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 propose a lightweight end-to-end neural network model for automated Korotkoff sound phase recognition and subsequent blood pressure (BP) measurement, aiming to improve measurement accuracy and population adaptability. Methods We developed a streamlined architecture integrating depthwise separable convolution (DSConv), multi-head attention (MHA), and bidirectional gated recurrent unit (BiGRU). The model directly processes Korotkoff sound time-series signals to identify auscultatory phases. Systolic BP (SBP) and diastolic BP (DBP) were determined using phase Ⅰ and phaseⅤdetections, respectively. Given the clinical relevance of phase Ⅳ for specific populations (e.g., children and pregnant women, denoted as DBPⅣ), BP values from this phase were also recorded.Results The study enrolled 106 volunteers with 70 males and 36 females at mean age of (40.0±12.0) years. The model achieved 94.25% phase recognition accuracy. Measurement errors were (0.1±2.5) mm Hg (SBP), (0.9±3.4) mm Hg (DBPⅣ), and (0.8±2.6) mm Hg (DBP). Conclusion Our method enables precise phase recognition and BP measurement, demonstrating potential for developing population-adaptive blood pressure monitoring systems.

Objective: To explore the independent and interactive effects of school green space exposure and outdoor activity duration on screening myopia among primary and secondary school students, so as to provide theoretical support for the prevention and control of screening myopia in children and adolescents. Methods: From September to November 2023, 117 487 primary and secondary school students from 497 schools were selected using a cluster random sampling method, covering 98 counties (cities, districts) in Jiangsu Province. Data on the students screening myopia status and associated health influencing factors were collected and analyzed. School green space exposure was quantified using the normalized difference vegetation index (NDVI), which was extracted with ArcGIS Pro software; meanwhile, information on students outdoor activity duration was gathered through self reported questionnaires. Multivariate Logistic regression was applied to assess the independent and interactive effects of green space exposure and outdoor activity duration on screening myopia among primary and secondary school students. Results: Univariate analysis showed that there were statistically significant differences in screening myopia detection rates among primary and secondary school students of different genders, NDVI groups, every outdoor activity duration, monitoring points, school stages, parents educational level, and whether they lived on campus or had parents with screening myopia ( χ 2=88.91-1 950.08, all P <0.05); as the school age and sedentary time increased, the detection rate of screening myopia in primary and secondary school students also increased ( χ 2 trend =8 410.15, 2 028.91, both P <0.05). Independent effects showed that compared to the low NDVI group, the medium and high NDVI groups had lower risks of screening myopia ( OR =0.93, 0.95, both P <0.05). Compared to those with outdoor activity duration<2 h/d, students with outdoor activity duration≥2 h/d had a lower risk of screening myopia ( OR =0.96, P <0.05). When stratified by school level, compared to the low NDVI group, the medium NDVI group had lower risks of screening myopia in primary and junior high schools (primary school: OR =0.91; junior high school: OR =0.88, both P <0.05). Compared to those with outdoor activity duration<2 h/d, junior high school students with outdoor activity duration≥2 h/d had a lower risk of screening myopia ( OR = 0.90, P <0.05). When stratified by monitoring site, urban primary and secondary school students in the medium and high NDVI groups and those with outdoor activity duration≥2 h/d had lower risks of screening myopia ( OR =0.92, 0.92, 0.93, all P <0.05). Interactive effects showed that when medium or high NDVI was combined with outdoor activity duration≥2 h/d, the risks of screening myopia among primary and secondary school students were lower (medium NDVI×≥2 h/d: OR =0.89; high NDVI×≥ 2 h/d : OR =0.89, both P <0.05), and the combined effect was superior to that of a single factor. Conclusion Green space exposure and outdoor activity duration have negative correlations with screening myopia among primary and secondary students, and the combined effect is better than that of a single factor.

The randomized controlled trials (RCTs) regarding acupuncture direction published from January 1st, 2013, to November 7th, 2023 were searched in China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and VIP Chinese Journal Database. As a result, 21 RCTs were included. The problems identified included conceptual misunderstandings regarding acupuncture direction, incomplete selection strategies, confounding research factors, and inaccuracies in reporting. Based on the findings, four strategic approaches for enhancing therapeutic efficacy through acupuncture direction were summarized: aligning needle direction with the meridian pathway, directing the needle toward the lesion site, orienting the needle toward adjacent acupoints, and targeting special anatomical structures. Two additional strategies were proposed for optimizing the procedure: simplifying acupuncture operations and directing the needle toward safe anatomical sites. Recommendations were made to improve the rationality of research factor settings and the completeness of acupuncture operation reporting. Furthermore, three methods for reporting acupuncture direction were discussed: reporting the tip-pointed position, reporting the insertion angle and orientation, and reporting azimuth and polar angles, aiming to promote greater standardization and completeness in acupuncture practice and reporting.
Acupuncture Therapy/standards* ; Humans ; Acupuncture Points ; Randomized Controlled Trials as Topic ; Meridians

Subtype classification of age-related macular degeneration (AMD) based on optical coherence tomography (OCT) images serves as an effective auxiliary tool for clinicians in diagnosing disease progression and formulating treatment plans. To improve the classification accuracy of AMD subtypes, this study proposes a keypoint-based, attention-enhanced residual network (KPA-ResNet). The proposed architecture adopts a 50-layer residual network (ResNet-50) as the backbone, preceded by a keypoint localization module based on heatmap regression to outline critical lesion regions. A two-dimensional relative self-attention mechanism is incorporated into convolutional layers to enhance the representation of key lesion areas. Furthermore, the network depth is appropriately increased and an improved residual module, ConvNeXt, is introduced to enable comprehensive extraction of high-dimensional features and enrich the detail of lesion boundary contours, ultimately achieving higher classification accuracy of AMD subtypes. Experimental results demonstrate that KPA-ResNet achieves significant improvements in overall classification accuracy compared with conventional convolutional neural networks. Specifically, for the wet AMD subtypes, the classification accuracies for inactive choroidal neovascularization (CNV) and active CNV reach 92.8% and 95.2%, respectively, representing substantial improvement over ResNet-50. These findings validate the superior performance of KPA-ResNet in AMD subtype classification tasks. This work provides a high-accuracy, generalizable network architecture for OCT-based AMD subtype classification and offers new insights into integrating attention mechanisms with convolutional neural networks in ophthalmic image analysis.
Tomography, Optical Coherence/methods* ; Humans ; Macular Degeneration/diagnostic imaging* ; Neural Networks, Computer

Objective:To identify the key epithelial cell characteristics that can accurately diagnose eosinophilic chronic sinusitis with nasal polyps（ECRSwNP） through nasal brush sampling and comparing with the pathological results of nasal polyp tissue sections. Methods:Ninety-one patients underwent surgery in the Ophthalmology and ENT Department of the Second People's Hospital of Longgang District, Shenzhen, from January 2022 to July 2024 were selected. The cohort comprised 58 males and 33 females（mean age: 41.4 years; range: 12.0-71.0）. The clinical characteristics of the patients, including gender, age, disease duration, smoking and drinking history, asthma history, subjective symptoms, sinus CT, and nasal endoscopy scores, were recorded. Nasal brush sampling of nasal polyps and inferior turbinate mucosa was performed before surgery to obtain cytological specimens, and nasal polyp tissues were collected during surgery. The demographic and clinical characteristics of patients with eosinophilic and non-eosinophilic nasal polyps were compared, as well as the relationship between nasal brush cytology of nasal polyps and inferior turbinate and nasal polyp histopathology. Statistical analysis was performed using SPSS 23.0 software. Results:Among the 91 patients, no significant differences were observed between ECRSwNP and NECRSwNP patients in terms of age, gender, smoking status, alcohol consumption, and disease duration. The nasal brush cell population in ECRSwNP patients was more likely to contain eosinophils（P<0.001） and less likely to contain lymphocytes and plasma cells（P<0.001）. Additionally, the ciliated cells in ECRSwNP patients exhibited larger widths（P=0.036）, shorter cilium lengths（P<0.001）, and more disordered arrangements（P<0.001） compared to NECRSwNP patients. In nasal brush cells from the inferior turbinate, ECRSwNP patients also showed shorter cilium lengths（P<0.001） and shorter cilia（P=0.024） compared to NECRSwNP patients. Conclusion:There are significant differences in obtaining epithelial cytological information from nasal polyps or inferior turbinates through nasal brush sampling between ECRSwNP and NECRSwNP patients.
Humans ; Male ; Female ; Middle Aged ; Adult ; Nasal Polyps/complications* ; Sinusitis/complications* ; Aged ; Chronic Disease ; Adolescent ; Nasal Mucosa/pathology* ; Young Adult ; Rhinitis/complications* ; Eosinophilia/pathology* ; Child ; Eosinophils/pathology* ; Rhinosinusitis

OBJECTIVE To investigate the improvement mechanism of Huatan tongmai decoction on rats with polycystic ovary syndrome （PCOS） by regulating autophagy through phosphatidylinositol-3-kinase（PI3K）/protein kinase B（AKT）/mammalian target of rapamycin （mTOR） pathway. METHODS A total of 40 rats were randomly divided into blank group （purified water）， model group （purified water）， traditional Chinese medicine group [Huatan tongmai decoction， 24 g/（kg·d）] and chemical drug group [metformin， 0.16 g/（kg·d）]， with 10 rats in each group. Except for blank group， other groups were given a combination of high-fat diet and intragastric administration of 1 mg/kg letrozole suspension to establish PCOS rat model. After modeling， they were given relevant medicine or water intragastrically， once a day， for 42 consecutive days. After the last administration， the pathological and ultrastructural changes of ovarian tissue were observed. The levels of follicle stimulating hormone （FSH）， testosterone （T）， estradiol （E2） ，luteinizing hormone （LH） in serum were detected，and the LH/FSH ratio was calculated. mRNA expressions of Beclin-1， p62 and microtubule-associated protein 1 light chain 3 （LC3） in ovarian tissue were detected. The expressions of related proteins of PI3K/AKT/mTOR pathway and autophagy in rat ovarian tissues were also detected. RESULTS Compared with blank group， the pathological damage and ultrastructural changes of the ovarian tissue in the model group rats were obvious， and a large number of autophagosomes could be seen in cells. The levels of T and LH and the LH/FSH ratio in serum， as well as mRNA and protein expressions of Beclin-1 and LC3， were increased significantly （P＜0.05）， while the levels of E2 and FSH in serum， as well as mRNA and protein expressions of p62 and the phosphorylation levels of PI3K， AKT and mTOR proteins in ovarian tissue， were significantly decreased （P＜0.05）. Compared with model group， the pathological damage of ovarian tissue in the administration groups was significantly reduced， the number of autophagosomes was smaller， and the expression levels of the above indicators were significantly reversed （P＜0.05）. CONCLUSIONS Huatan tongmai decoction can inhibit autophagy in ovarian granular cells by activating the PI3K/AKT/mTOR pathway， regulate the secretion of sex hormones， alleviate pathological damage in ovarian tissues， and promote normal follicular development， thereby exerting an ameliorative effect on PCOS rats.

Bone morphogenetic proteins (BMPs) are multifunctional growth factors of the transforming growth factor β (TGF-β) superfamily. They regulate steroid secretion from mammalian granulosa cells, promote granulosa cell survival and proliferation, and inhibit follicular atresia, luteinization, and granulosa cell apoptosis, thereby promoting the development and maturation of mammalian follicles. At the same time, BMPs play an important role in embryonic morphogenesis, induction of uterine receptivity, and blastocyst attachment. This paper describes the effects of BMPs on mammalian follicular and embryonic development and the roles of BMPs in female reproduction, focusing on the process in which BMPs promote follicular maturation by regulating steroid secretion from granulosa cells during mammalian oocyte maturation. This review aims to provide a reference for further research on mammalian oocyte culture and improvement of reproductive efficiency in female animals.
Animals ; Embryonic Development/drug effects* ; Female ; Bone Morphogenetic Proteins/pharmacology* ; Reproduction/physiology* ; Humans ; Granulosa Cells/cytology* ; Oocytes

Objective To investigate the effect of extracorporeal diaphragmatic pacing(EDP)on wea-ning patients undergoing mechanical ventilation after acute Stanford type A aortic dissection(ATAAD)sur-gery.Methods A total of 80 patients who underwent ATAAD surgery and required mechanical ventilation in the cardiac intensive care unit(CCU)of our hospital from October 2023 to October 2024 were selected as the study subjects.They were randomly divided into a control group and an intervention group using a random number table method,with 40 patients in each group.Both groups of patients received conventional clinical drug therapy,mechanical ventilation support,and rehabilitation exercises after surgery.The intervention group additionally underwent EDP therapy on this basis.The clinical data,mechanical ventilation time,weaning out-comes,oxygenation index,tidal volume,and changes in diaphragm function parameters were compared be-tween two groups of patients.Results Compared with the control group,the intervention group had a shorter mechanical ventilation time[77.00(59.00,133.63)h]vs.54.50(49.00,105.25)h],offline success rate(72.5％vs.90.0％),oxygenation index[202.90(178.63,240.05)mmHg vs.236.50(196.00,293.75)mm-Hg],higher tidal volume[(496.00±111.95)mL vs.(563.23±133.98)mL],with a statistically significant difference(P＜0.05).Compared with the control group,diaphragmatic excursion(DE)of both sides[11.90(8.50,16.50)mm vs.15.30(12.20,19.80)mm;12.60(10.80,14.90)mm vs.14.70(11.43,19.20)mm]and diaphragmatic thickening fraction(DTF)of left and right side[21.75％(17.53％,27.13％)vs.26.30％(21.10％,32.40％);24.00％(17.68％,29.35％)vs.28.30％(22.43％,33.40％)]of the intervention group were higher,and the differences were statistically significant(P＜0.05).Conclusion EDP can enhance the function of the diaphragm in patients,shorten the duration of mechanical ventilation,improve the success rate of wea-ning,and improve the weaning outcomes of mechanically ventilated patients after ATAAD surgery.