ObjectiveTo perform a genome-wide association study of rubella virus vaccine strain BRD-Ⅱ, so as to fully grasp the sequence characteristics of this genome. MethodsSecond-generation sequencing method was used to conduct the whole-genome sequencing on the vaccine strain BRD-Ⅱ, and the affinity tree of this genome with some vaccine strains and wild-type rubella virus strains was analyzed using the maximum likelihood method. The average genetic distance of nucleic acid sequence of each vaccine strain protein was determined. And homology comparison of structural proteins of each rubella vaccine strain, plus the comparison between this genome with the AY258323.1 genome sequence, were conducted to analyze the homology of E1 protein between the wild-type rubella virus reference strain and vaccine strain BRD-Ⅱ. ResultsThe sequencing results showed that the BRD-Ⅱ strain was a single-molecule single-stranded positive-strand ribonucleic acid (RNA), composed of 9 778 nucleotides, with a GC content of 69.35 %. The C protein was composed of 300 amino acids, the E2 glycoprotein was composed of 282 amino acids, and the E1 glycoprotein was composed of 481 amino acids. The results of preliminary analysis showed that the average genetic distances of nucleic acid sequences were 0.066 700 for the P150 protein, 0.061 933 for the P90 protein, 0.057 850 for the C protein, 0.068 167 for the E2 protein, and 0.068 833 for the E1 protein, respectively. The amino acid sequences in the E2 protein and E1 protein regions of the two BRD-Ⅱ strains did not change, confirming the conserved regions of the E1 protein by comparison. ConclusionThe sequence characteristics of the genome are clarified, which have laid a broad foundation for the subsequent detection of the genetic stability of the main antigen genes.

Objective To evaluate the clinical efficacy of plasma exchange(PE)and double plasma molecular absorption system(DPMAS)in the treatment of primary biliary cholangitis(PBC)and the effect of this therapy on prognosis.Methods The clinical data on 526 PBC patients in our hospital from December 2013 to January 2022 were retrospectively analyzed.The patients were divided into different groups according to different therapies and then matched with propensity.The changes in symptoms,laboratory indexes and MELD scores were compared between two groups before and after treatment,and the clinical efficacy of artificial liver treatment for PBC patients was assessed.The effect of this treatment on the survival outcomes in these patients via comparing the cumulative survival rates at 3,6 and 12 months between the two groups.Results The efficiency was better in the group with artificial liver treatment in addition medical therapy than the group with medical treatment alone,the difference was statistically significant(76.7%vs.55.8%,χ2 = 4.214,and P = 0.040).Cox proportional risk regression showed that TBIL was an independent risk factor affecting the 3-,6-,or 12-month survival in PBC patients.Conclusions Artificial liver support system can effectively relieve symptoms,reduce levels of ALT,AST and TBIL,improve blood coagula-tion function,and lower MELD scores in PBC patients.This therapy revealed a trend of improvement in 3-,6-,or 12-month survival outcomes.

In this paper， the name， origin， quality evaluation， producing area and processing methods of Lablab Semen Album in the famous classical formulas were researched by reviewing the ancient materia medica， medical books， prescription books and modern literature. The results showed that the name of Lablab Semen Album in the past dynasties was mostly derived from its shape and color， called Biandou and Baibiandou. The mainstream origin used in the past dynasties was Lablab purpureus， the medicinal parts were mainly white mature seeds， with the addition of the leaves in the Song dynasty and the flowers in the Ming dynasty. Since modern times， the authentic producing areas of Lablab Semen Album are Suzhou， Zhejiang and other places， and now mainly produced in Chuxiong and Xinping， Yunnan and Panzhihua， Sichuan. The traditional quality evaluation of Lablab Semen Album is evaluated as large， solid， full and white. The harvesting time of this herb is recorded from the eighth to the ninth lunar month in related literature， the pods are picked when the seeds are ripe， and the seeds are dried in the sun. In ancient times， the processing of Lablab Semen Album mainly consisted of frying the seeds with skin and then pulverizing for use， or soaking and peeling seeds for raw use. Based on the conclusion of the textual research， it is recommended that the seeds or flowers of the white flowering plants of L. purpureus， a member of the leguminosae， should be used in the famous classical formulas， and the dried seeds or dried flowers of Lablab Semen Album can be used as medicine if the formula did not clearly indicate processing requirements.

ObjectiveTo conduct the sequencing and preliminarily analysis of the whole genome of BCG Shanghai D₂PB302 strain （hereinafter referred to as BCG Shanghai D₂ strain）， which has been used exclusively for the vaccine production in China. MethodsThe DNA of of BCG Shanghai D₂ strain （D2-JIA12-1） was extracted， and the whole genome was sequenced by Pacbio-RS Ⅱ. The sequence data was assembled by Smrtlink and polished with the illumina data. Genes， tRNA and rRNA were predicted based on the sequence data. The functional annotation of predicted genes was performed through BLASTP. The IVE-TB antigen gene and MTBVAC were selected as the target sequences to be compared with Mycobacterium tuberculosis H37Rv （NC_000962.3）. ResultsThe sequence length of BCG Shanghai D₂ strain was 4 045 232 bp， and the GC content was 65.66%. A total of 4 259 protein-encoding genes were predicted， with an average gene size of 933 bp. 2 476 genes had biological functions and others were hypothetical proteins.144 virulence genes were obtained by comparing with the VFDB. There were 29 type Ⅶ secretion system genes and 10 PE/PPE protein family genes. ConclusionThe whole genome sequence of BCG Shanghai D₂ strain is clarified. It lays a broad foundation for subsequent detection of the stability of major antigen genes.

Clinical application of doxorubicin (DOX) is heavily hindered by DOX cardiotoxicity. Several theories were postulated for DOX cardiotoxicity including DNA damage and DNA damage response (DDR), although the mechanism(s) involved remains to be elucidated. This study evaluated the potential role of TBC domain family member 15 (TBC1D15) in DOX cardiotoxicity. Tamoxifen-induced cardiac-specific Tbc1d15 knockout (Tbc1d15^CKO) or Tbc1d15 knockin (Tbc1d15^CKI) male mice were challenged with a single dose of DOX prior to cardiac assessment 1 week or 4 weeks following DOX challenge. Adenoviruses encoding TBC1D15 or containing shRNA targeting Tbc1d15 were used for Tbc1d15 overexpression or knockdown in isolated primary mouse cardiomyocytes. Our results revealed that DOX evoked upregulation of TBC1D15 with compromised myocardial function and overt mortality, the effects of which were ameliorated and accentuated by Tbc1d15 deletion and Tbc1d15 overexpression, respectively. DOX overtly evoked apoptotic cell death, the effect of which was alleviated and exacerbated by Tbc1d15 knockout and overexpression, respectively. Meanwhile, DOX provoked mitochondrial membrane potential collapse, oxidative stress and DNA damage, the effects of which were mitigated and exacerbated by Tbc1d15 knockdown and overexpression, respectively. Further scrutiny revealed that TBC1D15 fostered cytosolic accumulation of the cardinal DDR element DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Liquid chromatography-tandem mass spectrometry and co-immunoprecipitation denoted an interaction between TBC1D15 and DNA-PKcs at the segment 594-624 of TBC1D15. Moreover, overexpression of TBC1D15 mutant (∆594-624, deletion of segment 594-624) failed to elicit accentuation of DOX-induced cytosolic retention of DNA-PKcs, DNA damage and cardiomyocyte apoptosis by TBC1D15 wild type. However, Tbc1d15 deletion ameliorated DOX-induced cardiomyocyte contractile anomalies, apoptosis, mitochondrial anomalies, DNA damage and cytosolic DNA-PKcs accumulation, which were canceled off by DNA-PKcs inhibition or ATM activation. Taken together, our findings denoted a pivotal role for TBC1D15 in DOX-induced DNA damage, mitochondrial injury, and apoptosis possibly through binding with DNA-PKcs and thus gate-keeping its cytosolic retention, a route to accentuation of cardiac contractile dysfunction in DOX-induced cardiotoxicity.

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

Purpose To investigate and summarize the clinicopathological features,immunophenotype,diagnosis and differential diagnosis of anaplastic thyroid carcinoma(ATC).Methods The clinicopathological features and follow-up data of 15 patients with ATC were reviewed and retrospectively ana-lyzed,and the histological features,immunophenotypic,and molecular features were observed.Results There were 8 males and 7 females with a mean age of 63.5 years.The largest tumor diameter was 45.9 mm(range,20-73 mm).Macroscopically,the tumors appeared nodular or lobulated,mostly firm to hard,with a cut surface of gray-white or gray-yellow in color,and were accompanied by hemorrhage,necrosis,and cystic changes.Mi-croscopically,the tumor exhibited diverse structures and cellular morphology mainly composed of epithelioid,spindle,multinu-cleated giant cells,rarely rhabdoid morphology(2 cases)and heterologous osteosarcomtoid differentiation(1 case).Two cases showed squamous cell carcinoma morphology as well.Among them,there were pure ATC in 11 cases while three cases had mixed papillary thyroid carcinoma components and one case had coexisting high-grade differentiated thyroid carcinoma compo-nent.Cervical lymph node metastasis was present in 6 cases.CK(AE1/AE3)expression was observed in 80%of the cases while PAX8 expression was seen in53.3%.Varying degrees of BRAF(VE1)expression were found in 42.9%whereas weak focal TTF-1 expression occurred only in two cases;and all cases did not express TG.Overall,genetic testing was performed in 8 cases(53.3%).The TP53 gene was the most frequently muta-ted gene(5/8,62.5%),followed by the RAS(3/8,37.5%)and BRAF(3/8,37.5%)genes,while the TERT combined with PIK3CA gene was mutated in only one case.Moreover,multiple gene mutations occurred simultaneously in five cases.Of the total fourteen patients who underwent follow-up,the mean and median survival times were 13.9 and 5.0 months,respec-tively.The disease-specific mortality rate reached 78.6%.Conclusion ATC is extremely rare,displaying unique histolog-ical characteristics,often accompanied by various gene muta-tions.It has a poor prognosis;therefore,establishing a defini-tive pathological diagnosis provides valuable evidence for predic-ting patient outcomes and guiding clinical management.

Objective:To investigate the clinicopathological features,immunophenotype,and prognosis of head and neck spindle cell squamous cell carcinoma(SCSCC)to improve the understanding and diagnosis of this tumor.Methods:Clinicopathological data collected from January 2012 to December 2022 at the First Affiliated Hospital,Air Force Military Medical University from 20 patients with head and neck SCSCC were retrospectively reviewed for histological morphology and immunophenotype.In situ and fluorescence in situ hybridization were performed to detect EBV-encoded ribonucleic acid(EBER)status and MDM2 gene amplification,respectively.Results:The median age among the 20 SCSCC cases was 67 years with a male-to-female ratio of 4∶1.Tumor locations were laryngeal(35.0%)and sinonasal(30.0%).SCSCC presented as polypoid or exogenous growths(61.5%),often with surface ulceration(90.0%).Histologically,sarcomatoid growth pat-terns were exhibited in 75.0%of the patients(n=15),while the remainder showed granular tissue-like or angiosarcomatoid patterns.Most tumors(65.0%)displayed components of conventional squamous cell carcinomas,with a predominant occurrence of high to moderate dif-ferentiation(91.7%).In terms of immunohistochemistry,AE1/AE3 was expressed in 83.3%(15/18)of cases,while p63 and p40 expression rates were 62.5%and 66.7%,respectively.All cases were negative for EBER.The Ki-67 proliferation index ranged 10%-70%.Overall,33.3%(1/3)of the cases showed MDM2 gene amplification.Among these,the median follow-up time for 18 patients was 18.3 months(range:1-92 months),with 6 survivors and 12 deaths.Conclusions:Head and neck SCSCC is more prevalent among elderly male smokers,predominantly exhibits a polypoid growth pattern,and does not display human papillomavirus or Epstein-Barr virus infection.Diagnosis requires a compre-hensive evaluation of clinical and pathological features and immunophenotype.Surgical resection is the primary treatment method.

Objective:To investigate the role of the CXC chemokine receptor 1 (CXCR1)/CXC chemokine ligand 8 (CXCL8) axis in the abnormal proliferation of bile duct epithelial cells in primary biliary cholangitis (PBC).Methods:30 female C57BL/6 mice were randomly divided into the PBC model group (PBC group), reparixin intervention group (Rep group), and blank control group (Con group) in an in vivo experiment. PBC animal models were established after 12 weeks of intraperitoneal injection of 2-octanoic acid coupled to bovine serum albumin (2OA-BSA) combined with polyinosinic acid polycytidylic acid (polyI:C). After successful modelling, reparixin was injected subcutaneously into the Rep group (2.5 mg · kg -1 · d -1, 3 weeks). Hematoxylin-eosin staining was used to detect histological changes in the liver. An immunohistochemical method was used to detect the expression of cytokeratin 19 (CK-19). Tumor necrosis factor-α (TNF-α), γ-interferon (IFN-γ) and interleukin (IL)-6 mRNA expression were detected by qRT-PCR. Western blot was used to detect nuclear transcription factor-κB p65 (NF-κB p65), extracellularly regulated protein kinase 1/2 (ERK1/2), phosphorylated extracellularly regulated protein kinase 1/2 (p-ERK1/2), Bcl-2-related X protein (Bax), B lymphoma-2 (Bcl-2), and cysteine proteinase-3 (Caspase- 3) expression. Human intrahepatic bile duct epithelial cells were divided into an IL-8 intervention group (IL-8 group), an IL-8+Reparicin intervention group (Rep group), and a blank control group (Con group) in an in vitro experiment. The IL-8 group was cultured with 10 ng/ml human recombinant IL-8 protein, and the Rep group was cultured with 10 ng/ml human recombinant IL-8 protein, followed by 100 nmol/L Reparicin. Cell proliferation was detected by the EdU method. The expression of TNF-α, IFN-γ and IL-6 was detected by an enzyme-linked immunosorbent assay. The expression of CXCR1 mRNA was detected by qRT-PCR. The expression of NF-κB p65, ERK1/2 and p-ERK1/2 was detected by western blot. A one-way ANOVA was used for comparisons between data sets. Results:The results of in vivo experiments revealed that the proliferation of cholangiocytes, the expression of NF-κB and ERK pathway-related proteins, and the expression of inflammatory cytokines were increased in the Con group compared with the PBC group. However, reparixin intervention reversed the aforementioned outcomes (P<0.05). In vitro experiments showed that the proliferation of human intrahepatic cholangiocyte epithelial cells, the expression of CXCR1 mRNA, the expression of NF-κB and ERK pathway-related proteins, and the expression of inflammatory cytokines were increased in the IL-8 group compared with the Con group. Compared with the IL-8 group, the proliferation of human intrahepatic cholangiocyte epithelial cells, NF-κB and ERK pathway-related proteins, and inflammatory indicators were significantly reduced in the Rep group ( P < 0.05). Conclusion:The CXCR1/CXCL8 axis can regulate the abnormal proliferation of bile duct epithelial cells in PBC, and its mechanism of action may be related to NF-κB and ERK pathways.

Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia (SCAP). We prospectively enrolled consecutive SCAP patients admitted to ICU. Bronchoscopy was performed at bedside within 48 h of ICU admission, and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid. The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy. Sixty-seven patients were included. Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota (R² = 0.033; P = 0.018), followed by acute kidney injury (AKI; R² = 0.032; P = 0.011) and plasma MIP-1β level (R² = 0.027; P = 0.044). Random forest identified that the families Prevotellaceae, Moraxellaceae, and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results. Multivariable Cox regression showed that the increase in α-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements. The positive bacteria lab test results, AKI, and plasma MIP-1β level were associated with patients' lung microbiota composition on ICU admission. The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.
Acute Kidney Injury/complications* ; Bacteria/classification* ; Chemokine CCL4/blood* ; Community-Acquired Infections/microbiology* ; Humans ; Lung ; Microbiota/genetics* ; Pneumonia, Bacterial/diagnosis* ; Prognosis ; RNA, Ribosomal, 16S/genetics*