This paper summarizes Professor WANG Xiuxia's clinical experience in treating hyperprolactinemia using the liver soothing therapy. Professor WANG identifies liver qi stagnation and rebellious chong qi （冲气） as the core pathomechanisms of hyperprolactinemia. Furthermore， liver qi stagnation may transform into fire or lead to pathological changes such as spleen deficiency with phlegm obstruction or kidney deficiency with essence depletion. The treatment strategy centers on soothing the liver， with a modified version of Qinggan Jieyu Decoction （清肝解郁汤） as the base formula. Depending on different syndrome patterns such as liver stagnation transforming into fire， liver stagnation with spleen deficiency， or liver stagnation with kidney deficiency， heat clearing， spleen strengthening， or kidney tonifying herbs are added accordingly. In addition， three paired herb combinations are commonly used for symptom specific treatment， Danggui （Angelica sinensis） with Chuanxiong （Ligusticum chuanxiong）， Zelan （Lycopus lucidus） with Yimucao （Leonurus japonicus） ， and Jiegeng （Platycodon grandiflorus） with Zisu （Perilla frutescens）.

ObjectiveThis study aims to investigate the mechanism in which Celastrus orbiculatus extract （COE） affects the proliferation and differentiation of gastric organoids and the expression of Lgr5 and thus reverses the precancerous lesions of gastric cancer （PLGC） by regulating the leucine-rich repeat containing G protein-coupled receptor 5 （Lgr5）/Wingless （Wnt）/β-catenin signaling pathway based on a gastric organoid injury model. MethodGastric organoids were established based on stem cells of the mouse gastric gland. Gastric organoid injury models were constructed by treating gastric organoids with N-methyl-N'-nitro-N-nitrosoguanidine （MNNG， 0.02 mg·L^-1）. Gastric organoid injury models were randomly divided into normal group， model group （0.02 mg·L^-1 MNNG）， low， medium， and high dose （5， 10， 20 mg·L^-1） groups of COE， and Wnt inhibitor Dickkopf-related protein 1 （DKK1） （0.5 mg·L^-1） group， and they were treated with respective agents for 24 h. The number and volume of gastric organoids under different drug concentrations were observed under a microscope. The viability of the gastric organoid injury models was detected by Methyl thiazolyl tetrazolium （MTT） assay. The morphology and pathology of gastric organoids were observed using Hematoxylin and Eosin （HE） staining. The expression levels of Lgr5， Mucin2 （MUC2）， Mucin5AC （MUC5AC）， Mucin6 （MUC6）， Wnt， and β-catenin in gastric organoids under different drug concentrations were detected by Western blot （WB）. ResultCompared with the normal group， the number， volume， and activity of gastric organoids in the model group were decreased （P<0.01）， while the expressions of Lgr5， MUC2， Wnt， and β-catenin were significantly increased （P<0.01）. The expressions of MUC5AC and MUC6 were significantly decreased （P<0.01）. Compared with the model group， the number and volume of gastric organoids in the low， medium， and high dose groups of COE were all improved （P<0.01）， and the vitality of gastric organoids was significantly enhanced （P<0.01）. The effect was the most significant at a COE concentration of 20 mg·L^-1 （P<0.01）. The expressions of Lgr5 and MUC2 in the medium and high dose groups of COE were significantly reduced （P<0.01）， while the expression of MUC5AC and MUC6 were significantly increased in the low， medium， and high dose groups of COE （P<0.05， P<0.01）. Compared with the model group， Wnt inhibitors could promote the expression of MUC5AC and MUC6 in gastric organoids （P<0.05， P<0.01） and reduce the expression of MUC2， Wnt， and β-catenin. In addition， the combined use of COE at high concentrations and Wnt inhibitors could further promote this trend （P<0.01）. ConclusionCOE inhibits the Wnt/β-catenin pathway by inhibiting the expression of Lgr5， MUC2， Wnt， and β-catenin and promoting the expression of MUC5AC and MUC6， thus promoting the proliferation and differentiation of gastric organoids and reversing the PLGC process.

BACKGROUND:As a common clinical digestive disorder,irritable bowel syndrome becomes an advantageous disease of acupuncture treatment.However,the therapeutic mechanisms remain unclear.The methodological characteristics of omics coincide with the multi-target and multi-level characteristics of acupuncture,providing the possibility of revealing the principle of acupuncture in the treatment of the disease. OBJECTIVE:To investigate the pathogenesis of irritable bowel syndrome with diarrhea(IBS-D)and the effect of acupuncture at the combined points(selected based on etiologies and symptoms)on IBS-D based on proteomics. METHODS:Twelve 3-month-old male Sprague-Dawley rats were randomly divided into three groups:a control group,an IBS-D model group and an acupuncture group.The IBS-D rat models were prepared using the CAS method.After successful modeling,bilateral Zusanli points,bilateral Neiguan points and Guanyuan points were selected for acupuncture treatment in the acupuncture group,with a frequency of 120 times/minute,1 minute of acupuncture every 4 minutes,and 15 minutes of needle retention,at an interval of 1 day every 6 days,for 28 days in total.Rats in the normal control group and the model group were not given any intervention.The pressure threshold of rat abdominal retraction reflex was measured to evaluate the visceral hypersensitivity of rats.Proteomics analysis was performed using the liquid chromatography-tandem mass spectrometry-based platform.MaxQuant software,Perseus software and DAVID,KOBAS,VENNY,STRING online tools were used for the bioinformatics analysis of proteomic data.Visualization analysis was done using Cytoscape 3.7.1 software. RESULTS AND CONCLUSION:There were 47 differentially expressed proteins between the IBS-D model and control groups.Function analysis of differentially expressed proteins revealed that the pathogenic mechanism of IBS-D was associated with abnormal energy metabolism,the imbalance of colon motor function and increased visceral sensitivity.Important proteins related to IBS-D pathogenesis included Atp5a1,Atp5c1,Idh3b,Atp2a3,Pdhb,Ppp1ca and Mapk3.Sixty-one differentially expressed proteins were identified between the acupuncture group and IBS-D model group.Acupuncture at the combined points reversed the up-regulation of nine differentially expressed proteins and the down-regulation of nine differentially expressed proteins.Bioinformatics analysis revealed that acupuncture at the combined points for IBS-D could function via multi-targets and multi-pathways,reverse the damage of energy metabolism caused by IBS-D,and play a role against oxidative stress and inflammation,thereby relieving pain and regulating the imbalance of intestinal function.Important proteins related to acupuncture effects included Atp5a1,Atp5c1,Pdhb,Sars,Uqcrc2,Prdx2,Prdx4,Ppp1ca,Manf and Tmsb4x3.All these findings preliminarily illustrate the potential molecular mechanisms of IBS-D and the effect of acupuncture at the combined points in the treatment of IBS-D at the protein level,which provide a basis for the clinical application of acupuncture at the combined points.

This paper summarized the experience of integrated acupuncture and moxibustion program in the treatment of bipolar disorder （BD）. The pathogenesis of BD is a complex of deficiency and excess， which is closely related to the liver failing to govern the free flow of qi， the spleen failing to transport， phlegm-heat harassing the heart spirit. The pathogenesis of depressive episode is mainly qi constraint， and the most common syndromes are liver qi constraint， liver constraint accompanied by spleen deficiency， phlegm and qi constraint， qi stagnation and blood stasis. The pathogenesis of manic episode is mainly fire-heat， and the most common syndromes are exuberant heat in yangming （阳明）， intense heart-liver fire， phlegm-fire disturbing heart， and exuberant fire damaging yin. BD can be treated by the integrated acupuncture and moxibustion program， in which acupuncture is used to soothe the liver and regulate the mind， and refined moxibustion is to unblock and replenish yang； collateral bloodletting and cupping is used to move qi and drain fire， and needle-embedding therapy can be used to consolidate the curative effect. These therapies together have the effects of soothing the liver and regulating qi， fortifying the spleen and dissolving phlegm， calming the heart and draining fire.

Objective To investigate the protective effect of dexmedetomidine(DEX)against erastin-induced ferroptosis in human renal tubular epithelial cells(HK-2 cells)and explore the underlying mechanism.Methods HK-2 cells were treated with erastin alone or in combination with different concentrations(2.5,5.0 and 10 μmol/L)of DEX,and the changes in cell viability were observed using CCK-8 assay.To explore the mechanism by which DEX inhibits erastin-induced ferroptosis,HK-2 cells were treated with erastin,erastin+10 μmol/L DEX,or erastin+10 μmol/L DEX+ML385(a Nrf2 inhibitor),after which the cell viability was assessed.The level of intracellular Fe2+was detected by cell ferrous iron colorimetric assay kit,and flow cytometry was performed to detect reactive oxygen species(ROS);MDA and reduced glutathione assay kits were used to detect the contents of MDA and GSH in the cells;The expressions of Nrf2,HO-1 and GPX4 proteins were detected by Western blotting.Results Erastin treatment significantly inhibited the viability of the cells,decreased GSH content,and increased intracellular levels of Fe2+,ROS and MDA.The combined treatment with 10 μmol/L DEX markedly increased the viability of the cells,increased GSH content,reduced the levels of Fe2+,ROS and MDA,and upregulated the protein expressions of Nrf2,HO-1 and GPX4 in the cells.The application of ML385 obviously blocked the protective effect of DEX and caused significant inhibition of the Nrf2/HO-1/GPX4 pathway,decreased the cell viability and GSH content,and increased the levels of Fe2+,ROS and MDA in HK-2 cells.Conclusion The protective effect of DEX against erastin-induced ferroptosis of HK-2 cells is probably mediated by activation of the Nrf2/HO-1/GPX4 pathway to inhibit oxidative stress.

Objective To evaluate the clinical effect of ultra-early endovascular treatment of ruptured tiny intracranial aneurysms(RTIAs).Methods A total of 35 patients with RTIAs who were treated with endovascular embolization within 24 hours after subarachnoid hemorrhage in our department from May 2017 to November 2022 were retrospectively analyzed.The basic clinical information,endovascular treatment results,clinical and imaging follow-up results were analyzed.Results The mean aneurysms maximum diameter is was(2.5±0.4)mm.Of these 35 patients with RTIAs,23 patients(65.7％)were treated with simple coil embolization,12 patients(34.3％)with stent assisted coiling.Immediate angiographic results showed that Raymond grade Ⅰ in 20 patients(57.1％),Ⅱ in 13(37.2％),Ⅲ in 2(5.7％).Perioperative complications occurred in 4 patients(11.4％),including Intraoperative aneurysm rupture in 2(5.7％),intra-stent thrombosis in 2(5.7％),massive cerebral infarction followed by decompressive craniectomy in 1,postoperative death in 1.Angiographic follow-up was performed in 24 patients(68.6％),recurrence in 1 patient receiving retreatment.Clinical follow-up were performed in 33 patients,The mRS of 0-2 were in 31 patients(93.9％).Conclusion Ultra-early endovascular treatment of RTIAs is effective and relatively safe,with favorable angiographic results and clinical outcomes at follow up.Intraoperative aneurysm rupture and thrombosis are the major perioperative complications.

Objective To compare the effect of rubber ring versus dental floss combined with hemoclipping assisted en-doscopic submucosal dissection(ESD)in the treatment of early gastrointestinal tumor.Methods A total of 103 patients with early gastrointestinal cancer were divided into the rubber band traction group(rubber band group,n=51)and the dental floss traction assist group(dental floss group,n=52)according to different assisted traction techniques during ESD.The basic con-ditions of the two groups were compared before operation,as well as the amount of submucosal injection,installation time of the traction device,the amount of bleeding during operation,the time of operation,the delayed bleeding after operation,one-time complete resection rate of tumor,days in hospital after operation and complication rate at 72 hours after operation.The degree of postoperative pain(VAS pain Score),follow-up quality of life(SF-36 Score)and complications 12 months after op-eration were also recorded.Results The intraoperative submucosal injection volume,intraoperative bleeding volume,num-ber of hemostatic clamp detachment,surgical time,complication rate 72 hour after operation and postoperative hospital stay were lower in the rubber band group than those in the dental floss group(P＜0.05).There was no significant difference in the number of delayed postoperative bleeding between the two groups(P＞0.05).After 12 months of follow-up,patients in the rubber band group had mild postoperative pain and good quality of life.The incidence of complications decreased within 12 months after surgery in the rubber band group(P＜0.05).Conclusion Compared with floss traction aid,rubber ring traction aid ESD can shorten the operation time and reduce postoperative complications,which is worth popularizing.

Objective To investigate the effect of Osteoporosis Self-Assessment Tool for Asia(OSTA)index on brachial ankle pulse wave velocity(baPWV)and its predictive value for peripheral atherosclerosis in menopausal women.Methods A total of 1 138 menopausal women who underwent physical examination at our hospital from January 2022 to December 2022 were enrolled in the study.General clinical data were collected,the OSTA index was calculated,and baPWV was measured.Patients were divided into the control group(n=539)and the peripheral atherosclerosis group(n=599)according to the baPWV values(peripheral atherosclerosis occurs with baPWV≥1 400 cm/s).Linear regression and Logistic regression were used to analyze the effect of OSTA index on baPWV in menopausal women.The predictive value of peripheral atherosclerosis was evaluated using the receiver operating characteristic(ROC)curve.Results The OSTA index was lower in the peripheral atherosclerosis group than that in the control group[-0.40(-2.20,1.00)vs.0.40(-0.60,1.40),P＜0.05].Univariate linear regression analysis was used to conclude that the OSTA index was an influencing factor of baPWV,and after correcting for risk factors,multivariate linear regression analysis indicated that OSTA index still affected the value of baPWV(P＜0.05).The linear regression equation was baPWV=-27.911-39.752×OSTA+6.444×SBP+7.008×DBP+11.506×HCY+27.942×Hs-CRP.Logistic regression analysis suggested that increased OSTA index was a protective factor for peripheral atherosclerosis(OR=0.664,95%CI:0.535-0.823,P＜0.001).ROC curve analysis suggested that OSTA index was-1.25 as the optimal cutoff point,which predicted peripheral atherosclerosis with an area under the curve of 0.619,a sensitivity of 36.2%and a specificity of 86.3%.Conclusion In menopausal women,OSTA index is an influential factor for baPWV,and increased OSTA index is a protective factor against peripheral atherosclerosis,which can be used to predict baPWV value.

Objective To investigate the protective effect of dexmedetomidine(DEX)against erastin-induced ferroptosis in human renal tubular epithelial cells(HK-2 cells)and explore the underlying mechanism.Methods HK-2 cells were treated with erastin alone or in combination with different concentrations(2.5,5.0 and 10 μmol/L)of DEX,and the changes in cell viability were observed using CCK-8 assay.To explore the mechanism by which DEX inhibits erastin-induced ferroptosis,HK-2 cells were treated with erastin,erastin+10 μmol/L DEX,or erastin+10 μmol/L DEX+ML385(a Nrf2 inhibitor),after which the cell viability was assessed.The level of intracellular Fe2+was detected by cell ferrous iron colorimetric assay kit,and flow cytometry was performed to detect reactive oxygen species(ROS);MDA and reduced glutathione assay kits were used to detect the contents of MDA and GSH in the cells;The expressions of Nrf2,HO-1 and GPX4 proteins were detected by Western blotting.Results Erastin treatment significantly inhibited the viability of the cells,decreased GSH content,and increased intracellular levels of Fe2+,ROS and MDA.The combined treatment with 10 μmol/L DEX markedly increased the viability of the cells,increased GSH content,reduced the levels of Fe2+,ROS and MDA,and upregulated the protein expressions of Nrf2,HO-1 and GPX4 in the cells.The application of ML385 obviously blocked the protective effect of DEX and caused significant inhibition of the Nrf2/HO-1/GPX4 pathway,decreased the cell viability and GSH content,and increased the levels of Fe2+,ROS and MDA in HK-2 cells.Conclusion The protective effect of DEX against erastin-induced ferroptosis of HK-2 cells is probably mediated by activation of the Nrf2/HO-1/GPX4 pathway to inhibit oxidative stress.

Objective:To construct A novel scoring model of immune signatures for colon cancer based on machine learning,which improve the survival prediction and immune therapy.Methods:Screening immune signatures from 1 301 immune-related genes(IRG)by the combined strategy of Lasso+bootstrap+multi Cox to calculate IRG scores of colon cancer patients from TCGA databases,and comprehensive the differences on function,prognostic status and immune therapy between high IRG scores group and IRG scores group.Results:Groups based on IRG scores were significantly different on the prognostic status of colon cancer patients,which were validated by other independent datasets.The IRG scores also could assess the effect of immune therapy of colon cancer.Conclusion:This study provides ideas for immune therapy and researches of colon cancer based on immune genes,and IRG scores can be used to assess the prognosis of colon cancer patients.