocytes： cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3 exhibited significant decreases as well （P<0.05）. ConclusionTGXTC may mitigate chondrocytes degeneration and alleviate KOA symptoms by reducing oxidative stress and suppressing the activation of PANoptosis pathways.

Objective To investigate the feasibility, safety, and clinical value of endoscopic-assisted skin-sparing mastectomy combined with immediate implant-based breast reconstruction performed as day surgery for breast cancer, aiming to provide a reference for major hospitals seeking to implement a day surgery model for breast cancer treatment. Methods We retrospectively analyzed the patients who underwent endoscopic-assisted skin-sparing mastectomy combined with immediate implant-based breast reconstruction for breast cancer at West China Hospital of Sichuan University from June 2021 to December 2022, and they were divided into a day surgery group and a conventional inpatient group based on their admission model. The operative indicators, Breast-Q scores, preoperative waiting time, length of hospital stay, hospitalization costs and complications of the two groups were analyzed. Results Except for intraoperative bleeding (P=0.007), the difference between the two groups in comparison of the rest of the operative indicators was not statistically significant (all P>0.05); there was no significant difference between the two groups in preoperative and postoperative Breast-Q scores (all P>0.05); the preoperative waiting time and length of stay in hospital of the day surgery group were 4.0 (3.0, 11.0) days and 1.0 (1.0, 1.0) days, respectively, which were significantly shorter than that of the conventional inpatient group; the postoperative pain score in the day surgery group [1.0 (1.0, 1.0) points] was lower than that in the conventional inpatient group [3.0 (3.0, 3.0) points], with a statistically significant difference between the two groups (P<0.001). Additionally, the total hospitalization costs for the day surgery group and conventional inpatient group were 50 656.5 (48 145.3, 62 597.3) RMB and 53 689.3 (50 469.1, 64 826.5) RMB, respectively.The total hospitalization cost in the day surgery group was significantly lower than that in the conventional inpatient group, with a statistically significant difference between the two groups (P=0.001). There was no statistically significant difference in complications between the two groups (all P>0.05). Conclusion Endoscopic-assisted skin-sparing mastectomy combined with immediate implant-based breast reconstruction in day surgery is feasible and safe. Without increasing postoperative complications, it effectively reduces hospitalization costs and shortens medical care time, demonstrating significant clinical value.

Methods: Fifty patients who underwent UBE-TLIF and 50 patients who underwent W-TLIF, each with >2 years of follow-up, were retrospectively analyzed. Outcomes included operative parameters, time to postoperative mobilization, paravertebral muscle atrophy and fat infiltration rates, clinical scores (Visual Analog Scale [VAS], Oswestry Disability Index [ODI], Japanese Orthopaedic Association [JOA]), modified Macnab criteria, fusion rates, and complications. Results: Compared with W-TLIF, the UBE-TLIF group had significantly less intraoperative blood loss, shorter operative times, and lower postoperative drainage volumes (p <0.05). The UBE-TLIF group showed faster postoperative recovery and shorter hospital stays. At 6 months, 1 year, and 2 years, W-TLIF patients had higher multifidus and erector spinae atrophy, and greater paravertebral muscle fat infiltration (p <0.05). The UBE-TLIF group also had lower VAS and ODI scores at 1 year and 2 years (p <0.05) and fewer surgical complications (6% vs. 10%). Fusion rates (94% vs. 92%) and modified Macnab outcomes (88% vs. 86%) were comparable (p >0.05). Conclusions UBE-TLIF is associated with reduced intraoperative trauma, quicker recovery, and fewer complications. In the long-term, it better preserves paravertebral muscle integrity and provides superior pain and functional outcomes.

Objective To explore the predictive value of forkhead box P3 (FOXP3) mRNA expression in cord blood derived regulatory T cells (Tregs) and the associated cytokines interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) for early-onset atopic dermatitis (AD) in infants. Methods The healthy full-term newborns delivered vaginally at Shanghai Fifth People’s Hospital from September 2023 to April 2024 were enrolled. Umbilical vein blood was collected at birth to measure FOXP3 mRNA expression by RT-PCR and IL-10 and TGF-β concentrations by ELISA. Follow-up was performed at 6 weeks, 3 months, and 6 months postnatally via telephone or outpatient visits to assess the occurrence of AD in infants. Based on the occurrence of AD at 6 months of age, the infants were divided into an AD group and a control group. The indicators related to mothers and infants were compared between the two groups. Logistic regression analysis was used to identify risk factors for the development of AD in infants within 6 months after birth, and a predictive model was constructed. The performance of the model in predicting early-onset AD was evaluated using receiver operating characteristic (ROC) curve analysis. Results A total of 59 infants completed 6-month follow-up, with 17 (28.8%) diagnosed with AD. No significant differences were observed in gestational age, sex, birth weight, presence of siblings, smoking expossure, maternal dietary preferences (egg, milk, or seafood intake), maternal age and education level, or cord blood IL-10 levels between two groups. There were significant differences in season of birth, family history of atopic disease, feeding method, and cord blood levels of FOXP3 mRNA and TGF-β between two groups (P＜0.05). Logistic regression analysis showed low levels of cord blood FOXP3 mRNA and TGF-β, and family history of atopic disease were risk factors for early-onset AD in infants (P＜0.05). A predictive model was constructed using risk factors. The area under the curve of the combined model was 0.821 (95%CI 0.680–0.962), with a sensitivity of 76.5% and a specificity of 85.7%. Conclusion Reduced cord blood FOXP3 mRNA and TGF-β level, and a family history of atopic diseases could be used to predict early-onset AD in infants.

Objective To compare the dosimetric differences between volumetric modulated arc therapy(VMAT)and intensity modulated radiation therapy(IMRT)in the irradiation of chest wall and upper and lower clavicle regions after radical mastectomy for breast cancer.Methods A total of 100 patients who were scheduled to receive radiotherapy after radical mastectomy were included and selected as research subjects.Patients were divided into the VMAT group and the IMRT group by random number table method,with 50 cases in each group.The target dose parameters,exposure dose of organs at risk,monitor unit(MU)and treatment time were compared between the two groups.Results There were no statistical differences in V95 and V110 between the VMAT group and the IMRT group(P＞0.05).The D2%in the VMAT group was lower than that of the IMRT group,while D98%and D50%were higher in the VMAT group than those in the IMRT group(P＜0.05).Target area uniformity and target area conformity were better in the VMAT group than those in the IMRT group(P＜0.05).There were no significant differences in mean cardiac dose(Dmean)and ipsilateral lung V5 and V10 between the VMAT group and the IMRT group(P＞0.05).The heart V20 and V30,contralateral lung Dmean,maximum spinal cord dose(Dmax),contralateral breast Dmean,ipsilateral lung Dmean,V20,V30 and mean MU were lower in the VMAT group than those in the IMRT group,and the treatment time was shorter than that in the IMRT group(P＜0.05).Conclusion In the irradiation treatment of chest wall and upper and lower clavicle regions after radical mastectomy,VMAT demonstrates superior dosimetric characteristics and higher treatment efficiency compared with IMRT,particularly in terms of target area uniformity,target area conformity and exposure doses to organs at risk.

Objective To compare the dosimetric differences between volumetric modulated arc therapy(VMAT)and intensity modulated radiation therapy(IMRT)in the irradiation of chest wall and upper and lower clavicle regions after radical mastectomy for breast cancer.Methods A total of 100 patients who were scheduled to receive radiotherapy after radical mastectomy were included and selected as research subjects.Patients were divided into the VMAT group and the IMRT group by random number table method,with 50 cases in each group.The target dose parameters,exposure dose of organs at risk,monitor unit(MU)and treatment time were compared between the two groups.Results There were no statistical differences in V95 and V110 between the VMAT group and the IMRT group(P＞0.05).The D2%in the VMAT group was lower than that of the IMRT group,while D98%and D50%were higher in the VMAT group than those in the IMRT group(P＜0.05).Target area uniformity and target area conformity were better in the VMAT group than those in the IMRT group(P＜0.05).There were no significant differences in mean cardiac dose(Dmean)and ipsilateral lung V5 and V10 between the VMAT group and the IMRT group(P＞0.05).The heart V20 and V30,contralateral lung Dmean,maximum spinal cord dose(Dmax),contralateral breast Dmean,ipsilateral lung Dmean,V20,V30 and mean MU were lower in the VMAT group than those in the IMRT group,and the treatment time was shorter than that in the IMRT group(P＜0.05).Conclusion In the irradiation treatment of chest wall and upper and lower clavicle regions after radical mastectomy,VMAT demonstrates superior dosimetric characteristics and higher treatment efficiency compared with IMRT,particularly in terms of target area uniformity,target area conformity and exposure doses to organs at risk.

Objective To investigate the effects of Danlong Xingnao Prescription on learning and memory ability and microglia activation in rats with vascular dementia(VD)based on HMGB1/RAGE/NF-κB pathway.Methods Ten rats were randomly selected from 72 rats as a sham-operation group.The remaining rats were treated with modified bilateral common carotid artery ligation method to prepare the VD model.The 50 successful model rats were randomly divided into model group,nimodipine group(10.8 mg/kg)and Danlong Xingnao Prescription low-,medium-and high-dosage groups(3.7,7.4,14.8 g/kg),with 10 rats in each group.The administration groups were given relevant solution for gavage,the sham-operation group and model group were given the same amount of normal saline for consecutive 28 d.Morris water maze test was performed to evaluate learning and memory abilities of rats,the morphology in the hippocampus were observed by HE staining,the contents of interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α in hippocampal tissue were detect by ELISA,RT-PCR was used to detect high mobility group protein B1(HMGB1),receptor of advanced glycation end product(RAGE),nuclear factor(NF)-κB p65 and regulatory RNase-1(Regnase-1)mRNA expression in hippocampal tissue,immunohistochemistry and Western blot were used to detect the protein expressions of ion calcium binding adapter molecule 1(Iba1),HMGB1,RAGE,NF-κB p65 and Regnase-1 in hippocampal tissue.Results Compared with the sham-operation group,the escape latency of rats was prolonged,and the number of crossings through the original platform was increased in the model group(P<0.01),the pyramidal cells in the hippocampus were reduced and irregularly shaped,with unclear cell and nuclear membranes,and a significant number of necrotic neurons were visible,the contents of IL-1β,IL-6 and TNF-α in hippocampal tissue increased(P<0.01),the mRNA expressions of HMGB1,RAGE and NF-κB p65 in hippocampal tissue increased(P<0.01),while the mRNA expression of Regnase-1 decreased(P<0.01),the protein expressions of Iba1,HMGB1,RAGE and NF-κB p65 increased(P<0.01),while the protein expression of Regnase-1 decreased(P<0.01).Compared with the model group,the escape latency of rats was shortened in Danlong Xingnao Prescription groups,the number of crossings through the original platform was reduced(P<0.05,P<0.01),the neuronal structure of hippocampal tissue was significantly improved,the number of necrotic neurons was reduced,and the contents of IL-1β,IL-6 and TNF-α in hippocampal tissue reduced(P<0.05,P<0.01),the mRNA expressions of HMGB1,RAGE and NF-κB p65 in hippocampal tissue decreased,the mRNA expression of Regnase-1 increased(P<0.05,P<0.01),the protein expression of Iba1,HMGB1,RAGE and NF-κB p65 decreased,the protein expression of Regnase-1 increased(P<0.05,P<0.01).Conclusion Danlong Xingnao Prescription can improve the learning and memory ability of VD rats,and its mechanism may be related to inhibiting the activation of HMGB1/RAGE/NF-κB pathway and increasing Regnase-1 expression,thereby inhibiting the activation of microglia.

Objective:To establish and validate the diagnostic model of acute pulmonary embolism (APE) based on clinical and laboratory variables.Methods:This retrospective analysis was conducted on patients with suspected APE who underwent CT pulmonary angiography at the First Affiliated Hospital of Henan University of Chinese Medicine between February 2015 and December 2023. The patients were randomly divided into a training set and a validation set at a ratio of 7∶3. Clinical and laboratory data of the enrolled patients were collected, and patients were divided into an APE group and a non-APE group according to CT pulmonary angiography results. In the training set, univariate and multivariate logistic regression as well as Lasso regression were used to identify risk factors for APE, and a diagnostic model was developed and validated. Receiver operating characteristic curves were plotted, and calibration and decision curves were used to assess the performance of the diagnostic model. The diagnostic efficacy of the model was compared with that of the Wells score and the revised Geneva score using the DeLong test.Results:A total of 752 patients were enrolled, aged (64±15) years, including 417 (55.5%) males. The training set included 526 patients and the validation set included 226 patients. The incidence of APE in this cohort was 48.7% (366/752), with 366 cases in the APE group and 386 in the non-APE group. Multivariable logistic regression analysis showed that cyanosis ( OR=8.88, 95% CI 2.04-49.11), elevated neutrophil count ( OR=1.82, 95% CI 1.06-3.15), elevated creatine kinase isoenzyme ( OR=3.45, 95% CI 1.76-6.91), decreased partial pressure of carbon dioxide ( OR=12.88, 95% CI 7.64-22.34), elevated age-adjusted D-dimer ( OR=2.53, 95% CI 1.10-6.20), prolonged thrombin time ( OR=4.08, 95% CI 2.06-8.33), and positive lower limb venous ultrasound for thrombus ( OR=4.39, 95% CI 2.59-7.58) were risk factors associated with APE. The area under the curve ( AUC) of the diagnostic model was 0.92 (95% CI 0.90-0.94) in the training set and 0.92 (95% CI 0.89-0.95) in the validation set. The diagnostic efficacy of this model was superior to that of the Wells score ( AUC: 0.92 vs. 0.63, P<0.01) and the revised Geneva score ( AUC: 0.92 vs. 0.59, P<0.01). Conclusion:The diagnostic model for acute pulmonary embolism constructed based on clinical and laboratory parameters demonstrates excellent diagnostic performance and may facilitate rapid and accurate screening in clinical practice.

Objective: Uterine cancer (UC) is a major cause of cancer-related deaths among women. This study assesses the global burden of UC from 1990 to 2021. Methods: Data from the Global Burden of Disease 2021 study were used to analyze UC incidence, mortality, and disability-adjusted life years (DALYs) across 204 countries.Age-standardized rates were evaluated by age and Socio-Demographic Index (SDI), with trends forecasted to 2036 using Bayesian models. Results: In 2021, the global incidence of UC reached 473,614 cases (95% uncertainty interval [UI]=4,29916–5,13667), with an age-standardized incidence rate of 5.41 per 100,000 (95% UI=4.90–5.87), showing an upward trend since 1990, particularly in high-SDI regions. However, the mortality rate in high SDI regions exhibited a declining trend, with an estimated annual percentage change (EAPC) of −0.25 (95% confidence interval=−0.42 to −0.08). Although the number of deaths globally has increased, the age-standardized mortality rate has decreased compared to 1990 (EAPC: −0.85). The global age-standardized DALYs also show a downward trend, except in high SDI and low-middle SDI regions. The highest incidence was observed among individuals aged 70–74 in 2021. By 2036, new cases are projected to rise, though incidence, mortality, and DALYs are expected to decline. Conclusion Regional disparities in the global UC burden highlight the need for tailored strategies, especially in low-income countries, to reduce its impact.