The relationship between genetic polymorphism of CYP2C19 and the efficacy of Helicobacter pylori eradication therapy in children / 中华儿科杂志

Objective: To investigate the relationship between genetic polymorphisms of cytochrome P450 2C19 (CYP2C19) and the efficacy of Helicobacter pylori (Hp) eradication therapy in children. Methods: The retrospective cohort study was conducted on 125 children with gastroscopy and positive rapid urease test (RUT) from September 2016 to December 2018 who presented to the Children's Hospital of Zhejiang University School of Medicine due to gastrointestinal symptoms including nausea, vomiting, abdominal pain, bloating, acid reflux, heartburn, chest pain, vomiting blood and melena. Hp culture and drug susceptibility test were carried out with gastric antrum mucosa before treatment. All the patients completed 2 weeks of standardized Hp eradication therapy and had 13C urea breath test 1 month after that, which was used to evaluate the curative effect. The DNA of gastric mucosa after RUT was analyzed and CYP2C19 gene polymorphism was detected. Children were grouped according to metabolic type. Combined with the results of Hp culture and drug susceptibility, the relationship between CYP2C19 gene polymorphism and the efficacy of Hp eradicative treatment was analyzed in children. Chi square test was used for row and column variables, and Fisher exact test was used for comparison between groups. Results: One hundred and twenty five children were enrolled in the study, of whom 76 were males and 49 females. The genetic polymorphism of CYP2C19 in these children found poor metabolizer (PM) of 30.4% (38/125), intermediate metabolizer (IM) of 20.8% (26/125), normal metabolizer (NM) of 47.2% (59/125), rapid metabolizer (RM) of 1.6% (2/125), and ultrarapid metabolizer (UM) of 0. There were statistically significant in positive rate of Hp culture among these groups (χ2=124.00, P<0.001). In addition, the successful rates of Hp eradication in PM, IM, NM and RM genotypes were 84.2% (32/38), 53.8% (14/26), 67.8% (40/59), and 0, respectively, with significant differences (χ2=11.35, P=0.010); those in IM genotype was significantly lower than that in PM genotype (P=0.011). With the same standard triple Hp eradicative regimen, the successful rate of Hp eradication for IM type was 8/19, which was lower than that of PM (80.0%, 24/30) and NM type (77.3%, 34/44) (P=0.007 and 0.007, respectively). There was a significant difference in the efficacy of Hp eradication treatment among different genotypes (χ2=9.72, P=0.008). According to the clarithromycin susceptibility result, the successful rate of Hp eradication treatment for IM genotype was 4/15 in the sensitive group and 4/4 in the drug-resistant group (χ2=6.97, P=0.018). Conclusions: The genetic polymorphism of CYP2C19 in children is closely related to the efficacy of Hp eradication treatment. PM has a higher successful rate of eradication treatment than the other genotypes.

Development and validation of a prognostic prediction model for patients with stage Ⅰ to Ⅲ colon cancer incorporating high-risk pathological features / 中华外科杂志

Objective: To examine a predictive model that incorporating high risk pathological factors for the prognosis of stage Ⅰ to Ⅲ colon cancer. Methods: This study retrospectively collected clinicopathological information and survival outcomes of stage Ⅰ~Ⅲ colon cancer patients who underwent curative surgery in 7 tertiary hospitals in China from January 1, 2016 to December 31, 2017. A total of 1 650 patients were enrolled, aged (M(IQR)) 62 (18)years (range: 14 to 100). There were 963 males and 687 females. The median follow-up period was 51 months. The Cox proportional hazardous regression model was utilized to select high-risk pathological factors, establish the nomogram and scoring system. The Bootstrap resampling method was utilized for internal validation of the model, the concordance index (C-index) was used to assess discrimination and calibration curves were presented to assess model calibration. The Kaplan-Meier method was used to plot survival curves after risk grouping, and Cox regression was used to compare disease-free survival between subgroups. Results: Age (HR=1.020, 95%CI: 1.008 to 1.033,P=0.001), T stage (T3:HR=1.995,95%CI:1.062 to 3.750,P=0.032;T4:HR=4.196, 95%CI: 2.188 to 8.045, P<0.01), N stage (N1: HR=1.834, 95%CI: 1.307 to 2.574, P<0.01; N2: HR=3.970, 95%CI: 2.724 to 5.787, P<0.01) and number of lymph nodes examined (≥36: HR=0.438, 95%CI: 0.242 to 0.790, P=0.006) were independently associated with disease-free survival. The C-index of the scoring model (model 1) based on age, T stage, N stage, and dichotomous variables of the lymph nodes examined (<12 and ≥12) was 0.723, and the C-index of the scoring model (model 2) based on age, T stage, N stage, and multi-categorical variables of the lymph nodes examined (<12, 12 to <24, 24 to <36, and ≥36) was 0.726. A scoring system was established based on age, T stage, N stage, and multi-categorical variables of lymph nodes examined, the 3-year DFS of the low-risk (≤1), middle-risk (2 to 4) and high-risk (≥5) group were 96.3%(n=711), 89.0%(n=626) and 71.4%(n=313), respectively. Statistically significant difference was observed among groups (P<0.01). Conclusions: The number of lymph nodes examined was an independent prognostic factor for disease-free survival after curative surgery in patients with stage Ⅰ to Ⅲ colon cancer. Incorporating the number of lymph nodes examined as a multi-categorical variable into the T and N staging system could improve prognostic predictive validity.

Clinical significance and changes of homocysteine, vitamin B12 and folic acid in diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the changes of serum homocysteine(Hcy), vitamin B12(VitB12)and folic acid in the serum of patients with diabetic retinopathy(DR), and to explore their significance in the occurrence and development of DR.METHODS: A case-control study was designed. A total of 95 patients with DR(DR group), 94 patients with diabetes mellitus(DM group)treated in endgcrinology department and 87 patients with age-related cataract(normal control group)from the ophthalmology department of Shenzhen People's Hospital between July 2021 and January 2022 were selected. Fasting venous blood was collected and serum was separated. The concentration of Hcy in serum was detected by enzyme linked immunosorbent assay(ELISA), and chemiluminescence immunoassay was used to detect the concentration of VitB12 and folic acid. Pearson linear correlation analysis was used to evaluate the correlation between Hcy and clinical parameters. Multivariate linear regression analysis was used to evaluate the main factors which affect Hcy level. Receiver operating characteristic(ROC)curve was designed to analyze the diagnostic value of serum Hcy, VitB12 and folic acid in DR.RESULTS: The concentration of serum Hcy in DR group was 16.52±3.54 μmol/L, which was significantly higher than that in DM group(10.86±3.47 μmol/L)and control group(6.84±1.39 μmol/L; all P&#x0026;#x003C;0.05); The concentration of VitB12 in the serum of the control group was 501.79±108.95 pmol/L, which was higher than that in DM group(478.57±57.85 pmol/L)and DR group(455.88±181.49 pmol/L), but the difference was not statistically significant(P=0.054); The concentration of folic acid in serum of control group was 10.31±2.43 nmol/L, which was higher than that of DM group(9.94±1.90 nmol/L)and DR group(7.27±2.79 nmol/L), and the difference between DR group and DM group was statistically significant(P&#x0026;#x003C;0.05); In DR group, Hcy expression was weakly positively correlated with triglyceride and low density lipoprotein(r=0.208, P=0.043; r=0.240, P=0.019). Multivariate linear regression showed that low density lipoprotein was an important factor which affect the expression of Hcy in DR patients. ROC curve shows that Hcy has important value in the diagnosis of DR.CONCLUSIONS: Hcy, VitB12 and folic acid are differentially expressed in DR group, DM group and normal control group. Hcy may be involved in the pathogenesis of DR, and it has important value in the diagnosis of DR. In addition, low density lipoprotein is also an important factor which affects the expression of Hcy.

Analysis on echocardiographic data of fetal heart defects at high altitude in Yunnan province and surrounding high altitude areas / 中华心血管病杂志

Objective: To explore the current situation of fetal heart defects in Yunnan Province and surrounding high altitude areas and the social factors affecting pregnancy outcome. Methods: This is a retrospective study. Pregnant woman who underwent fetal echocardiography and diagnosed as fetal cardiac defects in Yunnan Fuwai Cardiovascular Hospital from June 2017 to January 2021 were included. According to the clinical prognostic risk scoring system and grading criteria of fetal cardiac birth defects, the cases were divided into grade Ⅰ to Ⅳ. The disease distribution and proportion of each prognostic grade, pregnancy outcomes were analyzed and compared. The cases were divided into continued pregnancy group and terminated pregnancy group according to pregnancy outcome. The social factors that may affect the selection of pregnancy outcomes were analyzed by multivariate logistic regression analysis. Results: A total of 4 929 fetal echocardiography examination data were collected, and 4 464 cases (90.57%) were from Yunnan Province and surrounding high altitude areas. 2 166 cases of heart defects were finally analyzed, including 998 cases of congenital heart disease (CHD), 93 cases of cardiac tumors, cardiomyopathy and arrhythmia, 1 075 cases of foramen ovale, ductus arteriosus abnormalities and normal variations. The pregnant women were (29.2±5.0) years old with (25.6±3.8) gestational weeks. The number of cases with prognostic grade from Ⅰ to Ⅳ was 1 037 (47.88%), 620 (28.62%), 314 (14.50%), and 44 (2.03%), respectively. And 151 cases (6.97%) were not classified. The cases of normal variation and thin aortic arch development accounted for 42.66% (924/2 166), 5.22% (113/2 166), respectively. The top 3 diseases of grade Ⅱ were ventricular septal defect, coarctation of aorta and mild-moderate pulmonary stenosis, respectively, and their distribution was 11.63% (252/2 166), 3.92% (85/2 166) and 2.35% (51/2 166) respectively in all cases of heart defects, and 25.25% (252/998), 8.52% (85/998) and 5.11% (51/998) respectively in cases of CHD. Among the cases rated as grade Ⅲ and Ⅳ, most of them were complicated congenital heart disease, and the disease types are scattered. The more common cases in grade Ⅲ were complete transposition of great arteries (accounting for 2.40% (52/2 166) of all cases with heart defects, 5.21% (52/998) of all cases with CHD) and pulmonary artery occlusion (type Ⅰ to Ⅲ) with ventricular septal defect (accounting for 2.17% (47/2 166) of all cases with heart defects, and 4.71% (47/998) of all cases with CHD). In grade Ⅳ, single ventricle (0.74% (16/2 166) of all cases with heart defects, 1.60% (16/998) of all cases with CHD) and left ventricular dysplasia syndrome (0.65% (14/2 166) of all cases with heart defects, 1.40% (14/998) of all cases with CHD) are more common. A total of 1 084 cases were successfully followed up, and 675 cases were born, 392 cases were terminated, spontaneous abortion occurred in 17 cases. The proportion of terminated pregnancy cases was significantly increased from grade Ⅰ to Ⅳ, accounting for 5.24% (21/401), 27.78% (70/252), 89.54% (214/239) and 95.56% (43/45), respectively. Among the terminated pregnancy cases, those with grade Ⅲ accounted for the highest proportion (54.59% (214/392)). The distribution of terminated pregnancy cases was mainly complex congenital malformations or diseases with very poor prognosis (pregnancy outcome grade Ⅲ and Ⅳ), and proportion of terminated pregnancy with pregnancy outcome grade Ⅰ and Ⅱ cases (normal variation or good prognosis) accounted for 5.36% (21/392) and 17.86% (70/392), respectively. The results of multivariate logistic regression analysis showed that pregnant women with low education (high school and below: OR=2.73, 95%CI 1.26-5.93, P<0.001; illiteracy: OR=3.27, 95%CI 1.29-7.10, P<0.001) and low family income (Annual income<100 000 yuan: OR=2.47, 95%CI 1.69-5.12, P<0.001) were more likely to choose termination of pregnancy in case of fetal heart defect. Conclusion: In Yunnan province and the surrounding high altitude areas, the disease distribution of fetal heart defect is mainly simple or low-risk disease, but the complex malformation, especially the disease with poor pregnancy outcome, accounts for a relative high proportion. Pregnancy termination also occurs in some cases with good pregnancy outcome. The education level and family income of pregnant women may affect their choice of pregnancy outcome in case of fetal heart defect.

Wnt/b-Catenin Promotes the Osteoblastic Potential of BMP9 Through Down-Regulating Cyp26b1 in Mesenchymal Stem Cells

BACKGROUND@#All-trans retinoic acid (ATRA) promotes the osteogenic differentiation induced by bone morphogenetic protein 9 (BMP9), but the intrinsic relationship between BMP9 and ATRA keeps unknown. Herein, we investigated the effect of Cyp26b1, a critical enzyme of ATRA degradation, on the BMP9-induced osteogenic differentiation in mesenchymal stem cells (MSCs), and unveiled possible mechanism through which BMP9 regulates the expression of Cyp26b1. @*METHODS@#ATRA content was detected with ELISA and HPLC–MS/MS. PCR, Western blot, and histochemical staining were used to assay the osteogenic markers. Fetal limbs culture, cranial defect repair model, and micro–computed tomographic were used to evaluate the quality of bone formation. IP and ChIP assay were used to explore possible mechanism. @*RESULTS@#We found that the protein level of Cyp26b1 was increased with age, whereas the ATRA content decreased. The osteogenic markers induced by BMP9 were increased by inhibiting or silencing Cyp26b1 but reduced by exogenous Cyp26b1. The BMP9-induced bone formation was enhanced by inhibiting Cyp26b1. The cranial defect repair was promoted by BMP9, which was strengthened by silencing Cyp26b1 and reduced by exogenous Cyp26b1. Mechanically, Cyp26b1 was reduced by BMP9, which was enhanced by activating Wnt/b-catenin, and reduced by inhibiting this pathway. b-catenin interacts with Smad1/5/9, and both were recruited at the promoter of Cyp26b1. @*CONCLUSIONS@#Our findings suggested the BMP9-induced osteoblastic differentiation was mediated by activating retinoic acid signalling, viadown-regulating Cyp26b1. Meanwhile, Cyp26b1 may be a novel potential therapeutic target for the treatment of bone-related diseases or accelerating bone-tissue engineering.

The diagnostic value of serum levels of pro calcitonin, β2 defensins, C-reactive protein and the positive rate of group B streptococci in preterm premature rupture of membranes with amniotic infection / 中国医师杂志

Objective:To explore the diagnostic value of serum levels of pro calcitonin (PCT), β2 defensins (HBD-2), C-reactive protein (CRP) and the positive rate of group B streptococci (GBS) in preterm premature rupture of membranes (PROM) with amniotic infection.Methods:This study was a retrospective study. 156 pregnant women with preterm PROM who were diagnosed by the Obstetrics Department of the Hospital of Southern University of Science and Technology from January 2017 to January 2022 were selected as the study subjects. According to whether there was amniotic infection, they were divided into 57 infected women and 99 non infected women. The levels of serum PCT, HBD-2 and CRP before delivery were compared between the two groups, and the positive rate of GBS in vaginal discharge was detected, and the receiver operating curve (ROC) was used to analyze the value of various indicators in diagnosing amniotic cavity infection in preterm PROM mothers.Results:The serum levels of PCT, HBD-2, CRP, and GBS positivity in the infected group were significantly higher than those in the non infected group, with statistically significant differences (all P<0.01); The area under the curve (AUC) value, sensitivity, and specificity of serum PCT for diagnosing preterm PROM with amniotic cavity infection were 0.894, 82.56%, and 80.74%, respectively; The AUC value of HBD-2 for diagnosing preterm PROM with amniotic cavity infection was 0.792, the sensitivity was 70.78%, and the specificity was 77.59%; The AUC value, sensitivity, and specificity of CRP in diagnosing preterm PROM with amniotic cavity infection were 0.756, 68.94%, and 72.78%, respectively; The positive rate of GBS in vaginal discharge was 0.733, the sensitivity was 64.91%, and the specificity was 81.82%. Conclusions:The serum levels of PCT, HBD-2, CRP and the positive rate of GBS in vaginal discharge of pregnant women with preterm PROM complicated with amniotic infection will increase significantly. All indicators have high practical value for the diagnosis of preterm PROM complicated with amniotic infection.

Effect of long-term combination anti-retroviral therapy on cardiovascular disease risks in human immunodeficiency virus/acquired immunodeficiency syndrome patients / 中华传染病杂志

Objective:To explore the risks of cardiovascular disease (CVD) and influencing factors in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients with long-term combination anti-retroviral therapy (cART).Methods:The baseline data from the multi-center prospective cohort of HIV/AIDS patients who received long-term cART from 2018 to 2020 were collected. cART-naive HIV/AIDS patients were matched by age and gender using the propensity score matching (PSM) as controls. Data collection adverse events of anti-human immunodeficiency virus drugs reduced model (D: A: D[R]) score, Framingham risk score (FRS) and atherosclerotic cardiovascular disease (ASCVD) risk score were used to assess the 10-year CVD risk in patients with long-term cART treatment and in cART-naive patients. Logistic regression analysis was used to assess the risk factors related to high 10-year CVD risk.Results:A total of 301 HIV/AIDS patients received long-term cART and 300 cART-naive HIV/AIDS patients were included, with an average age of 39.8 years old. There were 490 male accounting for 81.5%. Based on the D: A: D [R] score, 4.3%(13/301) of patients in the long-term cART group had a 10-year CVD risk assessment of ≥10%, and 6.3%(19/300) of patients in the cART-naive group. Based on the FRS, 13.4%(36/269) of patients in the long-term cART group had a 10-year CVD risk assessment of ≥10%, and 10.6%(28/264) in the cART-naive group. Based on the ASCVD risk score, 10.4%(14/135) of patients in the long-term cART group had a 10-year CVD risk assessment of ≥7.5%, and 13.8%(17/123) in the cART-naive group. There was no significant difference in the prevalence of high 10-years CVD risk between the long-term cART group and the cART-naive group assessed by any of risk equations (all P>0.050). By multivariate logistic regression analysis, the risk factors associated with 10-year CVD risk ≥10% assessed by D: A: D[R] model were age≥50 years, smoking, hypertension, diabetes, dyslipidemia and CD4 + T lymphocyte count <200×10 6 cells/L (adjusted odds ratio ( AOR)=697.48, 4 622.28, 23.11, 25.95, 27.72 and 18.25, respectively, all P<0.010). The risk factors associated with 10-year CVD risk ≥10% assessed by FRS were age≥50 years, male, smoking, hypertension, diabetes and dyslipidemia ( AOR=53.51, 4.52, 36.93, 36.77, 6.15 and 3.84, respectively, all P<0.050). The risk factors associated with 10-year CVD risk ≥7.5% assessed by ASCVD risk score were age≥50 years, male, smoking, hypertension, diabetes ( AOR=18.48, 14.11, 14.81, 13.42 and 12.41, respectively, all P<0.050). Conclusions:Long-term cART has no significant effect on the 10-year CVD risk in HIV/AIDS patients. Higher CVD risk in HIV/AIDS patients are mainly associated with CD4 + T lymphocyte counts<200×10 6 cells/L and traditional CVD risk factors, including age≥50 years old, smoking, hypertension, diabetes and dyslipidemia.

Research progress and future development prospect of transanal total mesorectal excision / 中华胃肠外科杂志

Transanal total mesorectal excision (taTME) is one of the hotspots in colorectal surgery in recent years. Although most studies confirm that taTME is safe and feasible, some studies still showed that the morbidity of complication and local recurrence rate of taTME were higher than traditional laparoscopic surgery. This article reviews and analyzes the short-term and long-term outcomes of taTME and the related progress of postoperative function. The results showed that there were no significant differences in the main short-term and long-term efficacy between taTME and traditional laparoscopic TME, but taTME had potential advantages in postoperative functional recovery. The results of case study after passing the learning curve suggested that taTME had better short-term and long-term efficacy. Moreover, with the maturity of taTME technology, transanal endoscopic surgery has gradually shown its advantages in the treatment of complex pelvic diseases. In the future, the application of single-port robot will further promote the development of natural orifice transluminal endoscopic colorectal surgery.

Efficacy of transanal hand-sewn reinforcement in low rectal stapled anastomosis in preventing anastomotic leak after transanal total mesorectal excision / 中华胃肠外科杂志

Objective: To explore the efficacy and feasibility of transanal hand-sewn reinforcement of low stapled anastomosis in preventing anastomotic leak after transanal total mesorectal excision (taTME). Methods: A descriptive cohort study was conducted. Clinical data of 51 patients with rectal cancer who underwent taTME with transanal hand-sewn reinforcement of low stapled anastomosis at Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2020 were retrospectively collected. Inclusion criteria: (1) age >18 years old; (2) rectal cancer confirmed by preoperative pathology; (3) distance from tumor to anal verge ≤ 8 cm according to pelvic MR; (4) the lesion was evaluated to be resectable before operation; (5) with or without neoadjuvant chemotherapy and radiotherapy; (6) taTME, end-to-end stapled anastomosis, and reinforcement in the anastomosis with absorbable thread intermittently were performed, and the distance between anastomosis and anal verge was ≤ 5 cm. Exclusion criteria: (1) previous history of colorectal cancer surgery; (2) emergency surgery due to intestinal obstruction, bleeding or perforation; (3) patients with local recurrence or distant metastasis; (4) the period of postoperative follow-up less than 3 months. The procedure of transanal hand-sewn reinforcement was as follows: firstly, no sign of bleeding was confirmed after checking the anastomosis. Then, the anastomosis was reinforced by suturing the muscle layer of rectum intermittently in a figure-of-eight manner using 3-0 single Vicryl. The entry site of the next suture was close next to the exit site of the last one. Any weak point of the anastomosis could also be reinforced according to the specimen from the circular stapler. The primary outcome were the incidence of anastomotic leak, methods of the secondary operation, anastomotic infection, anastomotic stricture, and conditions of Intraoperative and postoperative. Results: All the 51 enrolled patients completed surgery successfully without any conversion to open surgery. The median operative time was 169 (109-337) minutes, and the median intraoperative blood loss was 50 (10-600) ml. The median postoperative hospital stay was 8 (5-16) days. The mssorectum was complete and distal resection margin was negative in all patients. Postive circumferential resection margin was observed in 1 patients (2.0%). Twelve (23.5%) patients underwent prophylactic ileostomy. One patient developed anastomosis stricture which was cured by digital dilatation of the anastomosis. ISREC grade C anastomotic leak was observed in 3 (5.9%) male patients, of whom 2 cases did not received prophylactic ileostomy during the operation, and were cured by a second operation with the ileostomy and anastomotic repair. The other one healed by transanal repair of the anastomosis and anti-infection therapy. One (2.0%) patient suffered from perianal infection and healed by sitz bath and anti-infection therapy. No death was reported within 30 days after operation. Conclusion: Transanal hand-sewn reinforcement in low rectal stapled anastomosis in preventing anastomotic leak after taTME is safe and feasible.

Evaluation of hospital-community-family multiple maintenance chronic disease management model for people with cognitive impairment / 中华神经科杂志

Objective:To explore the construction of hospital-community-family multiple maintenance management model for Alzheimer′s disease (AD) population and its clinical intervention effect.Methods:Two hundred patients with AD admitted to the Second Affiliated Hospital of Nanchang University from January 2018 to December 2020 were selected as the research subjects, including 92 cases in control group and 108 cases in study group. The control group adopted the conventional management mode of hospital combined with family care. The study group adopted the hospital-community-family multiple maintenance management mode. The improvement of medication compliance, mental state, cognitive function and quality of life were compared between the two groups before intervention and six, nine and 12 months after intervention using neuropsychological scales.Results:Compared with before intervention (4.57±1.01 and 56.55±3.83), the scores of Morisky Medication Adherence Scale 8 (MMAS-8; 5.33±1.05, 5.84±1.17 and 5.91±1.24) and the World Health Organization Quality of Life Instrument, Short Form (WHOQOL-BREF; 59.23±3.43, 61.47±3.56 and 62.24±3.45) in the control group increased six, nine and 12 months after intervention ( t=5.003, 7.881, 8.037, 4.795, 8.823, 10.380, all P<0.05), while the scores of Montreal Cognitive Assessment (MoCA) Scale had no significant change. The scores of MMAS-8 (5.96±1.11, 7.13±1.09 and 7.15±1.11), MoCA (19.96±1.31, 20.36±1.47 and 20.42±1.52) and WHOQOL-BREF (62.76±3.52,65.25±3.43, and 65.87±3.56) in the study group increased six, nine and 12 months after intervention and were higher than those in the control group (MoCA: 19.03±1.48, 18.65±1.51 and 18.59±1.44; t=4.101, 8.064, 7.460, 4.713, 9.088, 8.693, 7.152, 7.633, 7.290, all P<0.05). There were significant differences between groups, time points and interaction between groups in the scores of MMAS-8, MoCA and WHOQOL-BREF. Conclusion:The construction of hospital-community-family multiple maintenance management model for AD patients has a positive effect on improving the quality of life and prognosis of AD patients, which is worthy of further promotion and application.

Light and heat of moxibustion for knee osteoarthritis：a multi-center randomized controlled trial / 中国针灸

OBJECTIVE@#To explore the clinical therapeutic effect of light and heat of moxibustion for knee osteoarthritis (KOA).@*METHODS@#A total of 216 patients with KOA were randomized into a traditional moxibustion group (72 cases, 8 cases dropped off), a moxibustion light group (72 cases, 9 cases dropped off) and a moxibustion heat group (72 cases, 10 cases dropped off).The special light-heat separation moxibustion cup was applied, the patients in the traditional moxibustion group received the treatment of moxibustion, the patients in the moxibustion light group received the treatment of moxibustion light and the patients in the moxibustion heat group received the treatment of moxibustion heat. The acupoint selection of the three groups was Neixiyan (EX-LE 4), Dubi (ST 35) and Zusanli (ST 36), the treatment was given 20 min each time, 3 times a week, 4 weeks were required totally, and the follow-up surveys were made 4 and 8 weeks after treatment. The scores of Western Ontario and McMaster University osteoarthritis index (WOMAC) and visual analogue scale (VAS) were observed before treatment, after 2 and 4 weeks of treatment, 4 and 8 weeks after treatment. The therapeutic effects were evaluated according to the criterion of patient global assessment (PGA) after 4 weeks of treatment and 8 weeks after treatment.@*RESULTS@#Compared with before treatment, the pain scores, stiffness scores, physical function scores and total scores of WOMAC were reduced after 2, 4 weeks of treatment and 4 weeks after treatment in the three groups (<0.05). The pain scores, stiffness scores, physical function scores and total scores of WOMAC were reduced 8 weeks after treatment in the traditional moxibustion group and the moxibustion heat group (<0.05). The stiffness score, physical function score and total score of WOMAC were reduced 8 weeks after treatment in the moxibustion light group (<0.05). The pain score, physical function score and total score of WOMAC in the traditional moxibustion group after 4 weeks of treatment were lower than the moxibustion light group (<0.05). Compared with before treatment, the VAS scores were reduced after 2, 4 weeks of treatment and 4 , 8 weeks after treatment in the three groups (<0.05). The improvement rates in the traditional moxibustion group and the moxibustion heat group after 4 weeks of treatment and 8 weeks after treatment were superior to the moxibustion light group (<0.05).@*CONCLUSION@#The light and heat of moxibustion have therapeutic effect for KOA, and the therapeutic effect of moxibustion heat is superior to moxibustion light.

Effect of Task-based Rehabilitation Training on Neural Circuit Plasticity and Forelimb Motor Function post Spinal Cord Injury in Mice / 中国康复理论与实践

Objective:To explore the effect of task-based rehabilitative training on neural circuit plasticity and forelimb motor function after C5 spinal cord injury in mice. Methods:A total of 21 healthy C57/BL mice were randomly and equally divided into sham group, model group and training group. The model was established by left C5 spinal cord crush injury. The lamina was removed without damaging the spinal cord in the sham group. Four weeks after injury, the training group received task-based rehabilitative training for four weeks. The horizontal ladder and rearing tests were used to assess motor function for forelimb before injury, and three days, two weeks, four weeks, six weeks and eight weeks after injury. The axons of the corticospinal tract in all mice were observed six weeks after injury by using biotinylated dextran amin (BDA) anterograde tracing. Eight weeks after injury, motor-evoked potential was applied to measure nerve conduction velocities in forelimb, while the axon sprouting and syntagmatic relation of neuron in the anterior horn of gray matter above lesion were observed by immunofluorescence double-labeling of BDA/neuron-specific nuclei protein (NeuN); the expression of Synapsin in the anterior horn of gray matter at lesion was observed by immunofluorescence double-labeling of NeuN/Synapsin I. Results:Eight weeks after injury, the latency of P1 and N1 was longer in the model group than in the sham group (P < 0.05), and was shorter in the training group than in the model group (P < 0.05). Compared with the sham group, the error rate of left forelimb increased, and the usage rate decreased (P < 0.05) in the model group and the training group; compared with the model group, the error rate of left forelimb decreased six weeks and eight weeks after injury (P < 0.05), and the usage rate increased eight weeks after injury (P < 0.05) in the treatment group. Compared with the model group, more axon sprouting co-localized with neurons in the anterior horn of gray matter above lesion (P < 0.05), and the expression of Synapsin I increased in the training group (P < 0.05). Conclusion:Task-based rehabilitative training could promote the neural circuit plasticity and improve the motor function of forelimb after spinal cord injury in mice.

Advances in research of hyaluronic acid modified nanomicelles for targeting tumor therapy and drug release behavior / 中国药科大学学报

@#Hyaluronic acid, also called hyaluronan(HA)is a biocompatible and biodegradable linear polysaccharide which is of interest for tumor targeting through cell surface CD44 receptors. It is widely applied in the field of tumor therapy as an anticancer drug delivery carrier, and has become a hot spot in the research of tumor targeted drug delivery system. In tumor drug therapy, the key to reduce toxicity is to actively target tumors by using anatomical, pathophysiological and microenvironmental differences between malignant tumors and normal tissues. Differentiation cluster 44(CD44)is a high-affinity receptor for HA, which can be marked as a tumor marker or a targeting receptor because it is overexpressed in tumor cells. The overexpression of CD44 receptors was observed in many tumors such as breast cancer, colorectal cancer, liver cancer and pancreatic cancer. The effect of hyaluronic acid drug nanocarriers on various tumors is briefly described, indicating that the overexpression of CD44 receptor is an ideal choice for the treatment of hyaluronic acid-based drug carriers. The CD44 ligand can increase the affinity of the nanocarrier for tumor cells by binding to the nano drug carrier. The HA structure is known for its potent tumor targeting effect due to the inclusion of CD44 ligand, which enhances uptake of tumor cells by the HA-CD44 receptor-mediated endocytosis pathway. The study reviewed the progression of hyaluronic acid nanomicelles in clinical tumor therapy and its release behavior. The percentage of drug release and release rate are the key factors in the overall efficacy of the treatment strategy. Therefore, a great number of studies have focused on inducing drug release in Cytosol by taking advantage of the difference between the internal and external environments of nanostructured micelles or through external stimulation post-treatment applications. The study proved that an acid environment is more favorable to achieve a greater release and drugs can be quickly and completely released in an oxygen-deficient environment. In addition, the great potential of hyaluronic acid nanomicelles in tumor therapy was also further identified in this article. In vitro and in vivo experimental studies have repeatedly shown that hyaluronic acid-based nanomicelles are a drug- and gene-specific targeting tumor delivery method, in combination with passive targeting, this active targeting strategy is a promising approach to providing chemotherapy drugs to CD44 overexpressing tumors. In conclusion, hyaluronic acid-based nanomicelles are biologically safe with great potential to drug release, blood compatibility and systemic tumor targeting which all implied it has good application prospects in clinical tumor treatment.

Clinical Efficacy of Modified Xiao Wuweizitang Combined with Massage Manipulation on Chronic Post-infection Cough / 中国实验方剂学杂志

Objective: To observe the effect of modified Xiao Wuweizitang combined with massage manipulation on chronic post-infection cough (syndrome of wind-pathogenic pulmonary embedding), and immunity and inflammatory factors. Method: One hundred and thirty-five patients were randomly divided into control group and observation group by random number table. Patients (59 cases) in control group got Suhuang Zhike capsules, 1 granule/time for 3 to 6-year-old children, 2 granules/time, 3 times/days for 6 to 12-year-old children, and massage manipulation, 1 time/day. Patients (63 cases) in observation group got modified Xiao Wuweizitang combined with massage manipulation. A course of treatment was 10 days. Before treatment, and at the 5th and 10th day after treatment, visual analogue score of cough (VAS), cough symptom, syndrome of wind-pathogenic pulmonary embedding and leicester cough questionnaire (LCQ) were scored. And levels of CD3+, CD4+, CD8+, CD4+/CD8+, interleukin-8, IL-4, tumor necrosis factor-α (TNF-α), substance P (SP) and calcitonin gene related peptide (CGRP) were detected. Result: At the 5th and 10th day after treatment, scores of VAS, cough symptom and syndrome of wind-pathogenic pulmonary embedding in observation group were lower than those in control group (Pχ2=7.513,Pχ2=4.356, PPPα, IL-8, IL-4, CGRP and SP were lower than those in control group (PConclusion: Modified Xiao Wuweizitang combined with massage manipulation can relieve cough symptom, shorten the cough course, increase rate of the disappearance of cough, improve the quality of life of children, regulate immune function of children, reduce airway inflammation, airway hyperresponsiveness and cough reflex sensitivity.

Ultrasonic diagnosis of neonatal pneumothorax / 中国小儿急救医学

Neonatal pneumothorax is one of the common acute and severe diseases in newborns. Neonatal pneumothorax is of acute onset, fast progress, and can be life-threatening if not handled timely. Therefore,early and accurate diagnosis of pneumothorax and timely intervention are important. Lung ultra-sound has a unique advantage in the diagnosis of pulmonary diseases,real-time convenience,high sensitivity and specificity. It is the frontier medical technology that can visually evaluate pneumothorax.

Systemic disseminated Mycobacterium fortuitum infection:one case report and literature review / 中国感染控制杂志

Objective To explore the clinical characteristics of systemic disseminated infection caused by Mycobacterium fortuitum (M.fortuitum), and improve the diagnostic rate and understanding of the disease.Methods One case of systemic disseminated M.fortuituminfection was reported, and analyzed in combination with relevant literatures.Results Patient was with multiple systemic involvement (including lung, lymph node, skin, joint), lymph node tissue culture was positive for M.fortuitum, patient was given clarithromycin+levofloxacin+linezolid for treatment, disease was remitted.Conclusion Systemic disseminated M.fortuituminfection is rare, and patient with GATA2 deletion and IFN-γautoantibody may be a potential mechanism, diagnosis is mainly based on pathological morphology and microbiological detection, but positive rate is low, diagnosis is difficult.

Bmi-1 as A Molecular Marker for Prognosis of Pediatric ALL / 中国实验血液学杂志

OBJECTIVE@#To study whether the Bmi-1 gene can be a biomarker for analysis of clinical risk stratification and prognosis of ALL patients.@*METHODS@#The expression level of Bmi-1 gene in bone marrow samples from 127 cases of newly diagnosed ALL was detected by qRT-PCR, at the same time the expression level of Bmi-1 protein in bone marrow samples from above-mentioned cases was detected by Western blot. The collected samples were divided into 3 groups: high, intermediate and low risk according to clinical risk stratfication, the relationship between Bmi-1 expression and risk grade of ALL patients was analyzed; at the same time the collected samples were divided into 2 groups: prednisone good response (PGR) and prednisone poor respouse (PPR) according to the sensitivity of prednison test, and the sensitivily to prednisone in 2 groups was compared; moreover, the collected samples were divided into 2 groups: high level and low level according to median of Bmi-1 level, and the relation of Bmi-1 level with prognosis of patients was analyzed by using the Kaplan-Meier method.@*RESULTS@#The expression level of Bmi-1 in low risk group was lowest, while that in high risk group was highest, however that in intermediat risk group was between the low and high risk groups, statistical analysis showed significant difference (P＜0.05). The expression level of Bmi-1 in PPR group was significantly higher than that in PGR group (P＜0.001). The Kaplan-Meier analysis showed that the RFS rate in Bmi-1 high expression group was significantly lower than that in Bmi-1 low expression group (73.0% vs 90.6%) (P＜0.001).@*CONCLUSION@#The Bmi-1 can be used as a molecular marker for the analysis of chinical risk and prognosis of pediatric ALL.

Visualization and quantification of myocardial mechanical changes of left ventricle in systemic lupus erythematosus patients using ultrasonic layer‐specific strain imaging / 中华超声影像学杂志

Objective To evaluate the damage of longitudinal mechanical parameters of left ventricular myocardium by ultrasonic layer‐specific strain imaging in patients with systemic lupus erythematosus ( SLE ) without conventional evidence of cardiovascular system involvement . Methods Seventy‐eight patients suffered from SLE without conventional evidence of cardiovascular system involvement ( SLE group ) and 48 healthy volunteers with age and sex matched ( control group ) were selected for this study . T he left ventricular conventional structure and functional parameters were measured by conventional echocardiography . T hen layer‐specific strain imaging was performed in both groups to obtain left ventricular endocardial myocardial global longitudinal strain ( GLSendo ) ,mid‐myocardial GLS ( GLSmid) ,epicardial GLS ( GLSepi) and basal segment ,middle segment and apex longitudinal strain ( LS) of all three layers of the myocardium . T hen the transmural difference of the GLS ( ΔLS ＝ GLSendo －GLSepi) were calculated . T he related parameters between these two groups were compared for difference and correlation analysis of related mechanical parameters were also made . Results ① T here was no significant difference in the left ventricular ejection fraction ( LVEF ) and left ventricular stroke volume ( LVSV ) between the two groups ( all P ＞0 .05 ) ; Compared with the control group ,the mean E/e in the SLE group was increased and the E/A ,E ,e were decreased ( all P ＜0 .05) ; however ,the incidence of left ventricular diastolic dysfunction in the SLE group ( 2/78 ) was not significantly different from that in the control group ( 0/48 ) ( P ＞0 .05 ) . ② T he myocardial global longitudinal strain( GLS ) of the two groups were decreased from endocardial to epicardial gradient ; the values of GLS and segmental LS of all three layers in the SLE group were decreased ( all P ＜0 .05) ; the ΔLS of the SLE group was decreased compared with the control group ( P ＜ 0 .05 ) ; the value of peak strain dispersion ( PSD ) were increased in SLE patients ( P ＜ 0 .05 ) . ③ T he correlation analysis showed the GLS of each layer of myocardium in SLE patients were negatively correlated with disease duration ( rs ＝ －0 .34～ －0 .36 ,all P ＜ 0 .05 ) and SLE disease activity index ( SLEDAI) ( rs ＝ －0 .25～ －0 .30 ,all P ＜0 .05 ) . Conclusions T he ultrasonic layer‐specific strain imaging can quantitatively detect the damage of mechanical parameters of left ventricle in SLE patients ,w hich is more sensitive than the conventional echocardiography in evaluating left ventricular systolic function . It may provide visual evidence for early diagnosis of cardica dysfunction in SLE patients .

Research progress of biological effects of deuterium-depleted water / 上海交通大学学报（医学版）

When the deuterium concentration of water is lower than 0.015%, the water is known as deuterium-depleted water (DDW), deuterium-poor water or super light water. Deuterium-depleted water may affect the biochemical and metabolic processes of living organisms, for it has some biological effects such as anticancer effect, antioxidant effect, hypoglycemic effect, antidepressant effect and so on. Deuterium-depleted water appears to have little toxic side effects and is convenient to administer, so it may act as an adjuvant therapeutic agent in clinical treatment of diseases. In this paper, advances in research on biological effects of deuterium-depleted water were reviewed.

Plasma exchange combined with double plasma absorption therapy improve the prognosis of acute-on-chronic liver failure / 中华肝脏病杂志

Objective@#To compare the efficacy and safety of plasma exchange (PE) combined with double plasma absorption and simple PE in the treatment of acute-on-chronic liver failure.@*Methods@#We retrospectively analyzed 251 cases of acute-on-chronic liver failure treated with artificial liver treatment since January 2015. Changes in clinical manifestations, laboratory tests, and complications of the patients before and after different modes of treatment were compared and short-term efficacy was tracked. In accordance with different data, t-test, Pearson's chi-squared test and Fisher's exact test were used for statistical analysis.@*Results@#The effectiveness of low-volume PE combined with double plasma molecular adsorption system (DPMAS) and equal amount of PE combined with DPMAS was significantly better than simple PE (83.7%, 84.05% and 82.15 vs 55.6%, P < 0.05) in early stage of liver failure. In late-stage of liver failure, there was no significant difference in the treatment efficiency of each group (P > 0.05). Bilirubin and bile acid levels were significantly decreased in combined treatment groups than that to simple PE group (P < 0.05). PTA and albumin improvement rate of DPMAS PE groups were significantly lower than that of simple PE group (P < 0.05). There was no statistical difference in adverse reactions between each group.@*Conclusion@#PE combined with DPMAS improves the treatment efficiency of early hepatic failure and decrease dosage of plasma when compared with simple PE. A beforehand DPMAS treatment after PE treatment can improve the adverse effects of DPMAS on blood coagulation function and albumin levels.