Persistent alterations in gray matter in COVID-19 patients experiencing sleep disturbances:a 3-month longitudinal study

Sleep disturbances are among the most prevalent neuropsychiatric symptoms in individuals who have recovered from severe acute respiratory syndrome coronavirus 2 infections.Previous studies have demonstrated abnormal brain structures in patients with sleep disturbances who have recovered from coronavirus disease 2019(COVID-19).However,neuroimaging studies on sleep disturbances caused by COVID-19 are scarce,and existing studies have primarily focused on the long-term effects of the virus,with minimal acute phase data.As a result,little is known about the pathophysiology of sleep disturbances in the acute phase of COVID-19.To address this issue,we designed a longitudinal study to investigate whether alterations in brain structure occur during the acute phase of infection,and verified the results using 3-month follow-up data.A total of 26 COVID-19 patients with sleep disturbances(aged 51.5±13.57 years,8 women and 18 men),27 COVID-19 patients without sleep disturbances(aged 47.33±15.98 years,9 women and 18 men),and 31 age-and gender-matched healthy controls(aged 49.19±17.51 years,9 women and 22 men)were included in this study.Eleven COVID-19 patients with sleep disturbances were included in a longitudinal analysis.We found that COVID-19 patients with sleep disturbances exhibited brain structural changes in almost all brain lobes.The cortical thicknesses of the left pars opercularis and left precuneus were significantly negatively correlated with Pittsburgh Sleep Quality Index scores.Additionally,we observed changes in the volume of the hippocampus and its subfield regions in COVID-19 patients compared with the healthy controls.The 3-month follow-up data revealed indices of altered cerebral structure(cortical thickness,cortical grey matter volume,and cortical surface area)in the frontal-parietal cortex compared with the baseline in COVID-19 patients with sleep disturbances.Our findings indicate that the sleep disturbances patients had altered morphology in the cortical and hippocampal structures during the acute phase of infection and persistent changes in cortical regions at 3 months post-infection.These data improve our understanding of the pathophysiology of sleep disturbances caused by COVID-19.

CHCHD2 Thr61Ile mutation impairs F1F0-ATPase assembly in in vitro and in vivo models of Parkinson's disease

Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucial mitochondrial protein,has been reported to cause Parkinson's disease.FIFO-ATPase participates in the synthesis of cellular adenosine triphosphate(ATP)and plays a central role in mitochondrial energy metabolism.However,the specific roles of wild-type(WT)CHCHD2 and T611-mutant CHCHD2 in regulating F1FO-ATPase activity in Parkinson's disease,as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1FO-ATPase activity,remain unclea r.Therefore,in this study,we expressed WT CHCHD2 and T61l-mutant CHCHD2 in an MPP^(+)-induced SH-SY5Y cell model of PD.We found that CHCHD2 protected mitochondria from developing MPP^(+)-induced dysfunction.Under normal conditions,ove rexpression of WT CHCHD2 promoted F1FO-ATPase assembly,while T61I-mutant CHCHD2 appeared to have lost the ability to regulate F1FO-ATPase assembly.In addition,mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2 and F1FO-ATPase.Three weeks after transfection with AAV-CHCHD2 T61I,we intraperitoneally injected 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this model.These findings suggest that WT CHCHD2 can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function.

KIF15, a key regulator of nasopharyngeal carcinoma development mediated by the P53 pathway

Background:Kinesin family member 15(KIF15)is a protein that regulates cell mitosis and plays an important role in the development and progression of several types of human cancers.However,the role of KIF15 in the development of nasopharyngeal cancer(NPC)is still unclear.Methods:The differential expression of KIF15 in NPC and para-carcinoma tissues was evaluated based on data collected from Gene Expression Omnibus(GEO)database and immunohistochemical analysis of clinical specimens collected from a patient cohort.Cell lines 5-8F and CNE-2Z were selected for the construction of KIF15‑knockdown cell models.CCK8 assay,flow cytometry,wound healing,Transwell and clone formation assays were used to detect the proliferation,apoptosis,migration,invasion and colony formation of NPC cells in vitro.A mouse xenograft model and the tail intravenous mouse distant transfer model were constructed for in vivo study.Furthermore,the potential molecular mechanisms underlying the effects of KIF15 were explored through western blot analysis,and several in vitro and in vivo functional assays were performed to explore its role in NPC.Results:The results revealed significantly higher expression of KIF15 in NPC tissues compared to para-carcinoma tissues.High levels of KIF15 expression were also associated with short overall survival(OS)and progression-free survival(PFS).Knockdown of the KIF15 gene led to a cell cycle arrest in the growth 2(G2)phase,inhibition of cell proliferation,migration,invasion,colony formation,and enhanced cell apoptosis.The in vivo murine xenograft experiments showed that down-regulation of the KIF15 gene could inhibit tumor growth and reduce the risk of liver and lung metastasis in NPC.Moreover,the evaluation of the molecular pathway showed that the mitogen-activated protein kinase/P53 pathways might be involved in the KIF15-induced regulation of NPC.Rescue assays indicated that Pifithrin-αcould counteract the pro-proliferative and pro-apoptotic effects mediated by KIF15.Conclusion:This work indicated that KIF15 overexpression accelerated the progression of NPC and promoted the development of distant metastases.Therefore,KIF15 may have an important role as a prognostic indicator and a potential drug target for the treatment of NPC.

Whole‑genome transcriptome and DNA methylation dynamics of pre‑implantation embryos reveal progression of embryonic genome activation in buffaloes

Background During mammalian pre-implantation embryonic development(PED),the process of maternal-to-zygote transition(MZT)is well orchestrated by epigenetic modification and gene sequential expression,and it is related to the embryonic genome activation(EGA).During MZT,the embryos are sensitive to the environment and easy to arrest at this stage in vitro.However,the timing and regulation mechanism of EGA in buffaloes remain obscure.Results Buffalo pre-implantation embryos were subjected to trace cell based RNA-seq and whole-genome bisulfite sequencing(WGBS)to draw landscapes of transcription and DNA-methylation.Four typical developmental steps were classified during buffalo PED.Buffalo major EGA was identified at the 16-cell stage by the comprehensive analy-sis of gene expression and DNA methylation dynamics.By weighted gene co-expression network analysis,stage-spe-cific modules were identified during buffalo maternal-to-zygotic transition,and key signaling pathways and biological process events were further revealed.Programmed and continuous activation of these pathways was necessary for success of buffalo EGA.In addition,the hub gene,CDK1,was identified to play a critical role in buffalo EGA.Conclusions Our study provides a landscape of transcription and DNA methylation in buffalo PED and reveals deeply the molecular mechanism of the buffalo EGA and genetic programming during buffalo MZT.It will lay a foundation for improving the in vitro development of buffalo embryos.

Clusterin:Review of research progress and looking ahead to direction in hepatocellular carcinoma

Liver cancer, a large proportion of which is hepatocellular carcinoma(HCC), is diagnosed in more than 700000 people each year worldwide. Liver cancer is particularly prevalent in Asia, Sub-Saharan Africa and the South Pacific, where hepatitis B and hepatitis C infection rates are very high. However, due to resistance to chemotherapy, patients with intermediate and advanced-stage disease cannot benefit from this treatment. Clusterin, which is overexpressed in many different cancers, is a stress-induced cytoprotective protein that confers treatment resistance. Custirsen(OGX-011) is a novel 2'-methoxyethyl modified phosphorothioate antisense oligonucleotide that targets secretory clusterin protein expression and is currently in clinical trials for patients with different cancers. In recent years, a number of different clinical trials have been performed, and two phase Ⅲ clinical trials of custirsen evaluating combinations with chemotherapy in patients with metastatic castration-resistant prostate cancer and metastatic non-small cell lung cancer are currently in progress. The aims of this review are to summarize the current state of research on clusterin, predict future research directions and analyze the potential of the clinical application of custirsen in HCC.

Laparoscopic vs open extended right hemicolectomy for colon cancer

AIM: to evaluate the feasibility, safety, and oncologic outcomes of laparoscopic extended right hemicolectomy (LERH) for colon cancer. METHODS: Since its establishment in 2009, the Southern Chinese Laparoscopic Colorectal Surgical Study (SCLCSS) group has been dedicated to promoting patients' quality of life through minimally invasive surgery. The multicenter database was launched by combining existing datasets from members of the SCLCSS group. The study enrolled 220 consecutive patients who were recorded in the multicenter retrospective database and underwent either LERH (n = 119) or open extended right hemicolectomy (OERH) (n = 101) for colon cancer. Clinical characteristics, surgical outcomes, and oncologic outcomes were compared between the two groups. RESULTS: There were no significant differences in terms of age, gender, body mass index (BMI), history of previous abdominal surgery, tumor location, and tumor stage between the two groups. The blood loss was lower in the LERH group than in the OERH group [100 (100-200) mL vs 150 (100-200) mL, P < 0.0001]. The LERH group was associated with earlier first flatus (2.7 +/- 1.0 d vs 3.2 +/- 0.9 d, P < 0.0001) and resumption of liquid diet (3.6 +/- 1.0 d vs 4.2 +/- 1.0 d, P < 0.0001) compared to the OERH group. The postoperative hospital stay was significantly shorter in the LERH group (11.4 +/- 4.7 d vs 12.8 +/- 5.6 d, P = 0.009) than in the OERH group. The complication rate was 11.8% and 17.6% in the LERH and OERH groups, respectively (P = 0.215). Both 3-year overall survival [LERH (92.0%) vs OERH (84.4%), P = 0.209] and 3-year disease-free survival [LERH (84.6%) vs OERH (76.6%), P = 0.191] were comparable between the two groups. CONCLUSION: LERH with D3 lymphadenectomy for colon cancer is a technically feasible and safe procedure, yielding comparable short-term oncologic outcomes to those of open surgery. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Rectal nonsteroidal anti-inflammatory drugs,glyceryl trinitrate,or combinations for prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis:A network meta-analysis

BACKGROUND Acute pancreatitis is the most common and severe complication of endoscopic retrograde cholangiopancreatography(ERCP).Recent evidence suggests that combinations based on rectal nonsteroidal anti-inflammatory drugs(NSAIDs)are more beneficial in preventing post-ERCP pancreatitis(PEP).Randomized controlled trials(RCTs)have also demonstrated the efficacy of glyceryl trinitrate(GTN).We conducted a network meta-analysis to compare NSAIDs and GTN for prevention of PEP and to determine whether they are better in combination.AIM To compare NSAIDs and GTN for prevention of PEP and to determine whether they are better in combination.METHODS A systematic search was done for full-text RCTs of PEP in PubMed,Embase,Science Citation Index,and the Cochrane Controlled Trials database.Inclusion and exclusion criteria were used to screen for eligible RCTs.The major data were extracted by two independent reviewers.The frequentist model was used to conduct this network meta-analysis and obtain the pairwise OR and 95%CI.The data were then extracted and assessed on the basis of the Reference Citation RESULTS Twenty-four eligible RCTs were selected,evaluating seven preventive strategies in 9416 patients.Rectal indomethacin 100 mg plus sublingual GTN(OR:0.21,95%CI:0.09–0.50),rectal diclofenac 100 mg(0.34,0.18–0.65),sublingual GTN(0.34,0.12–0.97),and rectal indomethacin 100 mg(0.49,0.33–0.73)were all more efficacious than placebo in preventing PEP.The combination of rectal indomethacin and sublingual GTN had the highest surface under the cumulative ranking curves(SUCRA)probability of(92.2%)and was the best preventive strategy for moderate-to-severe PEP with a SUCRA probability of(89.2%).CONCLUSION Combination of rectal indomethacin 100 mg with sublingual GTN offered better prevention of PEP than when used alone and could alleviate the severity of PEP.

Clinical stages of recurrent hepatocellular carcinoma: A retrospective cohort study

BACKGROUND Hepatocellular carcinoma(HCC)is the second leading cause of cancer-related death worldwide,and has relatively high recurrence rates.Few studies have been published on the clinical stages of recurrent HCC.AIM To assess the applicability of the Barcelona Clinic Liver Cancer(BCLC)staging for recurrent HCC and the need to establish clinical stage criteria for recurrent HCC.METHODS The clinicopathological data of 81 patients with recurrent HCC who were admitted to the Hospital of Guangxi Zhuang Autonomous Region from January 2013 to December 2017 were collected.The patients were divided into three groups according to the BCLC staging system as follows:(1)Group A with BCLC stage A,51 patients;(2)Group B with BCLC stage B,14 patients;and(3)Group C with BCLC stage C,16 patients.The median time to tumor recurrence and the median overall survival were compared.RESULTS The median time to tumor recurrence in groups A,B,and C was 16±1.5 mo,10±2.8 mo,and 6±0.5 mo,respectively,with a statistically significant difference among them(χ^(2)=70.144,P<0.05);no statistically significant difference was noted between group A and group B(χ^(2)=2.659,P>0.05),although there were statistically significant differences between group A and group C and between group B and group C(χ^(2)=62.110,and 19.972,P<0.05).The median overall survival in groups A,B,and C were 42±5.1 mo,22±3.1 mo,and 13±1.8 mo,respectively,with a statistically significant difference among them(χ2=38.949,P<0.05);there were statistically significant differences between group A and group B,group A and group C,and group B and group C(χ2=9.577,37.172,and 7.183,respectively;P<0.05).CONCLUSION There are different prognoses in recurrent HCC patients according to the BCLC staging.Therefore,BCLC staging is applicable to recurrent HCC and it is essential to formulate clinical stage criteria for recurrent HCC.

CircMAN1A2 promotes vasculogenic mimicry of nasopharyngeal carcinoma cells through upregulating ERBB2 via sponging miR-940

Nasopharyngeal carcinoma(NPC)is the most prevalent human primary malignancy of the head and neck,and the presence of vasculogenic mimicry(VM)renders anti-angiogenic therapy ineffective and poorly prognostic.However,the underlying mechanisms are unclear.In the present study,we used miR-940 silencing and overexpression for in vitro NPC cell EdU staining,wound healing assay and 3D cell culture assay,and in vivo xenograft mouse model and VM formation to assess miR-940 function.We found that ectopic miR-940 expression reduced NPC cell proliferation,migration and VM,as well as tumorigenesis in vivo.By bioinformatic analysis,circMAN1A2 was identified as a circRNA that binds to miR-940.Mechanistically,we confirmed that circMAN1A2 acts as a sponge for miR-940,impairs the inhibitory effect of miR-940 on target ERBB2,and then activates the PI3K/AKT/mTOR signaling pathway using RNA-FISH,dual luciferase reporter gene and rescue analysis assays.In addition,upregulation of ERBB2 expression is associated with clinical staging and poor prognosis of NPC.Taken together,the present findings suggest that circMAN1A2 promotes VM formation and progression of NPC through miR-940/ERBB2 axis and further activates the PI3K/AKT/mTOR pathway.Therefore,circMAN1A2 may become a biomarker and therapeutic target for anti-angiogenic therapy in patients with nasopharyngeal carcinoma.

Effect of Focused Cardiac Ultrasound in Combination with Lung Ultrasound on Critically Ill Patients: A Multicenter Observational Study in China

Objective Focused cardiac ultrasound(FCU)and lung ultrasound(LU)are increasingly being used in critically ill patients.This study aimed to investigate the effect of FCU in combination with LU on these patients and to determine if the timing of ultrasound examination was associated with treatment change.Methods This is a multicenter cross-sectional observational study.Consecutive patients admitted to the intensive care unit(ICU)were screened for enrollment.FCU and LU were performed within the first 24 h,and treatment change was proposed by the performer based on the ultrasound results and other clinical conditions.Results Among the 992 patients included,502 were examined within 6 h of ICU admission(early phase group),and 490 were examined after 6 h of admission(later phase group).The early phase group and the later phase group had similar proportions of treatment change(48.8%vs.49.0%,χ^(2)=0.003,P=0.956).In the multivariable analysis,admission for respiratory failure was an independent variable associated with treatment change,with an odds ratio(OR)of 2.357[95%confidence interval(CI):1.284-4.326,P=0.006];the timing of examination was not associated with treatment change(OR=0.725,95%CI:0.407-1.291,P=0.275).Conclusions FCU in combination with LU,whether performed during the early phase or later phase,had a significant impact on the treatment of critically ill patients.Patients with respiratory failure were more likely to experience treatment change after the ultrasound examination.

Comparative characterization of human fetal neural stem cells and induced neural stem cells from peripheral blood mononuclear cells

Human-induced neural stem cells(iNSCs)transplantation is a potential treatment of neurodegeneration diseases.However,whether the reprogrammed cells have the same characterizations as human fetal neural stem cells needs further exploration.Here we isolated human fetal neural stem cells from aborted 12-week fetal brains and compared with iNSCs reprogrammed from human peripheral blood mononuclear cells in gene expression,proliferation ability,differentiation capacity,and the responses to tumor necrosis factor-α.We found that iNSCs and NSCs both expressed neural stem cell markers Nestin,SOX1,and SOX2.However,only iNSCs can be patterned into dopaminergic neurons and motor neurons.Furthermore,both iNSCs and NSCs can differentiate into oligodendrocyte progenitor cells.In addition,a low dose of tumor necrosis factor-αdid not inhibit the proliferation and differentiation of iNSCs and NSCs.In conclusion,iNSCs have properties similar to,and even better than,fetal neural stem cells and may be suitable for disease modeling and transplantation.

Snare-assisted flexible endoscope in trans-gastric endoscopic gallbladder-preserving surgery:A pilot animal study

BACKGROUND Natural orifice transluminal endoscopic surgery(NOTES)gallbladder-preserving surgery by flexible endoscopy is an emerging technology.However,the gallbladder fails to obtain traction and positioning functions during the operation.AIM To evaluate the feasibility and safety of a new surgical method,“snare-assisted pure NOTES gallbladder-preserving surgery”.METHODS Eight miniature pigs were randomly divided into the experimental group[NOTES gallbladder-preserving surgery using the snare device,snare assisted(SA)]and the control group(NOTES gallbladder-preserving surgery without using the snare device,NC),with four cases in each group.The differences between the two groups of animals in operating time,operating workload,complications,adverse events,white blood cells,and liver function were determined.RESULTS No differences were found in the surgical success rate,gallbladder incision closure,white blood cell count,or liver function between the two groups.The total operating time,gallbladder incision blood loss,gallbladder disorientation time,gallbladder incision closure time,and workload scores on the National Aeronautics and Space Administration-Task Load Index were significantly reduced in the SA group(P<0.05).CONCLUSION These results indicated that snare-assisted pure NOTES gallbladder-preservation surgery using standard endoscopic instruments reduced the difficulty of operation,shortened operation time,and did not increase complications in pigs.A new method for pure NOTES gallbladder-preservation surgery was provided.

Hyperbaric oxygen protects against PC12 and H9C2 cell damage caused by oxygen-glucose deprivation/reperfusion via the inhibition of cell apoptosis and autophagy

In this study,we investigated the protective effect of hyperbaric oxygen(HBO)on PC12 and H9C2 cell damage caused by oxygen-glucose deprivation/reperfusion and its possible mechanism.PC12 and H9C2 cell oxygen-glucose deprivation/reperfusion model were established.Cells were divided into a control group,model group,hyperbaric air(HBA)group and HBO group.The cell viability was detected by the CCK8 assay.Hoechst 33342 and PI staining assays and mitochondrial membrane potential(MMP)assays were used to detect cell apoptosis.The ultrastructure of cells,including autophagosomes,lysosomes,and apoptosis,were examined using a transmission electron microscope.The expression of autophagy-related proteins was detected by cellular immunofluorescence and immunocytochemistry.Our results showed that HBO can significantly improve the vitality of damaged PC12 and H9C2 cells caused by oxygen–glucose deprivation/reperfusion.HBO can significantly inhibit apoptosis of PC12 and H9C2 cells caused by oxygenglucose deprivation/reperfusion.Importantly,we found that the protective mechanism of PC12 and H9C2 cell damage caused by oxygen-glucose deprivation/reperfusion may be related to the inhibition of the autophagy pathway.In this study,the results of cellular immunofluorescence and immunocytochemistry experiments showed that the 4E-BP1,p-AKt and mTOR levels of PC12 and H9C2 cells in the model group decreased,while the levels of LC3B,Atg5 and p53 increased.However,after HBO treatment,these autophagy-related indexes were reversed.In addition,observation of the cell ultrastructure with transmission electron microscopy found that in the model group,a significant increase in the number of autophagic vesicles was observed.In the HBO group,a decrease in autophagic vesicles was observed.The study demonstrated that hyperbaric oxygen protects against PC12 and H9C2 cell damage caused by oxygen-glucose deprivation/reperfusion via the inhibition of cell apoptosis and autophagy.

ZBTB7A governs 2-DG-inhibited glycolysis by regulating GLUT1 in nasopharyngeal carcinoma

Our previous studies suggested a potential interaction between the POK erythroid myeloid ontogenic factor ZBTB7A and glucose transporter 1(GLUT1)in nasopharyngeal carcinoma(NPC).This study was designed to confirm the interaction and further evaluate the precise mechanism by which ZBTB7A and GLUT1 regulate NPC development.The binding sites between ZBTB7A and the promoter of GLUT1 were predicted by bioinformatics.Gene expression was measured by quantitative real-time polymerase chain reaction(qPCR),western blotting,and immunohistochemistry.The activities of key glycolysis enzymes,including hexokinase(HK),pyruvate kinase(PK),lactate dehydrogenase(LDH),and lactate,were detected using specific enzyme-linked immunosorbent assay kits.The connection between ZBTB7A and GLUT1 was analyzed by dual-luciferase reporter assay and chromatin immunoprecipitation-qPCR.The vitality,proliferation,and tumorigenicity of the cells expressing different levels of ZBTB7A were tested by adding the glycolysis inhibitor 2-deoxy-D-glucose(2-DG),followed by MTT,colorimetric focus forming,and xenograft assays,respectively.Our results showed that high expression of GLUT1 was associated with late-stage NPC.After constructing stably transfected cells with lentiviruses,ZBTB7A was effectively knocked down in 5-8F cells(RNAi-5-8F)and overexpressed in 6-10B cells(ZBTB7A-6-10B).The up-or downregulation of GLUT1 secondary to ZBTB7A changes was also limited.The vitality and proliferation of the cells expressing low ZBTB7A were notably blocked by 2-DG.The cells expressing high ZBTB7A were not very sensitive to 2-DG.The growth of RNAi-5-8F xenografts was strongly suppressed by 2-DG.The activities of HK,PK,and LDH were suppressed by 2-DG in the cells expressing low ZBTB7A.RNAi-5-8F cells had the lowest 2-DG-induced lactate production.ZBTB7A directly suppressed the promoter region of GLUT1 to regulate GLUT1 expression.Thus,ZBTB7A controls the 2-DG-induced inhibition of glycolysis by affecting GLUT1.

Application effect of thoracoscopic tricuspid valvuloplasty in geriatric patients with tricuspid valve disease

BACKGROUND Thoracoscopic-assisted technology can ensure that doctors can implement minimally invasive treatment through the right intercostal incision or small incision of the lower sternum.This approach not only can achieve a cardiac correction effect equivalent to that of a thoracotomy but also has the benefit of a clear surgical field ensuring the safety of surgical treatment.AIM To investigate the effect of thoracoscopic tricuspid valvuloplasty in patients with tricuspid valve disease.METHODS A total of 41 patients with tricuspid valve disease underwent traditional thoracotomy treatment between January 2018 and June 2020.Forty-one patients with tricuspid valve disease who underwent thoracoscopic tricuspid valvuloplasty treatment between July 2020 and June 2021 in our hospital were selected as controls for our retrospective analysis.The study group underwent thoracoscopic tricuspid valvuloplasty,while traditional thoracotomy was performed in the control group.The operation conditions(the duration of extracorporeal circulation,aorta blocking,endotracheal intubation,and surgery),inflammatory response-related indices(C-reactive protein and white blood cell count)before and after surgery,parameters related to myocardial injury(myocardial troponin T,creatine kinase isoenzyme,creatine kinase,and lactate dehydrogenase),and the incidence of adverse events in the two groups was counted.RESULTS The duration of extracorporeal circulation(109.35±50.31 min),aortic occlusion(94.26±59.61 min),endotracheal intubation(12.59±3.54 h),and hospital stay(5.29±2.34 d)in the study group were shorter than those in the control group(114.91±46.98 min,101.37±61.44 min,13.11±4.01 h,7.09±3.11 d,respectively).The difference in hospital stay between the two groups was statistically significant(P<0.05).Serum C-reactive protein level(4.69±1.35 mg/L)and white blood cell count(6.21±1.97×10^(9)/L)in the study group were found to be not significantly different than those in the control group(5.01±1.18 mg/L,5.98±2.01×10^(9)/L,respectively;P>0.05).Myocardial troponin T(0.04±0.02 ng/mL),creatine kinase isoenzyme(4.02±1.11 mg/mL),creatine kinase(91.35±10.44 U/L),and lactate dehydrogenase(179.81±60.04 U/L)in the study group were also not statistically significant different than those in the control group(0.05±0.03 ng/mL,3.97±1.05 mg/mL,89.69±13.05 U/L,186.35±56.96 U/L;P>0.05).After the operation,serum C-reactive protein level(7.89±1.73 mg/L)and white blood cell count(10.76±2.35×10^(9)/L)in the study group were significantly lower than those in the control group(9.96±2.04 mg/L,14.84±3.07×10^(9)/L,respectively)(P<0.05).In addition,myocardial troponin T(0.89±0.32 ng/mL),creatine kinase isoenzyme(26.96±4.95 mg/mL),creatine kinase(608.32±202.33 U/L),and lactate dehydrogenase(282.56±101.34 U/L)in the study group were lower than those in the control group(2.61±0.69 ng/mL,34.37±6.87 mg/mL,689.94±214.64 U/L,369.15±114.46 U/L)(P<0.05).The incidence of adverse events in the study group(4.88%)was lower than that in the control group(19.51%)(P<0.05).CONCLUSION Thoracoscopic tricuspid valvuloplasty can achieve good results in treating patients with tricuspid valve disease,reduce the risk of adverse events,and promote the rapid recovery of patients.

Clinical differences between young and older patients with optic neuritis

Background:To compare clinical features in young(18-44 years)and older patients(>44 years)with optic neuritis(ON).Methods:This is a retrospective case series study.One hundred thirty-three young cases and 51 older cases diagnosed with ON were reviewed.Results:The older patients had lower proportion of disc swelling(37.3%vs.57.1%,P=0.016),but higher proportion of brain plaques(21.6%vs.7.5%,P=0.007)compared with the young patients.The proportion of patients suffered from hypertension or hyperglycemia was nearly 6 times higher in the older patients than in the young patients(29.4%vs.5.3%,P<0.001).There were no significant differences in other clinical parameters[including gender,eye pain,clinical evidence of multiple sclerosis and best corrected visual acuity(BCVA)]between the older and young patients.Conclusions:There are some distinct differences between young patients(18-44 years)and older patients(>44 years).Physicians should pay attention to the side effects of corticosteroids in elderly patients in clinical practice,although they are generally safe.

Adjuvant Therapy for Hepatocellular Carcinoma After Curative Treatment:Several Unanswered Questions

Most patients with hepatocellular carcinoma(HCC)have a poor prognosis.Hepatectomy and local ablation are the main curative treatments for HCC.Nevertheless,the recurrence rate after hepatectomy or ablation is up to 70%,which seriously affects patient prognosis.Several adjuvant therapies have been explored to reduce postoperative recurrence.However,although a variety of adjuvant therapies have been shown to reduce the recurrence rate and improve overall survival,a standard consensus of national HCC guidelines for adjuvant treatment is lacking.Therefore,there are significant differences in the recommendations for adjuvant therapy for HCC between the Eastern and Western guidelines.A variety of adjuvant treatment methods,such as antiviral therapy,transarterial chemoembolization or traditional Chinese medicine,are recommended by the Chinese HCC guidelines.However,Western guidelines make few recommendations other than antiviral therapy.Adjuvant immune checkpoint inhibitors are recommended only in the recently updated American Association for the Study of Liver Diseases guidelines.This review summarized the existing adjuvant therapy options after curative hepatectomy or ablation and discusses several important dilemmas of adjuvant treatments.

Chlorinated Polyfluoroalkyl Ether Sulfonic Acids(Cl-PFESAs)Are Associated with Eye Diseases in Humans and Eye Toxicity in Zebrafish

Evidence from animal experiments has shown that chlorinated polyfluoroalkyl ether sulfonic acids(Cl-PFESAs)can induce vision dysfunction in zebrafish.However,environmental epidemiological evidence supporting this hypothesis remains limited.In our case−control study,samples collected from 270 individuals(135 controls and 135 cases)from the Isomers of C8 Health Project data were analyzed for Cl-PFESAs.We also repeated our analysis on zebrafish to support our findings in humans and to decipher the mechanism underlying Cl-PFESA eye toxicity.The serum levels of per-and polyfluoroalkyl substances(PFASs)and alternatives were significantly higher in the cases than in the controls.Higher serum Cl-PFESA levels were associated with greater odds of eye diseases,and the trend showed a statistically significant dose-dependent relationship.The Shapley additive explanations(SHAP)value indicated that 8:2 Cl-PFESA was the dominant eye disease risk factor among the 13 studied PFASs.In zebrafish experiments,Cl-PFESAs induced eye toxicity in adult zebrafish by oxidative damage and cell apoptosis.Compared to the control group,there was significantly reduced thicknesses of the inner plexiform layer(IPL),outer plexiform layer(OPL),and retinal tissue in the zebrafish exposed to Cl-PFESAs.Our study provides human clinical and animal experimental data,showing that exposure to PFASs increases the odds of the development of eye toxicity.

Female urinary incontinence in China after 15 years’efforts:Resultsfrom large-scale nationwide surveys

Urinary incontinence(UI)is a disease that quietly yet seriously impacts women's health and represents a global health burden that is often neglected.This study aims to systematically assess the prevalence and dynamics of female UI in China,and can inform further policies and have international implications.This study used three nationwide investigations:A national cross-sectional survey in 2021;another nationwide cross-sectional survey in 2006;and data regarding the institutions and physicians providing pelvic floor rehabilitation services from 2005 to 2019.The weighted prevalence of female UI and its subtypes,including stress UI(SUI),urgency UI(UUI),and mixed UI(MUI),were estimated as primary outcomes.Knowledge,attitude and care-seeking behaviors of UI were evaluated.It was found that the weighted prevalence of female UI was 16.0%(95%CI,13.3%–19.1%)with SUI remaining the predominant subtype(7.0%)in 2021,followed by MUI(6.5%)and UUI(1.9%).The estimated absolute number of Chinese adult women with UI was 85.8 million in 2021.52.7%(95%CI,45.9%–59.4%)of women were aware that UI was a medical condition,and only 10.1%of women with UI sought health care.After 15 years of development,there were 8400 pelvic floor rehabilitation institutions and nearly 10,000 relevant physicians in ChinaDthey were found to be associated with UI prevalence.The UI prevalence in China was significantly lower in 2021 compared to that in 2006.Despite the achievement,UI remains a public health problem,especially given China's fast aging and three-child policy.More innovations,especially those that can facilitate care seeking,are needed to address this prevalent yet treatable condition.

Non-small cell lung cancer organoids:Advances and challenges in current applications

Lung cancer is emerging as a common malignancy worldwide,with non-small cell lung cancer(NSCLC)accounting for approximately 85%of all cases.Two-dimensional(2D)in vitro cell line cultures and animal models are currently used to study NSCLC.However,2D cell cultures fail to replicate the medication response and neoplastic heterogeneity of parental tumors.Animal models are expensive and require lengthy modeling cycles.The generation of in vitro three-dimensional(3D)tissue cultures called organoids,which exhibit multicellular,anatomical,and functional properties of real organs,is now achievable owing to advancements in stem cell culturing.The genetic,proteomic,morphological,and pharmacological characteristics of tumors are largely preserved in tumor organoids grown in vitro.The design and physiology of human organs can be precisely reconstructed in tumor organoids,opening new possibilities for complementing the use of animal models and studying human diseases.This review summarizes the development of NSCLC organoids and their applications in basic research,drug testing,immunotherapy,and individualized treatments.