AAV-mediated expression of p65shRNA and bone morphogenetic protein 4 synergistically enhances chondrocyte regeneration

BACKGROUND:Adeno-associated virus(AAV)gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent years.However,given the complexity of osteoarthritis pathogenesis,single gene manipulation for the treatment of osteoarthritis may not produce satisfactory results.Previous studies have shown that nuclear factorκB could promote the inflammatory pathway in osteoarthritic chondrocytes,and bone morphogenetic protein 4(BMP4)could promote cartilage regeneration.OBJECTIVE:To test whether combined application of AAV-p65shRNA and AAV-BMP4 will yield the synergistic effect on chondrocytes regeneration and osteoarthritis treatment.METHODS:Viral particles containing AAV-p65-shRNA and AAV-BMP4 were prepared.Their efficacy in inhibiting inflammation in chondrocytes and promoting chondrogenesis was assessed in vitro and in vivo by transfecting AAV-p65-shRNA or AAV-BMP4 into cells.The experiments were divided into five groups:PBS group;osteoarthritis group;AAV-BMP4 group;AAV-p65shRNA group;and BMP4-p65shRNA 1:1 group.Samples were collected at 4,12,and 24 weeks postoperatively.Tissue staining,including safranin O and Alcian blue,was applied after collecting articular tissue.Then,the optimal ratio between the two types of transfected viral particles was further investigated to improve the chondrogenic potential of mixed cells in vivo.RESULTS AND CONCLUSION:The combined application of AAV-p65shRNA and AAV-BMP4 together showed a synergistic effect on cartilage regeneration and osteoarthritis treatment.Mixed cells transfected with AAV-p65shRNA and AAV-BMP4 at a 1:1 ratio produced the most extracellular matrix synthesis(P<0.05).In vivo results also revealed that the combination of the two viruses had the highest regenerative potential for osteoarthritic cartilage(P<0.05).In the present study,we also discovered that the combined therapy had the maximum effect when the two viruses were administered in equal proportions.Decreasing either p65shRNA or BMP4 transfected cells resulted in less collagen II synthesis.This implies that inhibiting inflammation by p65shRNA and promoting regeneration by BMP4 are equally important for osteoarthritis treatment.These findings provide a new strategy for the treatment of early osteoarthritis by simultaneously inhibiting cartilage inflammation and promoting cartilage repair.

Targeted gene sequencing and bioinformatics analysis of patients with gallbladder neuroendocrine carcinoma:A case report

BACKGROUND Gallbladder neuroendocrine carcinoma(NEC)represents a subtype of gallbladder malignancies characterized by a low incidence,aggressive nature,and poor prognosis.Despite its clinical severity,the genetic alterations,mechanisms,and signaling pathways underlying gallbladder NEC remain unclear.CASE SUMMARY This case study presents a rare instance of primary gallbladder NEC in a 73-year-old female patient,who underwent a radical cholecystectomy with hepatic hilar lymphadenectomy and resection of liver segments IV-B and V.Targeted gene sequencing and bioinformatics analysis tools,including STRING,GeneMANIA,Metascape,TRRUST,Sangerbox,cBioPortal and GSCA,were used to analyze the biological functions and features of mutated genes in gallbladder NEC.Twelve mutations(APC,ARID2,IFNA6,KEAP1,RB1,SMAD4,TP53,BTK,GATA1,GNAS,and PRDM3)were identified,and the tumor mutation burden was determined to be 9.52 muts/Mb via targeted gene sequencing.A protein-protein interaction network showed significant interactions among the twelve mutated genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used to assess mutation functions and pathways.The results revealed 40 tumor-related pathways.A key regulatory factor for gallbladder NEC-related genes was identified,and its biological functions and features were compared with those of gallbladder carcinoma.CONCLUSION Gallbladder NEC requires standardized treatment.Comparisons with other gallbladder carcinomas revealed clinical phenotypes,molecular alterations,functional characteristics,and enriched pathways.

Surgical boot camp curriculum improves clinical competencies in senior medical students

To provide a clinical practice skills training curriculum for senior medical students,and to assess its effect on the students'clinical practice skills and operative performance.Surgical boot camp program was held by Jinan University.The 40-hour surgical boot camp program composed of lectures on clinical issues,clinical practice simulation,field anatomy,and simulated operation based on fresh cadavers.The participants were 24 undergraduates of 4th grade in medical school will enter hospitals to be preliminary interns.The results showed that 95.0%of students were satisfied with the surgical boot camp,and for the content setting,92.2%of students thought it was appropriate for them,and the training curriculum gave them a valuable clinical practice experience.

Early detection of multiple endocrine neoplasia type 1: A case report

BACKGROUND Multiple endocrine neoplasias(MENs)are a group of hereditary diseases invol-ving multiple endocrine glands,and their prevalence is low.MEN type 1(MEN1)has diverse clinical manifestations,mainly involving the parathyroid glands,gastrointestinal tract,pancreas and pituitary gland,making it easy to miss the clinical diagnosis.CASE SUMMARY We present the case of a patient in whom MEN1 was detected early.A middle-aged male with recurrent abdominal pain and diarrhea was admitted to the hos-pital.Blood tests at admission revealed hypercalcemia and hypophosphatemia,and emission computed tomography of the parathyroid glands revealed a hy-perfunctioning parathyroid lesion.Gastroscopy findings suggested a duodenal bulge and ulceration.Ultrasound endoscopy revealed a hypoechoic lesion in the duodenal bulb.Further blood tests revealed elevated levels of serum gastrin.Surgery was performed,and pathological analysis of the surgical specimens revealed a parathyroid adenoma after parathyroidectomy and a neuroendocrine tumor after duodenal bulbectomy.The time from onset to the definitive diagnosis of MEN1 was only approximately 1 year.CONCLUSION For patients who present with gastrointestinal symptoms accompanied by hyper-calcemia and hypophosphatemia,clinicians need to be alert to the possibility of MEN1.

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.

Eosinophilic solid and cystic renal cell carcinoma with aggressive behavior:Two case reports

BACKGROUND Eosinophilic solid and cystic(ESC)renal cell carcinoma(RCC),a unique and emerging subtype of RCC,has an indolent nature;in some rare instances,it may exhibit metastatic potential.Current cases are inadequate to precisely predict the clinical outcome of ESC RCC and determine treatment choices.CASE SUMMARY Herein,we report two patients with ESC RCC.Patient 1 was a young woman with classical pathological characteristics.Patient 2 was a 52-year-old man with multifocal metastases,involving the pulmonary hilar and mediastinal lymph nodes,liver,brain,mesosternum,vertebra,rib,femur,and symphysis pubis.Awareness of ESC RCC,along with its characteristic architecture and immunophenotype,would contribute to making a definitive diagnosis,even on core biopsy samples.CONCLUSION The discovery of ESC RCC molecular signatures may provide new therapeutic strategies in the future.

New recessive compound heterozygous variants of RP1L1 in RP1L1 maculopathy

AIM:To identify a maculopathy patient caused by new recessive compound heterozygous variants in RP1L1.METHODS:Comprehensive retinal morphological and functional examinations were evaluated for the patient with RP1L1 maculopathy.Targeted sequence capture array technique was used to screen potential pathologic variants.Polymerase chain reaction and Sanger sequencing were used to confirm the screening results.RESULTS:Fundus examination showed round macular lesions appeared in both eyes.Optical coherence tomography showed that the inner segment/outer segment continuity was disorganized and disruptive in the left eye,but it was uneven and slightly elevated in the right eye.Fundus autofluorescence showed patchy hyper-autofluorescence in the macula.Visual field examination indicates central defects in both eyes.Electroretinogram(ERG)and multifocal ERG showed no obvious abnormalities.Fundus fluorescein angiography in the macula showed obviously irregular hyper-fluorescence in the right eye and slightly hyper-fluorescence in the left eye.We found that the proband carried a missense variant(c.1972C>T)and a deletion variant(c.4717_4718del)of RP1L1,which were originated from the parents and formed compound heterozygous variants.Both variants are likely pathogenic according to the ACMG criteria.Multimodal imaging,ERG and detailed medical history are important diagnostic tools for differentiating between acquired and inherited retinal disorders.CONCLUSION:A maculopathy case with detailed retinal phenotype and new recessive compound heterozygous variants of RP1L1 is identified in a Chinese family,which expands the understanding of phenotype and genotype in RP1L1 maculopathy.

Drainage of ascites in cirrhosis

For cirrhotic refractory ascites,diuretics combined with albumin and vasoactive drugs are the first-line choice for ascites management.However,their therapeutic effects are limited,and most refractory ascites do not respond to medication treat-ment,necessitating consideration of drainage or surgical interventions.Con-sequently,numerous drainage methods for cirrhotic ascites have emerged,including large-volume paracentesis,transjugular intrahepatic portosystemic shunt,peritoneovenous shunt,automated low-flow ascites pump,cell-free and concentrated ascites reinfusion therapy,and peritoneal catheter drainage.This review introduces the advantages and disadvantages of these methods in different aspects,as well as indications and contraindications for this disease.

Factors affecting meibomian gland area loss in symptomatic adults

AIM:To characterize the distribution of meibomian gland(MG)area loss(MGL)and its relationship with demographic characteristics,mites,and symptoms.METHODS:This retrospective observational study included patients who visited the Dry Eye Clinic of Shenzhen Eye Hospital between June 2020 and August 2021.General patient characteristics,ocular symptoms,Demodex test results of the eyelid edges,and the results of a comprehensive ocular surface analysis were collected.MGL was analyzed using Image J software.RESULTS:This study enrolled 1204 outpatients aged 20-80(40.70±13.44)y,including 357 males(29.65%)and 847 females(70.35%).The patients were classified into mild(n=155;12.87%),moderate(n=795;66.03%),severe(n=206;17.11%),and extremely severe(n=48;3.99%)MGL groups.MGL was significantly larger in female than in male(P=0.006).The degree of MGL also significantly differed in age(P<0.001)and the more numbers of mites with severity(P<0.001).Multivariate disordered multinomial logistic regression analysis identified that female sex,older age,secretory symptoms,and a large number of mites were risk factors for MGL(P<0.05).CONCLUSION:Patients with MGL are more likely to be older,female,more numbers of mites,and increased secretion.

Inflammation-related iron metabolism disorders and anemia in patients with anti-glomerular basement membrane disease without overt bleeding:a case report

Anti-glomerular basement membrane(anti-GBM)disease is a rare small vessel vasculitis representing the most aggressive form of autoimmune glomerulonephritis.[1,2]Its overall incidence ranges from 0.60 to 1.79 per million population annually.[1]Anti-GBM disease is mediated by abnormal anti-GBM antibody production,which mainly targets GBM and thus contributes to rapid progressive glomerulonephritis with a distinctive pattern of diffuse crescentic formation in the glomeruli.

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.

Early detection of pancreatic cancer in patients with recurrent pancreatitis:A case report

BACKGROUND Pancreatic cancer presents a challenge with its low early diagnosis and treatment rates,leading to high metastasis and mortality rates.The median survival time for advanced pancreatic cancer is a mere 3 months.However,there's hope:small pancreatic cancers diagnosed at an early stage(T1)or those less than or equal to 1 cm in diameter boast an impressive 5-year survival rate of nearly 100%.This underscores the critical importance of early pancreatic cancer detection for significantly improving prognosis.CASE SUMMARY Pancreatic cancer,a malignant tumor of the digestive tract,poses challenges in both diagnosis and treatment due to its occult and atypical clinical symptoms.Clinically,patients with recurrent pancreatitis should be vigilant,as it may be indicative of pancreatic cancer,particularly in middle-aged and elderly patients.Here,we presented the case of a patient who experienced recurrent acute pancreatitis within a span of 2 months.During the initial episode of pancreatitis,routine imaging failed to identify the cause of pancreatic cancer.However,upon recurrence of acute pancreatitis,endoscopic ultrasonography(EUS)revealed a space-occupying lesion approximately 1 cm in size in the pancreatic body.Subsequent EUS coupled with fine-needle aspiration examination demonstrated atypical pancreatic gland epithelium.Ultimately,the patient underwent surgery and was diagnosed with an intraductal papillary mucinous tumor of the pancreas(severe epithelial dysplasia,focal cancer).CONCLUSION We recommend EUS for patients with recurrent pancreatitis of unknown etiology to exclude early pancreatic cancer.

Endoscopic“calabash”ligation and resection for small gastric mesenchymal tumors

BACKGROUND Gastric mesenchymal tumors(GMT)are identified as soft tissue neoplasms that arise from mesenchymal stem cells within the gastrointestinal tract.GMT pri-marily encompass gastric stromal tumors(GST),gastric leiomyomas,and gastric schwannomas.Although most GMT are benign,there are still potential malignant changes,especially GST.Thus,early surgical intervention is the primary treat-ment for GMT.We have designed a simple endoscopic“calabash”ligation and resection(ECLR)procedure to treat GMT.Its efficacy and safety need to be com-pared with those of traditional endoscopic techniques,such as endoscopic sub-mucosal excavation(ESE).AIM To assess the safety and effectiveness of ECLR in managing small GMT(sGMT)with a maximum diameter≤20 mm by comparing to ESE.METHODS This retrospective analysis involved patients who were hospitalized in our institution between November 2021 and March 2023,underwent endoscopic resection,and received a pathological diagnosis of GMT.Cases with a tumor diameter≤20 mm were chosen and categorized into two cohorts:Study and control groups.The study group was composed of patients treated with ECLR,whereas the control group was composed of those treated with ESE.Data on general clinical characteristics(gender,age,tumor diameter,tumor growth direction,tumor pathological type,and risk grade),surgery-related information(complete tumor resection rate,operation duration,hospitalization duration,hospitalization cost,and surgical complications),and postoperative follow-up were collected for both groups.The aforementioned data were subsequently analyzed and compared.RESULTS Five hundred and eighty-nine individuals were included,with 297 cases in the control group and 292 in the study group.After propensity score matching,the final analysis incorporated 260 subjects in each cohort.The findings indicated that the study group exhibited shorter operation duration and lowered medical expenses relative to the control group.Furthermore,the study group reported less postoperative abdominal pain and had a lower incidence of intraoperative perforation and postoperative electrocoagulation syndrome than the control group.There were no substantial variations observed in other parameters among the two cohorts.CONCLUSION ECLR is a viable and effective approach for managing sGMT.

Novel MIP gene mutation causes autosomal-dominant congenital cataract

●AIM:To identify disease-causative mutations in families with congenital cataract.●METHODS:Two Chinese families with autosomaldominant congenital cataract(ADCC)were recruited and underwent comprehensive eye examinations.Gene panel next-generation sequencing of common pathogenic genes of congenital cataract was performed in the proband of each family.Sanger sequencing was used to valid the candidate gene mutations and sequence the other family members for co-segregation analysis.The effect of sequence changes on protein structure and function was predicted through bioinformatics analysis.Major intrinsic protein(MIP)-wildtype and MIP-G29R plasmids were constructed and microinjected into zebrafish single-cell stage embryos.Zebrafish embryonic lens phenotypes were screened using confocal microscopy.●RESULTS:A novel heterozygous mutation(c.85G>A;p.G29R)in the MIP gene was identified in the proband of one family.A known heterozygous mutation(c.97C>T;p.R33C;rs864309693)in MIP was found in the proband of another family.In-silico prediction indicated that the novel mutation might affect the MIP protein function.Zebrafish embryonic lens was uniformly transparent in both wild-type PCS2+MIP and mutant PCS2+MIP.●CONCLUSION:Two missense mutations in the MIP gene in Chinese cataract families are identified,and one of which is novel.These findings expand the genetic spectrum of MIP mutations associated with cataracts.The functional studies suggest that the novel MIP mutation might not be a gain-of-function but a loss-of-function mutation.

Functional investigation and two-sample Mendelian randomization study of primary biliary cholangitis hub genes

BACKGROUND The identification of specific gene expression patterns is crucial for understanding the mechanisms underlying primary biliary cholangitis(PBC)and finding relevant biomarkers for diagnosis and therapeutic evaluation.AIM To determine PBC-associated hub genes and assess their clinical utility for disease prediction.METHODS PBC expression data were obtained from the Gene Expression Omnibus database.Overlapping genes from differential expression analysis and weighted gene coexpression network analysis(WGCNA)were identified as key genes for PBC.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses were performed to explore the potential roles of key genes.Hub genes were identified in protein-protein interaction(PPI)networks using the Degree algorithm in Cytoscape software.The relationship between hub genes and immune cells was investigated.Finally,a Mendelian randomization study was conducted to determine the causal effects of hub genes on PBC.RESULTS We identified 71 overlapping key genes using differential expression analysis and WGCNA.These genes were primarily enriched in pathways related to cytokinecytokine receptor interaction,and Th1,Th2,and Th17 cell differentiation.We utilized Cytoscape software and identified five hub genes(CD247,IL10,CCL5,CCL3,and STAT3)in PPI networks.These hub genes showed a strong correlation with immune cell infiltration in PBC.However,inverse variance weighting analysis did not indicate the causal effects of hub genes on PBC risk.CONCLUSION Hub genes can potentially serve as valuable biomarkers for PBC prediction and treatment,thereby offering significant clinical utility.

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.

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.

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.

The Value of γδ T Cells in Lung Infections and Advances in Diagnosis and Treatment

Lung infections are usually caused by pathogenic microorganisms and are a disease with high morbidity and mortality. In clinical practice, the use of broad-spectrum antibiotics has become increasingly common, but this has also led to the problem of antibiotic abuse and irrational use, which in turn has spawned the emergence of multidrug-resistant bacteria, making the treatment of lung infections more complex and difficult. In the human immune system, γδ T cells play a crucial role in defense against foreign pathogens and regulation of autoimmune responses. These cells act as a bridge between innate and adaptive immunity and can be rapidly activated in the early stages of infection to produce inflammatory factors and chemokines that attract other immune cells to the site of infection. Recent advances have shown that γδ T cells not only play a direct role in the innate immunity of pathogen infection, but are also involved in regulating the subsequent adaptive immune response. The aim of this review is to explore the mechanism of γδ T cells in lung infections and to summarize the current progress of clinical research, with the aim of providing new scientific basis and therapeutic strategies for the treatment of lung infections.