Based on the viewpoint of "sweat pore-qi and liquid-kidney collaterals"， it is believed that children's nephrotic syndrome is caused by the core mechanism of sweat pore constraint and closure， qi and liquid imbalance， and kidney collaterals impairment， and it is proposed that the treatment principle is to nourish the sweat pore， regulate qi and fluid， and supplement the kidney and unblock the collaterals. In clinic， guided by sequential therapy and according to the different disease mechanism characteristics of the four stages， including early stage of the disease， hormone induction stage， hormone reduction stage， hormone maintenance stage， the staged dynamic identification and treatment was applied. For early stage of the disease with edema due to yang deficiency， modified Zhenwu Decoction （真武汤） was applied to warm yang and drain water； for hormone induction stage with yin deficiency resulting in effulgent fire， modified Zhibai Dihuang Pill （知柏地黄丸） plus Erzhi Pill （二至丸） was used to enrich yin and reduce fire； for hormone reduction stage with qi and yin deficiency， modified Shenqi Dihuang Decoction （参芪地黄汤） was used to boost qi and nourish yin； for hormone maintenance stage， modified Shenqi Pill （肾气丸） was used to supplement yin and yang. Meanwhile， the treatment also attaches importance to the combination of vine-based or worm medicinals to dredge collaterals， so as to providing ideas for clinical treatment.

Disruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease (IBD). Traditional Chinese medicine Wuji Wan (WJW) is commonly used to treat digestive system disorders and showed therapeutic potential for IBD. In this interdisciplinary study, we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques. Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus, thereby facilitating the conversion of tryptophan into indole-3-acetic acid (IAA) and indoleacrylic acid (IA). These indole derivatives activated the aryl hydrocarbon receptor (AhR) pathway, which reduced colonic inflammation and restored the expression of intestinal barrier proteins. Interestingly, the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota. Finally, pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW. Overall, WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating Lactobacillus-IAA-AhR signaling pathway. This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.

OBJECTIVE To study the ameliorative effect and potential mechanism of curcumin on diabetes model rats with depression based on cAMP response element binding protein （CREB）/brain-derived neurotrophic factor （BDNF） signaling pathway. METHODS The diabetes model rat with depression was established by high fat and high sugar diet+intraperitoneal injection of streptozotocin+chronic unpredictable stress-induced depression. The successfully modeled rats were randomly divided into model group， positive control group （0.18 g/kg metformin and 1.8 mg/kg fluoxetine， gavage）， curcumin low-dose and high-dose groups （30， 60 mg/kg， gavage） and curcumin high-dose+CREB inhibitor group [60 mg/kg curcumin （gavage）+5 mg/kg CREB inhibitor 666-15 （intraperitoneal injection）]， with 12 rats in each group. Another 12 healthy rats were selected as the normal group. Each group was given a corresponding intervention for 4 weeks， the fasting blood glucose level of rats was detected， and the depression of rats was assessed. The levels of corticosterone （CORT） and inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin- 1β （IL-1β）， IL-6] in serum， and the levels of norepinephrine （NE） and 5-hydroxytryptamine （5-HT） in hippocampal tissue were determined. The pathological changes and neuronal apoptosis were observed in the hippocampal tissue of rats in each group； the expression levels of CREB， BDNF mRNA and protein in hippocampal tissue were detected. RESULTS Compared with the normal group， the hippocampal tissue of rats in the model group was severely damaged， and neurons were scattered， while the fasting blood glucose， the forced swimming immobility time， the tail suspension immobility time， serum levels of CORT， TNF-α， IL-1β and IL-6， and neuron apoptosis indexes were all increased or prolonged significantly （P＜0.05）. The levels of NE and 5-HT， the number of surviving neurons， and the expression levels of CREB and BDNF mRNA and protein in hippocampal tissue were decreased significantly （P＜0.05）. Compared with the 的model group， the damage to hippocampal tissue was relieved in the positive control group and curcumin groups， while the above indexes were improved significantly （P＜0.05）. The improvement effect of curcumin high-dose group was better than that of curcumin low-dose group （P＜0.05）. CREB inhibitor could significantly reverse the ameliorative effect of high-dose curcumin on the model rats （P＜0.05）. CONCLUSIONS Curcumin can improve the depression of diabetes model rats with depression， and relieve neuronal damage and inflammatory response， the mechanism of which may be associated with activating CREB/BDNF signaling pathway.

Objective To evaluate the long-term efficacy of transjugular intrahepatic portosystemic shunt(TIPS)with bare stents and Fluency covered stents in the treatment of portal hypertension,and to discuss its clinical value.Methods The clinical data of 29 patients with intractable ascites or esophagogastric fundus varices rupture and hemorrhage caused by cirrhotic portal hypertension,who received TIPS with bare stents and covered stents at the First Affiliated Hospital of Xinjiang Medical University of China(25 patients)and the Lishui Municipal Central Hospital of China(4 patients)between August 2012 and December 2017,were retrospectively analyzed.The patients were regularly followed up to check the survival status.The postoperative cumulative shunt patency rate and cumulative survival rate of the patients were analyzed by Kaplan-Meier method.Results The technical success rate of TIPS was 100％.The mean portal vein pressure was decreased from preoperative(40.21±3.24)cmH2O to postoperative(24.55±3.55)cmH2O(P＜0.05).The patients were followed up for 5.1-10.5 years.The postoperative 1-,3-,5-,7-year primary cumulative patency rates of the shunt were 89.7％,75.9％,75.9％ and 52.5％,respectively.The postoperative 5-,7-,9-and 10-year cumulative survival rates were 100％,66.9％,66.9％ and 33.4％,respectively.The incidence of hepatic encephalopathy was 13.8％(4/29).Conclusion Using bare stents combined with Fluency covered stents for TIPS is clinically safe and effective in the treatment of portal hypertension.This technique carries higher long-term shunt patency rate and low incidence of hepatic encephalopathy.Therefore,it can be used as a substitute for Viatorr stent when necessary.(J Intervent Radiol,2024,33:295-299)

OBJECTIVE To explore the effects of esmolol on cardiac function， inflammatory factors and serum microRNA （miR）-29a and miR-129-5p in patients with acute anterior ST-segment elevation myocardial infarction after percutaneous coronary intervention （PCI）. METHODS A total of 120 patients with acute anterior ST-segment elevation myocardial infarction undergoing PCI in our hospital from April 2021 to June 2023 were selected and divided into control group （60 cases） and study group （60 cases） according to the random number table method. The control group was given conventional treatment， and the study group was additionally given Esmolol hydrochloride injection based on the control group for one week. The levels of cardiac function indexes （left ventricular ejection fraction， left ventricular end-systolic volume index， left ventricular end-diastolic diameter， peak ejection fraction， cardiac output）， inflammatory factors （C-reactive protein， myeloperoxidase， interleukin-6， brain natriuretic peptide， homocysteine） myocardial enzyme indexes （creatine kinase isoenzyme， β2-microglobulin， cardiac troponin Ⅰ）， and serum expression of miR-29a and miR-129-5p were observed in two groups， and the occurrence of ADR was recorded. RESULTS After one week of treatment， left ventricular ejection fraction， peak ejection fraction， cardiac output， and the expression of miR-129-5p in two groups was significantly higher than before treatment （P＜0.05）， while left ventricular end-systolic volume index， left ventricular end-diastolic diameter， inflammatory factors and myocardial enzyme index levels， and the expression of miR-29a were significantly lower than before treatment （P＜ 0.05）. The study group was significantly better than the control group （except for the creatine kinase-MB） （P＜0.05）. There was no statistically significant difference in the incidence of symptomatic hypotension， symptomatic bradycardia， cardiogenic shock， and arrhythmia between two groups （P＞0.05）. CONCLUSIONS Esmolol can improve cardiac function， reduce inflammatory factors， lessen myocardial injury， and regulate serum expressions of miR-29a and miR-129-5p in patients with acute anterior ST- segment elevation myocardial infarction after PCI， with good safety.

OBJECTIVE To establish the quality standards of medicinal materials in light of related methods in the general principles of part four of Chinese Pharmacopoeia(2020 Edition), and to conduct systematic research on the Tibetan medicine "Yajima"(Chrysosplenium axillare). METHODS The powder characteristics of medicinal materials were described by microscopic identification method. Silica gel GF254 thin-layer plate was employed to establish a TLC identification method with 5-O-demethylapulein and oxyayanin A as reference substances. Loss on drying, total ash, acid-insoluble ash and ethanol-soluble extractives of 10 batches of Chrysosplenium axillare were determined according to the general principles of part four of Chinese Pharmacopoeia(2020 Edition). HPLC was used to establish the characteristic chromatogram of Chrysosplenium axillare, and the content determination method was established with chrysosplenoside I(CI) and chrysosplenoside A(CA) as the quality control index components of Chrysosplenium axillare. RESULTS The water content, total ash, acid-insoluble ash, ethanol-soluble extractive and the content of CI and CA of all samples varied in the ranges of 9.17%−12.52%, 14.11%−16.74%, 1.50%−4.72%, 32.77%−40.30%, 0.30%−0.99% and 0.28%−0.88%, respectively. CONCLUSION The identification and content determination methods of Yajima(Chrysosplenium axillare) are established for the first time. The methods are easy to operate and exclusive, which is of great significance to accurately evaluate the internal quality of medicinal materials and ensure the quality of drug used.

There are a total of 16 couplet medicines of Paeoniae Radix Alba and Glycyrrhizae Radix et Rhizoma in the book FU Qingzhu Nüke, covering a wide range of diseases such as leukorrheal diseases, menopathy, pregnancy, and puerperal diseases, and there is a fine sense of the dosage, processing, and proportion of the couplet medicines. Through analyzing the cases of Paeoniae Radix Alba and Glycyrrhizae Radix et Rhizoma couplet medicines and the characteristics of dosage, processing, and proportion, we conclude that Paeoniae Radix Alba and Glycyrrhizae Radix et Rhizoma couplet medicines are mainly as followed: smoothing liver and strengthening spleen in treating leukorrheal diseases to remove dampness and stop leucorrhoea; regulating liver and tonifying spleen in menopathy to regulate menstruation and relieve pain; nourishing blood and benefiting qi in pregnancy to lower adverse qi and tranquilize fetus to prevent miscarriage; regulating and tonifying qi and blood in puerperal diseases to eliminate pathogenic factors and promote lactation; suppressing hyperactive liver for descending adverse qi, and relieving spasm and pain in cases of miscarriage due to rage. In terms of dosage, Paeoniae Radix Alba is mainly used for three to five qian, and Glycyrrhizae Radix et Rhizoma is primarily used for one qian, and the dosage of the two medicinals is adjusted according to the degree of primary and secondary liver stagnation and spleen deficiency. In terms of processing, wine Paeoniae Radix Alba and raw Glycyrrhizae Radix et Rhizoma are primarily used. Stir-frying with wine can help Paeoniae Radix Alba nourish blood and promote blood circulation, tonifying without stagnation, and it is used in most of the diseases caused by liver qi stagnation or qi and blood deficiency. Glycyrrhizae Radix et Rhizoma used in raw is tonifying without causing stagnation, and it can also have the effect of purging fire. In terms of proportion, the ratio of Paeoniae Radix Alba to Glycyrrhizae Radix et Rhizoma is 5∶1 for liver stagnation restraining spleen, 3∶1 for qi and blood deficiency, and 1∶1 for obvious fire-heat. This paper analyses the application of Paeoniae Radix Alba and Glycyrrhizae Radix et Rhizoma couplet medicines in FU Qingzhu Nüke, aiming to deeply study and inherit the academic thought of FU Qingzhu, and to provide new ideas and method for the precise application of Paeoniae Radix Alba and Glycyrrhizae Radix et Rhizoma couplet medicines in clinical practice and researches.

Objective To investigate the relationship between the therapeutic effect of anti-vascular endothelial growth factor(VEGF)and cytokines in aqueous humor in patients with diabetic retinopathy(DR).Methods From July 2023 to December 2023,50 DR patients(56 eyes)who were treated with anti-VEGF drugs in the Department of Ophthal-mology,the Third Affiliated Hospital of Xinxiang Medical University were included in this study.The patients were divided into the diabetic macular edema(DME)group(30 patients,36 eyes)and the proliferative DR(PDR)group(20 patients,20 eyes).Patients in the DME group received an intravitreal injection of aflibercept once a month for three consecutive times,with aqueous humor extracted before each injection.Patients in the PDR group received an intravitreal injection of aflibercept one week before vitrectomy,with aqueous humor extracted before injection and during vitrectomy,respective-ly.The concentrations of vascular endothelial growth factor A(VEGF-A),placental growth factor(PLGF),interleukin(IL)-1β,IL-23,IL-17A,and tumor necrosis factor-α(TNF-α)in the aqueous humor were detected using the Luminex as-say.Before injection therapy,all patients underwent best corrected visual acuity(BCVA)and central macular thickness(CMT)examinations,and their correlations with cytokine concentrations in DR patients before injection therapy were ana-lyzed.Results Compared to before injection therapy,the concentrations of VEGF-A,PLGF,and IL-23 in the aqueous humor of patients in the DME group decreased significantly after treatment(all P＜0.05);additionally,the CMT de-creased,and the BCVA increased(both P＜0.05).After injection therapy,the concentrations of VEGF,PLGF,IL-1β,IL-23,IL-17A,and TNF-α in the aqueous humor of patients in the PDR group significantly decreased compared to before injec-tion therapy(all P＜0.05).Before injection therapy,the levels of VEGF-A,PLGF,and IL-23 in the aqueous humor of pa-tients in the DME group were higher than those in the PDR group,and the differences were statistically significant(all P＜0.05).The correlation analysis results showed that before injection therapy,VEGF was negatively correlated with BCVA(r=-0.767,P=0.004)and was positively correlated with CMT(r=0.662,P=0.019)and IL-23(r=0.765,P=0.004)in the DME group.There was no correlation between the cytokines in the aqueous humor of patients in the PDR group be-fore injection therapy(all P＞0.05).Conclusion Changes in the concentration of VEGF-A,PLGF,and IL-23 are closely related to the occurrence and development of DR.Anti-VEGF treatment can improve BCVA and decrease CMT in DME pa-tients.The expression level of IL-23 in aqueous humor can serve as a predictive factor for the anti-VEGF efficacy in DR pa-tients,providing new targets for early diagnosis and treatment of DR.

Hepatocellular carcinoma(HCC)is one of the most common tumor types and remains a major clinical challenge.Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC.However,few mitophagy inhibitors have been approved for clinical use in humans.Pyrimethamine(Pyr)is used to treat infections caused by protozoan parasites.Recent studies have reported that Pyr may be beneficial in the treatment of various tumors.However,its mechanism of action is still not clearly defined.Here,we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis.Mechanistically,Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells.In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29(SNAP29)-vesicle-associated membrane protein 8(VAMP8)interaction.Moreover,Pyr acted synergistically with sorafenib(Sora)to induce apoptosis and inhibit HCC proliferation in vitro and in vivo.Pyr enhances the sensitivity of HCC cells to Sora,a common chemotherapeutic,by inhibiting mitophagy.Thus,these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor.Notably,Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

Background and purpose:At present,there have been many reports on the study of methylation in cervical lesions,however it is still not clinically practical as a diagnostic and shunting index of cervical lesions.In this study,we intended to investigate the early diagnostic value of FAM19A4,PAX1 and miRNA124-2 methylation in promoter region in the progression of cervical lesions.Methods:A total of 129 liquid-based cytology specimens of different grades of cervical lesions diagnosed in the Third Affiliated Hospital of Zhengzhou University from Mar.2020 to Mar.2022.Methylation specific PCR(MSP)was used to detect the methylation changes of FAM19A4,PAX1 and miRNA124-2 genes in different cervical lesions.Receiver operating characteristic(ROC)curve was used to evaluate the diagnostic value of methylation changes of the three genes in cervical lesions.This study was approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University(No.2023-135-01).Results:All the specimens were collected and divided into 4 groups according to the histological results:42 cases of no intraepithelial lesions or malignant lesions(NILM),28 cases of low grade squamous intraepithelial lesion(LSIL),36 cases of high grade squamous intraepithelial lesion(HSIL),23 cases of squamous cervical cancer(SCC).With the increase in the level of cervical lesions,FAM19A4,PAX1 and miRNA124-2 gene methylation detection rates increased gradually,and the differences were statistically significant(P＜0.05).The methylation detection rates of FAM19A4,PAX1 and miRNA124-2 in HSIL group were 81.2%,80.5%and 71.8%,respectively,and the methylation detection rates of three genes in SCC group were up to 100.0%.Cytological diagnosis of cervical cancer showed the area under curve(AUC)was 0.731,with a sensitivity and a specificity of 65.9%and 80.4%,respectively.When FAM19A4,PAX1 and miRNA124-2 were used alone to diagnose HSIL+(HSIL and SCC),PAX1 methylation had the highest diagnostic efficiency,and the AUC was 0.925,with a sensitivity and a specificity of 92.8%and 87.3%.When the diagnosis was made in pairs,the AUC of FAM19A4 combined with PAX1 in the diagnosis of HSIL+was 0.930,with a sensitivity and a specificity of 95.7%and 87.1%,respectively.The AUC of FAM19A4 combined with miRNA124-2 in the diagnosis of HSIL+was 0.895,with a sensitivity and a specificity of 97.6%and 85.7%,respectively.The AUC of PAX1 combined with miRNA124-2 in the diagnosis of HSIL+was 0.928,with a sensitivity and a specificity of 95.7%and 89.1%,respectively.When the PAX1 and FAM19A4 combined with miRNA124-2 in the diagnosis of HSIL+,the AUC was 0.928,with a sensitivity and a specificity of 100.0%and 81.8%,respectively.Conclusion:The methylation of the promoter regions of the FAM19A4,PAX1 and miRNA124-2 genes demonstrates high sensitivity and specificity in diagnosing cervical lesions,indicating the potential for becoming novel indicators for early diagnosis of cervical lesions.