OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.

BackgroundThe comorbidity rate of bipolar disorder and borderline personality disorder （BPD） is high， and the cognitive impairment of comorbidity patients is more serious. ObjectiveTo explore the difference of cognitive function between bipolar disorder patients with BPD or not， so as to provide references for clinical diagnosis and treatment. MethodsUsing simple random sampling， 60 patients with bipolar disorder comorbidity BPD treated in the First Hospital of Hebei Medical University from April 2021 to April 2022 were selected as the research group， including 33 patients with bipolar depression and 27 patients with bipolar mania. At the same time， 60 patients with bipolar disorder were randomly selected as the control group， including 35 patients with bipolar depression and 25 patients with bipolar mania. The cognitive function of patients was evaluated by the Chinese version of Repeatable Battery for the Assessment of Neuropsychological Status （RBANS） and the Stroop Color Word Test. ResultsThe immediate memory， visual span， speech function and total score of RBANS in the comorbid group were lower than those in the non-comorbid group， and the differences were statistically significant （t=-2.356， -2.138， -3.306， -2.729， P<0.05 or 0.01）. The single word time， single color time， double word time and double color time in Stroop Color Word Test in comorbid group were longer than those in non-comorbid group， and the differences were statistically significant （t=4.808， 3.341， 5.249， 5.167， P<0.01）. The immediate memory， visual span， speech function and total score in RBANS of bipolar depression patients with comorbid BPD were lower than those of bipolar depression patients without comorbid BPD （t=-2.446， -2.407， -2.231， -2.078， P<0.05）， and the time of single word， single color， double word and double color in Stroop Color Word Test were longer than those of non-comorbid BPD patients （t=-3.652， 3.035， 4.406， 5.016， P<0.01）. The speech function and total score of RBANS in bipolar manic patients in comorbid group were higher than those in non-comorbid group （t=-2.777， -2.347， P<0.05 or 0.01）， and the time of single word， single color， double word and double color in Stroop Color Word Test were longer than those in non-comorbid group （t=3.600， 2.658， 2.943， 4.337， P<0.05 or 0.01）. ConclusionThe cognitive impairment of bipolar disorder patients comorbid with BPD is more severe than that of patients without comorbid with BPD. ［Funded by Medical Science Research Project of Hebei Province in 2022 （number， 20221407）］

Objective:A high-throughput assay for the detection of five common clinical Candidaemia pathogens was established by combining polymerase chain reaction (PCR) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS).Method:Establishment of methodology. We selected Candida albicans, Candida parapsilosis, Candida glabrata, Candida krusei, Candida tropicalis to be the target pathogens and the internal transcribed spacer (ITS) region as the target gene. Specific single base extension primers were designed to perform single base extension reaction in the same reaction system. MALDI-TOF MS was used to detect the characteristic peaks of each target pathogen. The sensitivity and specificity of the detection system were verified by using spiked blood samples. Totally 108 blood samples from proven or suspected candidaemia patients were collected from October 2021 to September 2022 in a hospital in Beijing. The results of nucleic acid mass spectrometry were compared with those of clinical blood culture. Results:The established nucleic acid mass spectrometry detection system can simultaneously detect five common clinical Candida species. Each strain can produce specific product peaks and there is no mutual interference between the strains. The detection limit of Candida albicans was 100 CFU/ml. The detection limit of Candida parapsilosis, Candida glabrata, Candida krusei and Candida tropicalis was 10 CFU/ml. For the 108 blood samples, the sensitivity, specificity, positive predictive value and negative predictive value of nucleic acid mass spectrometry were 94.74% (36/38), 97.14% (68/70), 92.31% (36/39) and 98.55% (68/69), respectively. The McNemar χ 2 test showed no significant difference between the two methods ( P>0.05), and the Kappa consistency test showed good consistency between the two methods ( Kappa=0.9, P<0.05). Conclusion:A nucleic acid mass spectrometry detection system suitable for clinical candida detection was successfully constructed, and the method validation results were consistent with the clinical blood culture.

Objective: To investigate the clinical outcomes and radiological results of arthroscopic autologous scapular spine bone graft transplant to treat shoulder recurrent instability. Methods: Data of 27 patients diagnosed as shoulder recurrent instability with the bone defect of 10%-15% from July 2016 to August 2018 who were treated by arthroscopic autologous scapular spine bone graft transplant were retrospectively analyzed. There were 20 males and 7 females with an average age of 30.8 years old (range, 19-50). The bone loss of the glenoid was 10%-15%. The time between the first dislocation and the surgery was 24.1±15.8 months. The patients were treated with arthroscopic autologous scapular spine bone graft transplant. Postoperatively the affected shoulder was immobilized by the abduction brace for 6 weeks, after that the passive motion was applied. Strengthening exercise began at 10-12 weeks and sports was allowed after 6 months. Constant-Murley score and the Disabilities of Arm, Shoulder and Hand (DASH) score were used to evaluate the shoulder function, and visual analogue score (VAS) score was used to evaluate the degree of pain. Computed tomography scans were obtained one week post-operation and at the latest follow-up, from which the length, width, height and volume of the bone graft were measured and the absorption rate of the bone graft was calculated. The subjective satisfaction degree of patients at the latest follow-up was also recorded. Results: All 27 patients were followed up for 19.8 months (range, 13-39 months). No infection or neurovascular injury was identified. At the latest follow-up, the Constant-Murley score was 85.15±5.62 (range, 76-94), the DASH score 13.39±5.51 (range, 3.19-21.95) and the VAS score 1.29±0.45 (range, 1-2), thus all of those were improved significantly compared to those of pre-operation. At the latest follow-up, the anterior flexion was 153°±24°, lateral rotation by side 38°±21°, internal rotation 70°±21°, and abduction was 139°±18°. At the latest follow-up, the absorption rate of the bone graft was 46.1%±20.6% (range, 24.0%-71.7%). Among all the 27 patients, 19 patients considered the outcome as very good, and 6 patients considered as good, 2 patients fair. Conclusion Arthroscopic autologous scapular spine bone graft transplant could successfully treat shoulder recurrent instability with glenoid bone loss at 10%-15%. This technique could achieve satisfactory clinical results, improve glenohumeral stability, decrease the re-dislocation rate.

Objective:To explore the factors related to cognitive dysfunction after traumatic brain injury.Methods:A total of 55 patients with traumatic brain injury were analyzed retrospectively. The clinical information about the patients, including age, gender, paralyzed side, course of the disease, type of injury, degree of injury, treatment, speech function (grades of Boston aphasia severity), swallowing function (7-level evaluation method), limb motor function (Brunnstrom stages of the upper limb, hand and lower limb), complications (tracheotomy, lung infection, urinary tract infection, pressure sores, electrolyte imbalance and hypoproteinemia), whether the patient received rehabilitation therapy, and D-dimer and coagulation examination results were recorded. Univariate analysis and ordered multi-class logistic regression analysis were conducted to screen the related factors using Rancho Los Amigos cognitive function grades as the dependent variable.Results:The results of the univariate analysis showed that consciousness, aphasia severity, swallowing ability, Brunnstrom stages, having received a tracheotomy, urinary tract infection, hypoproteinemia, fibrinogen and D-dimer all significantly predicted Rancho Los Amigos cognitive function grades. The logistic regression analysis showed that disordered consciousness, aphasia severity, Brunnstrom stage of the upper limbs, and urinary tract infection were significant predictors.Conclusions:Disordered consciousness, aphasia severity, Brunnstrom stage of the upper limbs, and urinary tract infection are factors related to cognitive dysfunction after traumatic brain injury.

Objective:To compare the accuracy and generalized robustness of three predictive models of knowledge-based treatment strategies for radiotherapy for optimized model selection.Methods:The clinical radiotherapy plans of 45 prostate cancer (PC) cases and 25 nasopharyngeal cancer (NPC) cases were collected, and analyzed using three models (Z, L and S model), proposed by Zhu et al, Appenzoller et al and Shiraishi et al, respectively, to predict the dose-volume histogram (DVH) of bladder and rectum on PC cases and that of left and right parotid on NPC cases. The prediction error was measured by the difference of area under the predicted DVH and the clinical DVH curves (|V (pre_DVH)-V (clin_DVH)|), where a smaller prediction error implies a greater prediction accuracy. The accuracies of these three models were compared on the single organ at risk (OAR), and the generalized robustness of models was evaluated and compared by calculating the standard deviation of the prediction accuracy on different OAR. Results:For bladder and rectum, the prediction error of L model (0.114 and 0.163, respectively) was significantly higher than those values of Z and S models (≤0.071, P<0.05); for left parotid gland, the predicted error of S model (0.033) did not present significant difference from those values of Z and L models (≤0.025, P>0.05); for right parotid gland, S model (0.033) demonstrated significantly higher prediction error than those of Z and L models (≤0.028, P<0.05). Regarding different OAR, S model showed a lower standard deviation of prediction accuracy when comparing to Z and L models (0.016, 0.018 and 0.060, respectively). Conclusions:In the prediction of DVH in bladder and rectum of PC, Z and S models were more accurate than L model. In contrast, Z and L models demonstrated higher accuracy than S model in the prediction of left and right parotid glands of NPC. In respect to different OAR, the generalized robustness of S model was superior than the other two models.

To explore diagnostic value of platelet count (PLT) ,plasma D– dimer (D‐D) , antithrombin Ⅲ(AT‐III) levels and UACR for microvascular disease (MVD) in type 2 diabetes mellitus (T2DM).Methods : A total of 284 T2DM patients treated in our hospital were divided into no MVD group (n＝144) and MVD group (n＝140) according to MVD condition .Another 120 healthy people were enrolled as healthy contrrol group .Levels of PLT ,plasma D‐D and AT‐Ⅲ,unine microalbuminuria (UMA) and creatinine (UCr) and UMA／UCr ratio (UACR) were measured and compared a‐mong all groups .The diagnostic value of combined detection of PLT ,plasma D‐D and AT‐Ⅲ levels and above triple detec‐tion combined UACR for MVD in T2DM were analyzed.Results : Compared with healthy control group ,there were signif‐icant reductions in levels of PLT [ (212.34 ± 51.23)×109／L vs.(116.46 ± 46.43)×109／L vs.(98.48 ± 35.66)× 109／L] and plasma AT‐III [(103.54 ± 7.23)% vs.(99.52 ± 4.24)% vs.(75.34 ± 5.31)%] ,and significant rise in levels of plasma D‐D [ (0.31 ± 0.16) mg／L FEU vs.(0.85 ± 0.33) mg／L FEU vs.(1.08 ± 0.52) mg／L FEU] and UCr [ (3.36 ± 1.56) mmol／L vs.(4.51 ± 1.79) mmol／L vs.(12.31 ± 5.12) mmol／L] in no MVD group and MVD group . And levels of PLT and plasma AT‐III of MVD group were significantly lower than those of no MVD group ,plasma D‐D and UCr levels of MVD group were significantly higher than those of no MVD group ( P＜ 0.01 all).Compared with healthy control group ,no MVD group ,there were significant rise in levels of UACR [ (11.25 ± 5.02) mg／mmol vs. (10.01 ± 4.39) mg／mmol vs.(59.89 ± 16.32) mg／mmol] , UMA [ (38.25 ± 17.22) mg／mmol vs.(41.11 ± 18.53) mg／L vs.(722.32 ± 101.54) mg／L] in MVD group ,and UACR of no MVD group was significantly lower than that of health control group (P＜0.05 or 0.01).Compared with single UACR detection and triple combined detection of PLT ,plasma D‐D and AT‐Ⅲ levels ,there were significant rise in sensitivity (85.51% vs.87.82% vs.90.33%) ,specificity (90.54%vs.85.32% vs.94.32%) and accuracy (82.33% vs.84.56% vs.90.21%) in triple detection combined UACR ( P＝0.001 all).Conclusion :Combined detection of PLT ,plasma D‐D and AT‐Ⅲ levels with UACR are significanly superior to combined detection for screening MVD in T2DM.

Objective To explore the virulence of enterovirus 71 from infected children in neonatal mice. Methods Three strains of EV71 were isolated from the mild, severe and dead patients. Symptoms, weight and death of mice were recorded throughout 14 days. The mice were sacrificed on the first, third, fifth, seventh and ninth days post infection to gain the tissue virus load including the liver, spleen, lung, intestine, brain and muscle tissue which were used to detect the virus tilter by real-time RT-QPCR, and pathological lesions using HE staining. Results As to the severity of symptoms, no significant difference was found between the severe and mild groups (P＝0. 693), which were more serious than that of the fatal group. (P＝0. 000 ＜ 0. 05/6, P＝0. 000 ＜ 0. 05/6). The survival rate of the mice with mild, severe and fatal virus infection was 77. 2%, 81. 7% and 97. 8%, respectively, and there was a significant difference among the three groups (P＝0. 0010 ＜ 0. 05, P＝0. 001 ＜ 0. 05, P＝0. 0004 ＜ 0. 05). Lung hemorrhage of the mild group was the most serious, and there were no significant differences in pathological lesions of the brain, muscle, spleen and intestine. Virus titer in the liver and muscle was higher than the other tissues and that in mild group of different tissues tended to be higher than the other two groups. Conclusions Neonatal mice infected with the mild strain of enterovirus 71 presents heaviest symptoms, which are not consistent with the outcomes of humans. It is considered to be related to the virus gene, host and other factors.

Objective To investigate the association between multiple single nucleotide polymorphisms (SNP) with esophageal and gastric cancer,and to search the shared genetic risk loci for esophageal and gastric cancer in Han population of Henan Province.Methods Five hundreds cases of esophageal cancer,600 cases of gastric cancer and 600 persons undergoing physical examination in the Henan Provincial Tumor Hospital were selected.Seven SNP loci were selected.The genotyping was performed by adopting the Sequenom MassAR-RAY SNP genoting technique.The relative odds ratios(OR) and 95 ％ confidence intervals(CI) were calculated by unconditional logistic regression.Results In allelic model,the two SNP loci were correlated with the risk of esophageal cancer,which were rs4785204 (OR =1.43,95 ％ CI:1.12-1.85,P =0.01) and rs4924935 (OR =0.76,95 ％CI:0.61-0.99,P=0.04).The four SNP loci were correlated with the risk of gastric cancer,gastric cancer,which were rs13361707(OR=1.23,95％CI:1.13-1.56,P=0.00),rs4779584(OR=1.25,95％CI:1.11-1.58,P=0.04),rs4785204(OR=1.24,95％CI:1.03-1.49,P=0.03)and rs4924935(OR=0.76,95％ CI:0.60-0.99,P =0.04).In the genetic model analysis,the four loci were significantly correlated with the risk of esophageal cancer,which were rs6687758,rs401681,rs4785204 and rs4924935(P＜0.05);the three loci were correlated with the gastric cancer,which were rs13361707,rs4779584 and rs4785204(P＜0.05).Conclusion Multiple SNP loci have the relationship with the risk of esophageal and gastric cancer in Han population of Henan Province.The genetic variation of rs4785204 and rs4924935 loci may simultaneously play an important role in the occurrence and development of esophageal and gastric cancer.

Objective To evaluate the clinical and radiological results of Phlios plate and Multiloc nail in treatment of proximal humerus fractures.Methods From February 2013 to December 2015,data of 37 cases of proximal humerus fractures who were treated by reduction and fixation using Phlios plate or Multiloc nail were retrospectively analyzed.In group one (Phlios plate),there were 10 males and 8 females,with an average age of 56.3±5.8 years,including 7 cases of Neer 2-part surgical neck fracture,6 cases of Neer 3-part fracture,4 cases of Neer 4-part fracture,and 1 case of fracture-dislocation.In group two (Multiloc nail),there were 8 males and 11 females,with an average age of 57.2±7.4 years,including 8 cases of Neer 2-part surgical neck fracture,9 cases of Neer 3-part fracture,1 case of Neer 4-part fracture,and 1 case of fracture-dislocation.Operation time,range of motion of shoulder joint,visual analogue scale (VAS) pain score,American Shoulder & Elbow Surgeon (ASES) score and ConstantMurley score were collected.Results All 37 patients were followed up for an average period of 15.5 months (range,12-36 months).The average bone healing time were 2.5±0.5 months (range,2-3 months)and 2.2±0.5 months (range,1.5-3 months) in the plate and nail group respectively.At the latest follow-up,average VAS score was 0.4±0.6 (range,0-2),the ASES score aver aged 85.4±6.8 points (range,73-96),Constant-Murley score averaged 83.4±7.3 points (range,71-94),and external rotation averaged 30.8°±10.0° (range,10°-50°) in plate group,while average VAS score was 0.2±0.4 (range,0-1),ASES score averaged 89.7± 5.6 points (range,80-98),Constant-Murley score averaged 88.5±6.8 points (range,76-98),and external rotation averaged 40.3°± 7.9° (range,20°-50°) in the intramedullary nailing group.One case had partial necrosis of humeral head in the plate group,while 1 case suffered absorption of the greater tuberosity in the nail group,with the complication rate of 5.6％ (1/18) and 5.3％ (1/19) respectively,without significant difference.The internal and external rotation degrees,ASES and Constant-Murley scores were better in nail group than those in plate group for 2-part fractures,while the forward elevation and abduction degrees were similar.Conclusion Similar results were achieved for the treatment of proximal humeral fractures by Phlios plate and Multiloc nail.The Multiloc nailing group had achieved superior outcomes in Neer-2-part proximal humeral fractures.