Astrocytes are a crucial type of glial cells in the central nervous system, not only maintaining brain homeostasis, but also actively participating in the transmission of information within the brain. Astrocytes have a complex structure that includes the soma, various levels of processes, and end-feet. With the advancement of genetically encoded calcium indicators and imaging technologies, researchers have discovered numerous localized and small calcium activities in the fine processes and end-feet. These calcium activities were termed as microdomain calcium activities, which significantly differ from the calcium activities in the soma and can influence the activity of local neurons, synapses, and blood vessels. This article elaborates the detection and analysis, characteristics, sources, and functions of microdomain calcium activities, and discusses the impact of aging and neurodegenerative diseases on these activities, aiming to enhance the understanding of the role of astrocytes in the brain and to provide new insights for the treatment of brain disorders.
Astrocytes/cytology* ; Humans ; Animals ; Calcium/metabolism* ; Calcium Signaling/physiology* ; Brain/physiology* ; Aging/physiology* ; Membrane Microdomains/physiology* ; Neurodegenerative Diseases/physiopathology*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective:To observe the clinical efficacy of exercise-based acupuncture in treating ischemic stroke and its effects in improving the patient's motor function and daily living ability. Methods:A total of 106 patients with motor dysfunction due to cerebral infarction were randomized into a trial group and a control group,each consisting of 53 cases.Both groups received conventional rehabilitation;in addition,the control group was given point-toward-point acupuncture at scalp points,and the trial group was offered exercise-based acupuncture,3 times weekly for 4 consecutive weeks.Before treatment,after 2 and 4 weeks of treatment,and at the 2-month follow-up,the Fugl-Meyer assessment(FMA)scale,Lovett scale for muscle strength,modified Ashworth scale(MAS),and activities of daily living(ADL)scale were used to assess the patient's motor function,muscle strength,muscle tension,and daily living ability. Results:After treatment,both groups gained improvements in motor function and daily living ability;after 4-week treatment and at the 2-month follow-up,the trial group had higher FMA and ADL scores than the control group(P<0.05).The MAS score decreased after treatment in both groups;after 2 and 4 weeks of treatment and at the 2-month follow-up,the MAS score was lower in the trial group than in the control group(P<0.05).After the intervention,the Lovett score increased in both groups;after 4 weeks of treatment,the Lovett score was higher in the trial group than in the control group(P<0.05). Conclusion:Based on routine rehabilitation,exercise-based acupuncture and scalp point-toward-point acupuncture both can improve the motor function and daily living ability in ischemic stroke patients;exercise-based acupuncture performs better than scalp point-toward-point acupuncture.

Objective To investigate the effect of injection volume on clinical efficacy after minimally invasive puncture and drainage in the treatment of moderate basal ganglia cerebral hemorrhage underlying controlling the dosage of drugs in the elderly.Methods After successfully inserting the puncture needle into the center point in the largest layer long axis,the liquid hematoma was aspirated,and 40,000 units urokinase was injected into the hematoma cavity twice a day(2 mL in the small volume Group(SG),and 4 mL in the large volume group(LG),respectively).The needle were then adjusted and removed according to the hematoma clearance.The clearance rate of hematoma,intracranial pressure,edema volume,mortality,incidence of complications,neurological deficit score(NDS)and activities of daily living(ADL)were compared and analyzed.Results There were no significant differences in the first hematoma clearance rate,postoperative ICP and mortality between the two groups(P>0.05).Comparing to the SG,there was a relative higher postoperative hematoma clearance rate and lower volume of perihematoma edema in the LG(P<0.05).Meanwhile,the needle retention time,urokinase usage and cumulative complications at 28 days after operation were lower than in the SG(P<0.05).For two parameters representing long-term outcome,the NDS and ADL scores were much better in LG than in SG(P<0.05).Conclusion Large volume injection can effectively drain the hematoma,shorten the needle retention time,reduce the usage of urokinase,decrease the incidence of postoperative complications and improve the prognosis of patients,thereby providing effective and safe method in treating moderate basal ganglia cerebral hemorrhage in the elderly.

Objective:To evaluate the efficacy and side effects of venetoclax combined with azacitidine chemotherapy in the treatment of previously untreated adult patients with acute myeloid leukemia(AML).Methods:A retrospective analysis was performed on 48 untreated adult AML patients admitted to the Department of Hematology,Affiliated Hospital of Jinggangshan University from January 2020 to December 2022.Among them,26 patients received venetoclax combined with azacitidine chemotherapy(observation group),and 22 patients received daunorubicin plus cytarabine chemotherapy(control group).The differences in complete response(CR)rate,objective response rate(ORR),progression-free survival(PFS),overall survival(OS)and adverse reactions(AR)were compared between the two groups.Results:There was no significant difference in age,sex ratio,absolute value of tri-lineage cell and proportion of bone marrow primordial cells between the two groups before treatment(all P＞0.05).The CR rate and the ORR rate of the observation group was significantly higher than that of the control group(P＜0.05).After treatment,there were no significant difference in the adverse reactions such as myelosuppression,granulocytosis,secondary infection,mucosal damage,liver and kidney damage,cardiotoxicity and gastrointestinal toxicity between the two groups(P＞0.05).The median PFS and the median OS of the observation group were significantly better than those of the control group(P＜0.05).Conclusion:The remission rate of venetoclax combined with azacitidine was higher than that of conventional chemotherapy in previously untreated adult acute myeloid leukemia.Venetoclax combined with azacitidine chemotherapy could reduce hematologic related side reactions and prolong the remission period and survival of AML patients.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Objective:To investigate the cause of death, survival time, and risk factors in patients diagnosed with Alzheimer′s disease (AD) at memory clinic.Methods:The patients with AD were enrolled from the memory clinic at Huashan Hospital, Fudan University between August 2002 and December 2006. Baseline data were collected and 7 rounds of telephone follow-up visits were conducted to track clinical outcomes. For death cases, the date and cause of death were recorded. Patients were divided into several subgroups based on gender and baseline cognition [Mini-Mental State Examination (MMSE) score]. Kaplan-Meier analysis and Cox proportional hazards regression models were constructed to analyze the survival time of patients and identify the risk factors.Results:A total of 499 patients were enrolled, including 199 males and 300 females. The follow-up time was 5.5(3.4,7.4) years, with longest follow-up time of 19.3 years. The median survival time after symptom onset was 11.8 years (95% CI 10.2-13.4 years), which was 12.4 years (95% CI 11.2-13.5 years) in females, significantly longer than that in males (10.2 years, 95% CI 9.6-10.8 years, logrank test, P=0.010). The median survival time after diagnosis was 8.3 years (95% CI 7.3-9.4 years), which was 8.8 years (95% CI 6.9-10.6 years) for women, significantly longer than that for men (6.8 years, 95% CI 5.7-7.9 years, logrank test, P=0.001). Patients with baseline MMSE scores≥15 ( n=265) had a median survial of 11.4 years (95% CI 9.5-13.2 years), significantly longer than those with poorer cognitive function (baseline MMSE scores<15; n=234, 7.4 years, 95% CI 6.4-8.4 years, logrank test, P<0.001). Multivariable Cox proportional hazards regression analysis showed that aging ( HR=1.027, 95% CI 1.002-1.052, P=0.034), lower body mass index (BMI; HR=1.081, 95% CI 1.023-1.139, P=0.007), lower baseline MMSE score ( HR=1.056, 95% CI 1.026-1.086, P<0.001), diabetes ( HR=1.716, 95% CI 1.076-2.735, P=0.023), and history of falls ( HR=1.536,95% CI 1.007-2.341, P=0.046) were independent risk factors for death (all P<0.05). During the follow-up, 224 of the participants died. Except for 62 cases of unknown reason, the top 6 causes of death were pneumonia (39 cases, 24.1%), cerebrovascular disease (24 cases, 14.8%), circulatory system disease(21 cases, 13.0%), multi-organ failure (17 cases, 10.5%), tumor (13 cases, 8.0%), eating disorders and malnutrition (13 cases, 8.0%). Conclusions:In the current study, the median survival time after onset for patients with AD was 11.8 years; aging, lower BMI, lower baseline cognition, comorbidities, and history of falls were independent risk factors for death; pneumonia was the most common cause of death.

Objective:To preliminarily investigate the applicability of a poliovirus pseudovirus-based neutralization assay in evaluating the immunogenicity of recombinant poliovirus vaccines and their in vivo potency in rats. Methods:Serum samples from rats immunized with recombinant poliovirus vaccines were tested using both the pseudovirus neutralization assay and the live-virus neutralization assay with Sabin strain. The consistency and correlation of the two methods were analyzed using the Kappa test and Spearman′s rank correlation.Results:For the neutralizing antibodies against typeⅠ, Ⅱ, and Ⅲ polioviruses, the Kappa values for consistency analysis of the two methods were 0.914, 1.000, and 0.751, respectively ( P<0.001), and the correlation coefficients ( R values) were 0.833, 0.927, and 0.859, respectively ( P<0.001). Conclusions:The test results of the two methods are consistent and show a good correlation, indicating that the pseudovirus neutralization assay can be applied to evaluating the immunogenicity of poliovirus vaccines and also can be used in rat potency tests.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective To investigate the protective effect of herba artemisiae scopariae extract on multidrug resistance protein 3(MDR3)gene mutation-induced neonatal parenteral nutrition-associated cholestasis(PNAC)and its possible mechanism.Methods ①Human primary hepatocytes were treated with cell culture in vitro,CRISPR/Cas9 lentivirus infection and MDR3 mutant gene lead-in.The levels of hepatic and biliary biochemical indexes[alanine transaminase(ALT),aspartate transaminase(AST),total bilirubin(TBil),direct bilirubin(DBil),indirect bilirubin(IBil),total bile acid(TBA)]in the supernatant of hepatocytes before and after 16,32,48 hours were compared to determine the time required for fatty acid induction of PNAC hepatocyte model with MDR3 gene mutation.② Human primary hepatocytes were divided into blank control group,MDR3 gene wild type group,MDR3 gene mutation group,and herba artemisiae scopariae extract intervention group according to random number table method.The blank control group was treated with culture medium only,the MDR3 gene wild type group was infected with lentivirus and mixed with wild type MDR3 gene and culture medium,the MDR3 gene mutation group was infected with lentivirus and cultured in culture medium with the mutant genes lead-in of LV-MDR3KI(c.485T>A,c.2793insA,c.1031G>A,c.3347G>A)mutation,while the MDR3 mutant gene was lead-in by lentivirus infection and cultured in culture medium,and then pretreated with 100 g/L herba artemisiae scopariae extract in the herba artemisiae scopariae extract intervention group,then the four groups of hepatocytes were induced with 1%fat emulsion,and the treatment time was the time needed to construct the PNAC hepatocytes model with MDR3 gene mutation.The levels of ALT,AST,TBil,DBil,IBil and TBA in the supernatant of hepatocytes were measured by enzyme-linked immunosorbent assay(ELISA).The mRNA expression abundance of adenosine triphosphate binding cassette proteins(ABCB4,ABCB11,ABCC2,ABCC3,ABCC4)encoding MDR3,bile salt export pump(BSEP),multidrug resistance associated protein(MRP)2-4,and tumor necrosis factor-α(TNF-α)genes were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Results Compared to the blank control group and MDR3 gene wild type group,there was no significant difference in the levels of ALT,AST,TBil,DBil,IBil,TBA in the supernatant of MDR3 gene mutant group before and 16 hours after induction with 1%fat emulsion,however after treated with 1%fat emulsion for 32 hours and 48 hours,the levels of ALT,AST,TBil,DBil,IBil,TBA in the supernatant of MDR3 mutant hepatocytes were significantly increased(P<0.05),consequently the time required for fatty acid induction of PNAC hepatocyte model was 32 hours.At 32 hours after treatment with fat emulsion,the levels of ALT,AST,TBil,DBil,TBA in the supernatant of hepatocytes in the herba artemisiae scopariae extract intervention group were significantly decreased[ALT(ng/L):148.3±2.3 vs.164.9±7.0,AST(ng/L):2767.4±78.8 vs.3239.4±107.1,TBil(μmol/L):7.6±0.2 vs.13.6±0.3,DBil(μmol/L):1.8±0.1 vs.5.7±0.2,TBA(μmol/L):3.4±0.2 vs.6.7±0.1,all P<0.05].The ABCB4,ABCC2,ABCC3,ABCC4 mRNA expression of MDR3,MRP2,MRP3,MRP4 in the blank control group,MDR3 wild type group,MDR3 gene mutation group and the herba artemisiae scopariae extract intervention group had no significant difference.The expression of TNF gene mRNA was highly expressed in MDR3 gene mutation group(2-??Ct:1.258±0.200 vs.1.001±0.052),and was low expressed in the herba artemisiae scopariae extract intervention group(2-??Ct:0.387±0.247 vs.1.258±0.200),and there was a significant difference between the two groups(both P<0.05).Compared to the MDR3 gene mutation group,the ABCB11 gene encoding BSEP mRNA expression in the herba artemisiae scopariae extract intervention group was significantly increased(2-??Ct:2.955±0.479 vs.1.333±0.529,P<0.05).Conclusion The herba artemisiae scopariae extract has a protective effect on PNAC induced by MDR3 gene mutation,which may be related to antagonizing inflammatory reaction,decreasing the expression of TNF mRNA and improving the expression of ABCB11 gene encoding BSEP.