ObjectiveTo explore the mechanism of Huoxue Rongluo prescription （HXRLP） in repairing the blood-brain barrier （BBB） after ischemic stroke （IS）. MethodsMale C57BL/6 mice were randomly divided into sham operation （Sham） group， cerebral infarction model （MCAO） group， environmental circadian disruption with cerebral infarction model （ECD-MCAO） group， low-， medium-， and high-dose HXRLP （HXRLP-L， M， and H） groups （8.5， 17， 34 g·kg^-1·d^-1， respectively）， and positive drug butylphthalide （NBP） group （0.23 mL·d^-1）. In the Sham group， only the exposed blood vessels were isolated without suture insertion. In the other groups， the middle cerebral artery occlusion （MCAO） model of mice was prepared. In the ECD-MCAO group， HXRLP groups， and NBP group， the environmental circadian disruption （ECD） model was prepared. The mice in the Sham group， MCAO group， and ECD-MCAO group were given the same volume of soybean oil by gavage， while those in the other groups were given the corresponding drugs by gavage. Samples were collected after 7 consecutive days of administration. The mNSS score was used to evaluate the repair effect of HXRLP on neurological deficits after IS. Hematoxylin-eosin （HE） staining was used to assess the impact of HXRLP on the pathological damage of brain tissue after IS. 2，3，5-Triphenyltetrazolium chloride （TTC） staining and cerebral blood perfusion status were used to evaluate the repair effect of HXRLP on brain tissue damage after IS. Evans blue staining and transmission electron microscopy were used to evaluate the improvement effect of HXRLP on the permeability injury of BBB after IS. Immunofluorescence （IF） staining was used to observe the expression of von Willebrand Factor （vWF）， brain and muscle Arnt-like 1 （Bmal1）， and Occludin in brain tissue. Western blot was used to detect the protein expression of Bmal1， Occludin， tight junction protein （Claudin-5）， vascular endothelial growth factor （VEGF）， and angiopoietins（Ang）， and related analysis was conducted. ResultsCompared with the Sham group， the MCAO group exhibited significantly aggravated neurological deficits， cerebral infarction volume， brain pathological damage， and BBB leakage （P0.01） and significantly reduced cerebral blood perfusion （P0.01）. The expression of Bmal1， vWF， vascular endothelial growth factor A （VEGFA）， and Ang in brain tissue was significantly enhanced （P0.01）， while the expression of Occludin and Claudin-5 was significantly weakened （P0.01）. Compared with the MCAO group， the ECD-MCAO group showed significantly aggravated neurological deficits， cerebral infarction volume， and BBB leakage （P0.01）， obviously worsened brain pathological damage （P0.05）， significantly reduced cerebral blood perfusion （P0.01）， and significantly decreased expression of Bmal1， vWF， VEGFA， Ang， Occludin， and Claudin-5 in brain tissue （P0.01）. Compared with the ECD-MCAO group， the HXRLP groups of all doses presented significantly improved neurological deficits， cerebral infarction volume， brain pathological damage， and BBB leakage （P0.01）， significantly increased cerebral blood perfusion （P0.01）， and enhanced expression levels of Bmal1， vWF， VEGFA， Ang， Occludin， and Claudin-5 in brain tissue （P0.01）. ConclusionHXRLP can regulate the clock protein Bmal1 and promote the expression of VEGFA， Ang， Occludin， and Claudin-5， thereby improving BBB damage after IS.

Objective:To describe the distribution characteristics of alcohol consumption in adult twins in the Chinese National Twin Registry (CNTR), and further explore the influence of genetic factors on alcohol consumption in adult twins.Methods:The subjects of the study were twins registered by CNTR in 11 project areas across China from 2010 to 2018. A total of 56 966 twins (28 483 pairs) aged 18 years and above who answered questions about drinking behavior were included, and the random effect model was used to describe the population and regional distribution characteristics of alcohol consumption. Intra-pair analysis was performed to calculate the concordance rate and heritability of their alcohol consumption.Results:The age of all subjects was (36.6±12.0) years, and current drinkers accounted for 16.6% (9 461/56 966) of all subjects. In men, those aged 50-59 years, those in northern China, those living in rural area, those with low education level and those with high BMI, the proportions of current drinkers were higher. After excluding 468 pairs of twins who had stopped alcohol use and 21 764 pairs of twins who had no drink or had small amount drink, an intra-pair analysis was conducted in 4 929 pairs of same-sex twins, and found that the concordance rate of alcohol consumption was 64.0% (2 059/3 215) in monozygotic twins, and 52.6% (902/1 714) in dizygotic twins, the difference was significant ( P<0.001), and the heritability of alcohol consumption was 24.1% (95% CI: 18.9%- 29.3%). The further stratified analysis found that in southern men, the heritability was highest in those aged 40-49 years (36.1%, 95% CI: 21.6%-50.7%), while in northern men, the heritability was highest in those aged 50-59 years (34.2%, 95% CI: 18.1%-50.3%). Conclusions:In adult twins in China, there were population and regional differences in the distribution of alcohol consumption behavior, and alcohol consumption was influenced by genetic factors, and gender, age and region had potential modifying effects.

Objective:To describe the distribution characteristics of alcohol consumption in adult twins in the Chinese National Twin Registry (CNTR), and further explore the influence of genetic factors on alcohol consumption in adult twins.Methods:The subjects of the study were twins registered by CNTR in 11 project areas across China from 2010 to 2018. A total of 56 966 twins (28 483 pairs) aged 18 years and above who answered questions about drinking behavior were included, and the random effect model was used to describe the population and regional distribution characteristics of alcohol consumption. Intra-pair analysis was performed to calculate the concordance rate and heritability of their alcohol consumption.Results:The age of all subjects was (36.6±12.0) years, and current drinkers accounted for 16.6% (9 461/56 966) of all subjects. In men, those aged 50-59 years, those in northern China, those living in rural area, those with low education level and those with high BMI, the proportions of current drinkers were higher. After excluding 468 pairs of twins who had stopped alcohol use and 21 764 pairs of twins who had no drink or had small amount drink, an intra-pair analysis was conducted in 4 929 pairs of same-sex twins, and found that the concordance rate of alcohol consumption was 64.0% (2 059/3 215) in monozygotic twins, and 52.6% (902/1 714) in dizygotic twins, the difference was significant ( P<0.001), and the heritability of alcohol consumption was 24.1% (95% CI: 18.9%- 29.3%). The further stratified analysis found that in southern men, the heritability was highest in those aged 40-49 years (36.1%, 95% CI: 21.6%-50.7%), while in northern men, the heritability was highest in those aged 50-59 years (34.2%, 95% CI: 18.1%-50.3%). Conclusions:In adult twins in China, there were population and regional differences in the distribution of alcohol consumption behavior, and alcohol consumption was influenced by genetic factors, and gender, age and region had potential modifying effects.

Objective:To analyze the mutation spectrum and regional distribution of susceptibility pathogenic genes in Chinese chronic pancreatitis (CP) patients.Methods:A retrospective analysis was conducted on 1 758 sporadic CP patients who underwent gene sequencing for pathogenic mutations of four major susceptibility genes ( SPINK1, PRSS1, CTRC, and CFTR) at the First Affiliated Hospital of Naval Medical University from December 2010 to November 2022. Pathogenic mutations of four major susceptibility genes were detected by using the next-generation sequencing, and both known and novel pathogenic mutations were validated by Sanger sequencing. The ethnic and regional distributions of pathogenic mutations across different ethnic groups were compared. The ArcMap 10.7 software was used to provide the distribution map of common CP pathogenic mutations in China, and regional differences of these mutations were assessed. According to seven major geographical regions in China, we also evaluated the enrichment differences of CP pathogenic mutations in North China region, Northeast China region, East China region, Central China region, South China region, Southwest China region, and Northwest China region. Results:Among 1 758 CP patients, 50.23% (883/1 758) carried pathogenic mutations, and the SPINK1 pathogenic mutations were most predominated (39.31%). Among them, c.194+2T>C mutations accounted for 94.21% of all SPINK1 mutations. 32.59% (573/1 758) of patients carried single heterozygous mutation of one susceptibility gene, and 4.61% carried homozygous mutation of SPINK1 c.194+2T>C. There was no statistically significant difference on the overall pathogenic mutation carrying rate between Han and ethnic minority patients, whereas the mutation carrying rate of SPINK1 c.194+2T>C was significantly higher among Han patients than among ethnic minorities (37.48% vs 20.00%, P<0.05). Among 31 provinces and cities, the mutation carrying rate of CP patients in Tianjin, Guangdong, Yunnan, Hubei and Anhui were all higher than 60.00%. The SPINK1 mutations accounted for the highest proportion of pathogenic mutations across all provinces (33.33% to 61.54%), and SPINK1 c.194+2T>C was the most prevalent mutation. The mutation carrying rate of SPINK1 c.194+2T>C was higher than 40.00% in Jilin, Liaoning, Tianjin, Anhui, Jiangxi, Hubei, Henan, and Guangdong. Distribution analysis of seven geographic regions showed that the overall carrying rate of pathogenic mutations in North China region was significantly lower than that in Central China region (represented by Henan, Hubei, and Hunan; 38.38% vs 58.15%), and the differences were statistically significant ( P<0.05). Additionally, although the carrying rate of SPINK1 c.194+2T>C was highest in Central (41.85%) and Northeast China region (38.78%), no significant differences were found among different regions. Conclusions:Genetic factors was the main etiology of CP in China, with SPINK1 c.194+2T>C mutations being most prevalent. The carrying rates of common susceptibility genes of CP were highest in Central China region as well as SPINK1 c.194+2T>C mutation.

Objective:To analyze the mutation spectrum and regional distribution of susceptibility pathogenic genes in Chinese chronic pancreatitis (CP) patients.Methods:A retrospective analysis was conducted on 1 758 sporadic CP patients who underwent gene sequencing for pathogenic mutations of four major susceptibility genes ( SPINK1, PRSS1, CTRC, and CFTR) at the First Affiliated Hospital of Naval Medical University from December 2010 to November 2022. Pathogenic mutations of four major susceptibility genes were detected by using the next-generation sequencing, and both known and novel pathogenic mutations were validated by Sanger sequencing. The ethnic and regional distributions of pathogenic mutations across different ethnic groups were compared. The ArcMap 10.7 software was used to provide the distribution map of common CP pathogenic mutations in China, and regional differences of these mutations were assessed. According to seven major geographical regions in China, we also evaluated the enrichment differences of CP pathogenic mutations in North China region, Northeast China region, East China region, Central China region, South China region, Southwest China region, and Northwest China region. Results:Among 1 758 CP patients, 50.23% (883/1 758) carried pathogenic mutations, and the SPINK1 pathogenic mutations were most predominated (39.31%). Among them, c.194+2T>C mutations accounted for 94.21% of all SPINK1 mutations. 32.59% (573/1 758) of patients carried single heterozygous mutation of one susceptibility gene, and 4.61% carried homozygous mutation of SPINK1 c.194+2T>C. There was no statistically significant difference on the overall pathogenic mutation carrying rate between Han and ethnic minority patients, whereas the mutation carrying rate of SPINK1 c.194+2T>C was significantly higher among Han patients than among ethnic minorities (37.48% vs 20.00%, P<0.05). Among 31 provinces and cities, the mutation carrying rate of CP patients in Tianjin, Guangdong, Yunnan, Hubei and Anhui were all higher than 60.00%. The SPINK1 mutations accounted for the highest proportion of pathogenic mutations across all provinces (33.33% to 61.54%), and SPINK1 c.194+2T>C was the most prevalent mutation. The mutation carrying rate of SPINK1 c.194+2T>C was higher than 40.00% in Jilin, Liaoning, Tianjin, Anhui, Jiangxi, Hubei, Henan, and Guangdong. Distribution analysis of seven geographic regions showed that the overall carrying rate of pathogenic mutations in North China region was significantly lower than that in Central China region (represented by Henan, Hubei, and Hunan; 38.38% vs 58.15%), and the differences were statistically significant ( P<0.05). Additionally, although the carrying rate of SPINK1 c.194+2T>C was highest in Central (41.85%) and Northeast China region (38.78%), no significant differences were found among different regions. Conclusions:Genetic factors was the main etiology of CP in China, with SPINK1 c.194+2T>C mutations being most prevalent. The carrying rates of common susceptibility genes of CP were highest in Central China region as well as SPINK1 c.194+2T>C mutation.

Objective:To evaluate the quality of life (QoL) of Chinese chronic pancreatitis (CP) patients based on the Chinese version of the pancreatitis quality of life Instrument (PANQOLI) and explore its impact factors.Methods:404 patients with CP admitted to the Department of Gastroenterology of the First Affiliated Hospital of Naval Medical University between September 2021 and January 2022 were enrolled. The Chinese version of PANQOLI was used for questionnaire survey on QoL of CP patients. Univariate analysis and multiple linear regression analysis were used to explore the impact factors for QoL of CP patients.Results:The total score of QoL of 404 Chinese CP patients was 28-94(72.47±13.61), which declined by 29.64% compared to the highest total score (103) in the Chinese version of PANQOLI. Score of physical function, role function, emotional function, and self-worth domain was 25.63±4.84, 13.86±2.78, 16.98±6.21 and 16.00±4.65, respectively. Compared to the highest scores (30, 25, 24 and 24), the scores of aforementioned four domains declined by 14.57%, 44.56%, 29.25% and 33.33%, respectively. Univariate analysis showed that sex, age, employment status, smoking, alcohol consumption, and frequency of pancreatitis recurrence were significantly associated with QoL of CP patients. Multiple linear regression analysis indicated that older age (coefficient=-0.127), unemployment status (coefficient=-0.106), smoking (coefficient=-0.176), and high frequency of pancreatitis recurrence (coefficient=-0.123) were independent factors for QoL of CP patients (all P value <0.05). Conclusions:The Chinese version of PANQOLI could be effectively applied to Chinese CP patients. Older age, unemployment, smoking, and pancreatitis attacks were risk factors for QoL of CP patients, indicating that the formulation of personalized intervention measures may help to improve QoL of CP patients.

Objective:To investigate the relationship between pancreatic fibrotic marker transforming growth factor-β(TGF-β) and platelet derived growth factor-BB(PDGF-BB) and serum glycated hemoglobin (HbA1c) levels in patients with type 3c diabetes mellitus secondary to chronic pancreatitis(CP-T3cDM).Methods:The clinical data of 39 patients with CP-T3cDM admitted to the Department of Gastroenterology of the First Affiliated Hospital of Naval Medical University between February 2018 and August 2020 were collected, and the patients' age, gender, body mass index, duration of chronic pancreatitis and diabetes mellitus, smoking history, alcohol consumption history, serum HbA1c level at admission, degree of pancreatic atrophy, morphology of the main pancreatic duct, and treatment of diabetes mellitus were recorded. Serum TGF-β and PDGF-BB were detected by ELISA. Patients were divided into high and low level group according to the median TGF-β and PDGF-BB levels, respectively. Clinical characteristics of patients were compared between the TGF-β and PDGF-BB high and low level group. The correlation between TGF-β, PDGF-BB and HbA1c was analyzed by Spearman's correlation analysis.Results:A total of 39 CP-T3cDM patients were included; 35 were male and 4 were female. The age of first onset of chronic pancreatitis was (42±14) years old, and the duration of diabetes mellitus was 24(4, 36) months. The serum HbA1c level was (7.8±1.6)%, and the serum TGF-β and PDGF-BB levels were 20.5(10.5, 43.1) and 647.5(276.9, 1349.2)pg/ml, respectively. The serum HbA1c levels of patients in the high-level group of serum TGF-β and PDGF-BB were significantly higher than those in the corresponding low-level group [8.6%(7.4%, 9.9%) vs 6.7%(6.2%, 7.8%) and 8.6%(7.4%, 9.6%) vs 6.7%(6.1%, 7.8%), respectively] , and the difference was statistically different (both P value <0.01), while none of other indicators showed statistically significant differences between both groups. The correlation analysis showed that the levels of TGF-β and PDGF-BB were significantly positively correlated with HbA1c level ( r=0.45, 0.53, both P value <0.01). Conclusions:Increased pancreatic fibrosis in patients with CP-T3cDM was an important factor contributing to elevated blood glucose level. Patients with higher serum pancreatic fibrotic factors exhibited a significant increase in HbA1c level.

Objective: To investigate the early clinical effects of tantalum augment assisted with 3D technology in treating acetabular bone defects of Paprosky type III in revision total hip arthroplasty (THA). Methods: From May 2013 to July 2017, a total of 16 patients (18 hips) undergoing revision THA were retrospectively analyzed, including 11 males and 5 females aged 58.06±8.29 years (range 44-69 years). There were 3 cases with infective loosening and 15 cases with aseptic loosening, 13 cases with Paprosky IIIA type bone defects and 5 cases with IIIB type bone defects. 3D technology was used for precise planning before operation. The tantalum augment and cup were used to repair acetabular bone defects during operation. Cup anteversion, abduction angle, ratio of the lateral and contralateral vertical distance of the center of rotation, ratio of the lateral and contralateral horizontal distance of the center of rotation and femoral offset were measured preoperatively and postoperatively. The percentages of hips located in Lewinnek safe zone were calculated preoperatively and postoperatively. Postoperative radiographic evidence of loosening and Harris score were collected at the end of the follow-up. Results: The percentage of the hips located in Lewinnek safe zone increased from 22% (4/18) preoperatively to 61% (11/18) postoperatively. The mean anteversion of the operative side was 11.99°±6.91° (range 1.71°-26.36°) postoperatively. The mean abduction angle of the operative side was 44.91°±5.93° (range 35.6°-56.0°). The mean ratio of the lateral and contralateral vertical distance of the center of rotation was 1.10±0.20 (range 0.87-1.62). The mean ratio of the lateral and contralateral horizontal distance of the center of rotation was 1.00±0.18 (range 0.69-1.46) and the mean ratio of the lateral and contralateral femoral offset was 1.01±0.66 (range 0.51-3.56). All the patients were followed-up for an average of 27.72±12.18 months (range 14-53 months). No complications, such as periprosthetic joint infection, dislocation or aseptic loosening, were observed in all patients. The mean Harris score was 77.28±4.80 (range 65-85) at 6 months postoperatively and 80.9±5.2 (range 69-89) at the end of the follow-up. Conclusion Using tantalum augmentassisted with 3D technology to re construct Paprosky type III severe bone defects of the hip can increase the accuracy of the acetabular cup positioning. The short-term outcomes are satisfying and no early prosthetic loosening was observed.

Objective To delay the atrophy of denervated skeletal muscle by baby-sitting in reverse end-to-side fashion and explore the feasibility of this operation to improve the recovery of denervated muscle in rats.Methods From July,2015 to March,2016,32 female SD rats were divided into 4 groups randomly and the tibial nerve of each rats was transected.In immediate repair group,the transected tibial nerve was sutured in situ.In unprotected group,the tibial nerve stump was putting-aside.The sural nerve was transected in other 2 groups.The proximal sural nerve was connected to the distal tibial nerve stump directly in end-to-end (ETE) protected group and to the side of the distal tibial nerve stump in end-to-side (ETS) protected group.After 3 months,connected the two ends of tibial nerve except immediate repair group.After another 3 months,the tibial nerve functional index,electrophysiological testing,histology and morphology were examined.Results The gastrocnemius muscle was atrophy obviously in unprotected group,while in other groups the muscle structure was well protected.The tibial nerve functional index (-39.54±24.32),motor nerve conduction velocity[(30.25±12.65)m/s],and muscle contraction [(0.98 ± 0.38)N)] indicated that the gastrocnemius muscle function in ETS protected group was statistically better recovery than in unprotected group [-75.65±32.13,(24.93±8.69)m/s and (0.64±0.20)N,respectively] and ETE protected group [-62.34± 21.65,(16.90±7.92)m/s and (0.75-±0.15)N,respectively](P＜0.05).The contractility of muscle were poor recovery in ETE protected group,which was similar to unprotected group(P＞0.05).Conclusion Sensory nerve baby-sitting in reverse end-to-side fashion is a effective method to improve the recovery of denervated muscle in rats.

This study was aimed to discuss the relations between relieving depression and benefit findings for advanced cancer patients.A total of 80 advanced cancer patients with the anxiety / depression assessment of more than 7 points and less than 15 points,were randomly divided into the intervention group and the control group,in comprehensive hospitals.Finally,76 cases were included with 39 cases in the intervention group,and 37 cases in the control group.The progressive muscle relaxation training (PMRT) was used in the control group.Traditional Chinese medicine (TCM) special technique (i.e.,TCM five-element musicotherapy plus PMRT) was used in the intervention group.The reduced fraction of the Benefit Finding Scale (BFS) and the Hospital Anxiety and Depression Scale (HADS) were used in the effect evaluation after 8-week intervention.The results showed that after 8-week treatment,the reduced fractions of BFS and HADS in the intervention group were obviously higher than the control group with statistical significance.The variation tendencies of BFS and HADS in the intervention group were obviously higher than the control group with statistical significance.There were 8 individual values in BFS of the intervention group were higher than the control group with statistical significance.It was concluded that the benefit findings for advanced cancer patients were related to the application of TCM special techniques,can improve the levels of benefit findings among advanced cancer patients.It enriched and perfected the depression regulation plan of cancer patients by TCM special techniques.