Objective To explore the number of peripheral blood regulatory T cells (Treg) in patients with chronic kidney disease (CKD) and its correlation with vascular calcification. Methods This was a single-center, cross-sectional, and observational study. Non-dialysis patients with CKD treated at Zhongshan Hospital, Fudan University from March 2021 to March 2022 were enrolled. Abdominal aortic calcification (AAC) was assessed using lateral abdominal X-ray. Number of Treg and cytokine levels were measured by flow cytometry. Logistic regression analysis was performed to evaluate the related factors for AAC in CKD patients. Results A total of 83 patients were included, aged 17–86 years, with 57 males (68.7%). The distribution of CKD stages was as follows: stage G1 in 7 patients (8.4%), stage G2 in 17 patients (20.5%), stage G3 in 21 patients (25.3%), stage G4 in 19 patients (22.9%), and stage G5 in 19 patients (22.9%). No AAC was observed in patients with stages G1 and G2, while the prevalence of AAC in patients with stages G3, G4, and G5 was 23.8%, 21.1%, and 26.3%, respectively. Compared with stage G1 patients, those with stages G3–5 showed decreased number of peripheral blood Treg and elevated levels of interleukin (IL)-6 and IL-17F (P＜0.05). The area under the receiver operating characteristic curve for number of peripheral blood Treg in predicting AAC in CKD patients was 0.766 (95%CI 0.652–0.879, P＝0.002). Logistic regression analysis showed that decreased number of Treg was related factor for AAC in CKD patients (OR＝0.957, 95%CI 0.922–0.992, P＝0.018). Conclusion As CKD progresses, number of peripheral blood Treg significantly decreases, which is correlated with AAC in CKD patients.

OBJECTIVE: To identify the underlying molecular mechanism of Modified Hu-Lu-Ba-Wan (MHW) in alleviating renal lesions in mice with diabetic kidney disease (DKD). METHODS: The db/db mice were divided into model group and MHW group according to a random number table, while db/m mice were settled as the control group (n=8 per group). The control and model groups were gavaged daily with distilled water [10 mL/(kg·d)], and the MHW group was treated with MHW [17.8 g/(kg·d)] for 6 weeks. After MHW administration for 6 weeks, indicators associated with glucolipid metabolism and urinary albumin were tested. Podocytes were observed by transmission electron microscopy. Kidney transcriptomics was performed after confirming therapeutic effects of MHW on DKD mice. The relevant target of MHW' effect in DKD was further determined by enzyme-linked immunosorbent assay, Western blot analysis, immunohistochemistry, and immunofluorescence staining. RESULTS: Compared with the model group, MHW improved glucose and lipid metabolism (P<0.05), and reduced lipid deposition in the kidney. Meanwhile, MHW reduced the excretion of urinary albumin (P<0.05) and ameliorated renal damage. Transcriptomic analysis revealed that the inflammation response, particularly the interleukin-17 (IL-17) signaling pathway, may be responsible for the effect of MHW on DKD. Furtherly, our results found that MHW inhibited IL-17A and alleviated early fibrosis in the diabetic kidney. CONCLUSION MHW ameliorated renal damage in DKD via inhibiting IL-17A, suggesting a potential strategy for DKD therapy.
Animals ; Diabetic Nephropathies/genetics* ; Interleukin-17/antagonists & inhibitors* ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Kidney/ultrastructure* ; Podocytes/metabolism* ; Mice ; Albuminuria ; Lipid Metabolism/drug effects* ; Mice, Inbred C57BL

Aim To investigate the effect of Senecio scandens Buch.-Ham on inflammatory pain mediated by mast cell P2X7 receptor.Methods Using the ATP-induced foot inflammatory pain,immunofluores-cence and toluidine blue staining techniques were used to investigate whether Senecio scandens has inhibitory effect on P2X7 receptor on mast cells.Using the calci-um ion imaging experimental technology,to explore whether Senecio scandens inhibit the intracellular cal-cium ion enrichment caused by activation of P2X7 re-ceptor on mouse peritoneal mast cell.The whole-cell patch clamp technique was used to investigate whether senecio scandens could inhibit the inward current in-duced by activation of P2X7 receptor on mouse perito-neal mast cell.Results In vivo,Senecio scandens alle-viate ATP induced inflammatory pain(3.9 g·kg-1:P＜0.05),and significantly inhibited the infiltration of P2X7 receptor-positive mast cells(3.9 g·kg-1:P＜0.05).Knockout of mast cell can reduce the analgesic effect of Senecio scandens(3.9 g·kg-1:P=0.645).In vitro.The experiment results show that senecio scandens can significantly inhibit the calcium influx(300 mg·L-1:P＜0.05;1 g·L-1:P＜0.01;3 g·L-1:P＜0.01)and the inward current mediated by P2X7 receptor in mast cell(1 g·L-1:P＜0.01).Conclusion Senecio scandens alleviate inflammatory pain by inhibiting mast cell P2X7 receptor.

Objective To develop dynamic prediction models based on multiple postnatal time points to support early diagnosis and individualized intervention for bronchopulmonary dysplasia(BPD)in preterm infants with gestational age<32 weeks.Methods Clinical data of 472 preterm infants with gestational age<32 weeks admitted to the Second Xiangya Hospital of Central South University between January 2016 and November 2020 were retrospectively analyzed.Multivariable logistic regression was applied to develop five independent prediction models at postnatal days 1,7,14,21,and 28.The performance of the models was assessed using the area under the receiver operating characteristic curve(AUC)and the Hosmer-Lemeshow test.Results Baseline characteristics such as gestational age and birth weight differed significantly between the BPD group(n=147)and the non-BPD group(n=325)(P<0.05).Predictors of BPD evolved across time points:on day 1,key predictors included gestational age,birth weight,Score for Neonatal Acute Physiology II(SNAP-II),invasive mechanical ventilation,and fraction of inspired oxygen>30%;by day 7,additional variables emerged,including fasting duration>2 days,mean feeding advancement rate<8.5 mL/(kg·d),neonatal respiratory distress syndrome,apnea of prematurity,and positive sputum culture;from day 14 onward,nutrition-and treatment-related indicators were incorporated additionally.The models demonstrated good discrimination at postnatal days 1,7,14,21,and 28,with AUCs of 0.917,0.927,0.939,0.944,and 0.968,respectively,and good calibration(Hosmer-Lemeshow P>0.05).Internal validation showed AUCs ranging from 0.899 to 0.958,indicating robust performance.Conclusions Dynamic postnatal prediction models incorporating indicators spanning perinatal factors,respiratory support,nutritional management,and therapeutic interventions demonstrate high predictive performance and facilitate dynamic risk assessment for BPD in preterm infants with gestational age<32 weeks.

Objective:To discern the association between autism-like behaviors and resilience within the ado-lescent demographic.Methods:A total of 7 063 middle school students were selected to assess ASD-like behaviors and resilience in adolescents using the Autism Spectrum Screening Questionnaire(ASSQ)as well as the Resilience Scale for Chinese Adolescent(RSCA).Subgroups bounded by P5 and P95 of the total ASSQ score,a comparative analysis of the resilience scores between these groups was executed.A correlation evaluation and linear regression a-nalysis was carried out between ASSQ and RSCA scores from all participants.Results:The RSCA scores within the high ASSQ scoring group,were inferior to those in the low scoring group.ASSQ scores were negatively correlated with RSCA scores for the full sample(Ps＜0.01);Social interaction scores on the ASSQ were negatively correlated with the five-factor RSCA scores(β=-0.23,-0.27,-0.11,-0.23,-0.37,Ps＜0.05).Conclusion:There was a negative association between autism spectrum disorder-like behaviors and resilience in adolescents,with more severe social interaction symptoms being associated with poorer resilience.

Objective:To discern the association between autism-like behaviors and resilience within the ado-lescent demographic.Methods:A total of 7 063 middle school students were selected to assess ASD-like behaviors and resilience in adolescents using the Autism Spectrum Screening Questionnaire(ASSQ)as well as the Resilience Scale for Chinese Adolescent(RSCA).Subgroups bounded by P5 and P95 of the total ASSQ score,a comparative analysis of the resilience scores between these groups was executed.A correlation evaluation and linear regression a-nalysis was carried out between ASSQ and RSCA scores from all participants.Results:The RSCA scores within the high ASSQ scoring group,were inferior to those in the low scoring group.ASSQ scores were negatively correlated with RSCA scores for the full sample(Ps＜0.01);Social interaction scores on the ASSQ were negatively correlated with the five-factor RSCA scores(β=-0.23,-0.27,-0.11,-0.23,-0.37,Ps＜0.05).Conclusion:There was a negative association between autism spectrum disorder-like behaviors and resilience in adolescents,with more severe social interaction symptoms being associated with poorer resilience.

Objective To develop dynamic prediction models based on multiple postnatal time points to support early diagnosis and individualized intervention for bronchopulmonary dysplasia(BPD)in preterm infants with gestational age<32 weeks.Methods Clinical data of 472 preterm infants with gestational age<32 weeks admitted to the Second Xiangya Hospital of Central South University between January 2016 and November 2020 were retrospectively analyzed.Multivariable logistic regression was applied to develop five independent prediction models at postnatal days 1,7,14,21,and 28.The performance of the models was assessed using the area under the receiver operating characteristic curve(AUC)and the Hosmer-Lemeshow test.Results Baseline characteristics such as gestational age and birth weight differed significantly between the BPD group(n=147)and the non-BPD group(n=325)(P<0.05).Predictors of BPD evolved across time points:on day 1,key predictors included gestational age,birth weight,Score for Neonatal Acute Physiology II(SNAP-II),invasive mechanical ventilation,and fraction of inspired oxygen>30%;by day 7,additional variables emerged,including fasting duration>2 days,mean feeding advancement rate<8.5 mL/(kg·d),neonatal respiratory distress syndrome,apnea of prematurity,and positive sputum culture;from day 14 onward,nutrition-and treatment-related indicators were incorporated additionally.The models demonstrated good discrimination at postnatal days 1,7,14,21,and 28,with AUCs of 0.917,0.927,0.939,0.944,and 0.968,respectively,and good calibration(Hosmer-Lemeshow P>0.05).Internal validation showed AUCs ranging from 0.899 to 0.958,indicating robust performance.Conclusions Dynamic postnatal prediction models incorporating indicators spanning perinatal factors,respiratory support,nutritional management,and therapeutic interventions demonstrate high predictive performance and facilitate dynamic risk assessment for BPD in preterm infants with gestational age<32 weeks.

Aim To investigate the effect of Senecio scandens Buch.-Ham on inflammatory pain mediated by mast cell P2X7 receptor.Methods Using the ATP-induced foot inflammatory pain,immunofluores-cence and toluidine blue staining techniques were used to investigate whether Senecio scandens has inhibitory effect on P2X7 receptor on mast cells.Using the calci-um ion imaging experimental technology,to explore whether Senecio scandens inhibit the intracellular cal-cium ion enrichment caused by activation of P2X7 re-ceptor on mouse peritoneal mast cell.The whole-cell patch clamp technique was used to investigate whether senecio scandens could inhibit the inward current in-duced by activation of P2X7 receptor on mouse perito-neal mast cell.Results In vivo,Senecio scandens alle-viate ATP induced inflammatory pain(3.9 g·kg-1:P＜0.05),and significantly inhibited the infiltration of P2X7 receptor-positive mast cells(3.9 g·kg-1:P＜0.05).Knockout of mast cell can reduce the analgesic effect of Senecio scandens(3.9 g·kg-1:P=0.645).In vitro.The experiment results show that senecio scandens can significantly inhibit the calcium influx(300 mg·L-1:P＜0.05;1 g·L-1:P＜0.01;3 g·L-1:P＜0.01)and the inward current mediated by P2X7 receptor in mast cell(1 g·L-1:P＜0.01).Conclusion Senecio scandens alleviate inflammatory pain by inhibiting mast cell P2X7 receptor.

OBJECTIVE: To investigate whether the combination of chemotherapy with staged Chinese herbal medicine (CHM) therapy could enhance health-related quality of life (QoL) in non-small-cell lung cancer (NSCLC) patients and prolong the time before deterioration of lung cancer symptoms, in comparison to chemotherapy alone. METHODS: A prospective, double-blind, randomized, controlled trial was conducted from December 14, 2017 to August 28, 2020. A total of 180 patients with stage I B-IIIA NSCLC from 5 hospitals in Shanghai were randomly divided into chemotherapy combined with CHM (chemo+CHM) group (120 cases) or chemotherapy combined with placebo (chemo+placebo) group (60 cases) using stratified blocking randomization. The European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life-Core 30 Scale (QLQ-C30) was used to evaluate the patient-reported outcomes (PROs) during postoperative adjuvant chemotherapy in patients with early-stage NSCLC. Adverse events (AEs) were assessed in the safety analysis. RESULTS: Out of the total 180 patients, 173 patients (116 in the chemo+CHM group and 57 in the chemo+placebo group) were included in the PRO analyses. The initial mean QLQ-C30 Global Health Status (GHS)/QoL scores at baseline were 57.16 ± 1.64 and 57.67 ± 2.25 for the two respective groups (P>0.05). Compared with baseline, the chemo+CHM group had an improvement in EORTC QLQ-C30 GHS/QoL score at week 18 [least squares mean (LSM) change 17.83, 95% confidence interval (CI) 14.29 to 21.38]. Conversely, the chemo+placebo group had a decrease in the score (LSM change -13.67, 95% CI -22.70 to -4.63). A significant between-group difference in the LSM GHS/QoL score was observed, amounting to 31.63 points (95% CI 25.61 to 37.64, P<0.001). The similar trends were observed in physical functioning, fatigue and appetite loss. At week 18, patients in the chemo+CHM group had a higher proportion of improvement or stabilization in GHS/QoL functional and symptom scores compared to chemo+placebo group (P<0.001). The median time to deterioration was longer in the chemo+CHM group for GHS/QoL score [hazard ratio (HR)=0.33, 95% CI 0.23 to 0.48, P<0.0010], physical functioning (HR=0.43, 95% CI 0.25 to 0.75, P=0.0005), fatigue (HR=0.47, 95% CI 0.30 to 0.72, P<0.0001) and appetite loss (HR=0.65, 95% CI 0.42 to 1.00, P=0.0215). The incidence of AEs was lower in the chemo+CHM group than in the chemo+placebo group (9.83% vs. 15.79%, P=0.52). CONCLUSION The staged CHM therapy could help improve the PROs of postoperative patients with early-stage NSCLC during adjuvant chemotherapy, which is worthy of further clinical research. (Registry No. NCT03372694).
Humans ; Carcinoma, Non-Small-Cell Lung/surgery* ; Male ; Middle Aged ; Female ; Lung Neoplasms/pathology* ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Chemotherapy, Adjuvant ; Patient Reported Outcome Measures ; Quality of Life ; Aged ; Postoperative Period ; Prospective Studies

Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs). Our previous work identified that a phosphoglycerate mutase 1 (PGAM1) allosteric inhibitor, HKB99, exerts a range of anti-tumor activities in lung cancer. Here, we found that upregulation of PGAM1 correlates with increased levels of M2-like tumor-associated macrophages (TAMs) in human colon cancer samples, particularly in liver metastatic tissues. HKB99 suppressed tumor growth and metastasis in cell culture and syngeneic tumor models. M2-polarization, induced by colon cancer cell co-culture, was reversed by HKB99. Conversely, the increased migration of colon cancer cells by M2-TAMs was remarkably restrained by HKB99. Notably, a decrease in TAM infiltration was required for the HKB99-mediated anti-tumor effect, along with an increase in CD8⁺ T cell infiltration. Moreover, HKB99 improved the efficacy of anti-PD-1 treatment in syngeneic tumors. Overall, this study highlights HKB99's inhibitory activity in TAM-mediated colon cancer progression. Targeting PGAM1 could lead to novel therapeutic strategies and enhance the effectiveness of existing immunotherapies for colon cancer.