Objective To analyze the application of NCompass nitinol stone retrieval basket in ureteroscopic holmium laser lithotripsy, and to evaluate its roles in reducing stone retropulsion and improving stone-free rate(SFR)and stone acquisition rate.Methods A retrospective analysis was conducted on the data of patients with upper ureteral stones＞1 cm who underwent ureteroscopic holmium laser lithotripsy at China-Japan Friendship Hospital during Jan.2018 and Dec.2023, including 96 cases were in the NCompass group, and 68 cases in the non-basket group.The operation time, stone retropulsion rate, usage rate of flexible ureteroscopy, SFR and stone acquisition rate were compared between the two groups.Results There were no significant differences in the operation time [(29.2±8.4)min vs.(30.9±7.2)min, P=0.170] and stone retropulsion rate(15.6% vs. 27.9%, P=0.055)between the NCompass group and non-basket group.The NCompass group had significantly lower usage rate of flexible ureteroscopy than the non-basket group(24.0% vs. 47.1%, P=0.002), higher SFR 2 days(80.2% vs. 45.6%, P＜0.001)and 1 month(93.8% vs. 83.8%, P=0.040)after operation, as well as the stone acquisition rates 2 days(100% vs. 44.1%, P＜0.001)and 1 month(100% vs. 58.8%, P＜0.001)after operation. Conclusion The NCompass nitinol stone retrieval basket plays dual roles in ureteroscopic holmium laser lithotripsy, which can effectively intercept stones and extract stone fragments, thus significantly improving the SFR and stone acquisition rate, and reducing stone retropulsion and the use of flexible ureteroscopy.

ObjectiveTo investigate the association between insulin resistance （IR） and cardiovascular metabolic indicators， including blood pressure， blood lipids， and serum uric acid， in a middle-aged population. MethodsBased on the baseline survey of the Hong Sifang cohort of China National Salt Industry Group， a total of 575 participants were included. According to the homeostasis model assessment of insulin resistance， the participants were divided into an IR group （n=116） and a non-IR group （n=459）. Differences between the two groups were compared using the t-test and chi-square test. Multivariate logistic regression analysis was performed to evaluate the associations between IR and abnormalities in metabolic indicators. ResultsA total of 575 participants were included， including 390 men and 185 women， with a mean age of （48.58 ± 5.14） years and a mean body mass index （BMI） of （24.16 ± 2.97） kg/m². Blood pressure， serum uric acid， and blood lipid levels were significantly higher in the IR group than in the non-IR group （P<0.001）. After adjusting for potential confounders including age， sex， and BMI， IR was independently associated with hypertension， dyslipidemia， and hyperuricemia， with odds ratios （OR） and 95% confidence intervals （CI） of 2.57 （1.61-4.09）， 3.81 （2.36-6.17）， and 2.68 （1.53-4.71）， respectively （all P<0.001）. ConclusionInsulin resistance is significantly associated with multiple cardiovascular metabolic risk factors in the middle-aged population. Monitoring IR may contribute to the early prevention and control of cardiovascular diseases.

ObjectiveTo investigate the mechanisms of Zuojinwan in the treatment of colorectal cancer from the perspective of inhibiting M2 polarization of tumor-associated macrophages. MethodsA colorectal cancer mouse model was established by azoxymethane （AOM）/dextran sulfate sodium （DSS）. Body weight was recorded， disease activity index （DAI） and tumor number were calculated， and hematoxylin-eosin （HE） staining was used to observe colonic pathological changes. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-6 （IL-6）， transforming growth factor-β （TGF-β）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in colonic homogenates. Immunohistochemistry was used to detect proliferating cell nuclear antigen （PCNA） expression in the colon， and immunofluorescence was used to detect mannose receptor （CD206） expression in macrophages. In vitro， M2 macrophages were induced using IL-4/IL-13， and macrophages were treated with different concentrations of Zuojinwan-containing serum. CD206 and differentiation cluster 86 （CD86） were analyzed by flow cytometry. A CT26 and RAW264.7 macrophage co-culture system was established， and the migration and proliferation abilities of CT26 cells were detected using Transwell assays and trypan blue exclusion. Finally， proteomics was used to screen key proteins and signaling pathways involved in Zuojinwan-mediated inhibition of M2 polarization of tumor-associated macrophages in colorectal cancer， and Western blot was used for validation. ResultsIn animal experiments， compared with the blank group， mice in the model group showed significantly decreased body weight （P<0.05）， significantly increased DAI scores （P<0.01）， and significantly increased tumor number （P<0.01）， with severe colonic carcinogenesis and lymphatic metastasis. The protein expression levels of PCNA and CD206 were significantly increased （P<0.01）， and the levels of IL-6， IL-1β， TNF-α， and TGF-β in colonic homogenates were significantly increased （P<0.01）. Compared with the model group， mice in the Zuojinwan intervention group showed significantly higher body weight （P<0.05）， significantly decreased DAI scores （P<0.01）， and significantly reduced tumor numbers （P<0.01）. The protein levels of PCNA and CD206 were significantly decreased （P<0.05）， and the levels of IL-6， IL-1β， TNF-α， and TGF-β in colonic homogenates were significantly decreased （P<0.05）. In the CT26 and RAW264.7 co-culture system in vitro， compared with the blank group， co-culture with M2-type RAW264.7 macrophages significantly increased CT26 cell migration rate and proliferation number （P<0.01）. Compared with the M2 group （M2-type macrophages）， the proportion of CD86 was significantly increased in the Zuojinwan-containing serum group （P<0.01）， while the CT26 cell migration rate and proliferation number were significantly decreased in the 8% Zuojinwan-containing serum group （P<0.01）. Proteomics analysis indicated that tumor necrosis factor-α-induced protein 8-like protein 1 （TIPE1） may be a key target through which Zuojinwan regulates macrophage phenotypic transformation to inhibit colorectal cancer. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway showed the highest enrichment. Compared with the blank group， the levels of TIPE1， p-PI3K， and p-Akt in M2 macrophages were significantly increased （P<0.05，P<0.01）. After treatment with Zuojinwan-containing serum， the levels of TIPE1， p-PI3K， and p-Akt were significantly decreased （P<0.05，P<0.01）. ConclusionZuojinwan may inhibit colorectal cancer proliferation and migration by suppressing M2 polarization of tumor-associated macrophages， which may be associated with inhibition of the PI3K/Akt signaling pathway in tumor-associated macrophages.

ObjectiveTo investigate the mechanisms of Zuojinwan in the treatment of colorectal cancer from the perspective of inhibiting M2 polarization of tumor-associated macrophages. MethodsA colorectal cancer mouse model was established by azoxymethane （AOM）/dextran sulfate sodium （DSS）. Body weight was recorded， disease activity index （DAI） and tumor number were calculated， and hematoxylin-eosin （HE） staining was used to observe colonic pathological changes. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-6 （IL-6）， transforming growth factor-β （TGF-β）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in colonic homogenates. Immunohistochemistry was used to detect proliferating cell nuclear antigen （PCNA） expression in the colon， and immunofluorescence was used to detect mannose receptor （CD206） expression in macrophages. In vitro， M2 macrophages were induced using IL-4/IL-13， and macrophages were treated with different concentrations of Zuojinwan-containing serum. CD206 and differentiation cluster 86 （CD86） were analyzed by flow cytometry. A CT26 and RAW264.7 macrophage co-culture system was established， and the migration and proliferation abilities of CT26 cells were detected using Transwell assays and trypan blue exclusion. Finally， proteomics was used to screen key proteins and signaling pathways involved in Zuojinwan-mediated inhibition of M2 polarization of tumor-associated macrophages in colorectal cancer， and Western blot was used for validation. ResultsIn animal experiments， compared with the blank group， mice in the model group showed significantly decreased body weight （P<0.05）， significantly increased DAI scores （P<0.01）， and significantly increased tumor number （P<0.01）， with severe colonic carcinogenesis and lymphatic metastasis. The protein expression levels of PCNA and CD206 were significantly increased （P<0.01）， and the levels of IL-6， IL-1β， TNF-α， and TGF-β in colonic homogenates were significantly increased （P<0.01）. Compared with the model group， mice in the Zuojinwan intervention group showed significantly higher body weight （P<0.05）， significantly decreased DAI scores （P<0.01）， and significantly reduced tumor numbers （P<0.01）. The protein levels of PCNA and CD206 were significantly decreased （P<0.05）， and the levels of IL-6， IL-1β， TNF-α， and TGF-β in colonic homogenates were significantly decreased （P<0.05）. In the CT26 and RAW264.7 co-culture system in vitro， compared with the blank group， co-culture with M2-type RAW264.7 macrophages significantly increased CT26 cell migration rate and proliferation number （P<0.01）. Compared with the M2 group （M2-type macrophages）， the proportion of CD86 was significantly increased in the Zuojinwan-containing serum group （P<0.01）， while the CT26 cell migration rate and proliferation number were significantly decreased in the 8% Zuojinwan-containing serum group （P<0.01）. Proteomics analysis indicated that tumor necrosis factor-α-induced protein 8-like protein 1 （TIPE1） may be a key target through which Zuojinwan regulates macrophage phenotypic transformation to inhibit colorectal cancer. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway showed the highest enrichment. Compared with the blank group， the levels of TIPE1， p-PI3K， and p-Akt in M2 macrophages were significantly increased （P<0.05，P<0.01）. After treatment with Zuojinwan-containing serum， the levels of TIPE1， p-PI3K， and p-Akt were significantly decreased （P<0.05，P<0.01）. ConclusionZuojinwan may inhibit colorectal cancer proliferation and migration by suppressing M2 polarization of tumor-associated macrophages， which may be associated with inhibition of the PI3K/Akt signaling pathway in tumor-associated macrophages.

GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.

ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

ObjectiveTo observe the effect of Yangxin Tongmai Formula （养心通脉方） by midnight-noon ebb-flow administration method for rat models of premature coronary heart disease （PCHD） with blood stasis syndrome， and to explore the possible mechanism of action from the perspective of DNA methylation differential gene expression. MethodsThere were 3 SD rats in each of the blank group， model group and Yangxin Tongmai Formula group， and the rats in the model group and Yangxin Tongmai Formula group were fed with high-fat chow plus vitamin D3 by gavage plus isoproterenol hydrochloride by subcutaneous injection to construct rat models of PCHD with blood stasis syndrome. After successful modelling， rats in Yangxin Tongmai Formula group were gavaged with 18 g/（kg‧d） of Yangxin Tongmai Formula， and rats in blank group and the model group were gavaged with 4 ml/（kg‧d） of 0.9% NaCl solution， and serum samples of rats in each group were collected for DNA methylation sequencing after 3 weeks to screen for the relevant DNA methylation differentiation genes. In addition， rats with successful modelling of PCHD with blood stasis were randomly divided into model group， Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group ［18 g/（kg‧d） of Yangxin Tongmai Formula was gavaged twice in the heart channel period （12：00） and pericardium channel period （20：00）］， the Yangxin Tongmai Formula control group ［18 g/（kg‧d） of Yangxin Tongmai Formula was gavaged twice at 8：00 and 18：00］ and the Atorvastatin Calcium group ［atorvastatin calcium tablets solution 1.8 mg/（kg‧d） at the same intervention time as that in Yangxin Tongmai Formula control group］， and set up a blank group of 8 rats in each group. The model group and blank group were gavaged with 0.9% NaCl solution 4 ml/（kg‧d） for the same time as the Yangxin Tongmai Formula control group. After 3 weeks of gavage， the blood lipids ［including total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）］ levels of rats in each group were detected； the HE staining of myocardial tissues and thoracic aorta was used to observe the pathomorphological changes； the levels of serum inflammation indexes ［tumour necrosis factor alpha （TNF-alpha）， lipopolysaccharide （LPS）， and interleukin 10 （IL-10）］ were detected； immunoprecipitation-realtime fluorescence quantitative PCR was used to detect the relative expression of cardiac tissue screening differential genes. ResultsThe genes screened for differentially methylated regions were calmodulin 2 （Calm2）， calcium voltage-gated channel subunit α1s （Cacna1s）， and phospholipase Cβ1 （Plcb1）. Compared with the blank group， rats in the model group showed elevated levels of TC， LDL， TNF-α and LPS， and decreased levels of HDL and IL-10 （P＜0.05 or P＜0.01）； HE staining showed obvious swelling of myocardial fibres， accompanied by a large number of inflammatory cell infiltration， and thickening of the inner wall of the aortic vessels with internal wall damage， which was visible as a large number of lipid cholesterol crystals and obvious inflammatory cell infiltration. Compared with the model group， the TC， LDL， TNF-α and LPS contents of rats in the Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group， the Yangxin Tongmai Formula control group， and the atorvastatin calcium group all reduced， and the contents of HDL and IL-10 all elevated （P＜0.05）， with the improvement of myocardial tissue damage and the reduction of inflammatory infiltration， and the improvement of the damage of the inner lining of the thoracic aorta and the reduction of lipid infiltration. Compared with Yangxin Tongmai Formula control group， LDL， TNF-α and LPS contents reduced， and IL-10 contents increased in the midnight-noon ebb-flow administration method group （P＜0.05）. Compared with the model group， the relative expression of Calm2 and Plcb1 genes decreased and the relative expression of Cacna1s gene increased in Yangxin Tongmai Formula control group and the midnight-noon ebb-flow administration method group （P＜0.05）； compared with the Yangxin Tongmai Formula control group， the relative expression of Calm2 gene decreased and the relative expression of Cacna1s gene increased in the midnight-noon ebb-flow administration method group （P＜0.05）. ConclusionThe intervention of Yangxin Tongmai Formula in the heart channel period （12：00） and pericardium channel period （20：00） was more effective in improving the blood lipid level， inhibiting inflammation， and improving myocardial tissue damage in rats of PCHD with blood stasis syndrome， and Calm2 and Cacna1s genes may be the key targets of Yangxin Tongmai Formula in intervening the blood stasis syndrome of PCHD.

Objective:To explore the mediating role of activity of daily living between social support and cognitive function of rural elderly.Methods:A face-to-face questionnaire survey was conducted from July to August 2019 among 1 626 rural elderly people selected by multi-stage cluster random method in Guiyang City and Qiannan Prefecture, Guizhou Province.The contents include general situation, social support rate scale (SSRS), activity of daily living scale (ADL) and mini-mental state examination (MMSE). Partial correlation analysis and multiple linear regression analysis were used to analyze the relationship among social support, activity of daily living and cognitive function in the elderly by SPSS 23.0 software. AMOS 28.0 software was used to construct structural equation models, and Bootstrap method was used to test the mediating role of activity of daily living.Results:The scores of cognitive function, social support and activity of daily living of the rural elderly were (20.83±5.47), (34.96±6.42) and (16.51±3.29), respectively.There were statistically significant differences in the cognitive function scores among rural elderly with different levels of social support and activity of daily living( F=33.418, t=25.533, P<0.01). The partial correlation analysis showed that the social support score was positively correlated with the cognitive function score ( r=0.161, P<0.01), and the activity of daily living score was negatively correlated with scores of social support and cognitive function ( r=-0.083, -0.453, both P<0.01). Multiple linear stepwise regression analysis showed that social support, objective support dimensions, activity of daily living and instrumental activity of daily living were influencing factors of cognitive function of rural elderly( P<0.001).The results of structural equation model showed that the activity of daily living played a partial mediating role between social support and cognitive function in rural elderly, with the mediating effect of 0.046 (95% CI=0.025-0.075), accounting for 13.18% of total effect (effect value=0.349, 95% CI=0.277-0.415). Conclusion:The activity of daily living of rural elderly plays a partial mediating effect between social support and cognitive functioning.

Objective To investigate the comparative efficacy of different frequencies of pelvic floor electrical stimulation(PFES)on stress urinary incontinence(SUI)in rats.Methods Twenty female Sprague-Dawley rats were randomly divided into 6,15,30 and 50 Hz group by random number table method.All rats underwent vaginal dilatation(VD)to simulate postpartum SUI.One week after VD,the sneeze test was conducted to determine whether the modeling was successful.If the sneeze test was positive,the modeling was successful.The miniature and wireless electric pelvic floor stimulator were implanted into the pelvic floor muscle of the modeled rats,and PFES were treated for 2 weeks in each group at the rates of 6,15,30 and 50 Hz,respectively.The Leak point pressure(LPP)of all rats before VD,1 week after VD and 2 weeks after stimulation were measured by cystometrograms(CMGs)for comparison.Results LPP was significantly reduced in all groups of rats after VD 1 week(P<0.001).Compared with after VD 1 week,after two consecutive weeks of PFES at four different frequencies of 6,15,30 and 50 Hz,LPP was again significantly increased(P<0.001)and reached the baseline level(P>0.05)in all groups of rats.In the between-group comparison of the rats in each group,there was no significant difference in their LPP at baseline value,after VD 1 week and after stimulation 2 weeks(P>0.05).Conclusion The present study suggests that of the several stimulation frequencies explored so far,6 Hz may be a more appropriate choice for PFES.Further studies are still needed to evaluate more frequencies and the long-term efficacy of PFES.

AIM:To compare the effects and effi-cacy of methoxyamine and norepinephrine on sub-lingual microcirculation in patients with high-alti-tude septic shock.METHODS:A total of forty-six patients with septic shock from the Xining area of Qinghai Province were randomized into two groups:the M-hydroxylamine group(Group M,n=22)and the norepinephrine group(Group N,n=24).Baseline data as well as the incidence of acute kid-ney injury(AKI),distal limb necrosis/ischemia,and 28-day survival rates were documented.Sublingual microcirculation parameters were monitored and recorded at four time points:before treatment(T0),24 hours post-treatment(T1),48 hours post-treatment(T2),and 72 hours post-treatment(T3)using side-flow dark-field(SDF)imaging.The pa-rameters included total vascular density(TVD),per-fused vascular density(PVD),perfused vessel ratio(PPV),microvascular flow index(MFI),and hetero-geneity index(HI).Additionally,changes in heart rate(HR),mean arterial pressure(MAP),blood urea nitrogen(BUN),serum creatinine(Cr),and lac-tate(Lac)levels were also recorded.RESULTS:There were no significant differences between the two groups in terms of baseline data,incidence of AKI,distal limb necrosis/ischemia,and 28-day sur-vival rate.Additionally,there were no significant differences in HR,MAP,and Lac indices between the two groups at any time point.However,within-group comparisons showed that HR,MAP,and Lac indices improved over the course of treatment,with statistically significant differences.The BUN level at the T3 time point was significantly lower in the mehydroxyamine group compared to the nor-epinephrine group(P<0.05).Similarly,Cr levels were significantly lower at both T2 and T3 time points(P<0.05).There were no significant differenc-es in sublingual microcirculation indices between the two groups at any time point.However,TVD,PVD,PPV,MIF,and HI in both groups improved over the course of treatment,with statistically sig-nificant differences.CONCLUSION:Both methoxy-amine and norepinephrine can enhance both the macrocirculation and sublingual microcirculation in patients with septic shock at high altitudes.Addi-tionally,methoxyamine leads to a faster recovery of creatinine levels within 72 hours.