Objective: To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods: Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue. Results: Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated. Conclusion Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.

OBJECTIVE To explore the effect and mechanism of Zexie tang （ZXT） on reducing lipid accumulation through network pharmacology， and compare the difference of traditional decoction versus formula granules. METHODS The active components and targets of ZXT were identified using TCMSP and SwissTargetPrediction databases. GeneCards， OMIM， DisGeNET and TTD databases were used to analyze the related targets of non-alcoholic fatty liver disease （NAFLD）； protein-protein interaction network model was constructed by String database；“ ZXT-NAFLD target-pathway” network diagram was constructed by using CytoScape software； target enrichment analysis was performed by using Metascape platform. Fat accumulation model of human hepatocellular carcinoma HepG2 cells was established to observe the effects of traditional decoction and formula granules of ZXT on lipid accumulation of cells. RESULTS Alisol B， alisol C， 1-monolinolein and alisol B monoacetate were the key active components of ZXT in the treatment of NAFLD. The core targets included MDM2， MAPK1， PIK3CB， PRKCQ and MAPK14， etc. The core signaling pathways included endocrine resistance， insulin resistance and Th17 cell differentiation. Compared with model group， except for the Zexie formula granules group and Baizhu formula granules group， the absorbance values in all other administration groups were significantly decreased （P＜0.01）； the absorbance value of Baizhu traditional decoction group was significantly higher than that of ZXT traditional decoction group （P＜0.01）； the absorbance values of Zexie formula granule group and Baizhu formula granule group were significantly higher than that of ZXT formula granule group （P＜0.01）； the absorbance value of Zexie formula granule group was significantly higher than that of Zexie traditional decoction group （P＜0.01）； the absorbance value of Baizhu formula granule group was significantly higher than that of Baizhu traditional decoction group （P＜0.01）. CONCLUSIONS ZXT reduces lipid accumulation of human hepatocellular carcinoma cells through multiple components， multiple target and multiple pathways， and its traditional decoction and formula granules exhibit slightly different lipid-lowering effects.

In the strategic context of "healthy China"， the concept of "medicine and food homology"， rooted in the culture of traditional Chinese medicine （TCM）， has received unprecedented attention. In response to population aging in China， the health of the elderly has become the focus of public health attention， and proactive health is the key to healthy aging. From the perspective of the application of medicinal and edible materials in proactive health and technological responses to population aging for the first time， this paper firstly provided a systematic overview of medicinal and edible materials and the policies related to proactive health. Second， it summarized the situation of modern technology that accelerates the research and development of medicinal and edible products， as well as the current situation of various modern biotechnologies that reveal the mechanism of action of medicinal and edible materials. Third， it discussed the application scenarios of medicinal and edible materials in proactive health and technological responses to population aging， as well as the future research and development of medicinal and edible materials. By exploring in depth the unique value and importance of medicinal and edible materials， the paper lays a theoretical foundation for improving the health care capabilities of TCM and contributes new strategies derived from TCM to healthy aging.

ObjectiveTo investigate the risk factors for pyogenic liver abscess （PLA） comorbid with sepsis by analyzing clinical features， and to construct a predictive model. MethodsA retrospective analysis was performed for 489 patients who were hospitalized and diagnosed with PLA in The Affiliated Hospital of Xuzhou Medical University from January 2019 to December 2023， and according to the presence or absence of sepsis， they were divided into sepsis group with 306 patients and non-sepsis group with 183 patients. Related data were collected， including general information， laboratory markers， and outcome measures. The patients were further divided into a training set of 342 patients and a validation set of 147 patients at a ratio of 7∶3， and the training set was used for screening of variables and construction of a predictive model， while the validation set was used to test the performance of the model. An LASSO regression analysis was used for the screening of variables， and a multivariate Logistic regression analysis was used to construct the predictive model and plot a nomogram. The calibration curve， the receiver operating characteristic （ROC） curve， and the decision curve analysis were used for the validation of the model， and internal validation was performed for assessment. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical variables between groups. ResultsThere were significant differences between the sepsis group and the non-sepsis group in pulse rate， mean arterial pressure， duration pf symptoms， comorbidity of liver cirrhosis or malignant tumor， leukocyte count， neutrophil count， lymphocyte count， platelet count （PLT）， activated partial thromboplastin time， fibrinogen， C-reactive protein， aspartate aminotransferase， alanine aminotransferase， albumin， total bilirubin （TBil）， creatinine， potassium， and prognostic nutritional index （PNI） （all P<0.05）. In the training set， the LASSO regression analysis identified four predictive factors of pulse rate， PLT， TBil and PNI， and the multivariate Logistic regression analysis showed that pulse rate （odds ratio ［OR］=1.033， 95% confidence interval ［CI］： 1.006‍ ‍—‍ ‍1.061， P=0.018）， PLT （OR=0.981， 95%CI： 0.975‍ ‍—‍ ‍0.987， P<0.001）， TBil （OR=1.086， 95%CI： 1.053‍ ‍—‍ ‍1.125， P<0.001）， and PNI （OR=0.935， 95%CI： 0.882‍ ‍—‍ ‍0.988， P=0.019） were independent influencing factors for the risk of sepsis in patients with PLA. The model constructed based on these factors showed a good predictive ability， with an area under the ROC curve of 0.948 （95%CI： 0.923‍ ‍—‍ ‍0.973） in the training set and 0.912 （95%CI： 0.848‍ ‍—‍ ‍0.976） in the validation set. The decision curve analysis showed that the model has a good net benefit within the range of 0.3‍ ‍—‍ ‍0.9 for threshold probability. ConclusionThe nomogram prediction model constructed based on pulse rate， PLT， TBil， and PNI has a certain clinical value and can well predict the risk of sepsis in patients with PLA.

Objective: To explore the correlation between traditional Chinese medicine (TCM) constitution and depressive symptom among school aged children and adolescents, so as to provide evidences for informing constitution based regulation and prevention of depressive symptom. Methods: From June to December 2024, a total of 4 729 students aged 6-14 were recruited by cluster random sampling from 10 primary schools in Baoding (Hebei Province), Heze and Liaocheng (Shandong Province). General information, TCM constitution and depressive symptom were collected. Restricted cubic spline (RCS) models were used to analyze related factors and threshold effects of depressive symptom. Binary Logistic regression was applied to examine the association between depressive symptom and TCM constitution, with subgroup analyses conducted. Results: The detection rate of depressive symptom among the included children and adolescents was 25.82%. RCS analyses indicated non linear associations between depressive symptom and age (inflection point at 10 years old), bedtime (inflection point at 22:00), and wake up time (inflection point at 6:30 ) (all P non linearity <0.01). Linear associations were observed with body mass index (BMI) and sleep duration (all P non linearity > 0.05 ). After adjusting for covariates such as age, BMI and sleep status, binary Logistic regression analyses showed that Yin deficient constitution ( OR =1.26, 95% CI =1.09-1.45) and Phlegm-dampness constitution ( OR =1.42, 95% CI =1.11-1.82) were significantly associated with depressive symptom among children and adolescents (all P <0.05). Conclusions Depressive symptom among school aged children and adolescents is primarily associated with Yin deficiency and Phlegm dampness constitutions in TCM constitution. Active attention should be paid to susceptible TCM constitution among children and adolescents. Targeted health guidance and interventions should be implemented to improve TCM constitution health status for preventing the occurrence of depressive symptom.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective To explore the efficacy of retropubic midurethral synthetic sling(RMUS)in relieving urgency and urge urinary incontinence(UUI)symptoms in patients with mixed urinary incontinence(MUI).Methods Clinical data of 44 female MUI patients treated with RMUS during Jan.2018 and Dec.2020 in Shanghai Renji Hospital were retrospectively analyzed.All patients had positive results in stress test and Marshall-Marchetti test before operation,and 27 of them completed ICIQ-FLUTS-LF questionnaire.Urodynamic(UDS)tests suggested that 9 patients(20.5％)presented detrusor overactivity(DO).During RMUS procedure,the tension of the sling was adjusted based on the anatomical landmarks.The postoperative efficacy and improvement of urinary incontinence were analyzed.Results The patients aged(58.59±9.08)years,with a body mass index of 24.71±2.77.Among the 40 patients who completed telephone interview 2 years after surgery,the subjective cure rate was 85.0％(34/40).Among the 27 patients with records of questionnaires before and after surgery,there were significant differences in the incidence of urine leakage[100％(27/27)vs.18.5％(5/27)],stress urinary incontinence(SUI)[100％(27/27)vs.18.5％(5/27)]and UUI[70.4％(19/27)vs.29.6％(8/27)](P＜0.05).However,no statistical differences were found regarding nocturia voiding episode(≥1 times),urgency,dysuria,hesitancy,strain to void,intermittent stream and enuresis(P＞0.05).Based on preoperative UDS test,there were significant differences regarding the subjective cure rate in patients with or without preoperative DO[55.6％(5/9)vs.93.5％(29/31)],incidence of SUI[66.7％(4/6)vs.4.8％(1/21)],and UUI[66.7％(4/6)vs.19.0％(4/21)](P＜0.05),while there was no statistical difference regarding urgency[66.7％(4/6)vs.33.3％(7/21)](P＞0.05).Conclusion RMUS is effective in treating MUI patients with positive stress test and Marshall-Marchetti test results,which can relieve SUI and UUI symptoms,but has no effects on urgency symptoms.DO on preoperative urodynamics results in poorer subjective outcomes.

[Objective] To explore the application of pelvic floor ultrasonography in the treatment of mixed urinary incontinence (MUI) by transvaginal retropubic midurethral synthetic sling (RMUS), in order to understand the relationship between the morphological changes of pelvic floor structures and the efficacy of RMUS. [Methods] Clinical data of 44 female MUI patients undergoing RMUS during Jan.2018 and Dec.2020 were retrospectively analyzed.Urodynamics detected detrusor overactivity (DO) in 9 cases (20.5%). During RMUS procedure, the tension of the sling was adjusted based on the anatomical landmarks. The changes of ultrasonic parameters before and after operation, the relationship between the ultrasonic results, surgical efficacy and urodynamic results were analyzed. [Results] The patients averaged (58.59±9.08) years, with the body mass index being 24.71±2.77.The subjective cure rate was 91.3% (21/23) 3 months after surgery, and 85.0% (34/40) 2 years after surgery.Pelvic floor ultrasonography showed significant differences in posterior urethravesical angel at rest and during Valsalva, bladder neck descent distance and the rate of urethral funneling during Valsalva (P<0.05). According to the group analysis of the preoperative ultrasonic results, there was no statistical significance in the subjective cure rate between the funneling group and the non-funneling group during Valsalva, and the bladder neck non downward group/mild downward group/moderate downward group/severe downward group during Valsalva 3 months and 2 years after surgery (P>0.05). At 3-month follow-up, all pre-RMUS urethral funneling during Valsalva disappeared in patients without preoperative DO.Comparatively, 50.0% (3/6) urethral funneling still presented in DO patients, who had a lower cure rate (55.6%, 5/9) at the 2-year follow-up. [Conclusion] RMUS can reduce the posterior urethravesical angel at rest and during Valsalva, reduce bladder neck descent distance and the rate of urethral funneling during Valsalva in MUI patients, which can enhance urinary continence.There seems to be a correlation between DO and urethral funneling during Valsalva, while RMUS may potentially reverse the two markers.

To explore the value of CNVPLUS ?-array in the diagnosis of the DMD gene. A retrospective study was performed on 96 children who were clinically diagnosed with Duchenne or Becker muscular dystrophies(DMD/BMD) at the Department of Pediatric Endocrinology and Genetics of Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine from January 2014 to March 2023. DNA was extracted from these children′s peripheral blood and divided into two parts. Variations of the DMD gene were detected by using CNVPLUS ?-array and sequential testing of MLPA—NGS—Sanger. In the sequential method, single exon deletions detected by MLPA were first verified by polymerase chain reaction (PCR) and then were tested by Sanger′s sequencing if PCR results were normal. The results showed that, among 96 samples, 91 cases with the pathogenic variation of the DMD gene were detected by the CNVPLUS ?-array, including 76 cases with large deletion/duplication (copy number variation, CNV) and 15 cases with small variation (single nucleotide variant or small insertion/deletion, SNV/Indel). All samples were tested and diagnosed within 5 days. In contrast, 76 cases with pathogenic CNV and 20 cases with pathogenic SNV/Indel were detected in the DMD gene by sequential method. However, all of the experiments and diagnoses were completed within 48 days. Moreover, 5 cases with SNV/Indel in the DMD gene were correctly clustered after the operation mode was optimized. In summary, as a new micro-array integrating CNV and SNV probes, CNVPLUS ?-array can detect CNV and SNV/Indel in the DMD gene simultaneously while the application of CNVPLUS ?-array could save a lot of time and manpower. CNVPLUS ?-array had an excellent diagnostic performance for CNV of the DMD gene. As for SNV/Indel, the diagnostic performance was slightly poor and the operation mode should be optimized. If necessary, other testing technologies should be supplemented to reduce the risk of missed diagnosis.

Objective To observe the efficacy and safety of radiotherapy combined with programmed death receptor-1(PD-1)inhibitors and tyrosine kinase inhibitors(TKIs)for the treatment of microsatellite-stabilized(MSS)-type or mismatch-matched repair-normal(pMMR)-type colorectal cancer with liver metastases(CCLM).Methods Case data of 25 patients with MSS-type CCLM admitted to Jiangsu Provincial Cancer Hospital from April 2021 to August 2023 were retrospectively analyzed.They were divided into observation group(n = 12)and control group(n = 13).The observation group was given radiotherapy combined with PD-1 inhibitor and TKI treatment,and the control group was given TKI monotherapy.The baseline data,treatment effect,progression-free survival,and treatment-related adverse reactions of patients in the two groups were compared.Results The difference in baseline data between the two groups was not statistically significant(P＞0.05),the disease control rate(DCR)of the observation group was higher than that of the control group(P＜0.05),the progression-free survival(PFS)of the patients in the observation group was longer than that of the control group,but the difference was not statistically sig-nificant(P＞0.05),and the difference in the incidence of treatment-related adverse events(TRAE)between the two groups was not statistically significant(P＞0.05).Conclusion The treatment regimen of radiotherapy com-bined with PD-1 inhibitors and TKI drugs improved clinical efficacy and did not increase the incidence of adverse events when compared with TKI alone,which is a treatment regimen worthy of further validation.