A distributed lag non-linear time-series study of ambient temperature and healthcare-associated infections in Hefei, China.

Little is known about the effects of temperature on healthcare-associated infections (HAIs). A distributed lag non-linear model was used to estimate the association between ambient temperature and HAIs in Hefei, China. In total, 9,592 HAIs were included. The effect of low temperature (-0.1°C, 2.5th percentile) was significant on the current day (RR = 1.108, 95%CI:1.003-1.222), and then appeared on the 4th day (RR = 1.045, 95%CI:1.007-1.084) and the 5th day (RR = 1.033, 95%CI:1.006-1.061). The cumulative lag effects of low temperature lasted from the 5th to 10th days (RR = 1.123-1.143), and a long-term cumulative lag effect was observed on the 14th day (RR = 1.157, 95%CI:1.001-1.338). The lag effect of high temperature (31.0°C, 97.5th percentile) was not statistically significant. However, the effects of temperatures on HAIs were not significant among gender or age subgroups. This study suggests that the low temperatures have acute and lag effects on HAIs in Hefei, China.

The modification of meteorological factors on the relationship between air pollution and periodontal diseases: an exploration based on different interaction strategies.

We aimed to characterize the association between air pollutants exposure and periodontal diseases outpatient visits and to explore the interactions between ambient air pollutants and meteorological factors. The outpatient visits data of several large stomatological and general hospitals in Hefei during 2015-2020 were collected to explore the relationship between daily air pollutants exposure and periodontal diseases by combining Poisson's generalized linear model (GLMs) and distributed lag nonlinear model (DLNMs). Subgroup analysis was performed to identify the vulnerability of different populations to air pollutants exposure. The interaction between air pollutants and meteorological factors was verified in both multiplicative and additive interaction models. An interquartile range (IQR) increased in nitrogen dioxide (NO2) concentration was associated with the greatest lag-specific relative risk (RR) of gingivitis at lag 3 days (RR = 1.087, 95% CI 1.008-1.173). Fine particulate matter (PM2.5) exposure also increased the risk of periodontitis at the day of exposure (RR = 1.049, 95% CI 1.004-1.096). Elderly patients with gingivitis and periodontitis were both vulnerable to PM2.5 exposure. The interaction analyses showed that exposure to high levels of NO2 at low temperatures was related to an increased risk of gingivitis, while exposure to high levels of NO2 and PM2.5 may also increase the risk of gingivitis and periodontitis in the high-humidity environment, respectively. This study supported that NO2 and PM2.5 exposure increased the risk of gingivitis and periodontitis outpatient visits, respectively. Besides, the adverse effects of air pollutants exposure on periodontal diseases may vary depending on ambient temperature and humidity.

Prevalence of infections and antimicrobial use among hemodialysis outpatients: A prospective multicenter study.

Hemodialysis patients are vulnerable to infectious diseases and frequent receipt of antimicrobial agents. The aim of this study was to describe the prevalence and characteristics of infections and antimicrobials use among hemodialysis outpatients. We utilized the dialysis event surveillance protocol developed by the National Healthcare Safety Network to conduct a prospective multicenter study in Anhui, China. A total of 41 dialysis centers involving 7393 outpatients were included. Fistula was the most common type of vascular access (85.3%), followed by tunneled central line (12.7%), and non-tunneled central line (1.2%). There were 118 dialysis events with an overall pooled events rate of 1.60 per 100 patient-months. Intravenous antimicrobial start, positive blood culture, and pus, redness, or increased swelling at the vascular access site were detected at rates of 0.91, 0.23, and 0.46 per 100 patient-months, respectively. The prevalence of dialysis events was commonly higher in patients with a central line, and lower in patients with a fistula. Hemodialysis outpatients also had the noteworthy risks of nonaccess infections. Older age, female gender, and having a central line were associated with the increased risk of dialysis events. Findings recommend that regular monitoring and improvement strategies are warranted in management of infections among hemodialysis outpatients.

An 8-year point-prevalence surveillance of healthcare-associated infections and antimicrobial use in a tertiary care teaching hospital in China.

Healthcare-associated infections (HAIs) are a major worldwide public-health problem, but less data are available on the long-term trends of HAIs and antimicrobial use in Eastern China. This study describes the prevalence and long-term trends of HAIs and antimicrobial use in a tertiary care teaching hospital in Hefei, Anhui, China from 2010 to 2017 based on annual point-prevalence surveys. A total of 12 505 inpatients were included; 600 HAIs were recorded in 533 patients, with an overall prevalence of 4.26% and a frequency of 4.80%. No evidence was found for an increasing or decreasing trend in prevalence of HAI over 8 years (trend χ2 = 2.15, P = 0.143). However, significant differences in prevalence of HAI were evident between the surveys (χ2 = 21.14, P < 0.001). The intensive care unit had the highest frequency of HAIs (24.36%) and respiratory tract infections accounted for 62.50% of all cases; Escherichia coli was the most common pathogen (16.67%). A 44.13% prevalence of antimicrobial use with a gradually decreasing trend over time was recorded. More attention should be paid to potential high-risk clinical departments and HAI types with further enhancement of rational antimicrobial use.

A prospective surveillance study of healthcare-associated infections in an intensive care unit from a tertiary care teaching hospital from 2012-2019.

Healthcare-associated infections (HAIs) continue to be the most common adverse event affecting critically ill inpatients in intensive care units (ICUs). Limited data exist in the English literature on the epidemiology of HAIs in ICUs from China. The purpose of this prospective study was to understand the prevalence and trends of HAIs in the ICU to guide clinicians to take effective prevention and control measures. In total, 20 ICU beds in the hospital from January 2012 to December 2019 were selected for surveillance. HAI diagnosis and device-associated infection surveillance were based on the criteria set forth by the original Ministry of Health of the People's Republic of China. The full-time staff for HAI management monitored all patients who stayed in the ICU > 48 hours during the study period and calculated the device utilization ratio and device-associated infection rate. The rate of HAIs and the adjusted rate were 18.78 per 1000 patient-days and 5.17 per 1000 patient-days, respectively. The rates of ventilator-associated pneumonias, catheter-associated urinary tract infections, and central line-associated bloodstream infections were 22.68 per 1000 device-days, 2.40 per 1000 device-days, and 2.27 per 1000 device-days, respectively. A total of 731 pathogenic bacteria were detected in the patients with HAIs. Gram-negative and gram-positive bacteria accounted for 67.44% and 16.83%, respectively. Continuous target monitoring, regular analysis of high-risk factors, and timely intervention measures could effectively reduce HAIs in the ICU. Additionally, these findings could be used for developing new strategies to prevent and control HAIs in ICUs.

Prevalence and risk factors for colonisation and infection with carbapenem-resistant Enterobacterales in intensive care units: A prospective multicentre study.

OBJECTIVES: This study aimed to investigate the prevalence and risk factors for carbapenem-resistant Enterobacterales colonisation/infection at admission and acquisition among patients admitted to the intensive care unit. RESEARCH METHODOLOGY/DESIGN: A prospective and multicentre study. SETTING: This study was conducted in 24 intensive care units in Anhui, China. MAIN OUTCOME MEASURES: Demographic and clinical data were collected, and rectal carbapenem-resistant Enterobacterales colonisation was detected by active screening. Multivariate logistic regression models were used to analyse factors associated with colonisation/infection with carbapenem-resistant Enterobacterales at admission and acquisition during the intensive care unit stay. RESULTS: There were 1133 intensive care unit patients included in this study. In total, 5.9% of patients with carbapenem-resistant Enterobacterales colonisation/infection at admission, and of which 56.7% were colonisations. Besides, 8.5% of patients acquired carbapenem-resistant Enterobacterales colonisation/infection during the intensive care stay, and of which 67.6% were colonisations. At admission, transfer from another hospital, admission to an intensive care unit within one year, colonisation/infection/epidemiological link with carbapenem-resistant Enterobacterales within one year, and exposure to any antibiotics within three months were risk factors for colonisation/infection with carbapenem-resistant Enterobacterales. During the intensive care stay, renal disease, an epidemiological link with carbapenem-resistant Enterobacterales, exposure to carbapenems and beta-lactams/beta-lactamase inhibitors, and intensive care stay of three weeks or longer were associated with acquisition. CONCLUSION: The prevalence of colonisation/infection with carbapenem-resistant Enterobacterales in intensive care units is of great concern and should be monitored systematically. Particularly for the 8.5% prevalence of carbapenem-resistant Enterobacterales acquisition during the intensive care stay needs enhanced infection prevention and control measures in these setting. Surveillance of colonisation/infection with carbapenem-resistant Enterobacterales at admission and during the patient's stay represents an early identification tool to prevent further transmission of carbapenem-resistant Enterobacterales. IMPLICATIONS FOR CLINICAL PRACTICE: Carbapenem-resistant Enterobacterales colonization screening at admission and during the patient's stay is an important tool to control carbapenem-resistant Enterobacterales spread in intensive care units.

MicroRNAs and Exosomal microRNAs May Be Possible Targets to Investigate in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is defined as glucose intolerance that occurs during the second or third trimester of pregnancy. As the incidence of GDM rises, so does the risk of maternal and fetal complications with short- and long-term consequences. As a result, early diagnosis and treatment of this condition are important to avoiding adverse pregnancy outcomes. Exosomes are tiny vesicles secreted by living cells which contain a variety of bioactive substances. They are released by cells to facilitate cell-to-cell communication and regulate a variety of biological processes such as cellular immune response, inflammatory response, and apoptosis, among others. Many studies have recently confirmed that changes in the expression and secretion of exosomal miRNAs can be used as novel markers for the diagnosis, prognosis, and treatment of GDM. In this review, we summarized the various roles of exosomal miRNAs and circulating miRNAs in GDM. We found that the changes in the expression of certain miRNAs could be used to diagnosing GDM. Exosomal miRNAs target metabolic pathways, resulting in insulin resistance. We also highlighted the potential for miRNAs and exosomal miRNAs to be used as biomarkers for diagnosis or therapeutic agents.

Bloodstream Infections in Patients with Rectal Colonization by Carbapenem-Resistant Enterobacteriaceae: A Prospective Cohort Study.

Purpose: Carbapenem-resistant Enterobacteriaceae (CRE) infection has become a concerning threat, especially in hospital settings; however, its phenotypic characterization, association with rectal colonization and subsequent bloodstream infections (BSI) remain to be clarified. This study aimed to investigate the incidence and risk factors of CRE infection in rectal CRE carriers and to understand the clonality of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains and their association with subsequent BSI in these patients. Patients and Methods: This was a prospectively designed cohort study. Hospitalized patients treated at our institution from April 2019 to October 2020 with intestinal CRE carriage were screened at admission and weekly thereafter until death or discharge from the hospital. Stool and blood samples were obtained for strain growth and mass spectrometry. The colonization and clinical infection isolates were analyzed by antimicrobial susceptibility testing to identify CRE. The clonality of the CRE strains and their corresponding clinical infection strains was studied by whole-genome sequencing to explore the mechanism of drug resistance and evaluate possible transmission. CRE-associated risk factors were analyzed in combination with epidemiological data. Results: Of the 1203 patients, 85 were colonized by CRE and 21 developed CRE infection, of whom 13 developed CRE bloodstream infection (BSI). Ninety-one CRE strains were isolated from the rectal specimens of the 85 patients. Tracheotomy and chemotherapy in the past three months were independent risk factors for CRE infection in intestinal CRE carriers. ST11-KL64 (92.3%, 24/26) was the most dominant capsule and multilocus sequence typing (MLST) type among clonal CRKP isolates. Single-nucleotide polymorphism clustering showed homology of representative colonization and infection CRKP strain pairs (n=13) in the same patient. One group of leading clones was endemic in surgical intensive care units (ICUs). Twenty-four CRKP strains carried ß-lactamase K. pneumonia carbapenemase 2, and 73.1% (19 strains) of CRKP carried mucoid phenotype regulator genes A2 and iucABCD. Conclusion: In summary, intestinal CRE colonization was detectable at an elevated rate among hospitalized patients and prevalent in ICU patients, with potential rapid horizontal transmission, providing evidence that CRE BSI infection in hospitalized patients might be due to their colonized strains and indicates the correlation between intestinal colonization and BSI.

Contributions of ambient temperature and relative humidity to the risk of tuberculosis admissions: A multicity study in Central China.

BACKGROUND: As a communicable disease and major public health issue, many studies have quantified the associations between tuberculosis (TB) and meteorological factors with inconsistent results. The purpose of this multicenter study was to characterize the associations between ambient temperature, humidity and the risk of TB hospitalizations and to investigate potential heterogeneity. METHOD: Data on daily hospitalizations for TB, meteorological factors and ambient air pollutants for 16 cities in Anhui Province were collected from 2015 to 2020. A distributed lag nonlinear model (DLNM) was performed to obtain the estimates of meteorological-TB relationships by cities. Then, we used the multivariate meta-regression model to pool the city-specific estimates with air pollution, demographic indicators, medical resource and latitude as potential modifiers to explore the sources of heterogeneity. Finally, we divided the whole province into three regions to validate the meteorological-TB relationships by regions. RESULTS: The overall pooled temperature-TB association presented an approximate S-shaped curve, with relative risk (RR) peaking at 5 °C (RR = 1.536, 95% CI: 1.303-1.811) compared to the reference temperature (27 °C). Lag-response curve suggested that low temperature exposure increased the risk of TB hospitalizations at lag 0 and 1 day (lag0 day: RR = 1.136, 95% CI: 1.048-1.231, lag1 day: RR = 1.052, 95% CI: 1.023-1.082). However, the overall exposure-response curve between relative humidity and TB showed almost horizontal line with reference relative humidity to 78%. The residual heterogeneity ranged from 27.1% to 36.9%, with air pollution, latitude and medical resource explained the largest proportion. CONCLUSION: We found that low temperature exposure is associated with an acute increased risk of TB hospitalizations in Anhui Province. The association between temperature and TB admission varies depending on air pollution, latitude, and medical resources. Since the effect of short-term exposure to humidity is not significant, further studies are supposed to focus on the long-term effect of humidity.

Prevalence and associated factors of sharps injuries and other blood/body fluid exposures among healthcare workers: A multicenter study.

A multicenter study of sharps injuries (SIs) and other blood or body fluid (OBBF) exposures was conducted among 33,156 healthcare workers (HCWs) from 175 hospitals in Anhui, China. In total, 12,178 HCWs (36.7%) had experienced at least 1 SI in the previous 12 months and 8,116 HCWs (24.5%) had experienced at least 1 OBBF exposure during the previous 12 months.

Incidence and risk factors of kidney impairment on patients with COVID-19: A meta-analysis of 10180 patients.

BACKGROUND: The novel coronavirus is pandemic around the world. Several researchers have given the evidence of impacts of COVID-19 on the respiratory, cardiovascular and gastrointestinal system. Studies still have debated on kidney injury of COVID-19 patients. The purpose of the meta-analysis was to evaluate the association of kidney impairment with the development of COVID-19. METHODS: The PubMed, Embase and MedRxiv databases were searched until May 1, 2020. We extracted data from eligible studies to summarize the clinical manifestations and laboratory indexes of kidney injury on COVID-19 infection patients and further compared the prevalence of acute kidney injury (AKI) and the mean differences of three biomarkers between in ICU/severe and non-ICU/non-severe cases. Heterogeneity was evaluated using the I2 method. RESULTS: In the sum of 24 studies with 10180 patients were included in this analysis. The pooled prevalence of AKI, increased serum creatinine (Scr), increased blood urea nitrogen (BUN), increased D-dimer, proteinuria and hematuria in patients with COVID-19 were 16.2%, 8.3%, 6.2%, 49.8%, 50.1% and 30.3% respectively. Moreover, the means of Scr, BUN and D-dimer were shown 6.4-folds, 1.8-folds and 0.67-folds, respectively, higher in ICU/severe cases than in corresponding non-ICU/non-severe patients. The prevalence of AKI was about 30 folds higher in ICU/severe patients compared with the non-ICU/non-severe cases. CONCLUSIONS: Overall, we assessed the incidences of the clinic and laboratory features of kidney injury in COVID-19 patients. And kidney dysfunction may be a risk factor for COVID-19 patients developing into the severe condition. In reverse, COVID-19 can also cause damage to the kidney.

AmpR Increases the Virulence of Carbapenem-Resistant Klebsiella pneumoniae by Regulating the Initial Step of Capsule Synthesis.

BACKGROUND: Non-hypermucoviscous carbapenem-resistant Klebsiella pneumoniae with enhanced virulence lacking hvKP-specific virulence factors is uncommon, and the virulence mechanisms of this organism are not understood. METHODS: Following a retrospective study of carbapenem-resistant K. pneumoniae based on core genome multilocus sequence typing (cgMLST), isolates that caused high mortality were investigated with a genome-wide association study (GWAS), proteome analysis and an animal model. RESULTS: The subclone of sequence type 11 (ST11) K. pneumoniae, which belongs to complex type 3176 (CT3176) and K-locus 47 (KL47), was highlighted due to the high mortality of infected patients. GWAS analysis showed that transcriptional regulatory gene ampR was associated with the CT3176 isolates. In a mouse model, the mortality, bacterial load and pathological changes of mice infected with ampR-carrying isolates were distinct from those infected with ampR-null isolates. The ampR gene that enhances the virulence of the non-hypermucoviscous KL47 strain was unable to enhance the virulence of hypermucoviscous KL1 strain. Proteome analysis showed that the expression of WcaJ in the ampR + isolates was significantly higher than that in the ampR - isolates. Quantification of capsular polysaccharide confirmed that more capsule polysaccharide was produced by ampR+ and ampR-complementary strains compared to ampR- strains. It is suggested that the enhancement of the initial stage of capsule synthesis may be the cause of the enhanced virulence of these non-hypermucoviscous ST11 carbapenem-resistant K. pneumoniae isolates. CONCLUSION: Non-hypermucoviscous ST11 carbapenem-resistant K. pneumoniae with enhanced virulence warrants continued surveillance and investigation.

Rapid Identification of KL49 Acinetobacter baumannii Associated with Clinical Mortality.

OBJECTIVE: We aimed to establish a tool for rapid identification of KL49 Acinetobacter baumannii. METHODS: Based on the capsular polysaccharide (CPS) synthesis genes database, we investigated the distribution of K locus type 49 (KL49) genes in other KL types and established a rapid identification method for KL49. We collected 61 clinical carbapenem-resistant A. baumannii (CRAB) strains, identified KL49 by gtr100 detection, and used whole genome sequencing (WGS) for verification. A mouse pneumonia model was used to confirm the hypervirulence phenotype. We tested the presence of gtr100 gene in 165 CRAB strains from three provinces in China and evaluated the correlation of gtr100 carrying CRAB infection with mortality. RESULTS: The gtr100 gene is the CPS synthesis gene found only in KL49. We screened out nine WGS-validated KL49 strains from 61 CRAB clinical strains using polymerase chain reaction (PCR) to detect the gtr100 gene. The survival rates of KL49 strains were significantly lower than nonKL49 strains in a mouse pneumonia model. The survival rates of LAC-4 gtr100 knockout strain decreased significantly. Analysis of phylogenetics showed the worldwide spread of KL49 A. baumannii. Infection of gtr100 carrying CRAB is an independent risk for mortality (OR, 10.76; 95%CI: 3.08-37.55; p<0.001). CONCLUSION: The hypervirulence phenotype of KL49 CRAB and the association with mortality highlight the urgent need for implementing control measures. The rapid identification assay has the potential to facilitate early medical intervention and worldwide surveillance.

Exposure to infected/colonized roommates and prior room occupants increases the risks of healthcare-associated infections with the same organism.

BACKGROUND: The survival of pathogenic organisms in the healthcare environment plays a major role in acquiring healthcare-associated infections (HAIs). AIM: This meta-analysis was conducted to investigate whether pathogenic organisms can be transmitted from roommates and prior room occupants to other inpatients and thus increase the risks of HAIs. METHODS: PubMed (from January 1966) and Embase (from January 1974) were searched to identify studies up to March 2018. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Heterogeneity was assessed using the I-squared statistic. The random-effects model was applied which provides more conservative estimates. Subgroup analyses, cumulative meta-analysis, publication bias diagnosis, and sensitivity analysis were conducted. All the statistical analyses were performed using Stata statistical software version 9.0. RESULTS: Twelve studies including 33,153 subjects reported risk from exposure to infected/colonized roommates and nine studies including 49,839 subjects reported risk from infected/colonized prior room occupants. Exposure to infected/colonized roommates and prior room occupants were associated with the increased risks of HAIs with the same organism (odds ratio (OR) = 2.69, 95% confidence interval (CI) = 1.61-4.49; OR = 1.96, 95% CI = 1.36-2.68; respectively). Sensitivity analyses results did not show major changes in the overall findings. No publication bias was detected. CONCLUSIONS: This meta-analysis showed exposure to infected/colonized roommates and prior room occupants significantly increased the risks of HAIs with the same organism. Health authorities and hospitals should attach higher importance to the fact that current standards or practices for disinfection and isolation are often not sufficient to block transmission of pathogens in the healthcare settings, which may warrant enhanced terminal and intermittent disinfection and strict isolation for reducing HAIs.

MicroRNA-127 is a tumor suppressor in human esophageal squamous cell carcinoma through the regulation of oncogene FMNL3.

In this study, we investigated the expression patterns and functional roles of microRNA 127 (miR-127) and its target gene Formin-Like 3 (FMNL3) in human esophageal squamous cell carcinoma (ESCC). Quantitative RT-PCR (qRT-PCR) was used to compare miR-127 expression between ESCC cell lines and normal esophageal epithelium cell line, as well as paired ESCC tumors and adjacent normal esophageal tissues in 33 patients. We found miR-127 was aberrantly downregulated in both ESCC cell lines and human ESCC tumors. In ESCC cell lines TE-1 and ECA109 cells, lentiviral-induced miR-127 upregulation markedly inhibited cancer proliferation and migration in vitro, and tumorigenicity in vivo. Through dual-luciferase assay and qRT-PCR, FMNL3 was confirmed to be the downstream target gene of miR-127 in ESCC. Finally, FMNL3 was downregulated by siRNA in TE-1 and ECA109 cells. And we discovered that SiRNA-induced FMNL3 downregulation had tumor suppressive effect in ESCC, inhibiting cancer proliferation, migration in vitro, and tumorigenicity in vivo. These results suggest that miR-127 is downregulated and acting as tumor suppressor in ESCC. Inversely, FMNL3, the target gene of miR-127, is upregulated and acting as an oncogene in ESCC.

[Development study on model WY multi-functional thoracic cavity closed drainage system].

Based on the improved design of the existing thoracic cavity closed drainage system, a new multi-functional device is developed and is described here in detail. The device is more convenient and more efficient than the existing system. Besides, it has a function of autotransfusion. Animal experimental results show that it has attained the goal of the improved design.

[Diagnosis and management of spontaneous rupture of the esophagus].

OBJECTIVE: To explore guidelines of the diagnosis and management for spontaneous rupture of the esophagus. METHODS: Of the 15 patients suffering spontaneous rupture of the esophagus, 11 received surgical treatment while the other 4 received non-operative treatment. RESULTS: Eleven patients recovered smoothly and death occurred in 4 cases, with the total cure rate of 73%. CONCLUSION: Early diagnosis and operation are crucial for management of spontaneous rupture of the esophagus, and in cases of delayed diagnosis, indications for operation need to be extended.

[Lung transplantation for treatment of pulmonary cystic fibrosis: report of one case].

A right single lung transplantation was performed in a 17-year-old female patient with end-stage cystoid pulmonary fibrosis and without cardiopulmonary bypass in June 2003. The donor lung was perfused with cold UW solution with a cold ischemic time of 280 min. The patient weaned from ventilator on the next day of operation (18 h later) and was able to walk at the fourth day postoperatively. Immunosuppression included methylprednisolone used before FK 506, mycophenolate mofetil and prednisone dosed after operation. The patient remains well a month after operation with significant improvement of the lung function and enjoys normal life.

Radical resection of upper right lung under thoracoscopic guidance.

In recent years, thoracoscopic lobectomy has been rapidly developing and applied in China with an ever growing list of indications as the resectable range has been evolving from the peripheral type to the central type, from a diameter less than 3 cm to greater than 5 cm, and from lobectomy to pneumonectomy and segmental lung resection. This technique has become a routine option in our department. This video shows one case of thoracoscopic lobectomy with lymph node dissection for upper right lung cancer of 6 cm in diameter.

Ipsilateral versus bilateral limb-training in promoting the proliferation and differentiation of endogenous neural stem cells following cerebral infarction in rats.

We investigated the effects of ipsilateral versus bilateral limb-training on promotion of endogenous neural stem cells in the peripheral infarct zone and the corresponding cerebral region in the unaffected hemisphere of rats with cerebral infarction. Middle cerebral artery occlusion was induced in Wistar rats. The rat forelimb on the unaffected side was either wrapped up with tape to force the use of the paretic forelimb in rats or not braked to allow bilateral forelimbs to participate in training. Daily training consisted of mesh drum training, balance beam training, and stick rolling training for a total of 40 minutes, once per day. Control rats received no training. At 14 days after functional training, rats receiving bilateral limb-training exhibited milder neurological impairment than that in the ipsilateral limb-training group or the control group. The number of nestin/glial fibrillary acidic protein-positive and nestin/microtubule-associated protein 2-positive cells in the peripheral infarct zone and in the corresponding cerebral region in the unaffected hemisphere was significantly higher in rats receiving bilateral limb-training than in rats receiving ipsilateral limb-training. These data suggest that bilateral limb-training can promote the proliferation and differentiation of endogenous neural stem cells in the bilateral hemispheres after cerebral infarction and accelerate the recovery of neurologic function. In addition, bilateral limb-training produces better therapeutic effects than ipsilateral limb-training.