ObjectiveThis study aims to systematically evaluate the therapeutic effects of Huaihuasan on ulcerative colitis （UC） in the rats with the syndrome of dampness-heat in the large intestine and explore the potential mechanisms of action. MethodsA rat model of UC due to dampness-heat in the large intestine was successfully established by combining traditional Chinese medicine etiology with trinitrobenzenesulfonic acid （TNBS）/ethanol solution. Rats were randomly allocated into a normal group， a model group， a high-dose （10.58 g·kg^-1·d^-1） Huaihuasan group， a medium-dose （5.29 g·kg^-1·d^-1） Huaihuasan group， a low-dose （2.65 g·kg^-1·d^-1） Huaihuasan group， and a sulfasalazine （0.35 g·kg^-1·d^-1） group. The body weight changes and the diarrhea and bloody stool scores of the rats in each group were recorded. In addition， pathological changes of the colon tissue were observed to evaluate the therapeutic effects on the intestinal damage and inflammatory infiltration. Immunohistochemistry and real-time fluorescent quantitative PCR were employed to determine the expression levels of zonula occludens-1 （ZO-1） and Occludin in the colon tissue， the serum levels of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）， the expression of Toll-like receptor 4 （TLR4）， myeloid differentiation primary response 88 （MyD88）， and nuclear factor-κB p65 subunit （NF-κB p65） in the colorectum， and the mRNA levels of TLR4， MyD88， NF-κB p65， and IL-6 in the intestinal tissue. ResultsCompared with the model group， Huaihuasan effectively slowed down the trend of body weight loss （P<0.01）， mitigated diarrhea and bloody stool symptoms， reduce the disease activity index （DAI） （P<0.01）， restored the length of the colon （P<0.01）， and promoted the recovery of the colon tissue. The immunohistochemistry results showed that compared with the model group， Huaihuasan intervention promoted the expression of ZO-1 and Occludin （P<0.05）， reduced the serum levels of IL-6 and TNF-α （P<0.05， P<0.01）， and down-regulated the protein levels of TLR4， MyD88， and NF-κB p65 in the colon tissue （P<0.05， P<0.01） and the mRNA levels of TLR4， MyD88， NF-κB p65， and downstream IL-6 （P<0.05）. ConclusionHuaihuasan exerts significant therapeutic effects on UC due to dampness-heat in the large intestine by modulating the TLR4/NF-κB signaling pathway， reducing inflammatory mediator levels， and enhancing the intestinal barrier function. These findings provide theoretical support for the clinical application and mechanism study of Huaihuasan in the treatment of UC.

Gastric cancer(GC)is one of the most common tumors and the fourth leading cause of cancer-related death worldwide.Due to the lack of specific signs in early GC,most cases are diagnosed at an advanced stage,often accompanied by infiltration and distant metastasis.Although chemotherapy is the most commonly used treatment for gastric cancer,due to the emergence of drug resistance,many patients will still relapse after chemo-therapy,resulting in poor prognosis.Exosome(EXOs)in the Tumor micro environment(TME)can participate in intercellular communication and play an important role in GC distant metastasis and drug resistance.At present,the detailed mechanism of GC distant metastasis and drug resistance is still unclear.Identifying the exosome-induced mechanism involved in GC distant metastasis and drug resistance can help us find more reliable treatment methods for GC metastasis and drug resistance.This article reviews the mechanism of exosome in GC distant metastasis and drug resistance,in order to provide help for the diagnosis,treatment and research of GC.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

Objective:To observe the therapeutic effect of intraocular lens (IOL) protected phacoemulsification (PHACO) in patients with hard nucleus cataract.Methods:A randomized controlled clinical study was conducted.A total of consecutive 120 patients (120 eyes) with hard nucleus cataract of Emery grade Ⅳ or Ⅴ were enrolled from January 2019 to May 2022.The patients were randomly divided into PHACO group receiving routine PHACO, IOL protected PHACO group receiving PHACO under IOL protection, and extracapsular cataract extraction (ECCE) group receiving ECCE, with 40 cases (40 eyes) in each group.Finally, 99 patients completed the follow-up, including 30 cases (30 eyes) in PHACO group, 35 cases (35 eyes) in IOL protected PHACO group, and 34 cases (34 eyes) in ECCE group.The total operation time, intraoperative PHACO time and cumulative energy release of each patient were recorded.The corneal endothelial cell density (ECD), coefficient of variation in endothelial cell area (CV), hexagonal endothelial cell ratio (6A), corneal astigmatism and the number of eyes with different grades of uncorrected visual acuity were measured and compared after 3-month follow-up.The intraoperative and postoperative complications were recorded.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Yanbian University Hospital (NO.2023002).Patients were informed of study content and purpose and signed a consent form before treatment.Results:There was no significant difference in ultrasonic energy and time between PHACO group and IOL protected PHACO group ( P=0.691, 0.982).The total operation time was (38.81±2.73) and (36.45±3.45) minutes in PHACO group and IOL protected PHACO group, significantly shorter than (69.60±4.35) minutes in ECCE group (both at P<0.001).There was no significant difference in age, sex, lens nucleus hardness and other baseline data among the three groups before operation (all at P>0.05).Three months after operation, the number of patients with higher uncorrected visual acuity in PHACO group and IOL protected PHACO group was larger than that in ECCE group ( P=0.006, 0.007).The ECD and 6A in IOL protected PHACO group were (2 155.57±177.88)/mm 2 and (41.31±5.18)%, respectively, which were significantly higher than (1 912.64±224.11)/mm 2 and (36.18±3.27)% in PHACO group, and the CV in IOL protected PHACO group was (50.34±5.90)%, which was lower than (55.67±3.30)% in PHACO group, showing statistically significant differences ( P=0.007, 0.003, 0.005).At 1 week and 3 months after the operation, the corneal astigmatism was significantly lower in IOL-protected PHACO group than in ECCE group, but higher than in PHACO group, and the difference were statistically significant (all at P<0.05). Conclusions:Compared with conventional PHACO, IOL-protected PHACO can effectively reduce the damage of corneal endothelium caused by ultrasonic energy, shorten the operation time and reduce postoperative inflammatory reaction compared with ECCE, and does not significantly increase postoperative corneal astigmatism.IOL-protected PHACO is an effective improved surgical method for patients with hard nucleus cataract.

Purpose/Significance To analyze the network security risk events monitored by the situational awareness platform of large hospitals,to find out the causes,and to put forward solutions and suggestions for improvement.Method/Process Taking the First Affiliated Hospital of Zhengzhou University as an example,the paper analyzes risk events on the situational awareness platform,screens the risky ter-minals on the hospital intranet,carries out rectification and reinforcement,analyzes the department distribution and causes of risky termi-nals,and puts forward suggestions for improvement.Result/Conclusion The number of risky terminals in medical and technical depart-ments is large,mainly due to the lack of management and the lack of full coverage of antivirus software.Through the rectification and rein-forcement of risky terminals,the number of network security risk events has been significantly reduced.Strengthening the hospital terminal security management,enhancing staff awareness of network security,and strengthening network security protection in different areas can ef-fectively reduce the incidence of hospital network security risk events and improve the hospital network security protection capability.

AIM:To investigate the effects of the γ-aminobutyric acid(GABAergic)neural pathway from the anterior cingulate cortex(ACC)to the nucleus accumbens(NAc)on the regulation of irritable bowel syndrome(IBS)and its underlying mechanisms in mice.METHODS:(1)A C57BL/6J mice model of IBS was established by using chronic acute combing stress(CACS).The mice were divided into a normal group and an IBS group(n=8).The presence of IBS-like symptoms was determined through behavioural tests,an intestinal motility test and abdominal withdrawal reflex scores.(2)Fluorescence gold(FG)retrograde tracing and immunohistochemistry were used to investigate the ACC-NAc GABAergic neural pathway and to examine the activation of GABA in the ACC in IBS mice(n=8).(3)A total of 1.5 μL of normal saline(NS),GABAA receptor antagonist bicuculline(BIC)or agonist isoguvacine hydrochloride(Isog)was ad-ministered via a preburied catheter into the NAc of mice in IBS and normal groups.The mice were randomly divided into three groups(n=8):NS group,BIC group and Isog group.IBS-like symptoms were assessed.(4)The mice were prein-jected with AAV2/9-mDlx-iCre-WPRE-pA in the ACC and AAV2/2Retro Plus-hSyn-DIO-hM3D(Gq)-eGFP-WPRE-pA in the NAc and subsequently divided into four groups(n=8):NS(intraperitoneal injection)+NS(NAc microinjection)group,NS+BIC group,clozapine N-oxide(CNO)+NS group and CNO+BIC group.The mice who received AAV2/2Retro-hSyn-DIO-hM4D(Gi)-EGFP-WPRE-pA in the NAc were randomly divided into three groups(n=8):NS+NS group,NS+BIC group and CNO+NS group.Enzyme-linked immunosorbent assay(ELISA)was employed to estimate the expression levels of histamine and 5-hydroxytryptamine(5-HT)in colon tissue,and the effects of GABAergic neural pathways from ACC to NAc on IBS were studied.RESULTS:CACS induced IBS-like symptoms in mice.The results of FG retrograde tracing combined with fluorescence immunohistochemistry showed that GABA neurons of ACC could project to NAc.The injection of BIC in the NAc was found to significantly reduce anxiety-like behaviours,diarrheal symptoms and visceral hy-persensitivity in the IBS mice(P<0.05).Chemogenetic inhibition of the ACC-NAc GABAergic neurons ameliorated IBS-like symptoms in mice(P<0.05).CONCLUSION:The GABAergic pathway of ACC-NAc might be involved in the regu-lation of IBS in mice,which may be related to the release of histamine and 5-HT in colon tissue.

Objective To investigate the effect and mechanism of Houpu Sanwu decoction on subcutaneous tumors in C57BL/6J mice.Methods Mouse colorectal cancer MC-38 cells were injected subcutaneously into C57BL/6J mice to establish a subcutaneous tumor model of colorectal cancer.The model mice were then divided randomly into model control,Houpu Sanwu decoction(HPSWD)low dose,HPSWD medium dose,HPSWD high dose,5-fluorouracil(5-FU),and combination groups(5-FU+HPSWD medium dose)(n=6 mice per group).The mice were treated with normal saline and Houpu Sanwu decoction by gavage,or normal saline and 5-FU by intraperitoneal injection once a day for 24 consecutive days.During the intervention period,the mental state,diet,and other general conditions of the mice,as well as changes in tumor volume,were monitored regularly.At the end of the experiment,the subcutaneous tumors in each group were removed and weighed,and pathological features were examined by hematoxylin and eosin staining.Transmission electron microscopy,Western blot,and nanoparticle tracking analysis were used to identify exosomes derived from colorectal cancer tissues.Tumor mRNA and protein expression levels of Rab27a and the exosome markers CD63,TSG101,and ALIX were detected by reverse transcription-quantitative polymerase chain reaction and Western blot,respectively.Results Houpu Sanwu decoction inhibited tumor growth in mice.Tumor growth was inhibited to varying degrees in all the HPSWD dose groups and in the combination group.The HPSWD medium does group showed the greatest anticancer effect,and the combination group showed a synergistic effect with 5-FU.Houpu Sanwu decoction induced tumor necrosis in a dose-dependent manner,with a similar anticancer effect to 5-FU.Houpu Sanwu decoction also inhibited the protein and mRNA expression levels of Rab27a and the exosome-specific markers CD63,ALIX,and TSG101 in mice.Conclusions Houpu Sanwu decoction inhibits tumor growth and the secretion of exosomes,possibly by regulating Rab27a.

Sepsis is a systemic inflammatory syndrome induced by infection and other factors， with the number of patients worldwide exceeding 10 million each year. The pathophysiological mechanism is of this disease complex. Sepsis is often accompanied by endotoxin translocation， gastrointestinal dysfunction， inflammatory cytokine activation， immune dysregulation， coagulation disorder， multiple organ function impairment and many other body imbalances， as well as systemic inflammation， apoptosis， oxidative stress injury and other cell damage mechanisms. This disease causes a heavy medical burden due to the difficult diagnosis and treatment and the poor prognosis. Great progress has been achieved in the diagnosis and treatment of sepsis with traditional Chinese medicine （TCM） and western medicine. The value of western medicine in the diagnosis and treatment of sepsis is limited due to antibiotic resistance， hormone abuse， and high medical costs. Sepsis is classified as a warm disease or typhoid fever in TCM. Da Chengqitang is a classical formula in the Treatise on Typhoid Fever to deal with the excess syndrome of Yang brightness Fu-organ. Modern medicine has proved that Da Chengqitang has the effect of inhibiting oxidative stress， reducing inflammation， and delaying apoptosis by improving gastrointestinal dynamics and regulating intestinal microecology. On the basis of the previous theoretical basis and the rich experience in the medication， medical practitioners have proposed a new therapeutic concept of using Da Chengqitang in combination with western drugs from a holistic view involving both bacteria and toxicity for treating both the symptoms and the root cause， which has a wide range of application. The article reviews the classical research and latest findings of Da Chengqitang in the treatment of sepsis， with a view to clarifying the mechanism and advantages of this formula in the adjuvant treatment of sepsis， exploring its potential efficacy， and providing timely， adequate， and scientific theoretical support for the promotion of this formula in the clinical practice.

Organoid is a newly developed cellular there-dimensional culture system in recent years. Organoids have a three-dimensional structure, which is similar to that of the real organs. Together with the characteristics of self-renewal and reproduction of tissue origin, organoids can better simulate the function of real organs. Organoids provide a new platform for the study of organogenesis, regeneration, disease pathogenesis, and drug screening. The digestive system is an essential part of the human body and performs important functions. To date, organoid models of various digestive organs have been successfully established. This review summarizes the latest research progress of organoids of taste buds, esophagi, stomachs, livers and intestines, and prospects future application of organoids.
Humans ; Organoids ; Intestines ; Liver

The study was a retrospective study. The clinical data of 866 patients with IgA nephropathy (IgAN) in Beijing Anzhen Hospital, Capital Medical University from March 2010 to March 2021 were analyzed, to investigate the clinical pathology and renal prognosis of IgAN patients with intrarenal arteriolosclerosis, and to preliminarily explore whether abnormal activation of complement system is involved in the injury of arteriolosclerosis. The patients were divided into renal arteriolar lesions group and non-renal arteriolar lesions group according to the renal histopathology, and the differences of clinical pathological manifestations, prognosis between the two groups were compared. The results showed that, compared with the non-renal arteriolar lesions group ( n=236), IgAN patients in the renal arteriolar lesions group ( n=630) had higher proportions of hypertension and malignant hypertension, higher levels of urinary albumin-creatinine ratio, 24-hour urine protein quantification and serum uric acid, lower estimated glomerular filtration rate, and more severe MEST-C lesions of the Oxford classification (all P < 0.05). Cox regression analysis results showed that intrarenal arteriolosclerosis was the independent risk factor affecting the progression of IgAN to ESRD ( HR=6.437, 95% CI 2.013-20.585, P=0.002). Renal histopathology showed that the deposition of complement C3c on the wall of intrarenal arterioles in the renal arteriolar lesions group ( n=98) was stronger than that in non-renal arteriolar lesions group ( n=18, P < 0.05). IgAN patients with renal arteriolosclerosis present with serious clinical and pathological manifestations, and renal prognosis. Abnormal activation of complement system may be involved in the pathogenesis of intrarenal arteriolosclerosis.