Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

Alzheimer's disease (AD) is associated with the impairment of white matter (WM) tracts. The current study aimed to verify the utility of WM as the neuroimaging marker of AD with multisite diffusion tensor imaging datasets [321 patients with AD, 265 patients with mild cognitive impairment (MCI), 279 normal controls (NC)], a unified pipeline, and independent site cross-validation. Automated fiber quantification was used to extract diffusion profiles along tracts. Random-effects meta-analyses showed a reproducible degeneration pattern in which fractional anisotropy significantly decreased in the AD and MCI groups compared with NC. Machine learning models using tract-based features showed good generalizability among independent site cross-validation. The diffusion metrics of the altered regions and the AD probability predicted by the models were highly correlated with cognitive ability in the AD and MCI groups. We highlighted the reproducibility and generalizability of the degeneration pattern of WM tracts in AD.
Humans ; White Matter/diagnostic imaging* ; Diffusion Tensor Imaging/methods* ; Alzheimer Disease/complications* ; Reproducibility of Results ; Cognition ; Cognitive Dysfunction/complications* ; Brain/diagnostic imaging*

Objective: To explore the relationship between fasting blood glucose level and thromboembolism events in patients with non-valvular atrial fibrillation (NVAF). Methods: This was an observational study based on data from a multicenter, prospective Chinese atrial fibrillation registry cohort, which included 18 703 consecutive patients with atrial fibrillation (AF) in 31 hospitals in Beijing from August 2011 to December 2018. Patients were divided into 5 groups according to status of comorbid diabetes and fasting glucose levels at admission: normal blood glucose (normal glucose group), pre-diabetes group, strict glycemic control group, average glycemic control group and poor glycemic control group. Patients were followed up by telephone or outpatient service every 6 months. The primary follow-up endpoint was thromboembolic events, including ischemic stroke and systemic embolism. The secondary endpoint was the composite endpoint of cardiovascular death and thromboembolic events. Kaplan-Meier survival analysis and multifactorial Cox regression were used to analyze the correlation between fasting glucose levels and endpoint events. Results: The age of 18 703 patients with NVAF was (63.8±12.0) years, and there were 11 503 (61.5%) male patients. There were 11 877 patients (63.5%) in normal blood glucose group, 2 023 patients (10.8%)in pre-diabetes group, 1 131 patients (6.0%) in strict glycemic control group, 811 patients in average glycemic control group and 2 861 patients(4.3%) in poor glycemic control group. Of the 4 803 diabetic patients, 1 131 patients (23.5%) achieved strict glycemic control, of whom 328 (29.0%) were hypoglycemic (fasting blood glucose level<4.4 mmol/L at admission). During a mean follow-up of (51±23) months (up to 82 months), thromboembolic events were reported in 984 patients (5.3%). The survival curve analysis of Kaplan Meier showed that the incidence rates of thromboembolic events in normal glucose group, pre-diabetes group, strict glycemic control group, average glycemic control group and poor glycemic control group were 1.10/100, 1.41/100, 2.09/100, 1.46/100 and 1.71/100 person-years, respectively (χ²=53.0, log-rank P<0.001). The incidence rates of composite endpoint events were 1.86/100, 2.17/100, 4.08/100, 2.58/100, 3.16/100 person-years (χ²=72.3, log-rank P<0.001). The incidence of thromboembolic events and composite endpoint events in the other four groups were higher than that in the normal blood glucose group (P<0.001). Multivariate Cox regression analysis showed that compared with normal glucose group, the risk of thromboembolism increased in pre-diabetes group(HR=1.23, 95%CI 1.00-1.51, P=0.049), strict glycemic control group(HR=1.32, 95%CI 1.06-1.65, P=0.013) and poor glycemic control group(HR=1.26, 95%CI 1.01-1.58, P=0.044). Conclusion: Both high or low fasting glucose may be an independent risk factor for thromboembolic events in patients with NVAF.
Aged ; Atrial Fibrillation/complications* ; Blood Glucose/analysis* ; Fasting ; Humans ; Male ; Middle Aged ; Prospective Studies ; Thromboembolism/etiology*

From 2011 to 2020, there were 111 213 cases of rabies exposed people recruited from the rabies immunization clinic of a hospital in Beijing. The monthly distribution of patients in each year was not statistically significant (P>0.05). The distribution of patients showed remarkable seasonality, with the exposure peak from May to October. The ratio of male to female was 1∶1.3. The majority of patients were aged 20-29 years old (39.1%) and in-service personnel (56.5%). Level-Ⅱ wounds (84.2%) were more common than level-Ⅲ wounds (14.9%). The number of visits to level-Ⅲwounds increased rapidly since 2017. The most common injured body part was hand (60.7%). Dogs were the most common animal for injuries (60.6%), followed by cats (32.3%), of which most were host animals (75.5%). The vaccination rate from 2016 to 2020 [49.8% (24 276/48 703)] was significantly higher than that from 2011 to 2015[18.6% (6 559/35 272)](χ²=8597.18, P<0.001).
Ambulatory Care Facilities ; Animals ; Bites and Stings/epidemiology* ; Dogs ; Female ; Hospitals ; Humans ; Male ; Rabies/prevention & control* ; Rabies Vaccines/therapeutic use* ; Vaccination

Objective: To explore the feasibility and safety of intracardiac ultrasound-assisted atrial septal puncture (ASP) during radiofrequency ablation for atrial fibrillation. Methods: We enrolled 241 consecutive patients scheduled to radiofrequency ablation for atrial fibrillation in Beijing Anzhen Hospital from July to September 2020. Inclusion criteria: patients aged over 18 years with a clear electrocardiogram record of atrial fibrillation. Patients were divided into 2 groups: ASP with ultrasound-assisted X-ray (ultrasound group, n=123), ASP under X-ray alone (X-ray group, n=118). Clinical features of patients including age, sex, percent of paroxysmal atrial fibrillation, and repeat ablation, CHA₂DS₂-VASc score and past history (hypertension, diabetes mellitus, coronary artery disease, stroke/transient ischemic attack (TIA), valve diseases) and echocardiographic parameters (left atrial dimension, left ventricular ejection fraction, left ventricular end-diastolic dimension) were obtained and compared. The first-pass rate, radiation exposure time, duration of ASP, and complications of ASP were also compared between the two groups. Results: The age of patients in this cohort was (62.5±8.0) years, and the proportion of males was 57.0% (n=138). Among them, the proportion of paroxysmal atrial fibrillation was 56.0% (n=135), and the ratio of repeat ablation was 17.8% (n=43). Age, sex, percent of paroxysmal atrial fibrillation, history of hypertension, diabetes mellitus were similar between the two groups. The first-pass rate was significantly higher in the ultrasound group than in the X-ray group (94.3% (116/123) vs. 79.7% (94/118), P=0.001); the exposure time of X-ray was significantly shorter in the ultrasound group than in the X-ray group ((31.3±7.9) s vs. (124.8±35.7) s, P<0.001), while the duration of ASP was longer in the ultrasound group ((10.1±1.8) minutes vs. (8.2±1.3) minutes, P<0.001). In terms of complications, the incidence of puncture into the pericardium was lower in the ultrasound group (0 vs.3.4% (4/118), P=0.039); the rate of transient ST-segment elevation post ASP was similar between the ultrasound group and X-ray group (2.4% (3/123) vs. 1.7% (2/118), P=0.999). Conclusion: Intracardiac ultrasound-assisted atrial septal puncture can effectively improve the accuracy of atrial septal puncture, shorten the radiation exposure time, and reduce the complications related to atrial septal puncture.
Adult ; Aged ; Atrial Fibrillation/surgery* ; Catheter Ablation ; Feasibility Studies ; Heart Septal Defects, Atrial ; Humans ; Male ; Middle Aged ; Punctures ; Radiofrequency Ablation ; Stroke Volume ; Ventricular Function, Left

OBJECTIVE:To establish the method for simultaneous determination of berberine hydrochloride and baicalin in Jianpi zhixiening granules. METHODS:HPLC switching walvelength method was adopted. The determination was performed on Hypersil BDS C18 column with mobile phase consisted of methanol-0.45％ phosphoric acid solution-triethylamine(50:49:1,V/V/V) at the flow rate of 1.0 mL/min. The detection wavelength was set at 265 nm(berberine hydrochloride)and 280 nm(baicalin). The column temperature was set at 30 ℃,and sample size was 10 μL. RESULTS:The linear range of berberine hydrochloride and baicalin were 60.3-312.8 ng(r=0.9997)and 81.5-368.9 ng(r=0.9999). The limits of quantitation were 0.6668,0.7740 ng,andthe limits of detection were 0.2226,0.2580 ng,respectively. RSDs of intermediate precision,stability and repeatability tests were all lower than 1.0％. The recoveries were 96.48％-99.30％(RSD=1.06％,n=6) and 95.20％-99.39％(RSD=1.66％,n=6), respectively. RSDs of durability test were all lower than 2.0％. CONCLUSIONS:The method is simple, precise, stable, reproducible,accurate and durable. It can be used for simultaneous determination of berberine hydrochloride and baicalin in Jianpi zhixiening granules.

Objective To evaluate the actual effect of the schistosomiasis control program in Jiangsu Province from 2010 to 2015. Methods A total of 67 schistosomiasis-endemic counties in 10 cities were selected, and a combination of retrospective investigation and on-site investigation was adopted to collect and record the epidemic data of the counties from 2010 to 2015, and a retrospective survey database of epidemic situation was established. The effects of integrated control strategies with both Oncomelania hupensis snail control and infection source control were evaluated. Results From 2010 to 2015, 2 465 911 persons who lived in endemic areas were detected for schistosomiasis, with 16 974 positive cases of blood examinations, and 8 positive cases of fecal examinations. Totally 5 145 people with advanced schistosomiasis were treated and 40 460 people with the history of schistosome cercarial-infested water contact received the expanded chemotherapy. A total of 127 636 cattle raised in the endemic areas were detected, and 51 619 cattle (head-times) with the history of cercarial-infested water contact also received the expanded chemotherapy. The area with snails control by molluscicides was 18 604.84 hm². By the end of 2015, schistosomeinfected snails had not been found and there was no zoological schistosome infection for 5 consecutive years, and in addition, there had been no acute schistosome-infected persons for 6 consecutive years in the whole province. The area with snails dropped to 1 977.18 hm², with a decreasing rate of 55.24% compared with that in 2010. Conclusion After the implementation of the plan for the prevention and control of schistosomiasis in Jiangsu Province (2010–2015), the prevention and control of schistosomiasis has achieved remarkable effects and realized the goal of the plan.

Objective To explore the effects of low-dose X-ray irradiation effects on ischemic flap survival and its possible mechanism.Methods From June, 2014 to December, 2014, 80 SD rats were include in the study, the rats were randomly divided into 2 groups: the experimental group A and control group B.There were 40 rats in each group.The ischemic flaps with the size of 9 cm × 3 cm were designed on the back of the rats.The pedicle of the flaps was near to the tail.A sterile biological isolating membrane was placed under the flap to block the blood supply between muscular layer and flaps.The flaps were intermittently sutured into their original position.The group A was immediately received single and local irradiation of 0.2 Gy after surgery, The group B was not treated.On days 1 to 14 after operation,general observation,HE staining and the western blot of the flaps were performed to calculate the survival vate of the flaps, observe neovascularization and determin the content of VEGF and MMP-9, respectively.Results On the third, seventh and fourteenth days, survival rates of the flaps in the experimental group [(66.46 ± 4.37)％, (44.30 ± 3.86)％, (32.20 ± 4.22)％, respectively] were higher than the control group [(43.15 ± 5.03)％, (27.71 ± 3.20)％, (16.40 ± 5.34)％, respectively] after inspection, there were statistically significant differences between these indices (P ＜ 0.01), HE staining of the flaps in the experimental group were seen in the fibroblast infiltration and neovascularization were higher than that of control group, and experimental group within the lumen of blood vessels were arranged in order, the groups were visible tissue edema obviously control, neovascularization in small numbers, the lumen was irregular.On the third and seventh days, MVD rates of the flaps in the experimental group (85.54 ± 6.12, 44.32 ± 3.56, respectively) were higher than the control group (49.35 ± 4.75,18.75 ± 2.89,respectively) after inspection, there were statistically significant differences between these indices (P ＜ 0.01).VEGF and MMP-9 protein content in the flap for the seventh day in the experimental group were significantly higher than that of the control group.Conclusion Low-dose X-ray irradiation can promote the survival rate of ischemic flap, the mechanism may be related to the expression of VEGF and MMP-9 increased and promoted angiogenesis of the flaps after low-dose X-ray irradiation.

OBJECTIVETo explore and evaluate the therapeutic efficacy of surgical treatment for cancer of the pancreatic head.

METHODSThe clinical data of 96 patients with cancer of the pancreatic head admitted in our hospital from January 2002 to December 2009 were retrospectively analyzed. pancreatoduodenectomy was performed in 48 cases, extended pancreatoduodenectomy in 30 cases, and Roux-Y cholangiojejunostomy in 18 cases.

RESULTSThe 1, 2 and 3-year survival rates were 59.2%, 41.8% and 13.2%, respectively, in the patients treated with pancreatoduodenectomy, and 73.2%, 58.2% and 24.1%, respectively, in the patients treated with extended pancreatoduodenectomy. The 1, 2 and 3-year survival rates were 36.8%, 15.8% and 5.3%, respectively, in the patients with unresectable tumor who received radiotherapy and (or) chemotherapy in Roux-Y cholangiojejunostomy. The postoperative morbidity was 29.2%, 30.0% and 27.8% in the patients treated with pancreatoduodenectomy, extended pancreatoduodenectomy and Roux-Y cholangiojejunostomy, respectively.

CONCLUSIONSPancreatoduodenectomy is the most effective treatment. Extended pancreatoduodenectomy can improve the surgical resection rate, reduce the recurrence rate and improve the survival rate. Internal drainage is an important palliative measure.

Adult ; Aged ; Anastomosis, Roux-en-Y ; methods ; Female ; Follow-Up Studies ; Humans ; Jejunostomy ; methods ; Male ; Middle Aged ; Pancreatic Neoplasms ; mortality ; surgery ; Pancreaticoduodenectomy ; methods ; Postoperative Complications ; Retrospective Studies ; Survival Rate