Norovirus outbreaks in China, 2000-2018: A systematic review.

To understand epidemiological characteristics of norovirus outbreaks in China from 2000 to 2018 the literature on norovirus outbreaks was identified by searching WANFANG, CNKI, PubMed, and Web of Science databases before 31 December 2018. Statistical analyses were performed using Statistical Product Service Solutions software. RStudio1.4.1717 and ArcGIS trial version were used for plotting bar graphs and maps. A total of 419 norovirus outbreaks were reported in the 394 included articles, which occurred between June 2000 and October 2018, showing an overall increasing trend. The majority of outbreaks occurred in schools (52.28%, 218/417) and kindergartens (55/417, 13.19%). Person-to-person transmission (41.64%, 137/329) was most common, followed by food-borne transmission (75/329, 22.80%) and water-borne transmission (72/329, 21.88%). GII was the most predominant norovirus genogroup, with GII.4, GII.17 and GII.2 being the dominant genotypes in 2007-2013, 2014-2015, 2016-2017, respectively. Increased outbreaks were associated with the prevalence of new variants. Most norovirus outbreaks were reported in the southeast of the country. The number of norovirus outbreaks was positively associated with the per capita gross domestic product and the year-end resident population. Norovirus outbreaks have become an important public health problem in China. It is necessary to establish surveillance in hospitals and nursing homes. Genotyping of noroviruses is important for monitoring the circulating strains and improving the vaccine design, so it should be carried out in more regions.

Treatment of Hepatitis E.

Hepatitis E virus (HEV) infections are the most common cause of acute hepatitis, but they can also take a chronic course. There is no specific therapy for acute hepatitis, and current treatment is supportive. Choosing ribavirin as the first-line therapy for chronic HEV is advisable, especially in solid organ transplant patients. Pegylated interferon-α has been used successfully for treatment of hepatitis E but is associated with major side effects. Cholestasis is one of the most common, but devastating, manifestations in hepatitis E. Current therapy for HEV aims to treat symptoms. Therapy generally involves several measures, such as vitamins for adequate nutrition, albumin and plasma for supporting treatment, symptomatic treatment for cutaneous pruritus, and ursodeoxycholic acid and S-adenosylmethionine, and Traditional Chinese medicine for removing jaundice. Patients with underlying liver disease may develop liver failure. For these patients, supportive treatment is the foundation. Ribavirin has successfully been used to prevent liver transplantation. Prevention and treatment of complications are important for treatment of liver failure. Liver support devices are intended to support liver function until such time as native liver function recovers or until liver transplantation. Liver transplantation is widely considered as irreplaceable and definitive treatment for acute-on-chronic liver failure, particularly for patients who do not improve with supportive measures to sustain life.

Preparation of calcium phosphate cement and polymethyl methacrylate for biological composite bone cements.

BACKGROUND: We studied the biological safety, biomechanics, and tissue compatibility of calcium phosphate cement and Polymethyl Methacrylate composite bone cement mixed in different ratios. MATERIAL/METHODS: CPC and PMMA were mixed in different ratios (3:1, 2:1, 1:1, 1:2, 1:5, 1:10, 1:15, and 1:20). PMMA solvent is a general solvent containing a dissolved preparation of the composite bone cement specific to a given specimen to determine biological safety, biomechanics, and tissue compatibility. RESULTS: The CPC/PMMA (33%) group, CPC/PMMA (50%) group, CPC/PMMA (67%) group, and CPC/PMMA (75%) group were more in line with the composite bone cement without cytotoxicity requirements. The compressive strength of the CPC/PMMA (67%) group and CPC/PMMA (75%) group was 20 Mpa-30 Mpa, while that of the CPC/PMMA (4.8%) group, CPC/PMMA (6.25%) group, CPC/PMMA (9.1%) group, CPC/PMMA (16.7%) group, CPC/PMMA (33%) group, and CPC/PMMA (50%) group was 40 Mpa-70 Mpa. Curing time was longer in the CPC group (more than 11 min) and shorter in the PMMA group (less than 2 min). The results of weight loss rate showed that there were no significant differences between the CPC/PMMA group (4.8%, 6.25%, 9.1%, 16.7%, 33%) and PMMA control group (p>0.05). With the decrease of CPC content, the rate of weight loss gradually decreased. CONCLUSIONS: The CPC/PMMA (50%) group, CPC/PMMA (67%) group, and CPC/PMMA (75%) group provide greater variability and selectivity for the composite bone cement in obtaining better application.

Associations of Early Gut Microbiome and Metabolome with Growth and Body Composition of Preterm Infants Within the First 6 Months.

Objectives: This study aimed to explore the associations of growth and body composition with gut microbiome and metabolome in preterm infants. Materials and Methods: A prospective cohort study including 73 human milk-fed very preterm infants was conducted. During hospitalization, fecal samples were collected to detect microbes and metabolites using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry. Growth and body composition indices were measured at term equivalent age (TEA) and 6 months of corrected age (CA). Associations of the fecal microbiome and metabolome profiles with growth and body composition indices, as well as their changes, were analyzed. Results: A higher abundance of Streptococcus was associated with a lower fat-free mass (FFM) z-score at 6 months of CA (p = 0.002) and a smaller increase in FFM z-score from TEA to 6 months of CA (p = 0.018). Higher levels of 3'-sialyllactose and 6'-sialyllactose (6'-SL) in feces were correlated with a lower z-score of percentage body fat (PBF) (p = 0.018 and 0.020, respectively) and a lower z-score of fat mass (p = 0.044 and 0.043, respectively) at 6 months of CA. A higher level of 6'-SL in feces was correlated with a greater increase in FFM z-score from TEA to 6 months of CA (p = 0.021). Conclusions: This study sheds light on the role of specific microbial-host interactions in metabolic changes in preterm infants, indicating the potential role of sialylated human milk oligosaccharides in optimizing body composition.

Pathogen-specific alterations in intestinal microbiota precede urinary tract infections in preterm infants: a longitudinal case-control study.

Urinary tract infections (UTIs) are among the most common late-onset infections in preterm infants, characterized by nonspecific symptoms and a pathogenic spectrum that diverges from that of term infants and older children, which present unique diagnostic and therapeutic challenges. Existing data on the role of gut microbiota in UTI pathogenesis in this demographic are limited. This study aims to investigate alterations in gut microbiota and fecal calprotectin levels and their association with the development of UTIs in hospitalized preterm infants. A longitudinal case-control study was conducted involving preterm infants admitted between January 2018 and October 2020. Fecal samples were collected weekly and analyzed for microbial profiles and calprotectin levels. Propensity score matching, accounting for key perinatal factors including age and antibiotic use, was utilized to match samples from UTI-diagnosed infants to those from non-UTI counterparts. Among the 151 preterm infants studied, 53 were diagnosed with a UTI, predominantly caused by Enterobacteriaceae (79.3%) and Enterococcaceae (19.0%). Infants with UTIs showed a significantly higher abundance of these families compared to non-UTI infants, for both Gram-negative and positive pathogens, respectively. Notably, there was a significant pre-UTI increase in the abundance of pathogen-specific taxa in infants later diagnosed with UTIs, offering high predictive value for early detection. Shotgun metagenomic sequencing further confirmed the dominance of specific pathogenic species pre-UTI and revealed altered virulence factor profiles associated with Klebsiella aerogenes and Escherichia coli infections. Additionally, a decline in fecal calprotectin levels was observed preceding UTI onset, particularly in cases involving Enterobacteriaceae. The observed pathogen-specific alterations in the gut microbiota preceding UTI onset offer novel insight into the UTI pathogenesis and promising early biomarkers for UTIs in preterm infants, potentially enhancing the timely management of this common infection. However, further validation in larger cohorts is essential to confirm these findings.

Results of a phase III clinical trial with an HBsAg-HBIG immunogenic complex therapeutic vaccine for chronic hepatitis B patients: experiences and findings.

BACKGROUND & AIMS: Even though various experimental therapeutic approaches for chronic hepatitis B infection have been reported, few of them have been verified by clinical trials. We have developed an antigen-antibody (HBsAg-HBIG) immunogenic complex therapeutic vaccine candidate with alum as adjuvant (YIC), aimed at breaking immune tolerance to HBV by modulating viral antigen processing and presentation. A double-blind, placebo-controlled, phase II B clinical trial of YIC has been reported previously, and herein we present the results of the phase III clinical trial of 450 patients. METHODS: Twelve doses of either YIC or alum alone as placebo were administered randomly to 450 CHB patients and they were followed for 24weeks after the completion of immunization. The primary end point was HBeAg seroconversion, and the secondary end points were decrease in viral load, improvement of liver function, and histology. RESULTS: In contrast to the previous phase II B trial using six doses of YIC and alum as placebo, six more injections of YIC or alum resulted in a decrease of the HBeAg seroconversion rate from 21.8% to 14.0% in the YIC group, but an increase from 9% to 21.9% in the alum group. Decrease in serum HBV DNA and normalization of liver function were similar in both groups (p>0.05). CONCLUSIONS: Overstimulation with YIC did not increase but decreased its efficacy due to immune fatigue in hosts. An appropriate immunization protocol should be explored and is crucial for therapeutic vaccination. Multiple injections of alum alone could have stimulated potent inflammatory and innate immune responses contributing to its therapeutic efficacy, and needs further investigation.

[A multicenter study of the effectiveness of interferon alpha-1b (Hapgen) in treating HBeAg positive chronic hepatitis B patients].

To compare the efficacy and safety of interferon a-1b and interferon a-1b combined with lamivudine in the treatment of HBeAg positive chronic hepatitis B (CHB), to analyze the impact of variable factors on the efficacy, and to investigate the individualized anti-viral regimen for CHB patients. 111 CHB patients were enrolled and randomly divided into two groups. Group A: patients received interferon a-1b (49 patients, 50mug I. M. , qod. ) , Group B: interferon a-1b (idem) combined with lamivudine for 6-12 months or longer(62 patients, 100 mg, P.O. , q.d. ). (1) The HBeAg seroconversion rates of treatment by 12 and 18 months were 28.6% and 36.7% in group A, 29.0% and 38.7% in group B, respectively, no significant difference found between the two groups at the end of treatment (x2=0.003, P value is more than 0.05; x2=1.500, P value is more than 0.05). (2) The HBV DNA undetectable rates of treatment by 6 months, 12 months and 18 months were 8.2%, 53.1% and 57.1% in group A, 66.1%, 83.9% and 88.7% in group B, respectively, still no significant difference existed between the two groups (x2=38.150, P value is less than 0.05; x2=12.073, P value is less than 0.05, x2=14.459, P value is less than 0.05). (3) In group A, the HBeAg seroconversion rates for male and female patients were 34.5% and 40.0% respectively, no significant difference found between. As regard ages the rates were 34.9% and 50.0% for patients younger or more than 40 years of age, no significant difference existed between. The HBeAg seroconversion rate was higher in patients with lower baseline serum HBV DNA loads ( less than 6 log10 copies/ml) . (4) The rates of patients with fever and blood abnormality were 36.7% and 34.7% in group A, 32.3% and 27.4% in group B, respectively. The total incidences of adverse events were similar between group A and B (x2=0.244, P value is more than 0.05; x2=0.682, P value is more than 0.05). (5) The ratio of drug resistance in group B was only 1.6%. The adverse events of interferon a-1b treatment for CHB are low and mild. The HBeAg seroconversion rate persistently raises with the extension of interferon a-1b treatment course. The HBV DNA undetectable rate of interferon a-1b combined with lamivudine is significantly higher than that of interferon a-1b and the drug resistance of lamivudine can be reduced obviously by combination therapy.

The therapeutic effects of X-ray devitalization and replantation and alcoholic devitalization and replantation in adolescent patients with lower limb osteosarcoma.

OBJECTIVE: To compare and analyze the therapeutic effects of X-ray devitalization and replantation and alcoholic devitalization and replantation in adolescent patients with lower limb osteosarcoma. METHODS: We collected clinical data for 43 osteosarcoma patients with limb salvage treatment treated in our hospital from February 2014 to February 2018. The patients were divided into x-ray devitalization and replantation group (n=23) and alcoholic devitalization and replantation group (n=20) based on the treatment methods. The two groups were compared in operation duration, intraoperative blood loss, postoperative fracture healing time, length of tumor bones, MSTS score and ISOLS score, postoperative complications, postoperative follow-ups and postoperative recurrence and metastases. RESULTS: Operation duration and intraoperative blood loss of the alcoholic group were less than that of the X-ray group, while postoperative fracture healing time of the alcoholic group was longer than that of the X-ray group (P<0.05). For the X-ray group, MSTS score and ISOLO score of the final follow-up were 26.13±2.65 and 32.53±3.73 respectively. For the alcoholic group, MSTS score and ISOLO score of the final follow-up were 23.69±3.27 and 30.98±3.56 respectively. MSTS score of the X-ray group was higher than that of the alcoholic group (P<0.05). There were 2 cases of internal fixation failure and 2 cases of adhesive knee joints stiffness in the X-ray group. As for the alcoholic group, there were 2 cases of internal fixation failure and 2 cases of incision soft tissue infection. There were no statistically significant differences in postoperative complications, recurrence, and metastases between the two groups (P>0.05). CONCLUSION: Both methods are convenient, inexpensive, and effective for adolescent patients with lower limb osteosarcoma. Alcoholic devitalization and replantation results in shorter operation duration and less intraoperative blood loss, while X-ray devitalization and replantation results in better postoperative limb function restoration.

Association of NKG2D genetic polymorphism with susceptibility to chronic hepatitis B in a Han Chinese population.

Natural killer (NK) cells are important antiviral effectors of innate immunity because of their contribution to virus elimination. NK cell-mediated immunological reaction to hepatitis B virus (HBV) infection depends on a fine balance between inhibitory and activating receptors. The aim of the study was to investigate genetic polymorphisms in NK cell receptors (NKR)-KLRD1 (CD94), KLRK1 (NKG2D), KLRC4 (NKG2F), and KLRC1 (NKG2A)-to evaluate the association of NKR genetic polymorphisms with susceptibility to chronic hepatitis B in a Han Chinese population. Twelve single nucleotide polymorphisms (SNPs), including rs2302489 in CD94; rs2255336, rs2617160, rs7980470, rs 2734565, and rs17513986 in NKG2D; rs2617170, rs17549004, and rs3825295 in NKG2F; rs2734414, rs7301582, and rs2734440 in NKG2A, were selected in the present study. SNP genotyping was undertaken in 500 Han Chinese patients (285 patients with chronic hepatitis B and 215 patients who cleared HBV spontaneously) by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and by the TaqMan method. Single marker association analysis was conducted and the SNP rs2617160 with a TT genotype in NKG2D was associated significantly with an increased risk of chronic hepatitis B (P = 0.044; OR = 1.49; 95% CI = 1.01-2.19). Haplotype analysis with multiple loci indicated that there was no significant association between the haplotypes of the NKR genes and susceptibility to chronic hepatitis B. The SNP rs2617160 in NKG2D associated with susceptibility to chronic hepatitis B in a Han Chinese population.

A foodborne acute gastroenteritis outbreak caused by GII.P16-GII.2 norovirus in a boarding high school, Beijing, China: a case-control study.

OBJECTIVE: In December 2017, an acute gastroenteritis outbreak involving 61 students occurred in a boarding high school in Beijing, China. We conducted an outbreak investigation immediately in order to determine the cause of this outbreak and provide effective control measures. RESULTS: The laboratory inspection showed that this outbreak was caused by GII.P16-GII.2 norovirus. Risk factor analysis indicated that the lunch provided by Cafeteria 1 on Dec 12 might be the risk factor of the outbreak with an odds ratio (OR) of 3.800 (95% confidence interval [CI] 1.089-13.258). Additionally, a tray line server of Cafeteria 1 was found to have gastro-enteral symptoms recently. Based on the clinical symptoms and epidemiology investigation, the symptomatic server was considered to be the possible source of infection.

Lateral Subcutaneous Locking Compression Plate and Small Incision Reduction for Distal-third Diaphyseal Humerus Fractures.

OBJECTIVE: Iatrogenic radial nerve injury is a great challenge for orthopaedic surgeons who deal with distal-third diaphyseal humerus fractures. Conventional open reduction and internal fixation (ORIF) remains the gold standard, but complications such as nonunion and iatrogenic radial nerve injury still occur. We fixed the fractures with a lateral locking compression plate (LCP) subcutaneously after small incision reduction to protect the radial nerve. This study reports the clinical and radiographic outcomes of our modified method. METHODS: Thirty-eight patients with distal-third diaphyseal humerus fractures were treated with lateral subcutaneous LCP and small incision reduction at our department between September 2013 and August 2016. There were 33 males and 5 females, with an average age of 30.3 years (range, 17 to 49 years). All the cases were types A or B (AO/OTA classification, type A, 24 cases; type B, 14 cases). Among them, 6 cases were combined with preoperative radial nerve palsy. All patients were diagnosed with closed humeral fractures after X-ray examination, and had typical upper limb pain, swelling, and movement disorders. The operations were performed by a single surgeons' team. Union time, range of motion (ROM), University of California, Los Angeles (UCLA) shoulder rating scale, and Mayo Elbow Performance Index (MEPI) scores were assessed to evaluate the postoperative results. RESULTS: All patients were followed up for an average of 11.4 months (range, 3 to 36 months). The average operation time was 75.5 min (range, 60 to 150 min) and average intraoperative radiation exposure was 10.5 s (range, 8 to 18 s). Bony union was achieved in all cases after an average of 16.2 weeks (range, 12 to 25 weeks). No complications such as infection or screw and plate fracture occurred, and no iatrogenic radial nerve injury was observed. According to the UCLA shoulder rating scale, the average score was 33.7 (range, 31 to 35), with 33 excellent (86.8%) and 5 good cases (13.2%). They were all excellent according to their MEPI scores (ranging, 94 to 100, with an average of 97.4). The average operation time for secondary removal of the plate was 15.2 min (range, 10 to 20 min), and no complications such as infection or secondary radial nerve injury occurred. CONCLUSIONS: Lateral subcutaneous LCP and small incision reduction may reduce the risk of iatrogenic radial nerve injury significantly in the treatment of distal-third diaphyseal humerus fractures. It also leads to solid fixation, good postoperative function, and convenient removal of the plate without injuring the radial nerve.

Association of HLA-DQB1 gene polymorphisms with outcomes of HBV infection in Chinese Han population.

BACKGROUND: Host genetic factors and environmental factors including hepatitis B virus (HBV) genotype are widely studied for the different outcomes of HBV infection. Human leukocyte antigen (HLA) plays an important role in the immunological reaction to HBV infection. AIMS: To explore whether the HLA-DQB1 allele polymorphisms are associated with the outcome of HBV infection in a Chinese Han population. PATIENTS: One hundred and thirty three HBV subjects with spontaneous recovery and 151 chronic hepatitis B patients were recruited into this case-control study in the Beijing area of China. METHODS: Sequence specific primer-polymerase chain reaction (SSP-PCR) was used to detect 13 alleles of HLA-DQB1 gene and 13 alleles of HLA-DRB1 gene. Multivariate logistic regression model was performed to detect the association of candidate factors with outcome of HBV infection by SAS 9.1.2 software package. RESULTS: The frequency of HLA-DQB1*0502 allele in the chronic hepatitis B group was significantly higher than that in the group with spontaneous recovery independent of HLA-DRB1 (odds ratio 95%CI 1.8-190). In this study there was no evidence to indicate that cigarette smoking or alcohol consumption was associated with the outcome of HBV infection. CONCLUSION: HLA-DQB1*0502 is independently associated with the outcome of HBV infection and is one host genetic factor affecting HBV infection outcome. At the same time, we can not rule out the possibility that excluded genes and alleles may also affect outcome.

[Study on association between vitamin D receptor gene polymorphisms and the outcomes of HBV infection].

OBJECTIVE: To explore whether the vitamin D receptor gene (VDR) polymorphisms are associated with the outcomes of hepatitis B virus (HBV) infection in Chinese Han population. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the polymorphisms of Fok I locus in exon 2 and Taq I locus in exon 9 of VDR gene. One hundred and eighty-four chronic hepatitis B patients and 205 asymptomatic HBV carriers were recruited to make the comparison of frequencies of genotype and haplotype of the VDR gene between the patients and the carriers. RESULTS: The univariate analysis showed a significant difference in Fok I polymorphism between chronic hepatitis B patients group and asymptomatic HBV carriers group. The FF genotype frequency in chronic hepatitis B patients group was 44.6%,higher than 31.7% in asymptomatic HBV carriers group (P<0.05). After adjusting the confounders by multiple logistic regression analysis, the result still showed a significant difference in Fok I site polymorphism between chronic hepatitis B patients group and asymptomatic HBV carriers group (OR=1.95, P<0.05). The FT haplotype frequency in chronic hepatitis B patients group was higher than that in asymptomatic HBV carriers group (OR=1.45, P<0.05). The fT haplotype frequency in chronic hepatitis B patients group was lower than that in asymptomatic HBV carriers group (OR=0.72, P<0.05). CONCLUSION: VDR gene polymorphism may be an influence factor of genetic susceptibility to HBV infection.

[Association of Taq I T/C and Fok I C/T polymorphisms of vitamin D receptor gene with outcome of hepatitis B virus infection].

OBJECTIVE: To determine whether Taq I T/C and Fok I C/T polymorphisms of vitamin D Receptor (VDR) gene was associated with the outcomes of hepatitis B virus (HBV) infection. METHODS: A total of 212 HBV self-limited infection individuals, 244 asymptomatic HBsAg carriers and 391 chronic hepatitis B (HB) patients were recruited to conduct a case-control study. VDR-Taq I T/C and VDR-Fok I C/T polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequency of VDR-Fok I allele C in the chronic HB patients was 45.8%, significantly higher than 38.2% of the self-limited infection individuals (chi(2) = 6.43, P = 0.01). The frequencies of VDR-Fok I genotypes TT, TC, and CC in HB patients were 30.7%, 47.1%, and 22.2% respectively, and 41.0% (TT), 41.5% (TC), and 17.5% (CC) in the self-limited infection individuals. There was a statistically significant difference between HB patients and self-limited infection individuals (chi(2) = 6.76, P = 0.03). The results of univariate analysis showed that the subjects carrying VDR-Fok I CC/TC genotype had 1.57-fold elevated risk for developing chronic HB when they were infected HBV (OR = 1.57, P = 0.01). A multiple logistic regression analysis revealed that VDR-Fok I CC/CT was independently associated with chronic HB after adjusting both potential confounding effects of gender (OR = 1.70, P = 0.021). The statistically significant association between TaqI T/C polymorphism and outcome of HBV infection was not demonstrated in the study. The frequency of haplotype TC of VDR-TaqI and Fok I in HB patients was 2.3080%, significantly higher than 0.5391% of the self-limited infection individuals (chi(2) = 6.08, P = 0.01). However, the frequency of haplotype TT in the HB patients was 1.5283%, significantly lower than 3.7061% of the self-limited infection individuals (chi(2) = 5.65, P = 0.02) and 3.4820% of the HBV carriers (chi(2) = 5.12, P = 0.02). CONCLUSION: VDR gene polymorphism is probably an influence factor on the genetic susceptibility of HBV infection.

[Relationship between polymorphisms of vitamin D receptor gene and familial aggregation of HBsAg carriers].

OBJECTIVE: To determine whether -Taq I T/C and -Fok I C/T polymorphisms of vitamin D receptor (VDR) gene are associated with the familial aggregation of hepatitis B virus (HBV) infection. METHODS: Based on a population-based case-control family design, 288 family members from 27 case families and 230 family members from 27 control families were recruited. VDR gene polymorphisms were analyzed. VDR-Taq I T/C and VDR-Fok I C/T polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequency of VDR-Taq I TT genotype in the case families was significantly higher than that in the control families (P < 0.05) , however, the frequency of VDR-Fok I CC genotype in the case families was significantly higher than that in the control families (P < 0.05). The frequency of family members carriying Taq I T-Fok I C haplotype in the case families was significantly higher than that in the control families (OR = 1.67, P < 0.05), however, the frequency of family members carrying Taq I C-Fok I T haplotype in the case families was significantly lower than that in the control families (OR = 0. 24, P < 0.05). The similar results were found in the familial biological kinship relatives with any HBV-infected makers. CONCLUSION: VDR-Taq I and -Fok I gene polymorphisms are likely to play a substantial role in HBsAg familial aggregation.

[Association of TNFA polymorphisms with the outcomes of HBV infection].

OBJECTIVE: To explore whether the TNFA promoter single nucleotide polymorphisms (SNPs) are associated with the outcomes of hepatitis B virus(HBV) infection in Chinese Han population. METHODS: One hundred and forty-eight self-limited HBV infection subjects and 207 chronic hepatitis B patients were recruited. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequence specific primer-PCR(PCR-SSP) were used to detect the SNPs of five sites in TNFA promoter (-238G/A, -308G/A, -857C/T, -863C/A, -1031T/C). The frequency distributions of genotypes and haplotypes in different groups were analyzed by EPI and EH programs. RESULTS: The frequencies of -238GG genotype in chronic hepatitis B patients were significantly higher than that in self-limited infection subjects (P=0.02). The frequencies of -857TT genotype in chronic hepatitis B patients were clearly lower than that in self-limited infection subjects (P=0.02). Haplotypic frequencies of GGCCT (-238/-308/-857/-863/-1031) in chronic hepatitis B patients was significantly lower than that in self-limited infection subjects (P=0.03), and the frequencies of haplotype GGCAT or GGTAT in chronic hepatitis B patients were clearly higher than those in self-limited infection subjects (P=0.0001; P=0.004). CONCLUSION: TNFA promoter polymorphisms are important host genetic factors affecting the outcomes of HBV infection.

The relationship between serum interleukins and T-lymphocyte subsets in patients with severe acute respiratory syndrome.

OBJECTIVES: To observe the changes of serum interleukins (IL), T-lymphocyte subsets, and white blood cell (WBC) count in patients with severe acute respiratory syndrome (SARS), and to investigate the relationship between injured immune function, immune response and disturbed immune adjustment in SARS patients. METHODS: The levels of serum IL-2, IL-10, IL-12 and T-lymphocyte subset counts were measured in 35 clinically diagnosed SARS patients by using enzyme linked immunosorbant assay (ELISA). The relationship between the measured results and WBC count was further analyzed. RESULTS: The level of serum IL was increased to a great extent in the 35 SARS patients, and the levels of serum IL-2, IL-10 and IL-12 were 242.53 (92.69) pg/ml, 77.43 (63.37) pg/ml and 65.94 (43.21) pg/ml, respectively. The level of serum IL-2 increased markedly (P < 0.01). The peripheral blood CD(3)(+), CD(4)(+) and CD(8)(+) counts were lower than normal in 23 patients (67.7%), 26 patients (74.3%) and 15 patients (42.9%), respectively. The peripheral blood WBC counts were lower than 4.0 x 10(9)/L in 10 patients, and their CD(3)(+), CD(4)(+) and CD(8)(+) counts were 583.90 (315.58) x 10(6)/L, 272.00 (94.13) x 10(6)/L and 209.00 (72.21) x 10(6)/L, respectively. The peripheral blood WBC counts were (4.0 - 10.0) x 10(9)/L in 20 patients, and their CD(3)(+), CD(4)(+) and CD(8)(+) counts were 700.00 (502.96) x 10(6)/L, 347.00 (247.58) x 10(6)/L and 322.05 (228.47) x 10(6)/L, respectively. The peripheral blood WBC counts were higher than 10.0 x 10(9)/L in 5 patients, and their CD(3)(+), CD(4)(+) and CD(8)(+) counts were 1466.00 (630.86) x 10(6)/L, 783.00 (311.14) x 10(6)/L and 640.00 (294.40) x 10(6)/L, respectively. The decreased CD(3)(+), CD(4)(+) and CD(8)(+) counts were consistent with the decreased WBC counts. The level of IL in SARS patients was significantly higher than that in patients with chronic hepatitis B (P < 0.01). CONCLUSIONS: The level of serum IL is closely related to cell immunity in SARS patients. The level of serum IL is increased evidently while CD(3)(+), CD(4)(+) and CD(8)(+) counts decrease. Both serum IL and CD are associated with injury of immune function, and thus they could be regarded as a monitoring index for judging the condition of SARS patients and prescribing immune therapy.

[Chest X-ray features of severe acute respiratory syndrome and clinical staging].

OBJECTIVE: To establish a clinical staging system for patients with severe acute respiratory syndrome (SARS) based on clinical feature, laboratory tests as well as dynamic changes of chest X-ray images. METHOD: Dynamic changes of chest X-ray images and laboratory tests in 45 SARS patients managed from March to May, 2003 were analyzed. RESULTS: (1) Chest X-ray image: among 45 cases, 23 were common type: the time to appearance of unilateral patched shadow of the lung were 2 to 5 (2.9 +/- 1.0) days. The time to appearance of bilateral patched shadow of the lungs were 2 to 12 (6.9 +/- 2.5) days. The time to appearance of ground glass or consolidation in the lung were 6 to 19 (11.0 +/- 2.0) days. The time to the beginning of absorption of X-ray changes were 10 to 21 (15.0 +/- 4.1) days. The time for chest X-ray image to be absorbed completely were 18 to 46 (25.9 +/- 7.2) days. Twenty-two patients were severe type, in which the time to the appearance of ground glass of the lung were (9.0 +/- 3.2) days, with no significant difference when compared with common type (P < 0.05). However, the time to the beginning of absorption and complete absorption were (19.0 +/- 4.6) days (P = 0.009) and (36.0 +/- 8.1) days (P = 0.001), respectively. Noticeably, the time to pan-consolidation of the lung were less than 7 days in 7 fatal cases. (2) Laboratory tests: decrease in the number of lymphocytes and T lymphocyte subset were seen in the early stage. While the account recovered in 10 to 14 days of disease course in the 38 patients who survived, there was no recovery in 7 patients who died. CONCLUSIONS: SARS can be divided into five stages: incubation period 2 to 10 days, prodromal period 1 to 3 days, progressive period 4 to 7 days, advanced period 8 to 15 days were, convalescent period 16 to 24 days. The appearance of pan-consolidation in the lung in less than 7 days and/or unable to recover the number of lymphocytes and T lymphocyte subset will be associated with poor prognosis.

[Clinical manifestation, treatment, and outcome of severe acute respiratory syndrome: analysis of 108 cases in Beijing].

OBJECTIVE: To investigate the clinical manifestations, treatment, and outcome of severe acute respiratory syndrome (SARS). METHODS: The clinical data of 108 SARS in-patients were analyzed. RESULTS: Among the 108 cases, 35 males (32.4%) and 73 females (67.6%), aged 37 +/- 9 (range 13 approximately 83 years), most were white-collar workers, medical workers accounting for 28.7%. 87.0% had a definite contact history. 20.4% were complicated by other internal diseases. The main clinical manifestations included fever, cough, pectoralgia, chest distress, headache, etc. Involvement of multiple organs was often. The incubation period was 2 approximately 14 days. The course included early stage, progressive stage, climax, and convalescence. Mild type accounted for 4.6%, common type 39.8%, severe type 20.4%, and extremely severe type 35.2%. At the early stage, white blood cell count, lymphocyte count and ratio of lymphocyte, proalbumin, transferring, CD(3)(+), CD(4)(+), CD(8)(+) cell count were remarkably decreased, and C-reactive protein, alpha-acid glycoprotein, and alpha(2)-globulin were remarkably increased. X-ray chest film showed solitary or multiple local exudative changes, mostly in pulmonary lower field. During the progressive stage the hyaline or consolidation images were enlarged. High solution CT showed solitary or multiple cotton wadding like images and ground glass-like or consolidation images. Hypoxemia was common. At the progressive stage application of adrenocortical hormones and non-invasive mechanical ventilation helped stop the progress of disease. Ninety-four cases were discharged, 14 cases died. Traditional Chinese medicine (TCM) regards SARS as one of epidemic febrile diseases. Treatment by combination of TCM and Western medicine was effective. CONCLUSION: SARS mainly affects youth and people in their prime of life. It has its own characteristic clinical manifestations. The classification system of 5 types and 4 stages helps judge the condition. Treatment by combination of TCM and Western medicine is encouraged.

[Liver histological changes after lamivudine treating in chronic hepatitis B patients with HBeAg positive].

OBJECTIVES: To investigate the histological changes in liver biopsy tissues taken from chronic hepatitis B patients with HBsAg and HBeAg positive and ALT abnormal after lamivudine therapy for one year. METHODS: Lamivudine was given orally at the dose of 100 mg once a day for one year. 101 patients were enrolled into this open-label study. Paired liver biopsies from patients with hepatitis B before and after therapy with lamivudine were studied. Blinded biopsies were evaluated by a histopathologist and scored according to Knodell's histology activity index(HAI). RESULTS: 53.5% (54/101), 51.5% (52/101) and 31.7% (32/101) patients had a reduction of their total hepatic HAI score, necroinflammation and fibrosis scores by >or=2 points or 1 points at the end of one year of lamivudine therapy, compared with their pretreatment values, respectively. There were significant reduction of HAI score, necroinflammation and fibrosis scores from 8.0+/-4.7 to 5.2+/-3.3 (t=7.358, P<0.01), from 5.9+/-3.8 to 3.6+/-2.5 (t=7.298, P<0.01), and from 2.1+/-1.2 to 1.6+/-1.2 (t=3.827, P<0.01), respectively. The histological improvement was independent on the HBeAg seroconvertion during the therapy. CONCLUSION: Significant improvement in liver histology, both necroinflammation and fibrosis, can be obtained in the majority of patients treated with lamivudine for one year.