Primary drug resistance among HIV-1 patients in Hubei Province in 2020-2022 / 公共卫生与预防医学

Objective To investigate the prevalence of primary drug resistance among HIV-1 patients in Hubei Province from 2020 to 2022, and to provide corresponding basis and data support for HIV antiviral therapy (ART) in Hubei Province. Methods During 2020-2022, plasma samples of HIV-1 infected patients before ART were collected., Patients’ demographic data and baseline laboratory test data were also collected. HIV-1 pol region was amplified by in-house method for sub-type typing and drug-resistant mutation site analysis. Results The pol gene sequence was successfully amplified in 242 of 285 cases, with a success rate of 84.9%. CRF07_BC was the predominant HIV-1 sub-type, accounting for 47.11% (114/242), followed by CRF01_AE, accounting for 25.21% (61/242), sub-type B, accounting for 14.16% (35/242), and CRF55_01B, accounting for 4.13% (10/242). The primary resistance rate was 6.20% (15/242). The mutation site of nucleoside reverse transcriptase inhibitors (NRTIs) was mainly M184V, and the mutation sites of non-nucleoside reverse transcriptase inhibitors (NNRTIs) were mainly E138A/G/EG and V179E. These different mutation sites led to different degrees of drug resistance to 12 drugs. The incidence of drug resistance mutation of CRF55_01B sub-type was significantly higher than that of other sub-types. Conclusion The primary drug resistance rate of HIV-1 infected patients is at a slightly high level in Hubei Province, and close monitoring of primary drug resistance and mutation sites should be strengthened before ART, especially for CRF55_01B sub-type.

Long-term outcomes for epidemic viral pneumonia survivors after discharge from the intensive care unit: a systematic review

ABSTRACT Objective To review the long-term outcomes (functional status and psychological sequelae) of survivors of critical illnesses due to epidemic viral pneumonia before the COVID-19 pandemic and to establish a benchmark for comparison of the COVID-19 long-term outcomes. Methods This systematic review of clinical studies reported the long-term outcomes in adults admitted to intensive care units who were diagnosed with viral epidemic pneumonia. An electronic search was performed using databases: MEDLINE®, Web of Science™, LILACS/IBECS, and EMBASE. Additionally, complementary searches were conducted on the reference lists of eligible studies. The quality of the studies was assessed using the Newcastle-Ottawa Scale. The results were grouped into tables and textual descriptions. Results The final analysis included 15 studies from a total of 243 studies. This review included 771 patients with Influenza A, Middle East Respiratory Syndrome, and Severe Acute Respiratory Syndrome. It analyzed the quality of life, functionality, lung function, mortality, rate of return to work, rehospitalization, and psychiatric symptoms. The follow-up periods ranged from 1 to 144 months. We found that the quality of life, functional capacity, and pulmonary function were below expected standards. Conclusion This review revealed great heterogeneity between studies attributed to different scales, follow-up time points, and methodologies. However, this systematic review identified negative long-term effects on patient outcomes. Given the possibility of future pandemics, it is essential to identify the long-term effects of viral pneumonia outbreaks. This review was not funded. Prospero database registration: (www.crd.york.ac.uk/prospero) under registration ID CRD42021190296.

Using guinea pig as a model for evaluation of equine influenza vaccine

Equine influenza is a highly contagious viral disease, specially among 1-5 years old naive horses. Vaccination is considered the best way to control the disease spread and outbreaks. Although foals are the main animal used for evaluation of equine influenza vaccines, guinea pigs were chosen as an alternative model in the present work, as they have a negligible antibody titer against equine influenza virus and are cheaper and easier to handle than foals. Five equine influenza vaccine batches were evaluated in two animal models, foals and guinea pigs, by injection of two doses/animal with 4 weeks apart using 2 mL/animal/dose and evaluation of immune responses by hemagglutination inhibition test and enzyme-linked immunosorbent assay. On the 7th week post vaccination, equine influenza antibodies titers reached maximum values of 9-10.2 and 8.7-10 hemagglutination inhibition units for foals and guinea pigs, respectively; sample/negative ratios were 0.126-0.464 and 0.128-0.445 for both animals, respectively. The use of guinea pigs as an animal model for the evaluation of equine influenza vaccines could be recommended instead of foals.

La gripe equina es una enfermedad viral muy contagiosa, especialmente entre los caballos jóvenes de 1 a 5 años de edad. La vacunación se considera la mejor forma de controlar la propagación y los brotes de la enfermedad. Aunque los potros son el principal animal utilizado para la evaluación de vacunas contra la gripe equina, en el presente trabajo se eligieron cobayos como modelo alternativo, ya que tienen un título insignificante de anticuerpos contra el virus de la gripe equina y son más baratos y fáciles de manejar que los potros. Se evaluaron cinco lotes de vacunas contra la gripe equina en dos modelos animales, potros y cobayos, mediante la inyección de dos dosis/animal con 4 semanas de intervalo utilizando 2 mL/animal/dosis y la evaluación de las respuestas inmunitarias mediante la prueba de inhibición de la hemaglutinación y el ensayo inmunoenzimático. En la 7ª semana posvacunación, los títulos de anticuerpos contra la gripe equina alcanzaron valores máximos de 9-10,2 y 8,7-10 unidades de inhibición de la hemaglutinación para potros y cobayos, respectivamente; las relaciones muestras/negativos fueron de 0,126-0,464 y 0,128-0,445 para ambos animales, respectivamente. Podría recomendarse el uso de cobayos como modelo animal para la evaluación de vacunas contra la gripe equina, en lugar de potros.

Advances in indications of anatomical pulmonary segmentectomy for early-stage lung cancer / 中国胸心血管外科临床杂志

@#Whether anatomical segmentectomy can replace lobectomy in the treatment of early-stage lung cancer remains controversial. A large number of studies have been conducted for decades to explore whether pulmonary segmentectomy can treat early-stage lung cancer, which is actually to explore the indications of intentional segment-ectomy. With the development of scientific researches, it is found that many characteristics affect the malignancy of lung cancer, and the different grades of each characteristic affect the prognosis of patients. It is worth exploring whether different surgical approaches can be used for early-stage lung cancer with different characteristics and different grades. This article reviews the literature and studies to discuss the advances in indications of segmentectomy for early-stage lung in terms of tumor size, consolidation-to-tumor ratio, pathological classification and tumor location, respectively. The objective of this review is to help thoracic surgeons to objectively and scientifically select the surgical method according to the clinical characteristics of early-stage lung cancer.

Epidemiological analysis of rubella and genetic characteristics of 1E-L2 subtype strains in Liaoning Province in 2019 / 中国生物制品学杂志

@#Objective To understand the epidemiological characteristics of rubella in Liaoning Province in 2019,and analyze the epidemiological characteristics of rubella virus genotypes and gene subtypes at molecular level.Methods By collecting the incidence data of rubella in Liaoning Province in 2019 from the national notifiable infectious diseases reporting system,the epidemiological characteristics of rubella were analyzed.At the same time,the measles/rubella laboratory network of Liaoning Province was used to collect throat swab samples from suspected rubella outbreaks and sporadic cases.After three generations of blind transmission of positive samples,rubella virus isolates were obtained.Viral nucleic acid was extracted,amplified and the 739 bp nucleotide fragment sequence of E1 gene of positive rubella virus isolates was determined.The phylogenetic tree was constructed with the genotype reference strain sequences recommended by WHO and the published gene subtype reference strain sequences.The genotypes and subtypes were compared and the amino acid variation sites were analyzed.Results The reported incidence of rubella in Liaoning Province in 2019 was 0.927/100 000,which showed an obvious trend of recovery after a significant decrease in the incidence of rubella from 2017 to 2018,and the age of rubella patients was mainly 15 to 19 years old.A total of 55 rubella virus strains were isolated from 7 cities in Liaoning Province in 2019.Sequence phylogenetic analysis showed that all rubella isolates belonged to 1E-L2 gene subtype,which was also the dominant gene subtype of rubella epidemic in China.The nucleotide and amino acid homology among the strains were 99.051%～99.864% and 98.780%～100% respectively.Compared with the BRD-Ⅱ vaccine strain,the rubella isolates mainly showed A333T mutation and showed highly conserved amino acid sequence.Conclusion The 2019 rubella isolates in Liaoning Province were all 1E-L2 gene subtypes,which led to the resurgence of rubella epidemic.Therefore,molecular epidemiological surveillance of rubella virus should be further strengthened to provide a basis for the formulation and elimination of rubella prevention and control measures in Liaoning Province.

Differences in therapeutic effect and prognosis of different molecular subtypes of invasive lobular carcinoma of the breast treated with nab-paclitaxel / 肿瘤研究与临床

Objective:To explore the differences in therapeutic effect and prognosis of different molecular subtypes of breast invasive lobular carcinoma treated with nab-paclitaxel, so as to provide a basis for the selection of clinical drugs for breast cancer.Methods:The data of 180 patients with advanced invasive lobular carcinoma of the breast who were treated in Handan Central Hospital and the Fourth Hospital of Hebei Medical University from January 2017 to January 2020 were retrospectively analyzed, including 34 cases of Luminal A type, 92 cases of Luminal B type, 21 cases of human epidermal growth factor receptor 2 (HER2) overexpression type, and 33 cases of triple-negative type. The patients were treated with nab-paclitaxel, and the clinical curative effect was evaluated according to the solid tumor response evaluation criteria version 1.1 after 1 year of treatment, and the objective response rate (ORR) (calculated as complete remission + partial remission) and clinical benefit rate (CBR) (calculated as complete remission + partial remission + stable disease) were calculated; the occurrence of adverse reactions during the treatment was recorded. The Kaplan-Meier method was used to draw the progression-free survival (PFS) and overall survival (OS) curves for each subtype of patients, and the log-rank method was used to test them.Results:The differences in ORR and CBR among patients with the four subtypes of Luminal A, Luminal B, HER2 overexpression, and triple-negative were statistically significant (all P < 0.001), with the triple-negative type having the lowest ORR and CBR [21.2% (7/33) and 63.6% (21/33)] and the Luminal A type having the highest ORR and CBR [70.6% (24/34) and 100.0% (34/34)]. The ORR and CBR of Luminal B type were 45.7% (42/92) and 90.2% (83/92), and the HER2 overexpression type was 38.1% (8/21) and 90.5% (19/21). The differences in the incidence of myelosuppression, numbness of limbs, joint and muscle pain among the four subtypes were statistically significant (all P < 0.05), with the triple-negative type having the highest incidence of all of the above adverse reactions. The PFS and OS of triple-negative subtype were worse than those of Luminal A, Luminal B and HER2 overexpression subtypes, and the differences were statistically significant (all P < 0.05). Conclusions:The clinical response and prognosis of patients with different molecular subtypes of invasive lobular carcinoma is significantly different after nab-paclitaxel intervention, among which the prognosis of patients with triple-negative type is the worst, and the clinical medication can be guided according to the pathological test results.

Analysis of HIV-1 subtypes and pretreatment drug resistance in newly reported HIV/AIDS cases in Hangzhou, 2020-2022 / 中华微生物学和免疫学杂志

Objective:To analyze the HIV-1 subtypes and drug resistance among newly reported HIV/AIDS cases before antiretroviral therapy (ART) in Hangzhou.Methods:Blood samples were collected from newly diagnosed HIV-1/AIDS cases not receiving ART in Hangzhou from 2020 to 2022. HIV-1 pol gene was amplified and then sequenced. A phylogenetic tree was construct using MEGA7.0 software to analyse the HIV-1 subtypes, The sequences were submitted to the Stanford University drug resistance database to identify drug resistance mutation sites and drug sensitivity. Results:A total of 2 700 sequences were obtained. Twelve subtypes were identified, and the predominant subtypes were CRF07_BC (46.8%, 1 263/2 700) and CRF01_AE (34.6%, 933/2 700). The overall drug resistance rate before ART was 8.1% (220/2 700) and the resistance rates to protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) were 2.8% (75/2 700), 1.3% (36/2 700) and 4.4% (119/2 700), respectively. Among the 220 drug-resistant cases, mutations conferring resistance to PIs (Q58E), NRTIs (M184V/I) and NNRTIs (K103N/S and E138A/G/K/Q) were detected in 47 (21.4%), 13 (5.9%), 42 (19.1%) and 41 (18.6%) patients, respectively.Conclusions:HIV-1 genotypes were highly complex in newly reported HIV/AIDS cases in Hangzhou from 2020 to 2022. There were cases showing moderate or high resistance to backbone drugs before ART, indicating that HIV-1 monitoring should be strengthened to avoid treatment failure and reduce the spread of drug-resistant strains.

Genetic variation characteristics of HA gene of influenza A virus (H3N2) in Guizhou province from 2017 to 2019 / 中国基层医药

Objective:To analyze the genetic variation characteristics of the HA gene of influenza A virus (H3N2) in Guizhou province from 2017 to 2019. Methods:Twenty strains of influenza A virus (H3N2) were randomly selected from 10 network laboratories in Guizhou province for RNA extraction. Reverse transcriptase-polymerase chain reaction and sequencing were performed. The products were analyzed using bioinformatics software.Results:The nucleotide homology of the HA gene of the 20 strains was 97.7%-100%, which was highly homologous to the vaccine strains A/Hong-Kong/4801/2014 recommended by WHO in 2017 and A/Singapore-INFIMH/16-0019/2016 recommended by WHO in 2018, but they were significantly different from the vaccine strain A/Kansas/14/2017 recommended by WHO in 2019. Genetic analysis showed that the 20 strains were divided into two branches, and the strains that were prevalent in 2019 were located in different branches, with marked genetic differences. Key site analysis showed mutations in antigenic determinants A, B, C, and E and mutations in the anterior and posterior walls of receptor binding sites. Key site analysis also showed that there was an increase in the number of glycosylation sites compared with the vaccine strains prevalent in the same year. Genetic distance, antigen sites, and glycosylation sites were slightly different between virus strains prevalent in 2017-2018 and virus strains prevalent in 2019. Conclusion:The HA gene of the influenza A virus subtype H3N2 in Guizhou province from 2017 to 2019 showed heterogeneity and gene mutation, especially in 2019. Therefore, close monitoring of the genetic evolution of the influenza A virus subtype H3N2 is necessary.

The role of neutrophil CD 11b, soluble CD 14 subtype and mitochondrial coupling factor-6 in the risk stratification of disease outcome in neonatal sepsis and its clinical significance / 中国医师进修杂志

Objective:To investigate the role of neutrophil CD 11b (nCD 11b), soluble CD 14 subtype (sCD 14-St) and mitochondrial coupling factor-6 (CF-6) in the risk stratification of disease outcome in neonatal sepsis and its clinical significance. Methods:The clinical data of 121 septic neonates from July 2019 to March 2020 in Shanxi Children′s Hospital were retrospectively analyzed. According to the neonatal critical illness score (NCIS), the neonates were divided into non-critical group (NCIS>90 scores) with 35 cases, critical group (NCIS 70 to 90 scores) with 49 cases, very critical group (NCIS<70 scores) with 37 cases. There were 25 cases with poor prognosis (death), and 96 cases with good prognosis (survival). The C-reactive protein (CRP), procalcitonin (PCT), nCD 11b, sCD 14-St and CF-6 before treatment were detected. The correlation between nCD 11b, sCD 14-St, CF-6 and disease severity was analyzed by Spearman method; the value of nCD 11b, sCD 14-St and CF-6 in predicting poor disease outcome in sepsis neonates was analyzed by the receiver operating characteristic (ROC) curve. Results:The nCD 11b, sCD 14-St, CF-6, PCT and CRP in critical group and very critical group were significantly higher than those in non-critical group: (414.68 ± 93.29) and (532.74 ± 101.85) MFI vs. (325.45 ± 71.90) MFI, (892.40 ± 113.72) and (1 249.53 ± 95.41) ng/L vs. (784.66 ± 103.72) ng/L, (84.79 ± 28.35) and (121.66 ± 34.27) ng/L vs. (42.59 ± 13.51) ng/L, (19.24 ± 6.30) and (34.96 ± 11.95) μg/L vs. (8.89 ± 2.24) μg/L, (109.49 ± 36.77) and (247.13 ± 82.06) mg/L vs. (56.84 ± 17.25) mg/L; the indexes in very critical group were significantly higher than those in critical group, and there were statistical differences ( P<0.05). Spearman correlation analysis result showed that nCD 11b, sCD 14-St and CF-6 were positively correlated with disease severity in sepsis neonates ( r = 0.719, 0.813 and 0.823; P<0.01). The nCD 11b, sCD 14-St, CF-6, PCT and CRP in poor prognosis neonates were significantly higher than those in good prognosis neonates: (618.58 ± 146.92) MFI vs. (374.55 ± 120.03) MFI, (1 516.91 ± 194.38) ng/L vs. (828.13 ± 175.67) ng/L, (165.84 ± 25.63) ng/L vs. (62.51 ± 16.75) ng/L, (43.46 ± 10.14) μg/L vs. (20.19 ± 6.30) μg/L and (321.09 ± 94.56) mg/L vs. (88.24 ± 29.19) mg/L, and there were statistical differences ( P<0.01). ROC curve analysis result showed that the area under the curve (AUC) of nCD 11b, sCD 14-St and CF-6 for predicting poor disease outcome in sepsis neonates were 0.763, 0.796 and 0.838 (95% CI 0.678 to 0.836, 0.713 to 0.864 and 0.760 to 0.899), and the AUC of combination the 2 indexes was 0.921 (95% CI 0.858 to 0.962). Conclusions:The nCD 11b, sCD 14-St and CF-6 are associated with the disease severity and prognosis in sepsis neonates, and can be used as markers for risk stratification of disease outcome and assessment prognosis.

Study on the progress of HIV typing methods / 上海预防医学

As a retrovirus with high recombination and mutation rate， HIV targets CD4+ T lymphocytes， causing damage to the body's immune system and eventually leading to severe immune function defects. Different subtypes of the HIV virus exhibit significant sequence differences in their structural and regulatory genes， and this diversity is closely related to etiology， transmission， diagnosis， drug therapy， disease progression， and vaccine development. As a country with the largest number of HIV subtypes， rapid and accurate typing of the HIV virus holds great significance for China's efforts in disease prevention and control. This study provides a comprehensive reveiw of domestic and international HIV genotyping methods， and summarizes the clinical significance of different subtypes in order to provide reference for further research.

Traditional Chinese Medicine Intervenes in Atherosclerosis by Regulating TLR/NLRP3 Pathway via TRPV1/TRPA1 / 中国实验方剂学杂志

Atherosclerosis is a chronic inflammatory disease caused by lipid accumulation and vascular endothelial dysfunction. The Toll-like receptor （TLR）/nuclear transcription factor-κB （NF-κB） pathway and the NOD-like receptor protein 3 （NLRP3） inflammasome pathway play a proinflammatory role， while the transient receptor potential vanilloid subtype 1 （TRPV1） and transient receptor potential ankyrin 1 （TRPA1） play a protective role in the occurrence of atherosclerosis. We reviewed the relevant studies published in the last 10 years. The results showed that activation of TRPV1/TRPA1 could activate endothelial-type nitric oxide synthase （eNOS） and inhibit the generation of reactive oxygen species （ROS） and cholesterol crystal （CC） to modulate the TLR/NF-κB and NLRP3 inflammasome pathways， thereby inhibiting TLR/NLRP3-mediated inflammatory response. A variety of compound prescriptions and active components of Chinese medicinal materials can activate TRPV1/TRPA1 or its downstream pathway to regulate the TLR/NLRP3 pathway in atherosclerosis. This paper introduces the mechanisms of compound prescriptions and active components of Chinese medicinal materials in regulating the TLR/NLRP3 pathway via TRPV1/TRPA1 in atherosclerosis. This review provides new ideas for the research on the interactions between Chinese medicines in the treatment of atherosclerosis and provides a new strategy for the clinical treatment of atherosclerosis with traditional Chinese medicine.

Identification of M1 macrophage-related genes in rejection after kidney transplantation based on weighted gene co-expression network analysis / 器官移植

Objective To identify M1 macrophage-related genes in rejection after kidney transplantation and construct a risk prediction model for renal allograft survival. Methods GSE36059 and GSE21374 datasets after kidney transplantation were downloaded from Gene Expression Omnibus (GEO) database. GSE36059 dataset included the samples from the recipients with rejection and stable allografts. Using this dataset, weighted gene co-expression network analysis (WGCNA) and differential analysis were conducted to screen the M1 macrophage-related differentially expressed gene (M1-DEG). Then, GSE21374 dataset (including the follow-up data of graft loss) was divided into the training set and validation set according to a ratio of 7∶3. In the training set, a multivariate Cox's model was constructed using the variables screened by least absolute shrinkage and selection operator (LASSO), and the ability of this model to predict allograft survival was evaluated. CIBERSORT was employed to analyze the differences of infiltrated immune cells between the high-risk group and low-risk group, and the distribution of human leukocyte antigen (HLA)-related genes was analyzed between two groups. Gene set enrichment analysis (GSEA) was used to further clarify the biological process and pathway enrichment in the high-risk group. Finally, the database was employed to predict the microRNA (miRNA) interacting with the prognostic genes. Results In the GSE36059 dataset, 14 M1-DEG were screened. In the GSE21374 dataset, Toll-like receptor 8 (TLR8), Fc gamma receptor 1B (FCGR1B), BCL2 related protein A1 (BCL2A1), cathepsin S (CTSS), guanylate binding protein 2(GBP2) and caspase recruitment domain family member 16 (CARD16) were screened by LASSO-Cox regression analysis, and a multivariate Cox's model was constructed based on these 6 M1-DEG. The area under curve (AUC) of receiver operating characteristic of this model for predicting the 1- and 3-year graft survival was 0.918 and 0.877 in the training set, and 0.765 and 0.736 in the validation set, respectively. Immune cell infiltration analysis showed that the infiltration of rest and activated CD4+ memory T cells, γδT cells and M1 macrophages were increased in the high-risk group (all P < 0.05). The expression level of HLA I gene was up-regulated in the high-risk group. GSEA analysis suggested that immune response and graft rejection were enriched in the high-risk group. CTSS interacted with 8 miRNA, BCL2A1 and GBP2 interacted with 3 miRNA, and FCGR1B interacted with 1 miRNA. Conclusions The prognostic risk model based on 6 M1-DEG has high performance in predicting graft survival, which may provide evidence for early interventions for high-risk recipients.

New strategies for the treatment of carcinoma of unknown primary / 中华肿瘤杂志

Carcinoma of unknown primary (CUP) is a kind of metastatic tumor whose primary origin cannot be identified after adequate examination and evaluation. The main treatment modality of CUP is empiric chemotherapy, and the median overall survival time is less than 1 year. Compared with immunohistochemistry, novel method based on gene expression profiling have improved the sensitivity and specificity of CUP detection, but its guiding value for treatment is still controversial. The approval of immune checkpoint inhibitors and pan-cancer antitumor agents has improved the prognosis of patients with CUP, and targeted therapy and immunotherapy based on specific molecular characteristics are the main directions of future research. Given the high heterogeneity and unique clinicopathological characteristics of CUP, "basket trial" is more suitable for clinical trial design in CUP.

Investigation of androgen receptor-dependent alternative splicing has identified a unique subtype of lethal prostate cancer / 亚洲男科学杂志(英文版)

A complete proteomics study characterizing active androgen receptor (AR) complexes in prostate cancer (PCa) cells identified a diversity of protein interactors with tumorigenic annotations, including known RNA splicing factors. Thus, we chose to further investigate the functional role of AR-mediated alternative RNA splicing in PCa disease progression. We selected two AR-interacting RNA splicing factors, Src associated in mitosis of 68 kDa (SAM68) and DEAD (Asp-Glu-Ala-Asp) box helicase 5 (DDX5) to examine their associative roles in AR-dependent alternative RNA splicing. To assess the true physiological role of AR in alternative RNA splicing, we assessed splicing profiles of LNCaP PCa cells using exon microarrays and correlated the results to PCa clinical datasets. As a result, we were able to highlight alternative splicing events of clinical significance. Initial use of exon-mini gene cassettes illustrated hormone-dependent AR-mediated exon-inclusion splicing events with SAM68 or exon-exclusion splicing events with DDX5 overexpression. The physiological significance in PCa was investigated through the application of clinical exon array analysis, where we identified exon-gene sets that were able to delineate aggressive disease progression profiles and predict patient disease-free outcomes independently of pathological clinical criteria. Using a clinical dataset with patients categorized as prostate cancer-specific death (PCSD), these exon gene sets further identified a select group of patients with extremely poor disease-free outcomes. Overall, these results strongly suggest a nonclassical role of AR in mediating robust alternative RNA splicing in PCa. Moreover, AR-mediated alternative spicing contributes to aggressive PCa progression, where we identified a new subtype of lethal PCa defined by AR-dependent alternative splicing.

Identification of B(A) subtype and analysis of bood transfusion strategiaes / 中国输血杂志

【Objective】 To investigate the serology and genotype identification method of B (A) subtype patients. 【Methods】 Test tube method (serology) was used to confirm the clinically difficult ABO blood group samples of 3 patients with ABO blood group; ABO blood group was genotyped by real-time PCR, and the ABO gene exon 1-7 was sequenced to determine the genotype. 【Results】 The forward and reverse blood typing result of three patients was B (A) subtype all with ABO genotype B/O2 and c.640A> G mutation on B allele of exon 7, which meets the characteristics of ABO * BA.04 genotype. 【Conclusion】 The combination of serological and genetic testing could identify difficult blood types such as ABO subtypes accurately and ensure the safety of clinical blood use.

The S1P1 regulator IMMH002 and its therapeutic effect and mechanism on autoimmune hepatitis / 药学学报

This study assessed and explored the pharmacological effects and mechanisms of action of IMMH002 {2-amino-2-(2-(4ʹ-(2-ethyloxazol-4-yl)-[1,1ʹ-biphenyl]-4-yl)ethyl)propane-1,3-dio}, a selective sphingosine-1-phosphate receptor subtype 1 (S1P1) modulator, in a concanavalin A (ConA)-induced autoimmune hepatitis (AIH) mouse model. The experimental protocol strictly adhered to the guidelines of the Ethics Committee for Animal Research of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (Approval No.: 00004046). Male ICR mice were pre-treated with the drug for four days, followed by induction of AIH through tail vein injection of ConA protein. Liver function, hepatic tissue pathology, peripheral blood parameters, as well as immunoglobulin G (IgG), inflammatory cytokines, T cell distribution, and inflammatory pathways were evaluated in mice. Results demonstrated that IMMH002 significantly reduced liver function indicators such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alleviated hepatic tissue inflammation and necrotic damage, decreased serum IgG levels, and lowered the expression of inflammatory mediators including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ). Additionally, it facilitated T lymphocyte homing, downregulated the phosphorylation of nuclear factor kappa-B (NF-κB), IκB kinase β (IKKβ) and nuclear factor inhibitor protein-α (IκBα) proteins in hepatic tissue and cellular inflammation models. Collectively, IMMH002 effectively ameliorated ConA-induced autoimmune hepatitis in mice, exhibiting extensive anti-inflammatory and anti-necrotic effects, thereby laying a theoretical foundation for AIH clinical treatment.

Molecular detection and subtyping of Blastocystis sp. in pigs in Anhui Province / 中国血吸虫病防治杂志

Objective To investigate the prevalence and subtype distribution of Blastocystis sp. in pigs in Anhui Province. Methods A total of 500 stool samples were collected from large-scale pig farms in Bozhou, Anqing, Chuzhou, Hefei, Fuyang, and Lu’an cities in Anhui Province from October to December 2015. Blastocystis was detected in pig stool samples using a PCR assay based on the small subunit ribosomal RNA (SSU rRNA) gene, and positive samples were subjected to sequencing and sequence analysis. Blastocystis subtypes were characterized in the online PubMLST database, and verified using phylogenetic tree created with the neighbor-joining algorithm in the Meta software. Results The prevalence of Blastocystis infection was 43.2% (216/500) in pigs in 6 cities of Anhui Province, and all pig farms were tested positive for Blastocystis. There was a region-specific prevalence rate of Blastocystis (17.2% to 50.0%) (χ2 = 26.084, P < 0.01), and there was a significant difference in the prevalence of Blastocystis sp. among nursery pigs (39.6%), preweaned pigs (19.1%), and growing pigs (62.3%) (χ2 = 74.951, P < 0.01). Both online inquiry and phylogenetic analysis revealed ST1, ST3, and ST5 subtypes in pigs, with ST5 as the predominant subtype. Conclusion The prevalence of Blastocystis sp. is high in pigs in Anhui Province, with three zoonotic subtypes identified, including ST1, ST3, and ST5.

The predictive value of CT signs of mixed ground-glass nodules in pathological subtypes and differentiation of lung adenocarcinoma / 中国胸心血管外科临床杂志

@#Objective    To explore the predictive value of CT signs of mixed ground-glass nodules in the pathological subtype and differentiation of lung adenocarcinoma. Methods    The clinical data of 66 patients with mixed ground-glass nodules pathologically diagnosed as invasive adenocarcinoma (IAC) in the Second Department of Thoracic Surgery, the First Affiliated Hospital of Xiamen University from May to December 2021 were retrospectively analyzed, including 20 males and 46 females, aged 35-75 years. The CT findings were analyzed before operation, and the lesion profile was cut after operation to distinguish the ground-glass and solid components, and the pathological results of different positions were obtained. According to the postoperative pathological results, the patients were divided into a low-risk group (containing adherent type and no components of micropapillary subtype and solid subtype, n=16), a medium-risk group (containing niple or acinar type and no components of micropapillary subtype and solid subtype, n=38), and a high-risk group (containing micropapillary or solid subtype, n=12). The relationships between CT features and the pathological subtype and degree of differentiation were analyzed and compared. Results    In 66 patients with IAC, the infiltration degree of solid components was greater than that of ground-glass components. When the solid component ratio (CTR) was≥25% (sensitivity 90.2%, specificity 64.0%, P=0.005), and the average CT value was>−283.95 HU (sensitivity 82.9%, specificity 64.0%, P=0.000), the histological grade was more inclined to medium and low differentiation. The CTR, Ki-67, average CT value and histological grade of IAC in the medium- and high-risk groups were higher than those of nodules in the low-risk group. Conclusion    The infiltration degree of solid components is higher than that of ground-glass components in IAC mixed ground-glass nodules. The pathological subtype, Ki-67 expression and histological grade of lung adenocarcinoma can be predicted according to its CT characteristics, which has important clinical significance for determining the timing of surgery.

Comparison of somatic gene mutation between 114 cases with different subtypes of thyroid papillary carcinoma and the TCGA database / 预防医学

Objective@#To compare the difference in somatic gene mutation of PTC subtypes between 114 patients with papillary thyroid carcinoma (PTC) and The Cancer Genome Atlas (TCGA) database.@*Methods@#Totally 114 PTC patients admitted to The First Affiliated Hospital of Nanjing Medical University were recruited. The 18 hotspot genes associated with thyroid cancer were detected in thyroidectomy specimens were using next generation sequencing. PTC data were downloaded from the TCGA database in the cBioPortal website, and the difference in the somatic gene mutation was compared between 114 PTC patients and the TCGA database@*Results@#The 114 PTC patients included 73 women (64.04%) and had a mean age of (39.23±13.18) years. The prevalence of BRAF V600E (66.67% vs. 48.68%), TERTp (3.51% vs. 0.41%), PDGFRA (1.75% vs. 0%), PTEN (3.51% vs. 0.41%) and TP53 gene mutations (4.39% vs. 0.61%) was significantly higher among the 114 PCT patients than in the TCGA database (P<0.05). The prevalence of BRAF V600E (80.88% vs. 54.99%), TP53 (7.35% vs. 0.57%) and TSHR gene mutations (2.94% vs. 0%) was significantly higher in classical PTC(CPTC) patients than in the TCGA database, and the prevalence of BRAF V600E (36.84% vs.13.86%) and TERTp gene mutations (10.53% vs. 0%) was significantly higher in follicular variant PTC (FVPTC) patients than in the TCGA database. According to the American Thyroid Association Risk Stratification of Thyroid Cancer Recurrence, the prevalence of BRAF V600E and TP53 gene mutations was 77.14% and 8.57% among moderate-risk CPTC patients, the prevalence of BRAF V600E gene mutation was 27.27% among low-risk FVPTC patients, and the prevalence of TERTp gene mutation was 33.33% among moderate-risk FVPTC patients, which were all higher than in the TCGA database (55.10%, 0%, 3.28%, and 0%, respectively; P<0.05).@*Conclusion@#There are significant differences in the type and rate of somatic gene mutations between 114 PTC patients and the TCGA database.

Genetic Subtypes and Pretreatment Drug Resistance in the Newly Reported Human Immunodeficiency Virus-Infected Men Aged≥50 Years Old in Guangxi / 中国医学科学院学报

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ2=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.