Objective To understand the genotyping of human immunodeficiency virus (HIV) co-infected hepatitis C virus (HCV) patients in Yunnan Province, and to analyze the differences in viral load, biochemical indicators, and blood routine indicators among different genotypes, in order to provide a laboratory basis for the diagnosis and clinical treatment of HIV/HCV co-infected patients. Methods From November 2022 to June 2023, the serum samples and basic information of patients diagnosed with HIV/HCV co-infection were collected in the antiviral outpatient clinic of Yunnan Provincial Hospital of Infectious Diseases. The HCV viral load was detected by one-step qRT-PCR amplification, the positive samples were sequenced, and genotyping was determined based on NS5 gene sequence. The differences in biochemical and blood routine indexes between HIV patients co-infected with different HCV genotypes and low/high viral loads were analyzed. Results A total of 126 HIV/HCV co-infected patients were collected, including 20 HCV genotype 1 (15.9%), 91 HCV genotype 3 (72.2%), and 15 HCV genotype 6 (11.9%). The maximum and minimum viral load of the three HCV genotypes were as follows: HCV type 1 (1.0×108, 4.8×104 IU/mL), HCV type 3 (2.2×108, 2.9×102 IU/mL), and HCV type 6 (8.1×107, 6.8×104 IU/mL). The results showed that there was no significant difference between HIV co-infection with different genotypes of HCV and three HIV treatment schemes, including nucleoside reverse transcriptase inhibitors+integrase strand transfer inhibitors (NRTIs+INSTIs), nucleoside reverse transcriptase inhibitors+non-nucleoside reverse transcriptase inhibitors (NRTIs+NNRTIs) and nucleoside reverse transcriptase inhibitors+protease inhibitor (NRTIs+PLs), and the viral load of patients (P>0.05). The analysis of biochemical indexes such as total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CREA), and blood routine indexes such as white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB), platelet (PLT), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) among different HCV genotypes and low/high viral loads showed that there was no significant difference in biochemical indexes and blood routine indexes between low/high viral loads of HIV co-infected HCV patients (P>0.05); however, the biochemical indicators TBIL, IBIL and MCHC were significantly different statistically between patients with genotype 3 HCV infection and those with genotype 1 HCV infection (P<0.05), while other biochemical and blood routine indexes were not statistically different among different HCV genotypes (P>0.05). Conclusions There are six subtypes of HCV co-infection in HIV patients in Kunming, Yunnan Province, including three genes of genotype 1, 3, and 6. Among them, genotype 3 HCV is the main prevalent genetic virus among HIV co-infected populations. The TBIL, IBIL and MCHC values of HIV patients co-infected with HCV type 3 are different from those infected with HCV type 1.

Background and aim:Hepatitis B virus(HBV)-related gestational acute-on-chronic liver failure(ACLF)is a severe condition with limited treatment options.This study aimed to evaluate the efficacy and ideal timing of plasma exchange and continuous renal replacement therapy(CRRT)in managing pregnant women with HBV-related ACLF. Methods:This study retrospectively analyzed 51 eligible patients with HBV-related gestational ACLF between 2009 and 2020.Patients admitted to the study were divided into a conventional treatment group and a new treatment group according to whether they received the new management protocol,which included more aggressive plasma exchange(PE)and CRRT strategies.All 19 pregnant women with hepatic encephalopathy(HE)were divided into an early treatment group and a non-early treatment group according to whether PE therapy was initiated within three days.Our study had two primary objectives.Firstly,we aimed to evaluate the impact of PE and CRRT on puerperal survival.Secondly,we sought to assess the effects of early PE and CRRT regimens on puerperal survival in women with HE. Results:The levels of total bilirubin on the second day postpartum(D3),the third day postpartum(D4),and the fifth day postpartum(D6)were significantly lower in the new treatment group compared to the conventional treatment group(P=0.02,0.01,and 0.02,respectively).The ALT of D3 was significantly elevated in the new treatment group compared to the conventional treatment group(P=0.02).The incidence of HE overall increased from prenatal to postpartum D4,peaked on D4,and then gradually decreased from the fourth day postpartum(D5)(P=0.027).The first week after delivery revealed a significant difference in survival rate between the two groups,the conventional treatment group had statistically higher mortality rates compared to the new treatment group(P=0.002).Similarly,the entire puerperal period mortality rate of the conventional treatment group was statistically higher than the new treatment group(P=0.002).Moreover,among all patients with HE,the non-early treatment group showed significantly higher puerperal mortality rates compared to the early treatment group(P=0.006). Conclusions:Early PE and CRRT conducted within three days post-childbirth,enhance puerperal prog-nosis for HBV-related gestational ACLF.

In order to obtain a cell line which high expressed of rabies virus glycoprotein the produc-tion of rabies subunit vaccine,the RABV glycoprotein gene sequence was amplified by RT-PCR and cloned into the lentiviral expression vector.The recombinant plasmid pLV-RVG,envelope plasmid pMD2.0G and packaging plasmid psPAX2 were co-transfected into HEK-293T cells to harvest lentivirus and infect new HEK-293T cells.The 293T-RVG cell line was obtained by puro-mycin pressure screening.Indirect immunofluorescence assay(IFA)and Western blot showed that the 67 kD RABV-G protein was highly expressed in the cells.The neutralizing antibody titer reached 2.19 IU/mL within 14 days after immunization,which was higher than the internationally recognized protection threshold(0.5 IU/mL).This study showed that the cell line 293T-RVG with stable and high expression of rabies virus glycoprotein was successfully constructed.The cell line could protect mice against rabies virus challenge and could be used as a subunit vaccine with poten-tial for large-scale production and application.

OBJECTIVE: To assess the practical and health economical values of non-invasive prenatal test (NIPT) in Changsha Municipal Public Welfare Program. METHODS: A retrospective analysis was carried out on 149 165 women undergoing NIPT test from April 9, 2018 to December 31, 2019. For pregnant women with high risks, invasive prenatal diagnosis and follow-up of pregnancy outcome were conducted. The cost-benefit of NIPT for Down syndrome was analyzed. RESULTS: NIPT was carried out for 149 165 pregnant women and succeeded in 148 749 cases (99.72%), for which outcome were available in 148 538 (99.86%). 90% of pregnant women from the region accepted the screening with NIPT. 415 (0.27%) were diagnosed as high risk. Among these, 381 (91.81%) accepted amniocentesis, which led to the diagnosis of 212 cases of trisomy 21 (PPV=85.14%), 41 cases with trisomy 18 (PPV=48.81%) and 10 cases with trisomy 13 (PPV=20.83%). The sensitivity and specificity of NIPT for trisomy 21, trisomy 18 and trisomy 13 were (97.70%, 99.98%), (97.62%, 9.97%) and (100%, 99.97%), respectively. In addition, 213 and 30 cases were diagnosed with sex chromosomal aneuploidies (PPV=46.2%) and other autosomal anomalies (PPV=16.57%), respectively. For Down syndrome screening, the cost and benefit of the project was 120.79 million yuan and 1,056.95 million yuan, respectively. The cost-benefit ratio was 1: 8.75, and safety index was 0.0035. CONCLUSION NIPT is a highly accurate screening test for trisomy 21, which was followed by trisomy 18 and sex chromosomal aneuploidies, while it was less accurate for other autosomal aneuploidies. The application of NIPT screening has a high health economical value.
Aneuploidy ; Cost-Benefit Analysis ; Female ; Humans ; Noninvasive Prenatal Testing ; Pregnancy ; Retrospective Studies ; Trisomy 18 Syndrome/genetics*

Objective To investigate the rationality and efficacy of enhanced recovery after surgery (ERAS) in liver transplant recipients. Methods Clinical data of 465 liver transplant recipients were retrospectively analyzed. All recipients were divided into the ERAS group (n=163) and control group (n=302) according to whether they received ERAS. The severity of disease in the ERAS group was worse than that in the control group. Operation situations including the operation time, anhepatic phase and intraoperative blood transfusion volume of the liver transplant recipients were observed and recorded. Postoperative recovery conditions including the length of intensive care unit (ICU) stay, total length of hospital stay, total ventilator removal time at postoperative 28 d and postoperative re-intubation rate were recorded. The survival rates at 90 d, 180 d and 1 year after liver transplantation were calculated. The influencing factors of survival rate of liver transplant recipients were analyzed. Results The anhepatic phase in the ERAS group was 45 (39, 53) min, significantly longer than 40 (32, 48) min in the control group (P < 0.05). The volume of erythrocyte infusion in the ERAS group was 10 (7, 13) U, significantly less than 18 (10, 28) U in the control group (P < 0.05). The length of postoperative ICU stay and total length of hospital stay in the ERAS group were 135 (84, 212) h and 24 (18, 33) d, significantly shorter than 154 (103, 253) h and 34 (20, 50) d in the control group (both P < 0.05). Total ventilator removal time at postoperative 28 d was 26 (25, 27) d, significantly longer than 26 (23, 27) d in the control group (P < 0.05). The postoperative re-intubation rate in the ERAS group was 11.0%, significantly lower than 20.8% in the control group (P < 0.05). The 90 d, 180 d and 1-year survival rates in the ERAS group were 92.8%, which were significantly higher than 81.1%, 78.1% and 75.7% in the control group (all P < 0.05). ERAS and operation time were the independent influencing factors of survival rate of liver transplant recipients (both P < 0.05). Conclusions ERAS after liver transplantation can improve the survival rate of recipient, shorten the length of hospital stay, reduce the re-intubation rate and accelerate the rehabilitation after liver transplantation.

Objective: To investigate the molecular characteristics and tracing of the hemagglutinin (HA) gene, and to analyze the risk of human infection with influenza virus A (H7N9) in Guizhou Province, so that to provide evidence for the prevention and control of highly pathogenic avian influenza A (H7N9). Methods: Nucleic acids of 5 strains of H7N9 including 1 sample of the patient′s nasopharyngeal swab and 4 samples of the live poultry market (LPM) environment were extracted and HA genes were amplified and sequenced. Then the homology, genetic evolution and the pivotal sites related to receptor binding regions, pathogenicity and potential glycosylation of the avian influenza A (H7N9) viruses were analyzed by a series of bioinformatics softwares. Results: Homology analysis revealed that the homologies of nucleotide and amino-acid of the HA gene of H7N9 strains from the patient and LPM in Weining County, Guizhou Province were 99.8% and 99.6%, respectively, while those of 4 strains from LPM were both 100%. The homologies of nucleotide and amino-acid of the HA gene of H7N9 strains were the highest with the strain of A/Guangxi/5/2017 isolated from a Guangxi infected patient (99.7%-99.9% and 99.4%-99.8%, respectively), while those with the strain isolated from LPMs environment at the end of 2016 (A/Environment/Guangdong/C16283222/2016) were 99.0%-99.2% and 98.9%-99.2%, respectively. However, the homologies of nucleotide and amino-acid of the HA gene of H7N9 strains with A/Shanghai/2/2013 recommended by world health organization and the candidate vaccine strain A/Anhui/1/2013 were 96.8%-97.0% and 95.8%-96.2%, respectively. Phylogenetic analysis showed that the 5 strains had the nearest genetic distance to the strain A/Guangxi/5/2017. All the 5 strains cleavage site sequences of HA protein showed mutation of PEVPKRKRTAR↓GLF, and they were highly pathogenic avian influenza viruses mutant strains, which all had mutation of G186V at the receptor binding sites of HA gene, while no Q226L mutation was found. All 5 strains had new mutation of A363S, and new mutations of R56K and I297V were only found in the strain isolated from the patient. Among the five potential glycosylation motifs in the HA, only 421NWT and 493NNT had variation of the position post shift. Conclusions All the 5 H7N9 strains isolated in Weining County, Guizhou Province are highly pathogenic avian influenza mutative viruses. The current candidate vaccine may not provide a very good protection. The mutations of cleavage site of HA protein, G186V as well as other new mutation sites of HA may enhance the susceptibility and pathogenicity to human beings.

Objective: To evaluate the prognostic value of ¹⁸F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) in patients with diffuse large B cell lymphoma (DLBCL) undergoing autologous hematopoietic stem cell transplantation (auto-HSCT). Methods: Forty-eight patients with DLBCL treated at Peking University Cancer Hospital between November 2010 and December 2014 were assessed. All patients underwent PET/CT scanning prior to or after auto-HSCT. Correlation analysis was done based upon patients characteristics, PET/CT scan results and survival. Results: ①Among 48 patients, 27 was male, 21 female, median age was 43 (17-59) years old. ② Patients with negative pre-auto-HSCT PET/CT assessment demonstrated significantly better 3-year progression free survival (PFS) (87.1% vs 53.3%, χ²=7.02, P=0.019) and overall survival (OS) (90.3% vs 60.0%, χ²=6.51,P=0.022) than patients with positive pre-auto-HSCT PET/CT assessment. Three-year PFS (94.1% vs 30.0%, χ²=22.75, P=0.001) and OS (97.1% vs 40.0%, χ²=21.09, P=0.002) were also significantly different between patients with negative and positive post-auto-HSCT PET/CT assessment. ③ Multivariate analysis indicated a significant association of PFS (HR=13.176, P=0.005) and OS (HR=20.221, P=0.007) with post-auto-HSCT PET/CT assessment. Number of prior treatment regimens was associated with PFS (HR=10.039, P=0.040). ④ Harrell’s C index revealed that the value of combined use of number of prior treatment regimens and post-auto-HSCT PET/CT assessment was superior to either one used alone in PFS (Harrell’s C values were 0.976, 0.869 and 0.927 in combined use, number of prior treatment regimens and post-auto-HSCT PET/CT assessment, respectively), and the combined use of ECOG performance status and post-auto-HSCT PET/CT assessment significantly increased the Harrell’s C index in OS (Harrell’s C values were 0.973, 0.711 and 0.919 in combined use, ECOG performance status and post-auto-HSCT PET/CT assessment, respectively). Conclusions Post-auto-HSCT PET/CT assessment is the main predictor of outcomes in DLBCL patients receiving auto-HSCT. Combined use of post-auto-HSCT PET/CT assessment and number of prior treatment regimens and ECOG performance status is a better prognostic tool in patients with DLBCL undergoing transplantation.

Objective: To evaluate the clinical characteristics and survival outcomes of patients with de novo grade 3 or transformed follicular lymphoma (FL). Methods: Fifty-two patients treated at Peking University Cancer Hospital between January 2009 and September 2017 were assessed, including 28 patients with FL 3A grade, 13 patients with FL 3B grade, 11 patients with transformed FL. Baseline characteristics, survival and prognostic factors were analyzed. Results: ① Twenty-six male and 26 female patients were enrolled, including 28 patients with FL 3A grade, 13 patients with FL 3B grade, 11 patients with transformed FL. ②The 3-year progression-free survival (PFS) and overall survival (OS) for the entire cohort were 56.0% and 80.6%, respectively. Patients with international prognostic index (IPI) score 0-1 demonstrated significantly better 3-year PFS (80.3% vs 20.1%; t=18.902, P<0.001) and OS (95.7% vs 57.0%; t=10.406, P<0.001) than patients with IPI score 2-3. Three-year PFS (94.1% vs 37.2% vs 25.2%; P=0.002) and OS (100.0% vs 76.0% vs 59.8%; P=0.020) were also significantly different among patients with FLIPI 1 score 0-1, 2, ≥3. FLIPI 2 score was also identified as a prognostic factor for 3-year PFS (68.4%, 0, 0; P=0.001) and OS(87.5%, 76.2%, 0; P=0.003). ③Multivariate analysis indicated a significant association of PFS (HR=3.536, P=0.015) and OS (HR=15.713, P=0.015) with IPI. FLIPI 2 was associated with OS (score 0-1, HR=0.078, P=0.007; score 2, HR=0.080, P=0.022). Conclusion De novo grade 3 or transformed FL might be a group of curable disease with current treatment strategies. IPI is still a prognostic tool in this scenario.

OBJECTIVETo analyze mutations of SLC26A4 gene and explore their origins for a patient with enlarge vestibuar aqueduct syndrome.

METHODSClinical data and peripheral venous blood samples were collected from the patient and her parents. Genome DNA was extracted from the peripheral blood. All of the 21 exons of the SLC26A4 gene were amplified with PCR and subjected to directly sequencing.

RESULTSThe patient was found to have carried two mutant alleles of the SLC26A4 gene, namely c.1522A to G and c.1229C to T, which were inherited from her father and mother, respectively.

CONCLUSIONSLC26A4 c.1522A to G is likely to be a pathogenic mutation. Above results may facilitate genetic counseling and prenatal diagnosis for this family.

Adult ; Amino Acid Sequence ; Child ; Exons ; Female ; Hearing Loss, Sensorineural ; genetics ; Humans ; Male ; Membrane Transport Proteins ; genetics ; Molecular Sequence Data ; Pedigree ; Vestibular Aqueduct ; abnormalities

Objective To summarize the treatment experience of sepsis after liver transplantation.Methods The clinical features and treatment methods of 1 patient developing sepsis after liver transplantation, who was admitted and treated in the Surgical Intensive Care Unit of the Third Affiliated Hospital of Sun Yat-sen University in September 201 4,were retrospectively studied.The interpretation of International Guidelines for Management of Severe Sepsis and Septic Shock (SSC Guidelines)and relevant literature were reviewed.Results One male patient at the age of 50 years old developed high fever and decrease of blood pressure at 1 d after liver transplantation,and was diagnosed as septic shock.The symptoms were relieved after the appropriate treatment like goal-directed fluid resuscitation,anti-infection and blood purification,etc.And the patient was discharged in stable conditions.Conclusions It is easy to develop infection after liver transplantation and the fatality rate of sepsis caused by infection is high.Once the sepsis occurs,clinicians must perform early goal-directed therapy and bundle therapy according to the SSC Guidelines positively,and select the appropriate drugs according to the pathogen culture results in order to reduce the fatality rate.