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ObjectiveTo achieve high-dimensional prediction of class imbalanced of adverse drug reaction（ADR） of traditional Chinese medicine（TCM） and to classify and identify risk factors affecting the occurrence of ADR based on the post-marketing safety data of TCM monitored centrally in real world hospitals. MethodThe ensemble clustering resampling combined with regularized Group Lasso regression was used to perform high-dimensional balancing of ADR class-imbalanced data， and then to integrate the balanced datasets to achieve ADR prediction and the risk factor identification by category. ResultA practical example study of the proposed method on a monitoring data of TCM injection performed that the accuracy of the ADR prediction， the prediction sensitivity， the prediction specificity and the area under receiver operating characteristic curve（AUC） were all above 0.8 on the test set. Meanwhile， 40 risk factors affecting the occurrence of ADR were screened out from total 600 high-dimensional variables. And the effect of risk factors on the occurrence of ADR was identified by classification weighting. The important risk factors were classified as follows：past history， medication information， name of combined drugs， disease status， number of combined drugs and personal data. ConclusionIn the real world data of rare ADR with a large amount of clinical variables， this paper realized accurate ADR prediction on high-dimensional and class imbalanced condition， and classified and identified the key risk factors and their clinical significance of categories， so as to provide risk early warning for clinical rational drug use and combined drug use， as well as scientific basis for reevaluation of safety of post-marketing TCM.
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Objective:To report a newborn with Goltz syndrome and a de novo mutation in the PORCN gene. Methods:Clinical data collected from a newborn with Goltz syndrome were retrospectively analyzed. Peripheral venous blood samples were obtained from the newborn and her parents, genomic DNA was extracted, whole-exome sequencing was performed to screen disease-causing genes in the patient, and Sanger sequencing was conducted to verify the mutant genes.Results:The 7-hour-old female newborn presented with scalp defects, multiple epidermal defects on the face and inner side of both knee joints, deformity of the left auricle, syndactyly of the middle and ring fingers of the right hand as well as the great and second toes of the right foot, and lobster-claw deformity of the left foot. Genetic testing showed that a fragment TCCTTCCA was inserted at position 514-521 in exon 4 of the PORCN gene of the patient (c.514_521dupTCCTTCCA) , resulting in the substitution of serine by proline at amino acid position 175 (p.S175Pfs*14) , followed by translation termination at the 14th codon. This heterozygous mutation was not found in her parents. The patient was diagnosed with Goltz syndrome. Conclusions:There are various phenotypes of Goltz syndrome, and a confirmed diagnosis of Goltz syndrome can be made based on PORCN gene mutations and clinical manifestations. The heterozygous mutation c.514_521dupTCCTTCCA is a novel mutation.
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Objective@#To observe the changes of liver function, virology and serology and the safety of drug withdrawal in pregnant women who are chronic hepatitis B virus (HBV) carriers.@*Methods@#A prospective clinical cohort was established to enroll pregnant women who are chronic HBV carriers and they were divided into the nucleoside/nucleotide analogs (NAs) intervention group and the non-NAs intervention group according to patients' wishes. Liver function, HBV DNA and HBV serological markers were detected at gestation, postpartum 6 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks.@*Results@#351 patients were enrolled, 320 in the NAs intervention group and 31 in the non-NAs intervention group. The proportion of postpartum hepatitis flares in both groups was higher than that in pregnancy (39.4% vs 12.5%, P < 0.001; 38.7% vs 3.2%, P = 0.001). Six weeks postpartum was the peak period of hepatitis flares, and 96.0% (121/126) of the hepatitis flares occurred within 24 weeks postpartum. At 6 weeks postpartum, there were 6 cases of alanine aminotransferase (ALT) ≥ 10 times upper limit of normal (ULN) in the NAs intervention group. The rate of the hepatitis flare after drug withdrawal was 16.7% (34/203).@*Conclusion@#Regardless of the presence or absence of NAs intervention, pregnant women who are chronic HBV carriers have a certain proportion of hepatitis flares during pregnancy and postpartum, and the hepatitis flare even have a tendency to be severe. Therefore, drug withdrawal after delivery is not always safe, which requires close observation and classification. At 6 weeks postpartum, the incidence of hepatitis flares was high, and those who meet the treatment indications can get better therapeutic effects if given appropriate treatment. The vast majority (96%) of postpartum hepatitis flares occur within 24 weeks, so it is recommended to follow up to at least 24 weeks postpartum after discontinuation.
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Objective@#To explore clinical features and prognosis factors of surgical complications after intersphincteric resection (ISR) for low rectal cancer following neoadjuvant chemoradiotherapy.@*Methods@#The clinical data of 132 patients with low rectal cancer who underwent ISR following neoadjuvant chemoradiotherapy from September 2010 to June 2017 at Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University were retrospectively reviewed. There were 100 males and 32 females, with the age of (52.9±11.4) years and distance to anal verge of 3.9 cm. Records of perioperative complication (POC) within 30 days after surgery, anastomotic leakage (AL), and anastomotic stenosis (AS) were analyzed. POC was recorded according to the Clavien-Dindo classification. AL was graded by ISREC system and classified into the early AL within 30 days after surgery and delayed AL beyond 30 days. AS was defined as narrowing of the bowel lumen at the anastomosis that prevented passage through a colonoscope with a 12 mm diameter. According to the shape of narrowing, AS was recorded as the stenosis in situ or stenosis with long-segment bowel above. Univariate and multivariate analysis were used to identify risk factors of anastomotic complications.@*Results@#Among the 132 patients, full-dose radiotherapy and diverting stoma were performed in 128 (97.0%) patients, respectively. In entire cohort, AL was found in 41 (31.1%) patients, including 32 patients with clinical leakage (24.2%). The median time for diagnosis of AL was 37 days (2 to 214 days) after surgery. There were 25 patients (18.9%) who were diagnosed with delayed AL beyond 30 days. Chronic presacral sinus formation was detected in 22 of 129 (17.1%) patients at 12 months from surgery. Among the 128 eligible patients, 36 (28.1%) were diagnosed as AS, including 24 (18.8%) patients with stenosis in situ and 12 (9.4%) patients with bowel stenosis above. After a median follow-up of 26 months, 7(5.3%) patients received permanent colostomy and the other 20(15.2%) patients retained a persistent ileostomy, owing to anastomotic complications. Results of multivariate analysis showed that radiation colitis was an independent prognosis factor of AL after ISR (OR=5.04, 95% CI: 2.05 to 12.43, P=0.000); male gender (OR=5.19, 95% CI: 1.24 to 21.75, P=0.024) and AL (OR=8.49, 95% CI: 3.32 to 21.70, P=0.000) were independent prognosis factors of AS after ISR.@*Conclusions@#Surgical complications are common after ISR for low rectal cancer patients with neoadjuvant chemoradiotherapy. A high rate of AL is observed after long-term follow-up, which is associated with AS. Increasing awareness of anastomotic complications after ISR should be raised, especially for male patients with radiation colitis.
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OBJECTIVE:To observe the effects of butylphthalide combined with alteplase on neural funetion and cognitive function and serological indexes as homocysteine(Hcy)in patients with acute cerebral infarction(ACI).METHODS:Clinical information of 78 ACI patients in emergency department of our hospital during Feb.2140-Apr.2017 were analyzed and then divided into control group and observation group according to therapy plan,with 39 cases in each group. Both groups received conventional treatment and Aspirin enteric-coated tablets orally. Control group was given Alteplase for injection 0.9 mg/kg for verous thromblysis on the basis of conventional treatment. Observation group was additionally given Butyphthalide soft capsules 0.2 g orally,tid,on the basis of control group. Both groups were treated for consecutive 28 days. The clinical efficacies of 2 groups were observed. NIHSS and MMSE scores before treatment,3,7,14 and 28 d after treatment,the levels of Hcy,NSE and 6-k-PGF1a were observed in 2 groups;the occurrence of ADR was recorded. RESULTS:After treatment,total response rate of observation group was 92.31%,which was significantly higher than 71.79% of control group,with statistical significance(P<0.05). 3-28 d after treatment,NIHSS scores of 2 groups were decreased gradually and significantly lower than before treatment;MMSE scores of 2 groups were increased gradually and significantly higher than before treatment,with statistical significance(P<0.05 or P<0.01). 7-28 d after treatment,NIHSS score of observation group was significantly lower than that of control group at same time,while MMSE score was significantly higher than control group, with statistical significance(P<0.05 or P<0.01). After treatment,serum levels of Hcy and NSE in 2 groups were decreased significantly,and observation group was significantly lower than control group;the level of 6-k-PGF1a was increased significantly,and observation group was significantly higher than control group,with statistical significance(P<0.05 or P<0.01). There was no statistical significantce in the total incidence of ADR between 2 groups(P>0.05). CONCLUSIONS:Butylphthalide combined with alteplase can significantly improve neurologic impairment and cognitive function of ACI patients,reduce serum levels of Hcy and NSE and increase the level of 6-k-PGF1a. Clinical efficacy of it is significantly better than alteplase alone.
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<p><b>OBJECTIVE</b>To evaluate the short-term outcomes and perioperative safety of proximally extended resection for locally advanced rectal cancer after neoadjuvant chemoradiotherapy.</p><p><b>METHODS</b>From colorectal cancer database in The Sixth Affiliated Hospital of Sun Yat-sen University, a cohort of patients who underwent neoadjuvant chemoradiotherapy(1.8-2.0 Gy per day, 25-28 fractions, concurrent fluorouracil-based chemotherapy) followed by curative sphincter-preserving surgery for locally advanced rectal cancer between May 2016 and June 2017 were retrospectively identified. Exclusion criteria were synchronous colon cancer, intraoperatively confirmed distal metastasis, multiple visceral resection, and emergency operation. Thirty-one patients underwent proximal extended resection and two were excluded for incomplete extended resection, then 29 patients were enrolled as the extended group. Using propensity scores matching with 1/1 ration, 29 locally advanced rectal cancer patients who underwent conventional resection after neoadjuvant chemoradiotherapy at the same time were matched as the conventional group. Clinical data of two groups were analyzed, and the baseline characteristics and short-term outcomes were compared using the t test, χtest, or Mann-Whitney U test.</p><p><b>RESULTS</b>Two groups were well balanced with respect to the baseline characteristics after propensity score matching. As compared with conventional group, patients in extended group had longer surgical specimen [(18.8±5.1) cm vs.(11.6±3.4) cm, t=6.314, P=0.000] and longer proximal resection margin [(14.8±5.5) cm vs.(8.2±3.0) cm, t=5.725, P=0.000], but also had longer total operating time [(322.4±100.7) min vs.(254.6±70.3) min, t=2.975, P=0.004] and more intraoperative blood loss [100(225) ml vs. 100(50) ml, Z=-2.403, P=0.016]. No significant differences were observed in the length of distal resection margin, ratio of positive resection margin, number of retrieved lymph node, time of analgesic use, time of draining tube use, time to first flatus, time to first oral diet, and postoperative hospital stay. During the perioperative period of 30 days, the morbidity of complication in extended group and conventional group was 17.2%(5/29) and 34.5% (10/29), respectively (P=0.134).</p><p><b>CONCLUSION</b>Proximally extended resection is a radical and safe surgical alternative for locally advanced rectal cancer after neoadjuvant chemoradiotherapy, which can potentially reduce the risk of anastomosis complication.</p>
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In this paper,the constitute elements of Sino-US licensed doctors' practical skill examination evaluation index system are expounded.Through comparison,the differences on the formulation basis,classification principle,test content,and ability requirements are inferred;On the basis of referring to the advanced experience and practice of the United States,and by combining the requirements of the most basic requirements of global medical education,suggestions for improving the Chinese licensed doctors' practical skill examination evaluation index system are proposed in terms of integrating the test syllabus classification,adjusting the distribution of clinical practice ability examination content,increasing the proportion of medical humanities content test,as well as establishing a scientific examination evaluation index weight table.
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This paper briefly introduced the development course, present situation and characteris-tics of United States Medical Licensing Clinical skills examination. Based on the elaboration of four key elements, namely organization and management, subjects setting, method and form, and evaluation method-ology, we analyzed the advantages and disadvantages, to provide experiences and references for improving and perfecting our country's Medical Licensing Clinical skills examination.
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Objective The study was designed to evaluate the clinical efficacy of azithromycin in lung function of patients with IPF.Methods Randomized controlled trials were searched in CNKI,data-base of Wanfang and WeiPu,where azithromycin was used to patients with IPF.We extracted all data on lung functions,standardized mean difference (SMD)with 95% confidence intervals (CI )were pooled with Stata 11.0.Results Seven unique trials with 516 participants were identified.Be compared to pred-nisone,the patients with IPF received azithromycin experienced no improvement in FVC% [SMD = -2.00,95% CI =(-2.05,-1.95)],but it was found that azithromycin was superior to prednisone in in-crease the percentage of carbon monoxide diffusing [SMD =1.16,95% CI =(-2.83,5.16)]and de-cline the percentage of residual volume[SMD =3.00,95% CI =(1.04,4.96)].Azithromycin combined with prednisone were statistically superior to prednisone alone in improvement of FEV1 %[SMD =7.80, 95% CI =(5.92,9.67)],FVC%[SMD =7.23,95% CI =(4.89,7.56)]and lung carbon monoxide diffusion function[ml/(min·kpa))][SMD =40.62,95% CI =(38.96,42.28)].Conclusions Our study suggests that azithromycin significantly improvement pulmonary diffusion function in patients with IPF. Azithromycin combined with prednisone were more effective in improvement of FEV1 %,FVC% and lung diffusion function.
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To study the bacteriostat, anti-inflammatory and relieving itching effects of Yinyanjing gel. Methods: A double dilution method was used to detect the in vitro bacteriostat effect of Yinyanjing gel. The therapeutic effects of Yinyanjing gel on bacterial vaginitis were observed in rats. The antipruritic effect of Yinyanjing gel was observed in guinea pigs. Results:MIC for Staphy-lococcus aureus was 47. 39 mg·ml-1 , and that for Escherichia coli was 189. 59 mg·ml-1 . The therapeutic effects of Yinyanjing gel on bacterial vaginitis were significant. Yinyanjing gel showed notable antipruritic effect on the itching induced by histamine phosphate in guinea pigs. Conclusion:Yinyanjing gel exhibits significant effects of bactriostasis,anti-inflammation and relieving itching.
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Objective To study the effects of enteral nutrition( EN) on inflammatory factors and cardiac function in elderly patients with heart failure ( HF ) . Methods A total of 96 elderly patients with HF were enrolled in this study and randomly divided into treatment group A,treatment group B and control group( n= 32 in each group) . Patients in group A were provided with 500 mL of EN daily for 1 month, and those in group B were provided with the same dose of EN for 3 months. Control group was treated with normal diet. The nutrition status of each group was assessed by NRS2002. Meanwhile,all patients were evaluated by New York Heart Association(NYHA) class and left ventricle eject fraction(LVEF). The levels of BNP,IL-6, CRP and TNF-α were also measured before and after nutrition treatment. Results In group A and group B,BMI,TSF,AMC, TP,ALB and HGB increased. Symptoms of HF alleviated quickly and LVEF increased compared to the baseline. The levels of BNP,IL-6,CRP and TNF-α were significantly lower after treatment(P<0. 05) in both treatment groups,and the change in group B was more obvious(P<0. 01) than group A. However,in control group,there is neither evident improvement in cardiac function or nutrition status,nor in inflammatory factor levels. Conclusion Adding EN support to the normal treatment of heart failure in elderly malnourished patients with HF not only improves the function of heart and nutrition status, but also helps to support immune system so as to alleviate acute inflammatory response. The benefits from EN depend on the duration of therapy.
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To investigate the plasma thioredoxin-interacting protein ( TXNIP ) levels in different glucose tolerance groups and discuss the relationship between TXNIP and insulin resistance/β-cell dysfunction in diabetes and prediabetes, and to investigate the potential relationship between TXNIP and interleukin-1β( IL-1β) . According to oral glucose tolerance test, 93 participants were divided into 3 groups:diabetes mellitus group, prediabetes group, and normal glucose tolerance group. Plasma TXNIP, IL-1β, and other biochemical indices were measured. The relationship between TXNIP and glucose, IL-1β, homeostasis model assessment for insulin resistance ( HOMA-IR) , and homeostasis model assessment forβcell function ( HOMA-β) were analyzed by using multiple linear regression techniques and Pearson’s linear correlation analysis. Plasma TXNIP level was higher in prediabetes group compared with normal glucose tolerance group, but lower in prediabetes group compared with diabetes mellitus group[(355. 35±31. 88 vs 274. 36±33. 86, 426. 16±63. 15)pg/ml, P<0. 01 or P<0. 05]. TXNIP was positively correlated with IL-1βand HOMA-IR, but negatively correlated with HOMA-β. Multiple linear regression analysis indicated that IL-1βexerted significant influence on TXNIP ( P<0. 05 ). Plasma TXNIP level is affected by blood glucose concentration. There is a close relationship between TXNIP and IL-1β. In prediabetes patient, the TXNIP levels have already been raised.
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Objective To observe the expressions of Akt and ERK phosphorylation in abdominal aortic aneurysm of rat model, and explore the pathogenesis of abdominal aortic aneurysm. Methods The rat model of abdominal aortic aneu-rysm was established. The diameter of abdominal aorta was measured and the extended rate of the aorta was calculated. HE staining was used to observe the change of pathology. Immunohistochemistry and Western blot methods were used to detect the expressions of Akt and ERK phosphorylation in the level of protein. Results The dilation of aorta was significantly high-er in abdominal aortic aneurysm group than that of saline group and normal group (P＜0.05). HE staining showed structural disorder and inflammatory cell infiltration in abdominal aortic aneurysm group. The results of immunohistochemistry and Western blot results showed that phosphorylation of Akt expression was significantly higher in abdominal aortic aneurysm group than that of saline group and normal group (P＜0.05). There was no significant difference in phosphorylation of ERK expression between three groups (P>0.05). Conclusion PI3K/Akt signaling pathway may be involved in the development of abdominal aortic aneurysm.
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The result of medical licensing examination is an objective reflection of the quality of medical education. The average scores and pass rates of medical licensing examination of the military medical university including The Third Military Medical University, were under the national average levels, which made us find the problems, therefore, reflection on curriculum structure, teaching method, administration mode and continuing education should be integrated to the requirement of the medical licensing examination, so as to let the students meet the complex demand of the society, as well as the special requirement of military service.
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Objective To investigate the changes of serum thyroxine level in obstructive sleep apnea-hy-popnea syndrome(OSAHS) patients and to assess the role of serum thyroxine in the development of OSAHS. Meth-ods Polysomnography was used to examine the patients with OSAHS and fasting plasma serum thyroxine level were higher in obese OSAHS patients than in obese controls[ (43.56±3.48)cm vs (38.33±3.08)cm,t =4. 258,P < 0.05 ], in non-obese OSAHS patients than in non-obese control group [ (40.50±1.05 )cm vs (36.17±3.13 )cm, t = 3. 146 ,P < 0.05 ] . The levels of FT3 was (6.35±3.15 ) pmol/L in obese OSAHS patients and ( 4.08±2.37 ) pmol/L in control subjects ( t = 2.203 ,P < 0.05 ). That was ( 3.42±0.57 ) pmol/L in non-obese OSAHS patients related with AHI and microarousal index (r = 0. 500, P < 0.05;r = 0.561, P < 0.05 ), and FT4 was also positively with neck circumference( t = 0.489, P < 0.05 ), TSH level was negatively correlated with neck circumference ( t = - 0.500, P < 0.05 ) and was positively correlated with the percentage of body fat ( r = 0.498, P < 0.05 ). Conclu-sions The FT3 levels are significantly higher in the OSAHS patients than that in control subjects, though all FT3 lev-els are normal, suggesting that there are possibility to have abnormal metabolism. At the same time, FT3 level is posi-tively correlated with neck circumference ,suggesting that the OSAHS patients' higher neck circumference is correla-ted with thyroxine.
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OBJECTIVE:To observe the pharmacological effect of Ulinastatin on acute necrotizing pancreatitis in rats.METHODS:Animal models were divided into3groups:group A,sham operation;group B,acute necrotic pancreatitis given no treatment;group C,acute necrotic pancreatitis treated with Ulinastatin.The changes of AMS and TNF-?were compared at different time among3groups.RESULTS:AMS and TNF-?in group C were significantly different from those in group A and in group B.CONCLUSION:Ulinastatin could remarkably improve the prognosis of acute necrotic pancreatitis.
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AIM:To look for a better method to deal with interstitial lung disease,interferon-gamma(IFN-?)combined with methylprednisolone(M-pred)to influence human embryonic lung fibroblast on proliferation,collagen synthesis and the expression of transforming growth factor-?1(TGF-?1)protein and mRNA were investigated.METHODS:Exponentially growing cells were preincubated for 48 h before harvested.The microculture tetrazolium(MTT)assay was used to measure the inhibition ratios of M-pred combined with different concentrations of IFN-?.The expression of proliferation cell nuclear antigen(PCNA)was detected by immunocytochemical analysis.Hydroxyproline kit was adopted to detect collagen synthesis.The expressions of TGF-?1 mRNA and protein were detected respectively by RT-PCR and Western blotting.RESULTS:Methylprednisolone,IFN-? as well as the combination of methylprednisolone and IFN-? inhibited the proliferation of HELF and the expression of PCNA in comparison with control group(P
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AIM: To investigate the expression of iNOS in the lung of HPS rats treated with tumor necrosis factor-? monoclonal antibody(TNF-?-McAb) and to investigate the therapeutic mechanism of TNF-?-McAb on hepatopulmonary syndrome.METHODS: Male Sprague-Dawley rats,weighing(250?25)g,were randomized to sham operation group,common bile duct ligation(CBDL) group and CBDL+TNF-? McAb treatment group.Histopathological changes of the lung tissue were evaluated by hematoxylin and eosin staining.The mRNA expression of iNOS in the lungs of hepatopulmonary rats was examined by RT-PCR,while the changes of iNOS in the protein level were evaluated by immunohistochemistry and Western blotting.RESULTS: The inflammatory responses in the CBDL rats treated with TNF-?-McAb decreased than that in CBDL group.Compared to CBDL group,the distribution of iNOS protein and the mRNA expressions in the lung tissue in TNF-?-McAb group were inhibited.CONCLUSION: TNF-?-McAb inhibits the expression of iNOS and plays a role in the treatment of HPS.