Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking. Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns. Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023-1.954;P = 0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains. Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.

Aim To study the effect of three kinds of active ingredients of traditional Chinese medicine (sinomenine, rhynchophylline and isorhynchophylline) on dre-miR-723-5p expression in morphine-induced zebrafish brain. Methods Morphine was injected intraperitoneally to zebrafish, conditional position preference (CPP) was trained and then the behavioral of animals were observed; the miRNA expression profiles of morphine-additive zebrafish were determined by small RNA sequencing; qRT-PCR was used to verify the expression of dre-miR-723-5p, three target gene databases (miRanda, miRDB, andRNAhybrid) were used to predict the target genes of dre-miR-723-5p; Kobas 3.0 was used to perform Gene Ontology (GO) and KEGG pathway analysis of these target genes. Results Morphine-induced CPP model was established successfully. Compared with control group, the resident time and movement map in drug-pair box of zebrafish in model group significantly increased. After drug administration, the resident time and movement map in drug-pair box of zebrafish decreased. The verification results of qRT-PCR were consistent with the results of small RNA sequencing. Ninety-nine putative target genes of dremiR-723-5p that were common to all three target gene databases, which were mainly enriched in biological process, cell composition and molecular function, involved in the positive regulation of MAPK signaling pathway, lysosome, cytokine-cytokine receptor interaction, and apoptosis. Conclusion Morphine can increase the expression of dre-miR-723-5p in the zebrafish brain, which can be reversed by sinomenine, isorhynchophylline, and rhynchophylline treatment, and dre-miR-723-5p may participate in the mechanism underlying morphine-induced damage of brain.

OBJECTIVE: To investigate the clinical manifestations pathologic features, treatment options and prognosis of patients with bone lymphoma. METHODS: The clinical characteristics, pathologic features, treatment and prognosis of 34 BL patients diagnosed by histopathologic method or/and PET-CT and treated in first hospital of peking university from January 2004 to April 2018 were analyzed retrospectively. RESULTS: The median age of 34 BL patients was 56 years old, the male and female ratio was 1.43∶1 (24 /10). Among 34 patients, the patients with primary bone lymphoma(PBL) were 8 cases, the patients with secondary bone lymphoma(SBL) was 26 cases, the PBL and SBL ratio was 0.31∶1. Bone lymphoma lacks typical systemic symptoms, and its onset began mostly from bone pain and pathologic bone fracture. The most frequent pathological type of bone lymphoma in our study was diffuse large B-cell lymphoma (DLBCL), accounting for 55.88%. At present, the conventional treatment for bone lymphoma includes chemotherapy, or chemotherapy combined with radiotherapy and surgery, as well as hematopoietic stem cell transplantation. The average and median OS time of BL patients were 349 years and 3 years respectively, meanwhile the OS rate for three years and two years were 56.25% and 78.16%, respectively. Factors that affect survival of BL patients were PBL and SBL classification, pathological type, blood LDH level, and treatment methods. CONCLUSION Bone lymphoma is usually concealed onset，an adequate and adequate combination therapy can improve the survival rate and transplantation therapy plays an important role. Primary bone lymphoma is rare, the prognosis of patients with primary bone lymphoma is good, whereas the prognosis of patients with secondary bone lymphoma is poor.
Bone Neoplasms ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, Large B-Cell, Diffuse ; Male ; Middle Aged ; Positron Emission Tomography Computed Tomography ; Prognosis ; Retrospective Studies

Objective:To investigate the impact of dexamethasone on the balance of natural regulatory T cells(nTreg) and typeⅠ regulatory T cell(Tr1) in vitro.Methods:Peripheral blood lymphocytes(PBMCs) recruited from healthy donor,divided into dexam-ethasone stimulus group and negative control group.After 3 days treatment,cells were stained.The expression of CD25,CD127, Lymphocyte-activation 3 (LAG-3) and Forkhead box P3 (Foxp3) and frequency of Treg and Tr1 were analyzed by flow cytometry.Results:Compared to the control group,after stimulation with dexamethasone for 3 days,the percentage of CD4+T cells increased in a dose-dependent manner.The expression of CD25 and Foxp3 in CD4+T cells decreased significantly (P=0.006, P<0.000 1),while CD127 and LAG-3 expression increased significantly in CD4+T cells (P<0.000 1,P=0.011).Dexamethasone treatment significantly enhance the frequency of Tr1(P=0.051),reduce the frequency of Treg (P<0.001),and the ratio of Tr1/Treg also increased(P=0.044).Conclusion:Short-term treatment with dexamethasone in vitro change the balance of natural regulatory and type Ⅰ regulatory T cells.

We delineated the molecular characteristic of recombinant strain GⅡ.P16/GⅡ.2 of norovirus associated with acute viral gastroenteritis outbreaks in Fujian Province in winter of 2016.Norovirus were detected in specimens of patients collected from the gastroenteritis outbreaks by real time reverse transcription-PCR and reverse transcription-PCR (RT-PCR).The PCR products of the positive samples were purified,and partial RNA dependent RNA polymerase (RdRp) gene and partial capsid gene were sequenced.The sequences were analyzed using bioinformatics software and online database,and phylogenetic tree were also constructed.Norovirus were detected in all 18 stools.Analysis of 9 positive sequences indicated an emergence of norovirus GⅡ.P16/ GⅡ.2 and confirmed being the cause of gastroenteritis outbreaks.All the strains shared homology of 98％ with strains of Kawasaki 194 of Japan detected in 2016 and 97.7％-98.8％ with IPH2161-08VG06 of Belgium detected in 2008,RdRp and capsid separately.These outbreak strains showed some degree of differences from the predominant strain,2012 Sydney GⅡ.4 variant.This is the first time to have found norovirus GⅡ.P16/ GⅡ.2 causing viral gastroenteritis outbreaks in Fujian.More in-depth analysis of the Norovirus GⅡ.P16/ GⅡ.2 could be useful to optimize preventative strategies and develop new and more effective therapeutic measure.

Objective To confirm whether strain ratio should be added after evaluation of lesions with 5-point elasticity scoring for differentiating breast lesions on ultrasonic elastography(UE).Methods Eight hundred and forty-six consecutive female patients with 1 071 breast lesions were recruited into a multicenter retrospective study,which involved 8 centers across China.All the patients underwent the UE procedure and the strain ratios were calculated.The sensitivity,specificity,accuracy,PPV and NPV were calculated for each of the two evaluation systems and the areas under the ROC curve were compared.Results The strain ratios of 559 benign lesions(2.7±1.4)and 512 malignant lesions(8.1±5.9)were significantly different (P<0.001).When the cutoff point was 3.03,strain ratio method had 81.6% sensitivity,89.7% specificity,81.7% accuracy,80.2% PPV and 84.2% NPV.The areas under the ROC curve with the strain ratio method and 5-point scoring method were 0.865 and 0.862,respectively(P =0.622).For the lesions with elasticity score 3 and 4,the areas under the ROC curve of the two Methods were 0.71 1 and 0.629, respectively(P = 0.020).Conclusions Although the two UE Methods have similar diagnostic performance,separate calculation of the strain ratios seems compulsory,especially for the lesions with elasticity score 3 and 4.

This study was aimed to investigate the clinical manifestation, pathological features, treatment and related prognosis factors of primary mediastinal large B cell lymphoma (PMLBCL). The clinical data of 29 PMLBCL patients admitted in Peking University First Hospital were summarized and the related factors were analyzed retrospectively from January 2000 to November 2013. The results showed that 29 patients with the median age 32 were all pathologically diagnosed as PMLBCL. The main clinical features included mediastinal bulk mass (72.4%), superior vena caval syndrome (51.7%), dyspnea (62.1%), serous membrane fluid (48.3%), with 62.1% extranodal invasion and 62.1% extra-thoracic involvement. According to Ann-Arbor stage, 16 patients (55.1%) were classified to stage I/II and 13 patients (44.9%) to stage III/IV, 12 patients (41.4%) had B symptoms. Among the 29 patients, 2 patients failed to be followed and the others were followed for the median time of 29 months, 17 patients achieved CR, 5 patients achieved PR, 1 patient replaced and 4 patients died of disease progression. The 5-year overall survival rate (OS) was 85.2%, in which RCHOEP regimen group patients had OS 94.4% and CHOEP group patients had OS 75%; 8 patients underwent auto-HSCT and 1 patients underwent allo-HSCT who kept in CR state. Univariate analysis by log-rank test showed albumin level and LDH ≥ 2ULN, the initial therapy response and IPI score were prognostic factors , but neither were independent prognostic factors by Cox Regression Model. It is concluded that PMLBCL has distinct clinical features. RCHOEP chemotherapy regimen can achieve satisfactory results, but needs to be explored by further clinical trials.
Follow-Up Studies ; Humans ; Lymphoma, Large B-Cell, Diffuse ; diagnosis ; therapy ; Mediastinal Neoplasms ; diagnosis ; therapy ; Prognosis ; Retrospective Studies ; Survival Rate

Objective To compare the diagnostic value of sound velocity(SV) and real-time ultrasonic elastography in differentiating benign or malignant of breast lesions.Methods 75 patients with 99 lesions were examined with the zone speed index technique and real-time ultrasonic elastography respectively.Then the SVs of the lesions were calculated and elastography of the lesions were scored with 5-scoring method.The ROC curves were constructed with histology as the golden standard.Results There was significant difference between the SVs of benign and malignant breast lesions(P =0.0001).1561 m/s was the best cufoff point.And the areas under the curves (AUC) of SV and real-time ultrasonic elastography were 0.842 and 0.968,respectively.There was significant difference between the two methods of AUC (P =0.023).The sensitivity,specificity and accuracy for SV were 81.5％,91.7％,88.9％,respectively.There was no significant difference between sensitivity,specificity and accuracy of the two methods(P =1.0,P =0.125,P =0.146).Conclusions Both SV method and real-time ultrasonic elastography are helpful in the evaluation of benign or malignant of breast lesions.

Objective To investigate the value of ultrasonic elastography(UE) in diagnosing breast small masses (diameter≤10 mm). Methods The static sonograms of conventional ultrasound(US) and UE of the 274 breast small lesions which pathologically proved were reviewed. Images were assigned according to the B1-RADS criteria for US. The elastographic images were evaluated using improved 5-scoring system.Pathology was followed up as diagnostic criteria. The diagnostic performance of the 2 methods was evaluated with receiver operating characteristic curve(ROC). Results The areas under the ROC curve of the two modalities were 0. 891 (UE) and 0.742 (BI-RADS), respectively. The difference between them was significant. Conclusions UE is helpful in differentiating between malignant and benign breast small lesions.