MANAGEMENT OF MENEERE'S DISEASE—THE BEIJING TIANTAN HOSPITAL EXPERIENCE

Objective To report outcomes of nonsurgical and surgical management of Menire＇s disease at Beijing Tiantan Hospital. Methods Patients with Menire＇s disease were categorized into groups based on hearing and quality of life. Individualized management was provided, including life style modification, drug therapies, endolymphatic sac decompression and labyrin- thectomy. Treatment outcomes were evaluated during up to 24 months follow up. Results Eighty seven patients underwent life style modification and drug therapies. The vertigo control rate of Grade A and B was 76.9% and 83.8% respectively. Six patients received surgical management, including endolymphatic sac decompression （n = 5） and labyrinthecto- my （n = 1）. For these patients, the vertigo control rate of Grade A and B was 80% and 100%, respectively. Conclu- lsions Management of Meni6re＇s disease depends on several factors, i.e. severities of vertigo and hearing loss, quality of life, surgical contraindications and patient subjective desire. The treatment is drug therapies for the majority of patients, as well as life style modification. Surgical indications are rare and the least invasive procedures should be considered first. The results of surgery are generally satisfying.

Epidemiological characteristics of central nervous system tumors in children: a 5-year review of 3180 cases from Beijing Tiantan Hospital

Background:To describe the epidemiological characteristics of central nervous system(CNS)tumors in children,based on the neurosurgery department of Beijing Tiantan Hospital.Methods:From January 2015 to December 2019,3180 children were histopathologically diagnosed with CNS tumors based on the 2016 World Health Organization(WHO)classification of tumors.Patients were 0 to 15 years old.We analyzed age-related gender preferences,tumor locations,and the histological grades of the tumors.In addition,the epidemiological characteristics of the five most common intracranial tumors were compared to the previous studies.Results:In this study,intracranial and spinal tumors account for 96.4%(3066)and 3.6%(114)of all tumors,with a preponderance of supratentorial tumors(57.9%).Among all pediatric patients,low-grade tumors comprise 67.1%(2135).The integral gender ratio of males to females is 1.47:1 and the average age of patients is 7.59 years old.The five most common intracranial tumors are craniopharyngioma(15.4%),medulloblastoma(14.3%),pilocytic astrocytoma(11.8%),diffuse astrocytoma(9.8%),and anaplastic ependymoma(4.8%).Conclusions:Due to the lack of national data on childhood brain tumors,we used a large nationally representative population sample based on the largest pediatric neurosurgery center in China.We analyzed the data of the past 5 years,reflecting the incidence of CNS tumors in Chinese children to a certain extent,and laying a data foundation for subsequent clinical studies.

Providing uninterrupted care during COVID-19 pandemic: experience from Beijing Tiantan Hospital

background The COVID-19 pandemic has already stressed the healthcare system in the world.Many hospitals have been overwhelmed by the large number of patients with COVID-19.Due to the shortage of equipment and personnel and the highly contagious nature of COVID-19,many other healthcare services are on hold.However,at Beijing Tiantan Hospital,a rapid response system has been in place so that routine care is not interrupted.We,therefore,would like to share our hospital-wide prevention and management policy during this pandemic to help other healthcare systems to function in this crisis.Method Tiantan hospital is one of the leading neuroscience institutions in the world.With 1650 beds,its annual inpatient admission exceeds 30000 patients.Its COVID-19 rapid response policy was reviewed for its functionality.results There are nine key components of this policy:an incident management system;a comprehensive infection prevention and control,outpatient triage and flow system;a designated fever clinic;patient screening and administration;optimised surgical operations,enhanced nucleic acid testing;screening of returning employees;and a supervision and feedback system.In addition,a specific protocol was designed for treating patients with acute stroke.Conclusion A comprehensive policy is helpful to protect the employee from infection and to provide quality and uninterrupted care to all who need these,including patients with acute ischaemic stroke.

Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.

Association of DNA methylation/demethylation with the functional outcome of stroke in a hyperinflammatory state

Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke and has an important role in the functional outcome of hyperinflammatory stroke.

Efficacy and safety of percutaneous transhepatic biliary radiofrequency ablation in patients with malignant obstructive jaundice

BACKGROUND Percutaneous transhepatic cholangiodrainage(PTCD)and endoscopic retrograde cholangiopancreatography/endoscopic nasobiliary drainage are the most common clinical procedures for jaundice control in patients with unresectable malignant obstructive jaundice,yet the safety and effect of endobiliary radiofrequency ablation(EB-RFA)combined PTCD is rarely reported,in this article,we report our experience of EB-RFA combined PTCD in such patients.AIM To retrospectively study the efficacy and safety of EB-RFA combined PTCD in patients with unresectable malignant obstructive jaundice.METHODS Patients with unresectable malignant obstructive jaundice treated with EB-RFA under PTCD were selected,the bile ducts of the right posterior lobe was selected as the target bile ducts in all cases.The general conditions of all patients,preoperative tumour markers,total bilirubin(TBIL),direct bilirubin(DBIL),albumin(ALB),alkaline phosphatase(ALP),and glutamyl transferase(GGT)before and on the 7th day after the procedure,as well as perioperative complications,stent patency time and patient survival were recorded.RESULTS All patients successfully completed the operation,TBIL and DBIL decreased significantly in all patients at the 7th postoperative day(P=0.009 and 0.006,respectively);the values of ALB,ALP and GGT also decreased compared with the preoperative period,but the difference was not statistically significant.Perioperative biliary bleeding occurred in 2 patients,which was improved after transfusion of blood and other conservative treatments,pancreatitis appeared in 1 patient after the operation,no serious complication and death happened after operation.Except for 3 patients with loss of visits,the stent patency rate of the remaining 14 patients was 100%71%and 29%at the 1^(st),3^(rd),and 6^(th)postoperative months respectively,with a median survival of 4 months.CONCLUSION EB-RFA under PTCD in patients with unresectable malignant obstructive jaundice has a satisfactory therapeutic effect and high safety,which is worthy of further clinical practice.

Melatonin improves synapse development by PI3K/Akt signaling in a mouse model of autism spectrum disorder

Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrated to exhibit decreased density of dendritic spines.The role of melatonin,as a neuro hormone capable of effectively alleviating social interaction deficits and regulating the development of dendritic spines,in Ctnnd2 deletion-induced nerve injury remains unclea r.In the present study,we discove red that the deletion of exon 2 of the Ctnnd2 gene was linked to social interaction deficits,spine loss,impaired inhibitory neurons,and suppressed phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) signal pathway in the prefrontal cortex.Our findings demonstrated that the long-term oral administration of melatonin for 28 days effectively alleviated the aforementioned abnormalities in Ctnnd2 gene-knockout mice.Furthermore,the administration of melatonin in the prefro ntal cortex was found to improve synaptic function and activate the PI3K/Akt signal pathway in this region.The pharmacological blockade of the PI3K/Akt signal pathway with a PI3K/Akt inhibitor,wo rtmannin,and melatonin receptor antagonists,luzindole and 4-phenyl-2-propionamidotetralin,prevented the melatonin-induced enhancement of GABAergic synaptic function.These findings suggest that melatonin treatment can ameliorate GABAe rgic synaptic function by activating the PI3K/Akt signal pathway,which may contribute to the improvement of dendritic spine abnormalities in autism spectrum disorders.

Single-cell analysis of tumor microenvironment and cell adhesion reveals that interleukin-1 beta promotes cancer cell proliferation in breast cancer

Background: Triple-negative breast cancer(TNBC), which is so called because of the lack of estrogen receptors(ER), progesterone receptors(PR), and human epidermal growth factor receptor 2(HER2) receptors on the cancer cells, accounts for 10%–15% of all breast cancers. The heterogeneity of the tumor microenvironment is high.However, the role of plasma cells controlling the tumor migration progression in TNBC is still not fully understood.Methods: We analyzed single-cell RNA sequencing data from five HER2 positive, 12ER positive/PR positive, and nine TNBC samples. The potential targets were validated by immunohistochemistry.Results: Plasma cells were enriched in TNBC samples, which was consistent with validation using data from The Cancer Genome Atlas. Cell communication analysis revealed that plasma cells interact with T cells through the intercellular adhesion molecule 2–integrin–aLb2 complex, and then release interleukin 1 beta(IL1B), as verified by immunohistochemistry, ultimately promoting tumor growth.Conclusion: Our results revealed the role of plasma cells in TNBC and identified IL1B as a new prognostic marker for TNBC.

High-dose dexamethasone regulates microglial polarization via the GR/JAK1/STAT3 signaling pathway after traumatic brain injury

Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.

China stroke surveillance report 2021

Since 2015,stroke has become the leading cause of death and disability in China,posing a significant threat to the health of its citizens as a major chronic non-communicable disease.According to the China Stroke High-risk Population Screening and Intervention Program,an estimated 17.8 million[95%confidence interval(CI)17.6–18.0million]adults in China had experienced a stroke in 2020,with 3.4 million(95%CI 3.3–3.5 million)experiencing their first-ever stroke and another 2.3 million(95%CI 2.2–2.4 million)dying as a result.Additionally,approximately 12.5%(95%CI 12.4%–12.5%)of stroke survivors were left disabled,as defined by a modified Rankin Scale score greater than 1,equating to 2.2 million(95%CI 2.1–2.2 million)stroke-related disabilities in 2020.As the population ages and the prevalence of risk factors like diabetes,hypertension,and hyperlipidemia continues to rise and remains poorly controlled,the burden of stroke in China is also increasing.A large national epidemiological survey initiated by the China Hypertension League in 2017 showed that the prevalence of hypertension was 24.7%;the awareness,treatment,and control rates in hypertensive patients were:60.1%,42.5%,and 25.4%,respectively.A nationally representative sample of the Chinese mainland population showed that the weighted prevalence of total diabetes diagnosed by the American Diabetes Association criteria was 12.8%,suggesting there are 120 million adults with diabetes in China,and the awareness,treatment,and control rates in diabetic patients were:43.3%,49.0%,and 49.4%,respectively.The“Sixth National Health Service Statistical Survey Report in 2018”showed that the proportion of the obese population in China was 37.4%,an increase of 7.2 points from 2013.Data from 1599 hospitals in the Hospital Quality Monitoring System and Bigdata Observatory Platform for Stroke of China(BOSC)showed that a total of 3,418,432 stroke cases[mean age±standard error(SE)was(65.700±0.006)years,and 59.1%were male]were admitted during 2020.Of those,over 80.0%(81.9%)were ischemic stroke(IS),14.9%were intracerebral hemorrhage(ICH)strokes,and 3.1%were subarachnoid hemorrhage(SAH)strokes.The mean±SE of hospitalization expenditures was Chinese Yuan(CNY)(16,975.6±16.3),ranging from(13,310.1±12.8)in IS to(81,369.8±260.7)in SAH,and out-of-pocket expenses were(5788.9±8.6),ranging from(4449.0±6.6)in IS to(30,778.2±156.8)in SAH.It was estimated that the medical cost of hospitalization for stroke in 2020 was CNY 58.0 billion,of which the patient pays approximately CNY 19.8 billion.In-hospital death/discharge against medical advice rate was 9.2%(95%CI 9.2%–9.2%),ranging from 6.4%(95%CI 6.4%–6.5%)for IS to 21.8%(95%CI 21.8%–21.9%)for ICH.From 2019 to 2020,the information about 188,648 patients with acute IS receiving intravenous thrombolytic therapy(IVT),49,845 patients receiving mechanical thrombectomy(MT),and 14,087 patients receiving bridging(IVT+MT)were collected through BOSC.The incidence of intracranial hemorrhage during treatment was 3.2%(95%CI 3.2%–3.3%),7.7%(95%CI 7.5%–8.0%),and 12.9%(95%CI 12.3%–13.4%),respectively.And in-hospital death/discharge against medical advice rate was 8.9%(95%CI 8.8%–9.0%),16.5%(95%CI 16.2%–16.9%),and 16.8%(95%CI 16.2%–17.4%),respectively.A prospective nationwide hospital-based study was conducted at 231 stroke base hospitals(Level III)from 31 provinces in China through BOSC from January 2019to December 2020 and 136,282 stroke patients were included and finished 12-month follow-up.Of those,over 86.9%were IS,10.8%were ICH strokes,and 2.3%were SAH strokes.The disability rate[%(95%CI)]in survivors of stroke at 3-month and 12-month was 14.8%(95%CI 14.6%–15.0%)and 14.0%(95%CI 13.8%–14.2%),respectively.The mortality rate[%(95%CI)]of stroke at 3-month and 12-month was 4.2%(95%CI 4.1%–4.3%)and 8.5%(95%CI 8.4%–8.6%),respectively.The recurrence rate[%(95%CI)]of stroke at 3-month and 12-month was 3.6%(95%CI 3.5%–3.7%)and 5.6%(95%CI 5.4%–5.7%),respectively.The Healthy China 2030 Stroke Action Plan was launched as part of this review,and the above data provide valuable guidelines for future stroke prevention and treatment efforts in China.

Key Genes Involved in the Beneficial Mechanism of Hyperbaric Oxygen for Glioblastoma and Predictive Indicators of Hyperbaric Oxygen Prolonging Survival in Glioblastoma Patients

Objective The prognosis of glioblastoma is poor,and therapy-resistance is largely attributed to intratumor hypoxia.Hyperbaric oxygen(HBO)effectively alleviates hypoxia.However,the sole role of HBO in glioblastoma remains controversial.We previously reported that HBO can promote apoptosis,shorten protrusions,and delay growth of glioblastoma,but the molecular mechanism is unclear.We aimed to test candidate genes in HBO-exposed glioblastoma cells and to analyze their correlation with the survival of glioblastoma patients.Methods Glioblastoma cell lines exposed to repetitive HBO or normobaric air(NBA)were collected for RNA isolation and microarray data analysis.GO analysis,KEGG pathway analysis and survival analysis of the differentially expressed genes(DEGs)were performed.Results HBO not only inhibited hypoxia-inducing genes including CA9,FGF11,PPFIA4,TCAF2 and SLC2A12,but also regulated vascularization by downregulating the expression of COL1A1,COL8A1,COL12A1,RHOJ and FILIP1L,ultimately attenuated hypoxic microenvironment of glioblastoma.HBO attenuated inflammatory microenvironment by reducing the expression of NLRP2,CARD8,MYD88 and CD180.HBO prevented metastasis by downregulating the expression of NTM,CXCL12,CXCL13,CXCR4,CXCR5,CDC42,IGFBP3,IGFBP5,GPC6,MMP19,ADAMTS1,EFEMP1,PTBP3,NF1 and PDCD1.HBO upregulated the expression of BAK1,PPIF,DDIT3,TP53I11 and FAS,whereas downregulated the expression of MDM4 and SIVA1,thus promoting apoptosis.HBO upregulated the expression of CDC25A,MCM2,PCNA,RFC33,DSCC1 and CDC14A,whereas downregulated the expression of ASNS,CDK6,CDKN1B,PTBP3 and MAD2L1,thus inhibiting cell cycle progression.Among these DEGs,17 indicator-genes of HBO prolonging survival were detected.Conclusions HBO is beneficial for glioblastoma.Glioblastoma patients with these predictive indicators may prolong survival with HBO therapy.These potential therapeutic targets especially COL1A1,ADAMTS1 and PTBP3 deserve further validation.

Analysis of long-term outcome of modified gastric bypass for type 2 diabetes mellitus in Chinese patients

BACKGROUND Bariatric and metabolic surgery have been routinely performed following the rapid increase in obesity and metabolic diseases worldwide.Of all evolving procedures,Roux-en-Y gastric bypass(RYGB)is considered the gold standard for surgical treatment of patients with type 2 diabetes mellitus(T2DM)and obesity.RYGB was introduced in China nearly 20 years ago,but the number of RYGB surgeries only accounts for 3.1%of the total number of weight loss and metabolic surgeries in China,it’s effect on Chinese people still needs further study.AIM To investigate the effect and safety of a modified gastric bypass performed in Chinese patients with T2DM.METHODS Patients with obesity and T2DM who underwent modified gastric bypass,with>5-year follow-up data,were analyzed.RESULTS All 37 patients underwent uneventful laparoscopic surgery,no patient was switched to laparotomy during the surgery,and no severe complications were reported.Average weight and body mass index of the patients reduced from 84.6±17.3(60.0–140.0)kg and 30.9±5.0(24.7–46.2)kg/m2 to 67.1±12.2(24.7–46.2)kg and 24.6±3.9(17.7–36.5)kg/m2,respectively,and fasting plasma glucose and glycated hemoglobin decreased from 7.4±3.4 mmol/L and 8.2%±1.7%preoperatively to 6.5±1.3 mmol/L and 6.5%±0.9%5-years postoperatively,respectively.Only 29.7%(11/37)of the patients used hypoglycemic drugs 5-years postoperatively,and the complete remission rate of T2DM was 29.7%(11/37).Triglyceride level reduced significantly but high-density lipoprotein increased significantly(both P<0.05)compared with those during the preoperative period.Liver and renal function improved significantly postoperatively,and binary logistic regression analysis revealed that the patients’preoperative history of T2DM and fasting C-peptide were significant prognostic factors influencing complete T2DM remission after RYGB(P=0.006 and 0.012,respectively).CONCLUSION The modified gastric bypass is a safe and feasible procedure for Chinese patients with obesity and T2DM,exhibiting satisfactory amelioration of weight problems,hyperglycemia,and combination disease.

Rbm8a regulates neurogenesis and reduces Alzheimer's disease-associated pathology in the dentate gyrus of 5×FAD mice

Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hippocampal neurogenesis.Neurogenesis in the hippocampal dentate gyrus is likely to persist throughout life but declines with aging,especially in Alzheimer’s disease.Recent evidence indicated that RNA-binding protein 8A(Rbm8a)promotes the proliferation of neural progenitor cells,with lower expression levels observed in Alzheimer’s disease patients compared with healthy people.This study investigated the hypothesis that Rbm8a overexpression may enhance neurogenesis by promoting the proliferation of neural progenitor cells to improve memory impairment in Alzheimer’s disease.Therefore,Rbm8a overexpression was induced in the dentate gyrus of 5×FAD mice to validate this hypothesis.Elevated Rbm8a levels in the dentate gyrus triggered neurogenesis and abated pathological phenotypes(such as plaque formation,gliosis reaction,and dystrophic neurites),leading to ameliorated memory performance in 5×FAD mice.RNA sequencing data further substantiated these findings,showing the enrichment of differentially expressed genes involved in biological processes including neurogenesis,cell proliferation,and amyloid protein formation.In conclusion,overexpressing Rbm8a in the dentate gyrus of 5×FAD mouse brains improved cognitive function by ameliorating amyloid-beta-associated pathological phenotypes and enhancing neurogenesis.

Silencing of Jumonji domain-containing 1C inhibits the osteogenic differentiation of bone marrow mesenchymal stem cells via nuclear factor-κB signaling

BACKGROUND Osteoporosis is a common metabolic bone disorder induced by an imbalance between osteoclastic activity and osteogenic activity.During osteoporosis,bone mesenchymal stem cells(BMSCs)exhibit an increased ability to differentiate into adipocytes and a decreased ability to differentiate into osteoblasts,resulting in bone loss.Jumonji domain-containing 1C(JMJD1C)has been demonstrated to suppress osteoclastogenesis.AIM To examine the effect of JMJD1C on the osteogenesis of BMSCs and the potential underlying mechanism.METHODS BMSCs were isolated from mouse bone marrow tissues.Oil Red O staining,Alizarin red staining,alkaline phosphatase staining and the expression of adipo-genic and osteogenic-associated genes were assessed to determine the differen-tiation of BMSCs.Bone marrow-derived macrophages(BMMs)were incubated with receptor activator of nuclear factor-kappaΒligand to induce osteoclast differentiation,and osteoclast differen-tiation was confirmed by tartrate-resistant acid phosphatase staining.Other related genes were measured via reverse transcription coupled to the quantitative polymerase chain reaction and western blotting.Enzyme-linked immunosorbent assays were used to measure the levels of inflammatory cytokines,including tumor necrosis factor alpha,interleukin-6 and interleukin-1 beta.RESULTS The osteogenic and adipogenic differentiation potential of BMSCs isolated from mouse bone marrow samples was evaluated.JMJD1C mRNA and protein expression was upregulated in BMSCs after osteoblast induction,while p-nuclear factor-κB(NF-κB)and inflammatory cytokines were not significantly altered.Knockdown of JMJD1C repressed osteogenic differentiation and enhanced NF-κB activation and inflammatory cytokine release in BMSCs.Moreover,JMJD1C expression decreased during BMM osteoclast differentiation.CONCLUSION The JMJD1C/NF-κB signaling pathway is potentially involved in BMSC osteogenic differentiation and may play vital roles in the pathogenesis of osteoporosis.

Ki-67 Change in Anthracyline-containing Neoadjuvant Chemotherapy Response in Breast Cancer

Objective Anthracycline-containing regimens are irreplaceable in neoadjuvant chemotherapy(NAC)for breast cancer(BC)at present.However,30% of early breast cancer(EBC)patients are resistant to anthracycline-containing chemotherapy,leading to poor prognosis and higher mortality.Ki-67 is associated with the prognosis and response to therapy,and it changes after NAC.Methods A total of 105 BC patients who received anthracycline-containing NAC were enrolled.Then,the optimal model of Ki-67 was selected,and its predictive efficacy was analyzed.Immunohistochemistry(IHC)was used to determine the estrogen receptor(ER),progesterone receptor(PR),and human epidermal growth factor receptor 2(HER-2)status and Ki-67 level.Fluorescent in situ hybridization(FISH)was used to verify the HER-2 when the IHC score was 2+.Results The post-NAC Ki67 level after treatment with anthracycline drugs was lower than pre-NAC Ki-67(19.6%±23.3%vs.45.6%±23.1%,P<0.001).Furthermore,patients with the Ki-67 decrease had a border line higher pathological complete response(pCR)rate(17.2%vs.0.0%,P=0.068),and a higher overall response rate(ORR)(73.6%vs.27.8%,P<0.001),when compared to patients without the Ki-67 decrease.The ΔKi-67 and ΔKi-67%were valuable markers for the prediction of both the pCR rate and ORR.The area under the curve(AUC)for ΔKi-67 on pCR and ORR was 0.809(0.698-0.921)and 0.755(0.655-0.855),respectively,while the AUC for ΔKi-67% on pCR and ORR was 0.857(0.742-0.972)and 0.720(0.618-0.822),respectively.Multivariate logistic regression model 1 revealed thatΔKi-67 was an independent predictor for both pCR[odds ratio(OR)=61.030,95% confidence interval(CI)=4.709-790.965;P=0.002]and ORR(OR=10.001,95%CI:3.044-32.858;P<0.001).Multivariate logistic regression model 2 revealed thatΔKi-67%was also an independent predictor for both pCR(OR=408.922,95%CI=8.908-18771.224;P=0.002)and ORR(OR=5.419,95%CI=1.842-15.943;P=0.002).Conclusions The present study results suggest thatΔKi67 andΔKi67%are candidate predictors for anthracycline-containing NAC response,and that they may provide various information for further systematic therapy after surgery in clinical practice.

Celastrol inhibits inflammatory factors expression in glioblastoma

Background:Glioblastoma is one of the most common primary intracranial tumors of the central nervous system in adults.Although chemotherapy is an important component of glioblastoma treatment,its effectiveness remains unsatisfactory.Due to multiple immunosuppressive mechanisms,glioblastoma immunotherapy has not been effective in treating many patients as a result of the clinical breakthroughs in the field.Therefore,the development of cancer immunotherapy relies on the understanding of how tumors interact with the immune system and the analysis of their molecular determinants.This study identified the key interactions between immune cells in the glioma microenvironment using RNA microarrays and single-cell sequencing.Methods:First,we screened differentially expressed genes in tumor and control samples from GSE29796 and GSE50161 datasets using GEO2R.All differentially expressed genes were used to perform enrichment analysis and construct protein-protein interaction topological analysis to analyze the interaction between proteins.Using single-cell RNA sequencing data from the GSE162631 database,we identified immune cell types within the glioblastoma microenvironment,and validated the hub gene expression in these cells.In addition,based on the GEPIA and TIMER databases,hub genes were investigated and compared with immune infiltration to determine differential expression.Finally,CellChat was used to visualize the gene expression distribution and cell-to-cell communication analysis of the proteins between different types of cells.Results:We found that monocytes/macrophages may communicate with each other in the tumor microenvironment through MIF-(CD74+CXCR4)and MIF-(CD74+CD44).In addition,our study indicated that celastrol has the ability to inhibit inflammatory factors expression by MIF/CD74 signaling pathway in U87 cells.Conclusion:This study improved the effectiveness of cancer immunotherapy strategies and developed new ideas for immunotherapy that can be applied to glioblastoma.

Relationship of Retinal Nerve Fiber Layer Thickness and Retinal Vessel Calibers with Cognitive Impairment in the Asymptomatic Polyvascular Abnormalities Population

Objective Cognitive impairment(CI)in older individuals has a high morbidity rate worldwide,with poor diagnostic methods and susceptible population identification.This study aimed to investigate the relationship between different retinal metrics and CI in a particular population,emphasizing polyvascular status.Methods We collected information from the Asymptomatic Polyvascular Abnormalities Community Study on retinal vessel calibers,retinal nerve fiber layer(RNFL)thickness,and cognitive function of 3,785participants,aged 40 years or older.Logistic regression was used to analyze the relationship between retinal metrics and cognitive function.Subgroups stratified by different vascular statuses were also analyzed.Results RNFL thickness was significantly thinner in the CI group(odds ratio:0.973,95%confidence interval:0.953–0.994).In the subgroup analysis,the difference still existed in the non-intracranial arterial stenosis,non-extracranial carotid arterial stenosis,and peripheral arterial disease subgroups(P<0.05).Conclusion A thin RNFL is associated with CI,especially in people with non-large vessel stenosis.The underlying small vessel change in RNFL and CI should be investigated in the future.

Unraveling the complexities of adolescent depression:A call for action

The adolescent years are a period of profound change,both physically and psychologically.For many,these years are marked by excitement and exploration,but for others,they are fraught with challenges that can lead to significant mental health issues.Depression,in particular,has become an increasingly prevalent concern among adolescents worldwide,and its multifaceted etiology requires a comprehensive approach to understanding and intervention.A recent study on the relationships among negative life events,dysfunctional attitudes,social support,and depressive symptoms in Chinese adolescents offers valuable insights into the complex interplay between various factors contributing to adolescent depression.The authors explore a moderated mediation model to better understand how these factors interact with and contribute to the onset of depression.This article aims to delve into the key findings of the study,highlight its implications for clinical practice,and encourage further research in this critical area.

Ginger oil-loaded transdermal adhesive patch treats post-traumatic stress disorder

Objective:To find a viable alternative to reduce the number of doses required for the patients with post-traumatic stress disorder(PTSD),and to improve efficacy and patient compliance.Methods: In this study,we used ginger oil,a phytochemical with potential therapeutic properties,to prepare ginger oil patches.High-performance liquid chromatography(HPLC)was used to quantify the main active component of ginger oil,6-gingerol.Transdermal absorption experiments were conducted to optimize the various pressure-sensitive adhesives and permeation enhancers,including their type and concentration.Subsequently,the ginger oil patches were optimized and subjected to content determination and property evaluations.A PTSD mouse model was established using the foot-shock method.The therapeutic effect of ginger oil patches on PTSD was assessed through pathological sections,behavioral tests,and the evaluation of biomarkers such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),brain-derived neurotrophic factor(BDNF),and melatonin(MT).Results: The results demonstrated that ginger oil patches exerted therapeutic effects against PTSD by inhibiting inflammatory responses and modulating MT and BDNF levels.Pharmacokinetic experiments revealed that ginger oil patches maintained a stable blood drug concentration for at least one day,addressing the rapid metabolism drawback of 6-gingerol and enhancing its therapeutic efficacy.Conclusions: Ginger oil can be prepared as a transdermal drug patch that meets these requirements,and the bioavailability of the prepared patch is better than that of oral administration.It can improve PTSD with good patient compliance and ease of administration.Therefore,it is a promising therapeutic formulation for the treatment of PTSD.

Mental health and insomnia problems in healthcare workers after the COVID-19 pandemic:A multicenter cross-sectional study

BACKGROUND Healthcare workers(HCWs)are at increased risk of contracting coronavirus disease 2019(COVID-19)as well as worsening mental health problems and insomnia.These problems can persist for a long period,even after the pandemic.However,less is known about this topic.AIM To analyze mental health,insomnia problems,and their influencing factors in HCWs after the COVID-19 pandemic.METHODS This multicenter cross-sectional,hospital-based study was conducted from June 1,2023 to June 30,2023,which was a half-year after the end of the COVID-19 emergency.Region-stratified population-based cluster sampling was applied at the provincial level for Chinese HCWs.Symptoms such as anxiety,depression,and insomnia were evaluated by the Generalized Anxiety Disorder-7,Patient Health Questionnaire-9,and Insomnia Severity Index.Factors influencing the symptoms were identified by multivariable logistic regression.RESULTS A total of 2000 participants were invited,for a response rate of 70.6%.A total of 1412 HCWs[618(43.8%)doctors,583(41.3%)nurses and 211(14.9%)nonfrontline],254(18.0%),231(16.4%),and 289(20.5%)had symptoms of anxiety,depression,and insomnia,respectively;severe symptoms were found in 58(4.1%),49(3.5%),and 111(7.9%)of the participants.Nurses,female sex,and hospitalization for COVID-19 were risk factors for anxiety,depression,and insomnia symptoms;moreover,death from family or friends was a risk factor for insomnia symptoms.During the COVID-19 outbreak,most[1086(76.9%)]of the participating HCWs received psychological interventions,while nearly all[994(70.4%)]of them had received public psychological education.Only 102(7.2%)of the HCWs received individual counseling from COVID-19.CONCLUSION Although the mental health and sleep problems of HCWs were relieved after the COVID-19 pandemic,they still faced challenges and greater risks than did the general population.Identifying risk factors would help in providing targeted interventions.In addition,although a major proportion of HCWs have received public psychological education,individual interventions are still insufficient.