Multicenter Clinical Randomized Controlled Trial and Network Pharmacology Analysis of Zhenzhu Qingyuan Granules for the Treatment of Gastroesophageal Reflux Disease

Objective To evaluate the clinical efficacy and safety of Zhenzhu Qingyuan Granules through a clinical randomized controlled trial and to analyze the potential action targets and pathways of this formula using network pharmacology.Methods Patients with gastroesophageal reflux disease(GERD)of liver–stomach stagnant heat pattern who met the inclusion and exclusion criteria were randomly divided into the control group and the observation group.The control group received oral rabeprazole,whereas the observation group were given Zhenzhu Qingyuan Granules in addition to the rabeprazole.The treatment duration was 8 weeks.Clinical efficacy was observed in both groups after 8 weeks.Network pharmacology was used to analyze the action targets of ZhenzhuQingyuanGranules and the genes related to GERD,and core targets were inferred.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted to explore the potential mechanisms of this formula.Results The clinical research results showed that the total effective rate in the treatment group was 92.68%,compared with 70.00%in the control group,with a statistically significant difference(p<0.05).After treatment,both Chinese medicine syndrome score and endoscopic score improved in both groups compared with before treatment(p<0.05),and the treatment group showed greater improvement than the control group(p<0.05).Network pharmacology identified effective components of Zhenzhu Qingyuan Granules for treating GERD,including quercetin,luteolin,andβ-sitosterol,with potential action targets such as tumor protein 53(TP53),protein kinase B(AKT1),and tumor necrosis factor.Conclusion Zhenzhu Qingyuan Granules can significantly improve clinical symptoms in patients with GERD of liver–stomach stagnated heat pattern,enhance clinical efficacy,and have high safety.This formula may exert therapeutic effects through multiple targets and pathways.

Analysis of the causes of primary revision after unicompartmental knee arthroplasty: A case series

BACKGROUND Unicompartmental knee arthroplasty(UKA)has great advantages in the treatment of unicompartmental knee osteoarthritis,but its revision rate is higher than that of total knee arthroplasty.AIM To summarize and analyse the causes of revision after UKA.METHODS This is a retrospective case series study in which the reasons for the first revision after UKA are summarized.We analysed the clinical symptoms,medical histories,laboratory test results,imaging examination results and treatment processes of the patients who underwent revision and summarized the reasons for primary revision after UKA.RESULTS A total of 13 patients,including 3 males and 10 females,underwent revision surgery after UKA.The average age of the included patients was 67.62 years.The prosthesis was used for 3 d to 72 months.The main reasons for revision after UKA were improper suturing of the surgical opening(1 patient),osteophytes(2 patients),intra-articular loose bodies(2 patients),tibial prosthesis loosening(2 patients),rheumatoid arthritis(1 patient),gasket dislocation(3 patients),anterior cruciate ligament injury(1 patient),and medial collateral ligament injury with residual bone cement(1 patient).CONCLUSION The causes of primary revision after UKA were gasket dislocation,osteophytes,intra-articular loose bodies and tibial prosthesis loosening.Avoidance of these factors may greatly reduce the rate of revision after UKA,improve patient satisfaction and reduce medical burden.

Clinical observation of extraction-site incisional hernia after laparoscopic colorectal surgery

BACKGROUND Laparoscopic colorectal cancer surgery increases the risk of incisional hernia(IH)at the tumor extraction site.AIM To investigate the incidence of IH at extraction sites following laparoscopic colo-rectal cancer surgery and identify the risk factors for IH incidence.METHODS This study retrospectively analyzed the data of 1614 patients who underwent la-paroscopic radical colorectal cancer surgery with tumor extraction through the abdominal wall at our center between January 2017 and December 2022.Diffe-rences in the incidence of postoperative IH at different extraction sites and the risk factors for IH incidence were investigated.RESULTS Among the 1614 patients who underwent laparoscopic radical colorectal cancer surgery,303(18.8%),923(57.2%),171(10.6%),and 217(13.4%)tumors were ex-tracted through supraumbilical midline,infraumbilical midline,umbilical,and off-midline incisions.Of these,52 patients developed IH in the abdominal wall,with an incidence of 3.2%.The incidence of postoperative IH was significantly higher in the off-midline incision group(8.8%)than in the middle incision groups[the supraumbilical midline(2.6%),infraumbilical midline(2.2%),and umbilical incision(2.9%)groups](χ^(2)=24.985;P<0.05).Univariate analysis showed that IH occurrence was associated with age,obesity,sex,chronic cough,incision infection,and combined diabetes,anemia,and hypopro-teinemia(P<0.05).Similarly,multivariate analysis showed that off-midline incision,age,sex(female),obesity,incision infection,combined chronic cough,and hypoproteinemia were independent risk factors for IH at the site of laparoscopic colorectal cancer surgery(P<0.05).CONCLUSION The incidence of postoperative IH differs between extraction sites for laparoscopic colorectal cancer surgery.The infraumbilical midline incision is associated with a lower hernia rate and is thus a suitable tumor extraction site.

Long Non-coding RNA PCED1B Antisense RNA 1 Promotes Cell Proliferation and Invasion in Hepatocellular Carcinoma by Regulating the MicroRNA-34a/CD44 Axis

Objective This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1(PCED1B-AS1)in the development of hepatocellular carcinoma(HCC).Methods A total of 62 pairs of HCC tissues and adjacent non-tumor tissues were obtained from 62 HCC patients.The interactions of PCED1B-AS1 and microRNA-34a(miR-34a)were detected by dual luciferase activity assay and RNA pull-down assay.The RNA expression levels of PCED1B-AS1,miR-34a and CD44 were detected by RT-qPCR,and the protein expression level of CD44 was determined by Western blotting.The cell proliferation was detected by cell proliferation assay,and the cell invasion and migration by transwell invasion assay.The HCC tumor growth after PCED1B-AS1 was downregulated was determined by in vivo animal study.Results PCED1B-AS1 was highly expressed in HCC tissues,which was associated with poor survival of HCC patients.Furthermore,PCED1B-AS1 interacted with miR-34a in HCC cells,but they did not regulate the expression of each other.Additionally,PCED1B-AS1 increased the expression level of CD44,which was targeted by miR-34a.The cell proliferation and invasion assay revealed that miR-34a inhibited the proliferation and invasion of HCC in vitro,while CD44 exhibited the opposite effects.Furthermore,PCED1B-AS1 suppressed the role of miR-34a.Moreover,the knockdown of PCED1B-AS1 repressed the HCC tumor growth in nude mice in vivo.Conclusion PCED1B-AS1 may play an oncogenic role by regulating the miR-34a/CD44 axis in HCC.

The pathogenesis of chronic subdural hematoma in the perspective of neomembrane formation and related mechanisms

Chronic subdural hematoma(CSDH)is a disease characterized by capsuled blood products that progressively occupy the intracranial space,causing intracranial hypertension and compression in the brain.CSDH frequently occurs in all demographics,especially in the elderly,but the pathogenesis of CSDH remains unclear.In this review,we discuss the origin,development,and current treatment strategies of CSDH.For thefirst time,we analyzed the cellular and molecular compositions of hematoma membranes with a focus on neomembrane formation,a complex early-stage interactive event in hematoma pathogenesis.We hypothesize that in patients with CSDH,dural border cells(DBCs)might be induced to synthesize collagen or serum proteins might accumulate at the dura and arachnoid layers at the site of injury,thereby encapsulating the hemorrhage.Membrane formation may trigger inflammatory responses after subdural hemorrhage,promotingfibroblast-involved extracellular matrix(ECM)deposition and aberrant angiogenesis within the outer membrane.Consequently,ECM deposition and angiogenesis mutually influence each other and are modulated by inflammatory processes.By illustrating the complex and interactive mechanism of neomembrane formation,we aim to provide a novel insight into CSDH pathogenesis and propose directions for future research as well as advancements in treatment strategies for this disease.

Ligation-assisted endoscopic submucosal resection following unroofing technique for small esophageal subepithelial lesions originating from the muscularis propria

BACKGROUND The majority of esophageal subepithelial lesions originating from the muscularis propria(SEL-MPs)are benign in nature,although a subset may exhibit malignant characteristics.Conventional endoscopic resection techniques are time-consuming and lack efficacy for small SEL-MPs.AIM To evaluate the efficacy and safety of ligation-assisted endoscopic submucosal resection(ESMR-L)following unroofing technique for small esophageal SEL-MPs.METHODS From January 2021 to September 2023,17 patients diagnosed with esophageal SEL-MPs underwent ESMR-L following unroofing technique at the endoscopy center of Shenzhen People’s Hospital.Details of clinicopathological characteristics and clinical outcomes were collected and analyzed.RESULTS The mean age of the patients was 50.12±12.65 years.The mean size of the tumors was 7.47±2.83 mm and all cases achieved en bloc resection successfully.The average operation time was 12.2 minutes without any complications.Histopathology identified 2 Lesions(11.8%)as gastrointestinal stromal tumors at very low risk,12 Lesions(70.6%)as leiomyoma and 3 Lesions(17.6%)as smooth muscle proliferation.No recurrence was found during the mean follow-up duration of 14.18±9.62 months.CONCLUSION ESMR-L following roofing technique is an effective and safe technique for management of esophageal SEL-MPs smaller than 20 mm,but it cannot ensure en bloc resection and may require further treatment.

The impact of short-term changes in sleeping and eating patterns on glucometabolic health and gut microbiota in healthy young adults: a proof-of-concept controlled feeding study

Epidemiological studies showed that night workers are at higher risk of developing chronic metabolic diseases.However,no study has investigated the changes in circadian rhythms caused by a combined effect of sleep and diet in a real-life setting on cardiometabolic health,gut microbiota,and psychological status in healthy people.A 4-week step-wise misaligned-realigned controlled-feeding trial with a 2×2 factorial design(sleep and diet)was conducted on healthy young adults.At first,subjects experienced a one-week circadian rhythm misalignment with a high-fat fast-food diet,extended eating window,and delayed sleep schedules,then gradually transited to a complete circadian rhythm realignment with a high-fiber balanced diet,8-h timerestricted eating,and normal sleep schedules.Circadian rhythm misalignment led to significantly higher levels of fasting glucose and homeostatic model assessment for insulin resistance(HOMA-IR)of subjects compared to baseline and failed to recover to the baseline level in circadian rhythm realignments.Notably,the incremental area under the curve(iAUC)of postprandial glucose decreased with circadian rhythm adjustments as compared to that in circadian rhythm misalignment,suggesting circadian rhythm realignment by sleep or/and diet could partly restore glucose metabolism impaired by a short-term circadian rhythm misalignment.However,circadian rhythm changes did not result in overall perturbations of gut microbiota diversities.

Glucose metabolic reprogramming-related parameters for the prediction of 28-day neurological prognosis and all-cause mortality in patients after cardiac arrest:a prospective single-center observational study

BACKGROUND:We aimed to observe the dynamic changes in glucose metabolic reprogrammingrelated parameters and their ability to predict neurological prognosis and all-cause mortality in cardiac arrest patients after the restoration of spontaneous circulation(ROSC).METHODS:Adult cardiac arrest patients after ROSC who were admitted to the emergency or cardiac intensive care unit of the First Aflliated Hospital of Dalian Medical University from August 1,2017,to May 30,2021,were enrolled.According to 28-day survival,the patients were divided into a non-survival group(n=82) and a survival group(n=38).Healthy adult volunteers(n=40) of similar ages and sexes were selected as controls.The serum levels of glucose metabolic reprogrammingrelated parameters(lactate dehydrogenase [LDH],lactate and pyruvate),neuron-specific enolase(NSE) and interleukin 6(IL-6) were measured on days 1,3,and 7 after ROSC.The Acute Physiology and Chronic Health Evaluation II(APACHE II) score and Sequential Organ Failure Assessment(SOFA) score were calculated.The Cerebral Performance Category(CPC) score was recorded on day 28 after ROSC.RESULTS:Following ROSC,the serum LDH(607.0 U/L vs.286.5 U/L),lactate(5.0 mmol/L vs.2.0 mmol/L),pyruvate(178.0 μmol/L vs.70.9 μmol/L),and lactate/pyruvate ratio(34.1 vs.22.1) significantly increased and were higher in the non-survivors than in the survivors on admission(all P<0.05).Moreover,the serum LDH,pyruvate,IL-6,APACHE II score,and SOFA score on days 1,3 and 7 after ROSC were significantly associated with 28-day poor neurological prognosis and 28-day all-cause mortality(all P<0.05).The serum LDH concentration on day 1 after ROSC had an area under the receiver operating characteristic curve(AUC) of 0.904 [95% confidence interval [95% CI]:0.851–0.957]) with 96.8% specificity for predicting 28-day neurological prognosis and an AUC of 0.950(95% CI:0.911–0.989) with 94.7% specificity for predicting 28-day all-cause mortality,which was the highest among the glucose metabolic reprogramming-related parameters tested.CONCLUSION:Serum parameters related to glucose metabolic reprogramming were significantly increased after ROSC.Increased serum LDH and pyruvate levels,and lactate/pyruvate ratio may be associated with 28-day poor neurological prognosis and all-cause mortality after ROSC,and the predictive eflcacy of LDH during the first week was superior to others.

Research on the Employment View of Acupuncture and Tuina Undergraduates in Minority Border Areas from Students’ Perspective

With the popularization of higher education in China,the employment situation of college students is more complex and severe.This paper adopts the questionnaire method to explore the employment view of acupuncture and tuina undergraduates of Yunnan University of Traditional Chinese Medicine.The employment concept of acupuncture and tuina undergraduates in the minority border areas has changed greatly.After graduation,97.95%of students choose to work in fields related to medicine and acupuncture,prefer positions close to home,and are attracted to high-salary companies,among other factors.Therefore,enhancing the competitive advantages of medical students by guiding their career planning,providing employment selection advice,fostering innovation and entrepreneurship,improving basic skills,and offering graduate entrance examination guidance is crucial for broadening their employment opportunities.

Analysis of the Therapeutic Effect of Clopidogrel Bisulfate Tablets + Aspirin Enteric-Coated Tablets on Acute Myocardial Infarction

Objective:To investigate and analyze the clinical effect of clopidogrel bisulfate tablets combined with aspirin enteric-coated tablets on acute myocardial infarction(AMI)patients.Methods:The study period was from January 2020 to December 2023,the sample source was 82 AMI patients admitted to our hospital,grouped into an observation group(n=41)and a control group(n=41)by the numerical table method.The patients in the control group were treated with aspirin enteric-coated tablets,and the patients in the observation group were treated with aspirin enteric-coated tablets combined with clopidogrel bisulfate.The clinical efficacy,coagulation indexes,and the incidence of cardiovascular adverse events between the two groups were compared.Results:The clinical efficacy of the observation group was higher than that of the control group(P<0.05);the platelet aggregation rate(PAR)of the observation group was lower than that of the con-trol group after treatment(P<0.05),and there was no significant difference in the prothrombin time(PT)and activated partial thromboplastin time(APTT)between the two groups(P>0.05).The incidence of cardiovascular adverse events in the observation group was lower than that of the control group(P<0.05).Conclusion:The treatment effect of clopidogrel bisulfate tablets combined with aspirin enteric-coated tablets on AMI patients is remarkable.It reduces the PAR and the incidence of cardiovascular adverse events,so this treatment method should be popularized.

Single-cell transcriptomic dissection of the cellular and molecular events underlying the triclosan-induced liver fibrosis in mice

Background: Triclosan [5-chloro-2-(2,4-dichlorophenoxy) phenol, TCS], a common antimicrobial additive in many personal care and health care products, is frequently detected in human blood and urine. Therefore, it has been considered an emerging and potentially toxic pollutant in recent years. Long-term exposure to TCS has been suggested to exert endocrine disruption effects, and promote liver fibrogenesis and tumorigenesis. This study was aimed at clarifying the underlying cellular and molecular mechanisms of hepatotoxicity effect of TCS at the initiation stage.Methods: C57BL/6 mice were exposed to different dosages of TCS for 2 weeks and the organ toxicity was evaluated by various measurements including complete blood count, histological analysis and TCS quantification. Single cell RNA sequencing(scRNA-seq) was then carried out on TCS-or mock-treated mice livers to delineate the TCS-induced hepatotoxicity. The acquired single-cell transcriptomic data were analyzed from different aspects including differential gene expression, transcription factor(TF) regulatory network, pseudotime trajectory, and cellular communication, to systematically dissect the cellular and molecular events after TCS exposure. To verify the TCS-induced liver fibrosis,the expression levels of key fibrogenic proteins were examined by Western blotting, immunofluorescence, Masson’s trichrome and Sirius red stainings. In addition, normal hepatocyte cell MIHA and hepatic stellate cell LX-2 were used as in vitro cell models to experimentally validate the effects of TCS by immunological, proteomic and metabolomic technologies.Results: We established a relatively short term TCS exposure murine model and found the TCS mainly accumulated in the liver. The scRNA-seq performed on the livers of the TCS-treated and control groups profiled the gene expressions of > 76,000 cells belonging to 13 major cell types. Among these types, hepatocytes and hepatic stellate cells(HSCs)were significantly increased in TCS-treated group. We found that TCS promoted fibrosis-associated proliferation of hepatocytes, in which Gata2 and Mef2c are the key driving TFs. Our data also suggested that TCS induced the proliferation and activation of HSCs, which was experimentally verified in both liver tissue and cell model. In addition,other changes including the dysfunction and capillarization of endothelial cells, an increase of fibrotic characteristics in B plasma cells, and M2 phenotype-skewing of macrophage cells, were also deduced from the scRNA-seq analysis, and these changes are likely to contribute to the progression of liver fibrosis. Lastly, the key differential ligand-receptor pairs involved in cellular communications were identified and we confirmed the role of GAS6_AXL interactionmediated cellular communication in promoting liver fibrosis.Conclusions: TCS modulates the cellular activities and fates of several specific cell types(including hepatocytes, HSCs,endothelial cells, B cells, Kupffer cells and liver capsular macrophages) in the liver, and regulates the ligand-receptor interactions between these cells, thereby promoting the proliferation and activation of HSCs, leading to liver fibrosis.Overall, we provide the first comprehensive single-cell atlas of mice livers in response to TCS and delineate the key cellular and molecular processes involved in TCS-induced hepatotoxicity and fibrosis.

Betulinic acid-mediating miRNA-365 inhibited the progression of pancreatic cancer

Background:The dilemma of pancreatic cancer treatment has become a global challenge.For this reason,effective,feasible,and new medical methods are currently much-needed.Betulinic acid(BA)has been valued as a potential therapy for pancreatic cancer.However,the mechanism by which BA exerts an inhibitory effect on the development of pancreatic cancer remains elusive.Methods:A rat model and two cell models of pancreatic cancer were established,and the effect of BA on pancreatic cancer was verified in vivo and in vitro by using MTT,Transwell,flow cytometry,RT-PCR,Elisa and immunohistochemistry.At the same time,miR-365 inhibitors were introduced to test whether BA played a role in mediating miR-365.Results:BA can significantly inhibit the proliferation and invasion of pancreatic cancer cells and promote apoptosis.In vivo experiments,BA can significantly lower the number of cancer cells and tumor volume in the rat model of pancreatic cancer.In vitro,it was found that BA inhibited the protein level and phosphorylation level of AKT/STAT3 by mediating the expression of miR365/BTG2/IL-6.Like BA,miR-365 inhibitors also significantly inhibited cell viability and invasion ability,and inhibited the protein level and phosphorylation level of AKT/STAT3 by changing the expression of BTG2/IL-6,and their combination had a synergistic effect.Conclusion:BA inhibits AKT/STAT3 expression and phosphorylation by modulating miR-365/BTG2/IL-6 expression,and BA inhibits the progression of pancreatic cancer through the aforementioned mechanism.

Aluminum phosphate gel reduces early rebleeding in cirrhotic patients with gastric variceal bleeding treated with histoacryl injection therapy

BACKGROUND Esophageal-gastro varices bleeding(EGVB)is the most widely known cause of mortality in individuals with cirrhosis,with an occurrence rate of 5%to 15%.Among them,gastric varices bleeding(GVB)is less frequent than esophageal varices bleeding(EVB),but the former is a more critical illness and has a higher mortality rate.At present,endoscopic variceal histoacryl injection therapy(EVHT)is safe and effective,and it has been recommended by relevant guidelines as the primary method for the treatment of GVB.However,gastric varices after endoscopic treatment still have a high rate of early rebleeding,which is mainly related to complications of its treatment,such as bleeding from drained ulcers,rebleeding of varices etc.Therefore,preventing early postoperative rebleeding is very important to improve the quality of patient survival and outcomes.AIM To assess the efficacy of aluminium phosphate gel(APG)combined with proton pump inhibitor(PPI)in preventing early rebleeding after EVHT in individuals with GVB.METHODS Medical history of 196 individuals with GVB was obtained who were diagnosed using endoscopy and treated with EVHT in Shenzhen People's Hospital from January 2016 to December 2021.Based on the selection criteria,101 patients were sorted into the PPI alone treatment group,and 95 patients were sorted into the PPI combined with the APG treatment group.The incidences of early rebleeding and corresponding complications within 6 wk after treatment were compared between both groups.Statistical methods were performed by two-sample t-test,Wilcoxon rank sum test andχ2 test.RESULTS No major variations were noted between the individuals of the two groups in terms of age,gender,Model for End-Stage Liver Disease score,coagulation function,serum albumin,hemoglobin,type of gastric varices,the dose of tissue glue injection and EV that needed to be treated simultaneously.The early rebleeding rate in PPI+APG group was 3.16%(3/95),which was much lower than that in the PPI group(12.87%,13/101)(P=0.013).Causes of early rebleeding:the incidence of gastric ulcer bleeding in the PPI+APG group was 2.11%(2/95),which was reduced in comparison to that in the PPI group(11.88%,12/101)(P=0.008);the incidence of venous bleeding in PPI+APG group and PPI group was 1.05%(1/95)and 0.99%(1/101),respectively,and there was no significant difference between them(0.999).The early mortality rate was 0 in both groups within 6 wk after the operation,and the low mortality rate was related to the timely hospitalization and active treatment of all patients with rebleeding.The overall incidence of complications in the PPI+APG group was 12.63%(12/95),which was not significantly different from 13.86%(14/101)in the PPI group(P=0.800).of abdominal pain in the PPI+APG group was 3.16%(3/95),which was lower than that in the PPI group(11.88%,12/101)(P=0.022).However,due to aluminum phosphate gel usage,the incidence of constipation in the PPI+APG group was 9.47%(9/95),which was higher than that in the PPI group(1.98%,2/101)(P=0.023),but the health of the patients could be improved by increasing drinking water or oral lactulose.No patients in either group developed spontaneous peritonitis after taking PPI,and none developed hepatic encephalopathy and ectopic embolism within 6 wk of EVHT treatment.CONCLUSION PPI combined with APG can significantly reduce the incidence of early rebleeding and postoperative abdominal pain in cirrhotic patients with GVB after taking EVHT.

Celastrol mitigates inflammation in sepsis by inhibiting the PKM2-dependent Warburg effect

Background: Sepsis involves life-threatening organ dysfunction and is caused by a dysregulated host response to infection. No specific therapies against sepsis have been reported. Celastrol(Cel) is a natural anti-inflammatory compound that shows potential against systemic inflammatory diseases. This study aimed to investigate the pharmacological activity and molecular mechanism of Cel in models of endotoxemia and sepsis.Methods: We evaluated the anti-inflammatory efficacy of Cel against endotoxemia and sepsis in mice and macrophage cultures treated with lipopolysaccharide(LPS). We screened for potential protein targets of Cel using activity-based protein profiling(ABPP). Potential targets were validated using biophysical methods such as cellular thermal shift assays(CETSA) and surface plasmon resonance(SPR). Residues involved in Cel binding to target proteins were identified through point mutagenesis, and the functional effects of such binding were explored through gene knockdown.Results: Cel protected mice from lethal endotoxemia and improved their survival with sepsis, and it significantly decreased the levels of pro-inflammatory cytokines in mice and macrophages treated with LPS(P <0.05). Cel bound to Cys424 of pyruvate kinase M2(PKM2), inhibiting the enzyme and thereby suppressing aerobic glycolysis(Warburg effect). Cel also bound to Cys106 in high mobility group box 1(HMGB1) protein, reducing the secretion of inflammatory cytokine interleukin(IL)-1β. Cel bound to the Cys residues in lactate dehydrogenase A(LDHA).Conclusions: Cel inhibits inflammation and the Warburg effect in sepsis via targeting PKM2 and HMGB1 protein.

The prospects for bioprinting tumor models:recent advances in their applications

Three-dimensional(3D)tumor models prepared from patient-derived cells have been reported to imitate some of the biological development processes of in situ tumors in vitro.These 3D tumor models share several important characteristics with their in vivo tumor counterparts.Accordingly,their applications in tumor modeling,drug screening,and precision-targeted treatment are promising.However,the establishment of tumormodels is subject to several challenges,including advancements in scale size,repeatability,structural precision in time and space,vascularization,and the tumor microenvironment.Recently,bioprinting technologies enabling the editorial arrangement of cells,factors,and materials have improved the simulation of tumormodels in vitro.Among the 3D bioprinted tumor models,the organoidmodel has been widely appreciated for its advantages of maintaining high heterogeneity and capacity for simulating the developmental process of tumor tissues.In this review,we outline approaches and potential prospects for tumor model bioprinting and discuss the existing bioprinting technologies and bioinks in tumor model construction.The multidisciplinary combination of tumor pathology,molecular biology,material science,and additive manufacturing will help overcome the barriers to tumor model construction by allowing consideration of the structural and functional characteristics of in vitro models and promoting the development of heterogeneous tumor precision therapies.

Eff ects of continuous renal replacement therapy on infl ammation-related anemia, iron metabolism and prognosis in sepsis patients with acute kidney injury

BACKGROUND:This study aims to evaluate the eff ect of continuous renal replacement therapy(CRRT)on inflammation-related anemia,iron metabolism,and the prognosis in sepsis patients with acute kidney injury(AKI).METHODS:Sepsis patients with AKI were prospectively enrolled and randomized into the CRRT and control groups.The clinical and laboratory data on days 1,3 and 7 after intensive care unit(ICU)admission were collected.The serum interleukin(IL)-6,hepcidin,erythropoietin,ferritin,and soluble transferrin receptor(sTfR)were determined by enzyme-linked immunosorbent assay.The Sequential Organ Failure Assessment(SOFA)score and 28-day mortality were recorded.Data were analyzed using Pearson’s Chi-square test or Fisher’s exact test(categorical variables),and Mann-Whitney U-test or t-test(continuous variables).RESULTS:The hemoglobin and serum erythropoietin levels did not signifi cantly diff er between the CRRT and control groups though gradually decreased within the first week of ICU admission.On days 3 and 7,the serum IL-6,hepcidin,ferritin,and red blood cell distribution width significantly decreased in the CRRT group compared to the control group(all P<0.05).On day 7,the serum iron was significantly elevated in the CRRT group compared to the control group(P<0.05).However,the serum sTfR did not signifi cantly diff er between the groups over time.In addition,the SOFA scores were signifi cantly lower in the CRRT group compared to the control group on day 7.The 28-day mortality did not signifi cantly diff er between the control and CRRT groups(38.0%vs.28.2%,P=0.332).CONCLUSION:CRRT might have beneficial effects on the improvement in inflammationrelated iron metabolism and disease severity during the fi rst week of ICU admission but not anemia and 28-day mortality in sepsis patients with AKI.

Photodynamic therapy with TBZPy regulates the PI3K/AKT and endoplasmic reticulum stress-related PERK/eIF2α pathways in HeLa cells

Background:((1-triphenylaminebenzo[c][1,2,5]thiadiazole-4-yl)styryl)-1-methylpyridin methylpyridin-1-ium iodide salt(TBZPy)is a novel photosensitizer that displays excellent photodynamic properties.However,There are few reports on the mechanism of action of the TBZPy photodynamic.Previous studies revealed that photodynamic therapy(PDT)could induce endoplasmic reticulum stress by acting on the endoplasmic reticulum.Therefore,in this study,we investigated the effects of endoplasmic reticulum stress induced by TBZPy-PDT in treating High-risk human papillomavirus(HR-HPV)infection and their underlying mechanisms.Methods:The human cervical cancer cell line HeLa(containing whole genome of HR-HPV18)was treated with TBZPy-PDT.Cell migration,invasion,and colony-forming ability were evaluated using wound-healing,Transwell invasion,and colonyforming assays,respectively.Through western blot analysis,we determined the level of expression of the PI3K/AKT and PERK/eIF2αpathway proteins and the proteins associated with calcium trafficking and apoptosis.The calcium levels in the cytoplasm were detected via flow cytometry.Results:The result shows that TBZPy-PDT could inhibite the migration,invasion,and colony forming ability of infected HeLa cells by downregulating the PI3K/AKT pathway in vitro.And we found that TBZPy-PDT induced endoplasmic reticulum stress-specific apoptosis via the PERK/eIF2αpathway.Moreover,TBZPy-PDT increased the levels of calcium and calmodulin,while decreasing the levels of endoplasmic reticulum calcium-binding proteins.Conclusions:TBZPy-PDT is effective on treating human papillomavirus-infected cells.Targeting the PI3K/AKT and PERK/eIF2αpathways and the endoplasmic reticulum stress process may help improve the effects of TBZPy-PDT for treating high-risk human papillomavirus infection.

Age-related Changes in Humanin Expression in the Ovarian Tissue of Rat

Objective This study examined humanin expression in rat ovarian tissue,its cellular localization,and its correlation with rat age under physiological conditions.Methods A total of 40 Sprague-Dawley rats of various ages(2,12,30,and 60 days old and 1 year old)were grouped by age.Immunofluorescence and immunohistochemical techniques were used to observe humanin expression and cellular location in the ovarian tissues of rats from each age group.In addition,Western blotting and Real-time quantitative reverse transcription PCR(qRT-PCR)techniques were used to measure humanin expression level in the ovarian tissues of rats from each age group.Results The immunofluorescence and immunohistochemical results confirmed that humanin was expressed in rat ovarian tissues.In addition,cellular localization analysis showed that humanin was expressed in the cytoplasm of oocytes,interstitial cells,granulosa cells and theca cells in all levels of follicles after the primary follicles,and in the corpus luteum.The qRT-PCR results revealed that the level of humanin expression in the ovarian tissues of 12-day-old rats was non-significantly higher than that in the ovarian tissues of 2-day-old rats(P>0.05),whereas the levels of humanin expression in the ovarian tissues of 30-day-old,60-day-old,and 1-year-old rats were significantly lower than that in the ovarian tissues of 2-day-old rats(P<0.05).The Western blotting results demonstrated that the levels of humanin protein expression in the ovarian tissues of 60-day-old and 1-year-old rats were significantly lower than those of 2-day-old rats(P<0.01),whereas there was no significant difference in the level of humanin protein expression between the ovarian tissues of 12-day-old and 30-day-old rats.Conclusion This study confirmed that humanin is expressed in the cytoplasm of various cells in rat ovarian tissues.Moreover,the level of humanin expression was highest in the ovarian tissues of 12-day-old rats,and it subsequently decreased with age.The changes in the expression of humanin in the ovary of rats at different ages will lay the foundation for the role of humanin in ovarian aging.The effect of humanin on ovarian function is worthy of further study in the future.

Initial clinical experience with Xpert-Pro peripheral self-expanding stent system for internal carotid artery dissection:Two case reports

Background:The standard treatment for internal carotid artery(ICA)dissection is obscure.Current therapeutic strategies include the use of antiplatelet drugs,anticoagulant drugs,intravenous thrombolysis,and endovascular treatment.Endovascular treatment is important in acute internal carotid artery dissection.This study reports two acute internal carotid artery dissection cases that were treated successfully using the Xpert-Pro peripheral selfexpanding stent system.Case summary:The first case was of a 38-year-old male patient with transient speechlessness and paralysis of the right limb in July 2021.Cervical computed tomographic angiography(CTA)showed ICA occlusion on the left side.Digital subtraction angiography(DSA)showed severe stenosis of the C1 segment of the left internal carotid artery with intermural hematoma.The patient subsequently underwent Xpert-Pro peripheral self-expanding stent implantation,and his condition stabilized.The second case was of a 56-year-old male patient with speechlessness and paralysis of the right limb.Cervical CTA showed a dissected left ICA,and DSA showed an occluded left ICA and middle cerebral artery.The patient subsequently underwent stent implantation,and his condition stabilized.

Next-generation sequencing technology for the diagnosis of Pneumocystis pneumonia in an immunocompetent female:A case report

BACKGROUND Pneumocystis pneumonia(PCP)is a serious fungal infection usually seen in patients with human immunodeficiency virus,and it is more frequently found and has a high fatality rate in immunocompromised people.Surprisingly,it rarely occurs in immunocompetent patients.However,the clinical diagnosis of this pathogen is made more difficult by the difficulty of obtaining accurate microbiological evidence with routine tests.This case reports a PCP patient with normal immune function who was diagnosed through next-generation sequencing(NGS).CASE SUMMARY A 23-year-old female who had no special disease in the past was admitted to the hospital with a persistent fever and cough.Based on the initial examination results,the patient was diagnosed with bipulmonary pneumonia,and empirical broad-spectrum antibiotic therapy was administered.However,due to the undetermined etiology,the patient's condition continued to worsen.She was transferred to the intensive care unit because of acute respiratory failure.After the diagnosis of Pneumocystis jirovecii infection through NGS in bronchoalveolar lavage fluid and treatment with trimethoprim/sulfamethoxazole and caspofungin,the patient gradually recovered and had a good prognosis.CONCLUSION This case emphasizes that,for patients with normal immune function the possibility of PCP infection,although rare,cannot be ignored.NGS plays an important role in the diagnosis of refractory interstitial pneumonia and acute respiratory failure.