Objective:To explore the relationship between drug resistance occurrence and the distribution pattern of polymorphic loci in individuals with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) treated with highly active anti-retroviral therapy (HAART).Methods:HAART-failed HIV/AIDS patients who successfully amplified the gene sequences of the pol region between June 2015 and December 2021 from 16 prefecture-level administrative regions in Yunnan Province were included.The resistant sequences were classified using the human immunodeficiency virus (HIV) basic local alignment search tool (BLAST) and validated through MEGA 6.0, and the obtained sequences were submitted to the Stanford University HIV Drug Resistance Database to identify drug resistance loci. The distribution of polymorphic loci was analyzed across patients exhibiting varying degrees of drug resistance, different treatment regimens and distinct HIV-1 subtypes.Changes of the frequencies of polymorphic loci in patients with different degrees of drug resistance were analyzed using trend chi-square test. Statistical comparisons and further paired comparisons were performed using chi-square test.Results:Gene sequences were amplified from 1 453 patients, and the resistance testing results showed 954 sensitive, 224 potentially or low resistant, 189 moderately resistant, and 86 highly resistant patients. The frequencies of mutations I15V, L19I, D60E in the HIV-1 protease region (PR region) and E36A, T39D, S48T mutations in the HIV-1 reverse transcriptase region (RT region) showed a decreasing trend as the degree of HIV-1 resistance escalated ( χ2trend=19.86, 9.16, 13.66, 37.64, 18.44 and 40.86, respectively, all P<0.01). Conversely, the mutations V77I in the PR region and K122E in the RT region showed an ascending trend ( χ2trend=12.19 and 10.03, respectively, both P<0.01). Distinct treatment groups, namely zidovudine (AZT)+ lamivudine (3TC)+ lopinavir/ritonavir (LPV/r), AZT+ 3TC+ efavirenz (EFV), AZT+ 3TC+ nevirapine (NVP), and tenofovir (TDF)+ 3TC+ EFV, were examined. Statistically significant differences in the frequencies of mutations E35D, M36I, and D60E in the PR region, as well as S48T, K122E, and R211K in the RT region, were observed among these treatment groups ( χ2=22.46, 9.32, 14.46, 26.85, 18.92 and 24.26, respectively, all P<0.05). In paired comparisons, AZT+ 3TC+ LPV/r group displayed higher frequencies of E35D, M36I, and D60E mutations, the AZT+ 3TC+ EFV group showed a higher frequency of S48T mutation, the AZT+ 3TC+ NVP group showed a higher frequency of K122E mutation, and the TDF+ 3TC+ EFV group exhibited a higher frequency of R211K mutation, all with statistically significant differences (all P<0.008). The differences in the frequencies of T12S, I15V, L19I, M36I, V77I, L89M in the PR region and E53D, I135V, S162C, R211K, K277R in the RT region among circulating recombinant form (CRF)08_BC, CRF07_BC and CRF01_AE subtype group were statistically significant ( χ2=693.60, 712.51, 798.11, 434.85, 386.91, 657.78, 932.58, 409.21, 344.39, 469.44 and 260.48, respectively, all P<0.001). In paired comparisons, the frequencies of T12S, I15V, L19I, E53D, I135V, S162C and R211K in CRF08_BC subtype, the frequencies of V77I and K277R in CRF07_BC subtype, and the frequencies of M36I and L89M in CRF01_AE subtype were higher than those in the other two groups, and the differences were all statistically significant (all P<0.017). Conclusions:The polymorphic loci resulting from HIV-1 HAART failure show different distribution patterns across various degrees of drug resistance, treatment regimens and HIV-1 subtypes.These loci demonstrate both specific and shared characteristics. It is necessary to enhance the surveillance of select polymorphic loci.

Objective To investigate the influence factors of mortality among human immunodeficiency virus (HIV)-infected children under highly active antiretroviral therapy (HAART).Methods Retrospective cohort study of 652 children initiated HAART from 2005 to 2014 was conducted,and enrolled patients were followed-up until December,2015.Survival data was analyzed using Kaplan-Meier method and Cox regression model was used to identify independent predictors of mortality among these children on HARRT.Chi-square test and Fisher's exact test were used for comparison between groups.Results Overall,26 of the children died over a follow-up period of 3 116.24 child-years,with a mortality rate of 0.83 per 100 child-years.Twelve (46％)of deaths occurred during the first six months after starting HAART.Cox regression analysis of variables showed that the World Health Organization (WHO) clinical stages Ⅲ/Ⅳ (hazard rate [HR] =10.717,95％confidence interal [95％ CI]:4.189-4.749,P =0.000),baseline hemoglobin ＜ 80 g/L (HR =14.768,95 ％ CI:5.721-38.125,P =0.000),tuberculosis co-infection (HR =4.794,95％ CI:2.105-10.918,P =0.000),baseline CD4+T lymphocyte ＜ 50 cells/μL (HR =4.219,95％ CI:1.524-11.680,P =0.006),weight-for-age z-score ＜-2 (HR =2.983,95 ％ CI:1.094-8.135,P =0.033) were independently associated with death,whereas the age ＜ 7 year-old at HAART initiation was protectire (HR =0.293,95％ CI:0.126-0.684,P =0.005).Conclusions The mortality of children receiving HAART is strongly associated with WHO stages Ⅲ/Ⅳ,hemoglobin ＜ 80 g/L,weight-for-age z-score ＜-2,tuberculosis co-infection and older age at treatment.

Objective To compare the efficiencies of handheld ultrasound ,automated breast volume scanner ( ABVS) and breast specific gamma imaging (BSGI) in the diagnosis of breast cancer . Methods A retrospective review was performed in 200 women ( 210 breast lesions) underwent handheld ultrasound , ABVS and BSGI before surgery . The results were verified with histological examination . Results There was no obvious difference among the three methods in the sensitivity for the diagnosis of breast cancer( P >0 .05) . There was no difference of specificity between handheld ultrasound and ABVS ,BSGI( P = 0 .393 , 0 .139) . Compared with BSGI ,ABVS was an imaging modality with highest specificity for the diagnosis of breast cancer( P = 0 .021) ,and there was no difference between handheld ultrasound and ABVS ,BSGI ( P =0 .07 ,0 .29) . The areas under the ROC curve of handheld ultrasound ,ABVS and BSGI were 0 .855 ,0 .894 and 0 .818 ,respectively . The difference was obvious between ABVS and BSGI ( P = 0 .02) . Conclusions The diagnostic efficacy of ABVS in diagnosis of breast malignant lesions is similar to that of handheld ultrasound . BSGI has certain clinical value in the diagnosis of breast cancer ,and it is an effective supplement for breast cancer ultrasound examination .

OBJECTIVETo analyze the clinical phenotype of a Chinese pedigree affected with Papillon-Lefevre syndrome(PLS) and detect mutation of CTSC gene.

METHODSClinical phenotypes were noted, and oral examination for the proband was carried out for the clinical diagnosis of PLS. PCR and Sanger sequencing were used to identify potential mutation of the CTSC gene. Functional effect of the mutation was predicted with SIFT and PolyPhen-2. Swiss-Port was used to predict the tertiary structure of wild type and mutant proteins. The mRNA and protein expression were analyzed by real-time PCR and Western blotting.

RESULTSA homozygous mutation c.901G>A (p.G301S) in exon 7 of CTSC gene was identified in the patient. Both parents of the patient had carried a heterozygous c.901G>A mutation. The mutation was located in the conserved region of CTSC enzyme and was predicted to be damaging by changing the structure of the protein, which could affect the activity of Cathepsin C. However, no significant difference was found in the expression of p.G301S variant at the mRNA and protein levels compared with that of the wild type CTSC gene.

CONCLUSIONThe c.901G>A mutation of the CTSC gene was first reported in China, which has expanded its mutation spectrum.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Cathepsin C ; genetics ; Child, Preschool ; China ; Exons ; Female ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Papillon-Lefevre Disease ; enzymology ; genetics ; Pedigree

Objective To evaluate the efficacy of Jianpi-Xiaozheng recipe combined with chemotherapy in patients with late gastric cancer. Methods A total of 124 patients with late gastric cancer were randomly divided into a control group and a treatment group by random number table method, with 62 cases in each group. The patients in the control group received chemotherapy with S-1 and oxaliplatin (SOX), and those in the treatment group received Jianpi-Xiaozheng recipe combined with SOX chemotherapy. The treatment response was evaluated using the response evaluation criteria in solid tumors. The quality of life and physical status were evaluated with the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30) and Karnofsky Performance Status (KPS), respectivly. The serum levels of tumor biomarkers, carbohydrate antigen 199 (CA199) and carbohydrate antigen 72-4 (CA72-4) were detected before and after treatment. Results The response rate (complete or partial response) in the treatment group was significantly higher than that in the control group (62.9%vs. 43.5%;χ2=4.665, P=0.031). The scores of QLQ-C30 (46.8 ± 6.3 vs. 42.2 ± 5.9;t=4.196, P=0.001) and KPS (79.1 ± 7.8 vs. 72.0 ± 7.5;t=5.167, P=0.000) in the treatment group were significantly higher than those in the control group. The serum levels of CA199 (61.7 ± 16.5 U/ml vs. 113.3 ± 21.4 U/ml;t=15.036, P=0.000) and CA72-4 (27.9 ± 9.6 U/ml vs. 34.3 ± 9.7 U/ml;t=3.693, P=0.001) in the treatment group were significantly lower than those in the control group. Conclusions Jianpi-Xiaozheng recipe combined with chemotherapy can increase response rate, decrease the serum levels of tumor biomarkers, and improve the quality of life in patients with late gastric cancer.

Objective To clarify evaluation methodology of the accuracy of differential diagnosis of meningioma and glioma,taking magnetic resonance imaging (MRI) and vascular endothelial growth factor (VEGF) into account.Methods According to the unified standard of design,114 cases were selected,which were diagnosed by postoperative pathological in Shanxi Cancer Hospital from March 2010 to October 2012.On the basis of hospital routine inspection,all patients needed MRI scan,enhancement scan,VEGF,ALP and LDH,with pathological diagnosis of glioma or meningioma.Using ROC curve analysis which took VEGF,T2WI into account,the accuracy of differential diagnosis could be evaluated.Results The results showed that the differential diagnosis accuracy were high relatively,the area under the ROC curve was 91.34 ％.When the T2WI were equisignal,low signal or high signal respectively,the area under the curve ROC were 97.62 ％,90.00 ％,88.34 ％.Conclusion To consider the MRI T2WI and VEGF,ROC curve regression model analysis can enhance the differential diagnosis accuracy of meningioma and glioma.

Objective To explore the value of convergence symptom in predicting the treatment sensitivity and the prognosis of patients with breast infiltrating ductal carcinoma (IDC).Methods A retrospective review was performed in 46 women with 47 IDC lesions.Correlation between clinicopathological characteristics and convergence symptom was analyzed.Clinicopathological characteristics included tumor size,tumor grade,axillary lymph node state and the expression of ER,PR and H ER2.Results There was no obvious difference within different IDC groups by tumor size or axillary lymph node state in the presentation of convergence symptom (P ＞ 0.05).The convergence symptom was more common in grade Ⅱ IDC lesions than in grade Ⅲ IDC lesions and the difference was statistically significant (P =0.008).No difference was found between the presentation of convergence symptom and the expression of ER (P =0.055).Significant correlations were found between the presentation of convergence symptom and the expression of PR and HER2 (P ＜0.05).Conclusions Convergence symptom is helpful in predicting the treatment sensitivity and the prognosis of patients with breast infiltrating ductal carcinoma.

Objective To study the influence of different intensities of treadmill exercise training on bone biomechanical properties and the bone healing in type 2 diabetic model rats.Methods Fifty-two healthy 8-month-old male Sprague-Dawley rats were randomly divided into a control group (n =10) and a type 2 diabetic model group (n =42).Type 2 diabetes was modeled in rats of the model group by feeding feedstuff containing high glucose,fat and energy food for 4weeks,followed by a single intra-abdominal injection of streptozotocin.Thirty model rats were then randomized into 3 subgroups:type 2 diabetes group,a mild exercise group and a moderate exercise group.Different intensities of treadmill training protocols was administered accordingly for 8 weeks.The biomechanical indices of the femur bone including maximum load and stress,module and energy was measured with mechanical testing instrument.Results Compared with the control group,both maximum load and energy were decreased significantly in type2 diabetes group [(148.5±17.8)N vs (192.3±43.4)N] for maximum load,and (51.38 ±13.7)mJ vs (82.0 ± 30.8) mJ for maximum stress] (P ＜ 0.05,P ＜ 0.01).Compared with the type 2 diabetes group,maximum load and stress were increased significantly in the mild and moderate exercise groups(P ＜ 0.05,P ＜ 0.01).Maximum load and energy were improved more in the moderate exercise group than in the mild exercise group [(184.1 ± 26.6)N vs (165.4±21.5)N for maximum load and (83.59 ±29.96)mJ vs (62.33 ±14.32)mJ for maximum stress] (P ＜ 0.05).Conclusions A significant decrease of the bone biomechanical properties was observed in rats with experimental type 2 diabetes,which could be alleviated by treadmill exercise training.

ObjectiveStudy the effects of mitral valve replacement using video-assisted thorascoscopy compared with median sternotomy mitral valve replacement.MethodsBetween October 2003 and October 2011,72 cases suffer from mitral valve disease underwent video-assisted thorascoscopic mitral valve replacement,74 cases underwent median sternotomy procedure.CPB time,cross clamp time,ventilation time,drainage,ICU stay time and hospital stay time of the two groups were compared.Results It was longer that CPB time and cross clamp time in video-assisted thoracospic group than those of median sternotomy group.There was statistically significant difference.However there was no statistically significant differentce in ventilation time and ICU stay time between two groups.Drainage of video-assisted thoracospic group was less than median sternotomy group.And there was statistically significant difference.ConclusionAs long as strictly a good indication,mitral valve surgery can routinely be performed with video-assisted thoracospic.

Objective To determine the influence of aerobic exercise on advanced glycation end products (AGEs)in plasma using a rat model of type 2 diabetes,and to provide an experimental basis for explaining the rehabilitative mechanism of aerobic exercise in type 2 diabetes.Methods Fifty-two healthy 8-week-old male SpragueDawley rats were allocated at random into a normal control group(n=10)and a type 2 diabetes model group(n=42).The latter were overfed with a high-sugar,high-fat and high-energy diet for 4 weeks,then 30ms/kg of streptozotocin was injected intraperitoneally to create a model of type 2 diabetes.Thirty diabetic rats were then allocated at random into a diabetes control group,a low intensity exercise group and a moderate intensity exercise group with 10 in each group.The treadmill exercise was administered to the animals in the low and moderate exercise groups accordingly.Results Compared with the normal control group,plasma AGEs increased significantly in the diabetes control and moderate intensity exercise groups.Compared with the diabetes control group,AGEs in the lower intensity exercise group were significantly lower.Compared with the moderate intensity exercise group,plasma AGEs in the low intensity exercise group were somewhat lower,but not significantly.Conclusion Aerobic exercise can reduce plasma AGE levels in rats with a model of type 2 diabetes.The effect is probably related to decreasing excessive blood glncose and the exercise intensity.