Intervertebral disc degeneration （IVDD） is the core cause of chronic low back pain， which severely impairs patients’ quality of life and imposes a heavy social and medical burden. The hypoxia-pyroptosis-inflammation cascade mediated by hypoxia-inducible factor-1α （HIF-1α） is the core pathological mechanism driving the initiation and progression of IVDD. Natural active ingredients derived from traditional Chinese medicine （TCM） have become a research hotspot in the field of IVDD prevention and treatment due to their advantages of multi-target effects， favorable efficacy， and low toxicity. This paper systematically reviews the mechanism of HIF-1α-mediated hypoxia-pyroptosis-inflammation cascade in degenerative nucleus pulposus tissue and the intervention of related active ingredients. It is found that natural active ingredients such as baicalein， curcumin and resveratrol can intervene in the HIF-1α-mediated pathological cascade through four core links to delay IVDD progression： targeting the HIF-1α oxygen sensing pathway to block the initiation of pyroptosis cascade， inhibiting NOD-like receptor protein 3 inflammasome activation to cut off the cascade amplification of inflammatory signals， intervening in the Gasdermin D-mediated pyroptosis execution stage to protect cell membrane integrity， and regulating extracellular matrix metabolism to reconstruct intervertebral disc homeostasis.

ObjectiveTo evaluate the efficacy and possible mechanism of Wei's Huoxue Tongluo Formula （韦氏活血通络方，WHTF） in treating atrophic-stage non-arteritic anterior ischemic optic neuropathy （NAION） with qi deficiency and blood stasis. MethodsA total of 82 atrophic-stage NAION patients with qi deficiency and blood stasis were randomly divided into a treatment group and a control group， with 41 cases in each group. The treatment group was given oral administration of WHTF twice a day plus acupoint injection of distilled water 2 ml at Taiyang （EX-HN5） once daily， while the control group received injection of compound anisodine injection 2 ml at Taiyang （EX-HN5） once daily and oral administration of WHTF placebo twice a day. Both groups received treatment for a course of 14 days. The best-corrected visual acuity （BCVA）， optic disc perfusion density （PD）， flux index （FI）， macular superficial PD， vascular density （VD）， and traditional Chinese medicine （TCM） syndrome scores were compared between groups before treatment and on day 7 and day 14 of treatment. Additionally， mean defect （MD） and mean sensitivity （MS） of visual fields were measured before treatment and on day 14， along with safety evaluation. ResultsAfter treatment， both groups showed significant improvement in BCVA， visual field MD and MS， and TCM syndrome scores （P＜0.05 or P＜0.01）. On day 14 of treatment， the TCM syndrome score in the treatment group was significantly lower than that in the control group （P＜0.05）. There was no significant improvement in optic disc PD and FI， and macular superficial PD and VD after treatment in either group （P＞0.05） except that on day 7 the macular superficial foveal PD in the control group was significantly better than that in the treatment group （P＜0.05）. During the treatment period， no serious adverse events occurred in either group. ConclusionWHTF can improve the visual function indicators including visual acuity and visual field， as well as TCM syndrome scores in atrophic-stage NAION patients with qi deficiency and blood stasis. It shows clinical safety， although it does not appear to have a significant effect on optic disc or macular blood flow.

By analyzing the current application of multi-modal data in the diagnosis of gastric "inflammation-cancer" transformation， this study explored the feasibility and strategies for constructing a disease-syndrome integrated diagnosis and treatment system. Based on traditional Chinese medicine （TCM） phenomics， we proposed utilizing multi-modal data from literature research， cross-sectional studies， and cohort follow-ups， combined with artificial intelligence technology， to establish a multi-dimensional diagnostic and treatment index system. This approach aims to uncover the complex pathogenesis and transformation patterns of gastric "inflammation-cancer" progression. Additionally， by dynamically collecting TCM four-diagnostic information and modern medical diagnostic information through a long-term follow-up system， we developed three major modules including information extraction， multi-modal phenotypic modeling， and information output， to make it enable real-world clinical data-driven long-term follow-up and treatment of chronic atrophic gastritis. This system can provide technical support for clinical diagnosis， treatment evaluation， and research， while also offering insights and methods for intelligent TCM diagnosis.

Objective To evaluate the value of a nomogram model based on ultrasonographic features and inflammatory indicators in the preoperative noninvasive prediction of pathological grading of urothelial carcinoma of bladder(UCB).Methods A retrospective analysis was conducted on 471 patients with pathologically confirmed UCB,and the patients were assigned to high-grade group(401 cases)or low-grade group(70 cases).Basic clinical data(gender,age,macroscopic hematuria),ultrasonographic features(lesion location,blood flow signal,etc.),and blood inflammatory indicators(e.g.neutrophil-to-lymphocyte ratio[NLR])were collected.Independent predictors were screened using univariate and multivariate logistic regression,and a nomogram model was constructed.Model performance was evaluated using the receiver operating characteristic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results Multivariate logistic analysis identified gender(odds ratio[OR]=2.68),age(OR=1.08),macroscopic hematuria(OR=3.19),lesion located in the trigone(OR=4.59),positive blood flow signal(OR=2.87),and NLR(OR=1.03)were independent predictors of high-grade UCB(all P＜0.05).The combined model(clinical features+ultrasonographic characteristics+inflammatory indicators)achieved an area under curve(AUC)of 0.892,which was significantly higher than the clinical feature-only model(AUC=0.799)and the clinical+ultrasonographic model(AUC=0.856).The calibration curve demonstrated good consistency between predicted and actual outcomes,and DCA confirmed its optimal clinical net benefit.Conclusion The nomogram model integrating clinical features,ultrasonographic characteristics,and inflammatory indicators can effectively discriminate UCB pathological grading,providing a reliable preoperative noninvasive assessment tool for personalized treatment decisions.

Objective:To investigate expression and clinical significance of T cell activation related membrane molecules in infertility patients with polycystic ovary syndrome(PCOS).Methods:A total of 80 PCOS infertility patients who visited Second Affiliated Hospital of Hainan Medical College from January 2020 to June 2021 were selected as observation group,and 80 cases of women who underwent physical examination at same time were selected as control group.Expressions of membrane molecules related to T cell acti-vation in peripheral blood of patients between two groups were compared.Patients with PCOS infertility were divided into pregnant group[66(82.5％)]and non pregnant group[14(17.5％)]according to different prognosis.General clinical data,peripheral blood inflammatory factors and T cell activation related membrane molecules expressions were compared between two groups,focusing on correlation between T cell activation related membrane molecules expressions and prognosis of PCOS infertility patients,ROC curve and decision-making curve of T cell activation related membrane molecule expressions were drawn to predict prognosis of PCOS infer-tility patients,whose prediction efficiency and net profitability were further analyzed.Pearson correlation analysis was used to explore correlation between T cell activation related membrane molecules expressions and clinical characteristics of PCOS infertility patients.Results:CD4+CD45+T and CD4+CD63+T cells expressions in peripheral blood of patients in observation group were significantly higher than control group(P<0.05).Total testosterone(T),TNF-α,IFN-γ,CD4+CD45+T and CD4+CD63+T cells expressions of patients in non pregnancy group were significantly higher than pregnancy group(P<0.05).Multivariate Logistic regression analysis showed that CD4+CD45+T and CD4+CD63+T cells were independent predictors of prognosis of PCOS infertility patients(P<0.05),ROC analysis showed that AUC of CD4+CD45+T cells predicting prognosis of PCOS infertility patients was 0.756(0.721～0.826),and the best diag-nostic cut-off point was 48.1％,AUC of CD4+CD63+T cells was 0.746(0.711～0.834),and the best cut-off point for diagnosis was 31.2％,while AUC of CD4+CD45+T and CD4+CD63+T cells combination was 0.948(0.897～0.986).Decision curve analysis showed that combined prediction of CD4+CD45+T and CD4+CD63+T cells was higher than a single indicator.Correlation analysis showed that CD4+CD45+T and CD4+CD63+T cells expressions in peripheral blood of patients with PCOS infertility was related to T,TNF-α,insulin resistance index(HOMA-IR),IFN-γ,IL-2 and IL-10(P<0.05).Conclusion:The higher the CD4+CD45+T and CD4+CD63+T cells expressions in peripheral blood,the worse the prognosis of patients with PCOS infertility.

OBJECTIVE To analyze the differences in chemical composition of mussels from Shengsi,Zhoushan in different har-vest months,and to compare the differences in the composition of mussels from different origins,so as to provide ideas for the compre-hensive utilization of its resources.METHODS Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry(UHPLC-QqQ-MS)and spectrophotometry were used to analyze and evaluate the contents of nucleosides,amino acids,water-soluble proteins,total sugars and polysaccharides in mussels from Shengsi,Zhoushan in 12 months of the year and from 5 different origins;principal component analysis(PCA),partial least squares discriminant method(PLS-DA)and TOPSIS method were used to compre-hensively evaluate mussels.RESULTS A total of 16 amino acids and 11 nucleosides were detected in mussels.The average content of total amino acids in Shengsi mussels throughout the year was 4 851.74 μg·g-1,the average content of total nucleosides was 921.40 μg·g-1,and the average contents of water-soluble protein,polysaccharides,and total sugars were 51.32 mg·g-1,74.39 μg·g-1,and 417.22 mg·g-1,respectively.The nucleosides of Shengsi mussels were the highest in March and April,the ami-no acids and water-soluble proteins were the highest in April and May,and the polysaccharides and total sugars were the highest in Oc-tober and November.The PCA and PLS-DA results of the chemical components of different resources showed that there were great differences in Shengsi mussel samples harvested in different seasons.The entropy weight TOPSIS analysis showed that the comprehen-sive scores of Shengsi mussels in March and April(S7 and S8)were better than those in other areas,and the comprehensive score of Shengsi mussels in April(S8)was the highest,which was determined to be the best harvesting month.CONCLUSION The comparison results of multi-type resource chemistry show that there are great differences in the chemical compo-sition of Shengsi mussels in different harvesting seasons;the quality of Shengsi mussels is better than that of other areas;April is the best harvesting season,providing a reference for the quality evaluation and comprehensive development and utilization of mussels.

Objective:To investigate expression and clinical significance of T cell activation related membrane molecules in infertility patients with polycystic ovary syndrome(PCOS).Methods:A total of 80 PCOS infertility patients who visited Second Affiliated Hospital of Hainan Medical College from January 2020 to June 2021 were selected as observation group,and 80 cases of women who underwent physical examination at same time were selected as control group.Expressions of membrane molecules related to T cell acti-vation in peripheral blood of patients between two groups were compared.Patients with PCOS infertility were divided into pregnant group[66(82.5％)]and non pregnant group[14(17.5％)]according to different prognosis.General clinical data,peripheral blood inflammatory factors and T cell activation related membrane molecules expressions were compared between two groups,focusing on correlation between T cell activation related membrane molecules expressions and prognosis of PCOS infertility patients,ROC curve and decision-making curve of T cell activation related membrane molecule expressions were drawn to predict prognosis of PCOS infer-tility patients,whose prediction efficiency and net profitability were further analyzed.Pearson correlation analysis was used to explore correlation between T cell activation related membrane molecules expressions and clinical characteristics of PCOS infertility patients.Results:CD4+CD45+T and CD4+CD63+T cells expressions in peripheral blood of patients in observation group were significantly higher than control group(P<0.05).Total testosterone(T),TNF-α,IFN-γ,CD4+CD45+T and CD4+CD63+T cells expressions of patients in non pregnancy group were significantly higher than pregnancy group(P<0.05).Multivariate Logistic regression analysis showed that CD4+CD45+T and CD4+CD63+T cells were independent predictors of prognosis of PCOS infertility patients(P<0.05),ROC analysis showed that AUC of CD4+CD45+T cells predicting prognosis of PCOS infertility patients was 0.756(0.721～0.826),and the best diag-nostic cut-off point was 48.1％,AUC of CD4+CD63+T cells was 0.746(0.711～0.834),and the best cut-off point for diagnosis was 31.2％,while AUC of CD4+CD45+T and CD4+CD63+T cells combination was 0.948(0.897～0.986).Decision curve analysis showed that combined prediction of CD4+CD45+T and CD4+CD63+T cells was higher than a single indicator.Correlation analysis showed that CD4+CD45+T and CD4+CD63+T cells expressions in peripheral blood of patients with PCOS infertility was related to T,TNF-α,insulin resistance index(HOMA-IR),IFN-γ,IL-2 and IL-10(P<0.05).Conclusion:The higher the CD4+CD45+T and CD4+CD63+T cells expressions in peripheral blood,the worse the prognosis of patients with PCOS infertility.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Aim To investigate the effects of rutae-carpine(RUT)on lung inflammation in septic mice and the underlying mechanisms.Methods The sepsis mouse model was generated by intraperitoneal injection of lipopolysaccharide(LPS)at 5 mg·kg-1.The mice were randomly divided into the Control group,Model group,Low-dose,Medium-dose,High-dose RUT(5,10,20 mg·kg-1)treatment group and dexamethasone(DEX,2 mg·kg-1),with 10 mice in each group.The mice were intraperitoneally injected with RUT 30 min before LPS injection.HE staining was used to observe the morphology of lung tissues,and activity of my-eloperoxidase was determined to assess the neutrophil infiltration.Wet/dry weight ratio and Evan's blue ex-travasation of lung tissues were examined to assess lung edema.Survival analysis was performed to determine the in vivo protective effects of RUT.ELISA and quan-titative RT-PCR analysis were employed to determine the contents and gene expression of pro-inflammatory mediators,including tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β),IL-6,and IL-18 in lung tis-sues.Western blot was used to detect the protein levels of p38 MAPK,NF-κB,Caspase-1,NOD-like receptor family pyrin domain containing 3(NLRP3)and IL-18.Results RUT at 10-20 mg·kg-1 could dose-de-pendently inhibit leukocyte infiltration,reduce pro-in-flammatory mediator production,vascular permeability and wet/dry weight ratio in lungs,similar to the effects induced by DEX.The mice treated with RUT exhibited increased survival,down-regulated expressions of p-p38 MAPK,p-NF-κB,Caspase-1,NLRP3,and IL-18 pro-teins in lungs,with decreased IL-18 mRNA level.Conclusions RUT exhibits protective effects on sep-sis-induced lung injury,manifested by reduced inflam-mation and edema,potentially via inhibition of p38 MAPK signaling pathway and inflammasome formation.

Objective:To analyze the efficacy of total knee arthroplasty (TKA) with partial varus retention in the treatment of moderate knee varus.Methods:A retrospective analysis was conducted on the data of 613 osteoarthritis patients with moderate knee varus who underwent TKA at the First Affiliated Hospital of Nanjing Medical University from January 2010 to October 2019. According to whether a 2°-3° of knee varus was retained, the patients were divided into the retained varus group and the mechanical alignment group. The retained varus group included 318 cases, with 63 males and 255 females, aged 68.51±6.95 years (range, 46-86 years), and BMI of 26.99±3.66 kg/m 2 (range, 17.40-39.01 kg/m 2). Preoperative Kellgren-Lawrence (K-L) classification of knee osteoarthritis was grade III in 113 cases and grade IV in 205 cases. The mechanical alignment group included 295 cases, with 75 males and 220 females, aged 69.60±7.12 years (range, 52-87 years), and BMI of 26.95±3.94 kg/m 2 (range, 16.60-41.90 kg/m 2). Preoperative K-L classification was grade III in 102 cases and grade IV in 193 cases. Surgical duration, total blood loss, preoperative and postoperative varus angle, lower limb swelling on the fifth postoperative day, and postoperative complications were recorded. Follow-up were arranged at 3 months, 6 months, 1 year, and 5 years postoperatively. At each follow-up point, the visual analogue score (VAS) for knee pain, Hospital for Special Surgery (HSS) score, Forgotten Joint Score (FJS-12), and MOS item short-form health survey (SF-36) were assessed. Results:All 613 patients were successfully followed up, with a follow-up period of 5.25±1.02 years (range, 5.0-6.0 years). There were no statistically significant differences in gender, age, BMI, and K-L classification between the two groups ( P>0.05). The differences in postoperative varus angle, VAS scores, and HSS score were statistically significant from the preoperative values in both groups( P<0.05). The surgical duration of the retained varus group was 77.40±18.55 min, total blood loss was 920.78±407.26 ml, and lower limb swelling on the fifth postoperative day was 1.18±0.51 cm, all of which were lower than those in the mechanical alignment group: 85.31±22.15 min, 1127.14±580.08 ml, 3.22±0.52 cm, respectively, with statistically significant differences ( P<0.05). The VAS scores at postoperative day 5 and 3 months in the retained varus group were 5.08±0.72 and 2.18±1.09, respectively, which were lower than those in the mechanical alignment group: 5.80±0.81, 3.00±1.04, with statistically significant differences ( P<0.05). There were no statistically significant differences in VAS scores at 6 months, 1 year, and 5 years postoperatively between the two groups ( P>0.05). The HSS scores at 3 months and 6 months postoperatively in the retained varus group were 68.57±4.98 and 79.04±3.26, respectively, which were higher than those in the mechanical alignment group: 64.14±3.99, 77.73±4.04, with statistically significant differences ( P<0.05). There were no statistically significant differences in HSS scores at 1 year and 5 years postoperatively between the two groups ( P>0.05). The FJS-12 scores at 3 months and 6 months postoperatively in the retained varus group were 18.06±3.50 and 27.50±1.80, respectively, which were higher than those in the mechanical alignment group: 13.45±2.44, 24.23±1.59, with statistically significant differences ( P<0.05). There were no statistically significant differences in FJS-12 scores at 1 year and 5 years postoperatively between the two groups ( P>0.05). The SF-36 scores at 3 months and 6 months postoperatively in the retained varus group were 40.85±8.07 and 52.15±6.01, respectively, which were higher than those in the mechanical alignment group: 35.87±6.83, 47.28±5.38, with statistically significant differences ( P<0.05). There were no statistically significant differences in SF-36 scores at 1 year and 5 years postoperatively between the two groups ( P>0.05). The incidence of deep vein thrombosis in the lower limbs was 3.8% (12/318) in the retained varus group, which was lower than the 7.8% (23/295) in the mechanical alignment group, with a statistically significant difference ( P<0.05). Conclusion:In osteoarthritis patients with moderate knee varus undergoing TKA, retaining approximately 3° of varus can reduce surgical trauma and total blood loss, shorten surgical duration, alleviate postoperative pain and limb swelling, facilitate functional recovery, and improve patient satisfaction.