[A cross-sectional survey on the types of antiviral treatment plans for patients with chronic hepatitis B].

Objective: To understand the current antiviral treatment status and various clinical types of treatment plans in Xiamen City so as to explore ways to improve and optimize the diagnosis and treatment standards for chronic hepatitis B. Methods: A cross-sectional survey method was used to study the antiviral treatment status and treatment plans for chronic hepatitis B patients who visited and were diagnosed in the Department of Infectious Diseases and Hepatology of all tertiary hospitals in Xiamen City at 0:00~23:59 on May 25, 2022. Results: A total of 665 cases were surveyed in this study, with an antiviral treatment rate of 81.2%(540/665). The antiviral treatment rate of patients who accorded with the current guidelines for antiviral treatment indications was 85.8%(507/591). The antiviral treatment rate for 362 outpatients was 72.9%(264/362). Among them, the antiviral treatment rates were 80.1%, 89.3%, and 25.0%(226/282, 25/28, 13/52), respectively, for patients diagnosed with chronic hepatitis B, hepatitis B cirrhosis, and hepatitis B surface antigen-carrying status. The treatment plan for all outpatient patients was mainly oral nucleos(t)ide analogues, accounting for 59.1%(214/362). The antiviral treatment rate for 303 inpatients was 91.1%(276/303). The various clinical types of antiviral therapy rates among all patients were 70%~95%. The antiviral treatment plan for inpatients was mainly based on pegylated interferon alpha treatment, accounting for 72.6%(220/303). Conclusion: Antiviral treatment for chronic hepatitis B in Xiamen City can still be strengthened to meet the current demand for expanding antiviral treatment indications. Antiviral treatment rates and various types of treatment plans differ between outpatients and inpatients; thus, further awareness and acceptance of the goal of improving antiviral therapy, especially in outpatients, and the possibility for a clinical cure based on pegylated interferon alpha treatment are needed to maximize the benefit to more patients.

[Efficacy of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei].

Objective: To evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pseudomyxoma peritonei (PMP). Methods: In this descriptive case series study, we retrospective analyzed the records of PMP patients treated with CRS and HIPEC between January 2013 and June 2023 at Affiliated Cancer Hospital and Institute of Guangzhou Medical University. The inclusion criteria were as follows: (1) Aged 18 to 75 years and nonpregnant women. (2) Histologically confirmed diagnosis of pseudomyxoma peritonei. (3) Karnofsky Performance Scale (KPS)>70. (4) The functions of major organs such as the heart, liver, lungs, and kidneys can tolerate major surgery for long periods of time. (5) No evidence of extra-abdominal metastasis. Patients with extensive intra-abdominal adhesions or severe infectious diseases were excluded. The main outcomes were overall survival (OS) and postoperative major complications. The postoperative major complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). We used the peritoneal cancer index (PCI) score to quantitatively assess the peritoneal metastases and the completeness of cytoreduction (CCR) score at the end of surgery (CCR-0 and CCR-1 considered to be complete CRS). Results: A total of the 186 PMP patients with a median age of 56 (interquartile range extremes (IQRE), 48-64) years were included, 65 (34.9%) males and 121 (65.1%) females. The median peritoneal cancer index (PCI) score was 28 (20-34). Appendiceal origin accounted for 91.4%. Histological types were low grade in 99 patients (53.2%), high grade in 57 patients (30.6%), and 55 patients (29.6%) received complete cytoreduction (CCR-0/1). The median operative duration was 300 (211-430) minutes for all patients. Treatment-related 30-day mortality was 2.7%; 90-day mortality 4.3%; reoperation 1.6%; and severe morbidity 43.0%. Within the entire series, anemia(27.4%), electrolyte disturbance(11.6%), and hypoalbuminemia(7.5%) were the most frequent major complications (grade 3-4). The incidences of gastrointestinal anastomotic leakage, abdominal bleeding, and abdominal infection were 2.2%, 2.2%, and 4.3%, respectively. After a median follow-up of 38.1 (95%CI:31.2-45.1) months, the 5-year OS was 50.3% (95%CI: 40.7%-59.9%) with a median survival time of 66.1 (95%CI: 43.1-89.1) months. The survival analysis showed that patients with pathological low grade, low PCI, and low CCR score had better survival with statistically significant differences (all P<0.05). Further stratified into complete and incomplete CRS subgroups, the 5-year OS of the CCR-0 and CCR-1 subgroups was 88.9% (95%CI: 68.3%-100.0%) and 77.6% (95%CI: 62.7%-92.5%), respectively; and 42.0% (95%CI: 29.5%-54.5%) in the CCR-2/3 subgroup. Conclusions: CRS and HIPEC may result in a long-term survival benefit for PMP patients with acceptable perioperative morbidity and mortality. This strategy, when complete CRS is possible, could significantly prolong survival for strictly selected patients at experienced centers.

[Risk factors of early myocardial injury and the impact of early myocardial injury on prognosis of patients with extensive burns].

Objective: To analyze the risk factors of early myocardial injury and the impact of early myocardial injury on prognosis of patients with extensive burns. Methods: A retrospective case series study was conducted. From January 2018 to August 2022, 361 patients with extensive burns who met the inclusion criteria were admitted to Tongren Hospital of Wuhan University & Wuhan Third Hospital, including 231 males and 130 females, aged 50 (36, 58) years, with total burn area of 45% (35%, 60%) total body surface area. According to the highest level of creatine kinase isoenzyme-MB (CK-MB) within 72 h post injury, the patients were divided into early myocardial injury group (CK-MB≥75 U/L, 182 patients) and non-early myocardial injury group (CK-MB<75 U/L, 179 patients). The following data of patients in the 2 groups were collected and analyzed, including gender, age, total burn area, admission time post injury, combination with shock on admission, combination with inhalation injury on admission; the main blood test indexes such as myocardial enzyme spectrum, blood routine, liver and kidney function, and electrolytes within 72 h post injury; and treatment outcomes and fatality rate. Data were statistically analyzed with chi-square test, independent sample t test, or Mann-Whitney U test. The multivariate logistic regression analysis was conducted to screen the independent risk factors for early myocardial injury and for death in patients with extensive burns. Results: There were statistically significant differences in gender, combination with shock on admission, total burn area, and admission time post injury of patients between the two groups (with χ2 values of 6.40 and 6.10, Z values of 5.41 and 3.03, respectively, P<0.05). There were no statistically significant differences in age, combination with inhalation injury on admission of patients between the two groups (P>0.05). The CK-MB, creatine kinase, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase, white blood cell count, neutrophil-to-lymphocyte ratio (NLR), alanine aminotransferase (ALT), aspartate aminotransferase, potassium, and hemoglobin within 72 h post injury were significantly higher than those in non-early myocardial injury group (with Z values of 15.40, 6.26, 7.59, 7.02, 2.64, 4.53, 4.07, 6.32, and 4.12, t=2.34, respectively, P<0.05), while the level of calcium was significantly lower than that in non-early myocardial injury group (Z=2.72, P<0.05). There were no statistically significant differences in other blood test indexes of patients between the two groups (P>0.05). The total burn area, admission time post injury, NLR and ALT within 72 h post injury were the independent risk factors for early myocardial injury in patients with extensive burns (with odds ratios of 1.03, 1.07, 1.04, and 1.02, 95% confidence intervals of 1.02-1.05, 1.00-1.11, 1.02-1.07, and 1.00-1.03, respectively, P<0.05). The fatality rate of patients in early myocardial injury group was 8.8% (16/182), which was significantly higher than 2.8% (5/179) in non-early myocardial injury group (χ2 =5.93, P<0.05). Early myocardial injury, age, combination with shock on admission, and combination with inhalation injury on admission were the independent risk factors for death in patients with extensive burns (with odds ratios of 3.60, 1.04, 6.53, and 3.14, 95% confidence intervals of 1.17-11.05, 1.01-1.07, 1.39-30.68, and 1.15-8.56, respectively, P<0.05). Conclusions: The total burn area, admission time post injury, NLR and ALT within 72 h post injury were the independent risk factors for early myocardial injury in patients with extensive burns. Patients with extensive burns with early myocardial injury have a higher fatality rate, and early myocardial injury is an independent risk factor for the patients' death.

[Pan-cancer analysis of ubiquitin-specific protease 7 and its expression changes in the carcinogenesis of scar ulcer].

Objective: To explore the biological role and clinical significance of ubiquitin-specific protease 7 (USP7) in the carcinogenesis of scar ulcer. Methods: A retrospective observational study combined with bioinformatics analysis was used. The RNA expression profile data of USP7 in tumor and/or its corresponding paracancular normal tissue were obtained from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus database, and the RNA sequencing data were transformed by log2. The variations of USP7 gene were analyzed by cBioPortal database. The USP7 mRNA expression in tumor and adjacent normal tissue in TCGA database were obtained by using the "Gene_DE" module in TIMER 2.0 database. The survival rates of patients with high and low USP7 expression in cutaneous melanoma (SKCM), cervical squamous cell carcinoma (CESC), lung squamous cell carcinoma (LUSC), and head and neck squamous cell carcinoma (HNSC) were analyzed using the Gene Expression Profile Interactive Analysis 2 (GEPIA2) database, and the Kaplan-Meier survival curves were drawn. Sangerbox database was used to analyze the correlation of USP7 expression in pan-cancer with microsatellite instability (MSI) or tumor mutation burden (TMB) pan-cancer. Through the "correlation analysis" module in the GEPIA2 database, the correlation of USP7 expression in pan-cancer with the expression levels of five DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2, and EPCAM) and three essential DNA methyltransferases (DNMT)--DNMT1, DNMT3A, and DNMT3B were evaluated. The USP7 expression in CESC, HNSC, LUSC, and SKCM and its correlation with infiltration of immune cells (B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells) were analyzed by the "Immune-Gene" module in TIMER 2.0 database. The "Similar Genes Detection" module of GEPIA2 database was used to obtain the top 100 protein sets with similar expression patterns to USP7. Intersection analysis was performed between the aforementioned protein sets and the top 50 protein sets that were directly physically bound to USP7 obtained by using the STRING database. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were performed for the two protein sets mentioned above using the DAVID database. The samples of normal skin, hypertrophic scar, scar ulcer, and scar carcinoma with corresponding clinicopathologic features were collected from the Department of Pathology of Tongren Hospital of Wuhan University & Wuhan Third Hospital from October 2018 to October 2022, and the USP7 expression in tissue was detected by immunohistochemical method, with the number of samples of 6. Data were statistically analyzed with Log-rank test, one-way analysis of variance, and Bonferroni test. Results: In pan-cancer, the main gene variations of USP7 were mutation and amplification, and the top 3 tumors with the highest variation frequency (>6%) were bladder urothelial carcinoma, SKCM, and endometrial carcinoma. The main mutation of USP7 gene in pan-cancer was missense mutation. In SKCM with the highest mutation frequency, the main type of mutation was missense mutation in USP7_ICP0_bdg domain. USP7 mRNA expression in breast invasive carcinoma, bile duct carcinoma, colon carcinoma, esophageal carcinoma, HNSC, renal chromophobe cell carcinoma, hepatocellular carcinoma, lung adenocarcinoma, LUSC, prostate carcinoma, and gastric carcinoma was significantly higher than that in corresponding paracancer normal tissue (P<0.05). USP7 mRNA expression in glioblastoma multiforme, renal clear cell carcinoma, renal papillary cell carcinoma, and thyroid carcinoma was significantly lower than that in corresponding paracancular normal tissue (P<0.05). In addition, USP7 mRNA expression in SKCM metastases was much higher than that in primary tumor tissue (P<0.05). Survival curves showed no significant difference in survival rate between patients with high USP7 expression and patients with low USP7 expression in CESC, HNSC, LUSC, and SKCM (Log-rank P>0.05, with hazard ratios of 1.00, 0.99, 1.00, and 1.30, respectively). USP7 expression in colon cancer, colorectal cancer, thymic cancer, and thyroid cancer was negatively correlated with TMB (with Pearson correlation coefficients of -0.26, -0.19, -0.19, and 0.11, respectively, P<0.05). USP7 expression in glioma, CESC, lung adenocarcinoma, mixed renal carcinoma, and LUSC was positively correlated with MSI expression (with Pearson correlation coefficients of 0.22, 0.14, 0.15, 0.08, and 0.14, respectively, P<0.05), and USP7 expression in colon cancer, colorectal cancer, invasive breast cancer, prostate cancer, HNSC, thyroid cancer, and diffuse large B-cell lymphoma were significantly negatively correlated with MSI expression (with Pearson correlation coefficients of -0.31, -0.27, -0.13, -0.19, -0.16, -0.18, and -0.53, respectively, P<0.05). The expression of USP7 in CESC was positively correlated with that of both MSH2 and MSH6 (with Spearman correlation coefficients of 0.51 and 0.44, respectively, P<0.05), and the expression of USP7 in HNSC was positively correlated with the expression of EPCAM, MLH1, MSH2, MSH6, and PMS2 (with Spearman correlation coefficients of 0.39, 0.14, 0.49, 0.54, and 0.41, respectively, P<0.05), and the expression of USP7 in LUSC was positively correlated with the expression of EPCAM, MSH2, MSH6, and PMS2 (with Spearman correlation coefficients of 0.20, 0.36, 0.40, and 0.34, respectively, P<0.05), and the expression of USP7 in SKCM was positively correlated with the expression of EPCAM, MLH1, MSH2, MSH6, and PMS2 (with Spearman correlation coefficients of 0.11, 0.33, 0.42, 0.55, and 0.34, respectively, P<0.05). The expression of USP7 in CESC, HNSC, LUSC, and SKCM was significantly positively correlated with the expression of DNMT1, DNMT3A, and DNMT3B (with Spearman correlation coefficients of 0.42, 0.34, 0.22, 0.45, 0.52, 0.22, 0.36, 0.36, 0.22, 0.38, 0.46, and 0.21, respectively, P<0.05). The expression of USP7 in CESC, HNSC, LUSC, and SKCM was positively correlated with CD4+ T cell infiltration (with Partial correlation coefficients of 0.14, 0.22, 0.13, and 0.16, respectively, P<0.05). Being similar to the pattern of USP7 expression and ranked among top 100 protein sets, the top 5 proteins were C16orf72, BCLAF1, UBN, GSPT1, ERI2 (with Spearman correlation coefficients of 0.83, 0.74, 0.73, and 0.72, respectively, all P values<0.05). The top 50 protein sets that directly physically bind to USP7 overlapped with the aforementioned protein set by only one protein, thyroid hormone receptor interaction factor 12. KEGG enrichment analysis showed that USP7 related genes were involved in cell cycle, spliceosome, cell senescence, and p53 signal pathway. GO enrichment analysis showed that USP7 related genes were involved in transcriptional regulation, protein ubiquitination, DNA repair, and cytoplasmic pattern recognition receptor signal pathways. Analysis of clinical samples showed that USP7 expression was significantly higher in hypertrophic scars (0.35±0.05), scar ulcers (0.43±0.04), and scar cancers (0.61±0.03) than in normal skin (0.18±0.04), P<0.05. Conclusions: USP7 may be a clinical biomarker for the progression of cicatricial ulcer cancer.

A systematic review of the literature assessing the outcomes of stapled haemorrhoidopexy versus open haemorrhoidectomy.

BACKGROUND: Symptomatic haemorrhoids affect a large number of patients throughout the world. The aim of this systematic review was to compare the surgical outcomes of stapled haemorrhoidopexy (SH) versus open haemorrhoidectomy (OH) over a 20-year period. METHODS: Randomized controlled trials published between January 1998 and January 2019 were extracted from Pubmed using defined search criteria. Study characteristics and outcomes in the form of short-term and long-term complications of the two techniques were analyzed. Any changes in trend of outcomes over time were assessed by comparing article groups 1998-2008 and 2009-2019. RESULTS: Twenty-nine and 9 relevant articles were extracted for the 1998-2008 (period 1) and 2009-2019 (period 2) cohorts, respectively. Over the two time periods, SH was found to be a safe procedure, associated with statistically reduced operative time (in 13/21 studies during period 1 and in 3/8 studies during period 2), statistically less intraoperative bleeding (3/7 studies in period 1 and 1/1 study in period 2) and consistently less early postoperative pain on the visual analogue scale (12/15 studies in period 1 and 4/5 studies in period 2) resulting in shorter hospital stay (12/20 studies in period 1 and 2/2 studies in period 2) at the expense of a higher cost. In the longer term, although chronic pain in SH and OH patents is comparable, patient satisfaction with SH may decline with time and at 2-year follow-up OH appeared to be associated with greater patient satisfaction. CONCLUSIONS: SH appears to be safe with potential advantages, at least in the short term, but the evidence is lacking at the moment to suggest its routine use in clinical practice.

Pathogenic analysis of suspected COVID-19 patients in a SARS-CoV-2 non-epidemic area of China.

OBJECTIVE: The aim of this study is to find the distributions of pathogens in 164 suspected COVID-19 patients from the outpatient clinic of Shenjing Hospital of China Medical University from 24th January, 2020, to 29th February of 2020. PATIENTS AND METHODS: 164 COVID-19 suspected patients were from the Shengjing Hospital of China Medical University. Oropharyngeal swab specimens were acquired by respiratory doctors under standardized conditions. Specific nucleic acids of SARS-CoV-2, influenza A and B, respiratory syncytial virus A and B, adenovirus, parainfluenza virus, along with pneumonic mycoplasma were detected by real-time fluorescence PCR. Symptomatic, epidemiologic, laboratory and radiological data of the patients were obtained from the electronic medical record system of our hospital. RESULTS: Among the 164 patients, 3 were positive for SARS-CoV-2, 15 were positive for other respiratory viruses and 16 were positive for pneumonic mycoplasma. Of the positive patients above, 1 patient was co-infected with SARS-CoV-2 and adenovirus, and 1 was co-infected with influenza B and pneumonic mycoplasma. The 3 SARS-CoV-2 infected patients were clinically diagnosed as COVID-19 because they meet the diagnostic criteria listed in "Chinese Clinical Guidance for COVID-19 Pneumonia diagnosis and treatment", including epidemic history, symptom and pathogenic detection, as well as abnormalities of the laboratory and radiological data. However, the clinical characteristics of COVID-19 patients were non-specific compared to those of the patients infected with other respiratory viruses. CONCLUSIONS: The endemic common respiratory pathogens are more prevalent than SARS-CoV-2 in the SARS-CoV-2 non-epidemic areas of this research. Detection of the pathogen is the unique means for definite COVID-19 diagnosis.

[Changes in serum osteoprotegerin/receptor activator of nuclear factor-κB ligand and related indexes of calcium and phosphorus in the early stage of severe burn patients].

Objective: To investigate the early changes in serum osteoprotegerin/receptor activator of nuclear factor-κB ligand (RANKL) and related indexes of calcium and phosphorus in severe burn patients. Methods: Thirty severe burn patients who met the inclusion criteria and were admitted to Tongren Hospital of Wuhan University & Wuhan Third Hospital within 8 hours post injury from June 2017 to December 2018 were recruited into severe burn group (24 males and 6 females, aged (38±13) years). Ten healthy volunteers with normal physical examination results in the Physical Examination Center of the same hospital in the same period of time were recruited into healthy control group (7 males and 3 females, aged (37±8) years). A prospective controlled study was conducted. The fasting venous blood of 5 mL was taken from each patient in severe burn group on post injury day (PID) 1, 7, 14, 21, and 28, respectively, and the fasting venous blood of 5 mL was taken from each volunteer in healthy control group. The serum osteoprotegerin, RANKL, 25 hydroxyvitamin D, and parathyroid hormone (PTH) levels were determined by enzyme-linked immunosorbent assay, and the RANKL/osteoprotegerin ratio was calculated. Serum albumin, serum calcium, and serum phosphorus levels were determined by bromocresol green method, methylthymol blue method, and phosphomolybdic acid method, respectively. Data were statistically analyzed with Fisher's exact probability test, analysis of variance for repeated measurement, Mann-Whitney U test, independent sample t test, and Bonferroni correction. Results: (1) The serum osteoprotegerin levels of patients in severe burn group on PID 1, 7, 14, 21, and 28 were 155.11 (102.91, 187.02), 170.07 (84.60, 196.86), 174.95 (59.09, 208.35), 190.01 (47.08, 214.52), and 188.85 (58.73, 223.13) pg/mL, respectively, which were significantly higher than 33.34 (28.59, 45.68) pg/mL of volunteers in healthy control group, Z=-3.436, -4.311, -3.248, -2.811, -4.217, P<0.01. The serum levels of RANKL of patients in severe burn group on PID 1, 7, 14, 21, and 28 were (1 869±791), (1 746±857), (1 781±713), (2 015±825), and (2 272±583) pg/mL, respectively, significantly higher than (49±16) pg/mL of volunteers in healthy control group, t=12.600, 10.844, 13.294, 13.041, 20.880, P<0.01. The ratios of RANKL/osteoprotegerin of patients in severe burn group on PID 1, 7, 14, 21, and 28 were 12.23 (8.10, 24.73), 11.40 (8.25, 16.96), 11.15 (6.91, 38.32), 12.98 (9.22, 49.68), and 13.91 (10.29, 40.68), respectively, which were significantly higher than 1.17 (0.91, 1.74) of volunteers in healthy control group, Z=-4.560, -4.529, -4.529, -4.560, -4.623, P<0.01. (2) The serum level of 25 hydroxyvitamin D of patients in severe burn group on PID 1 was significantly lower than that of volunteers in healthy control group (Z=-2.749, P<0.01). Compared with those of volunteers in healthy control group, the serum levels of albumin of patients in severe burn group on PID 1, 7, 14, 21, and 28 were significantly lower (t=-4.374, -7.689, -8.257, -7.651, -6.259, P<0.01), the serum levels of PTH were significantly elevated (Z=-4.685, -4.685, -4.685, -4.654, -4.685, P<0.01), and the serum levels of phosphorus were not changed significantly. The serum levels of calcium of patients in severe burn group on PID 1, 7, 14, and 21 were significantly lower than the level of volunteers in healthy control group (Z=-2.375, -3.455, -2.442, -2.016, P<0.05 or P<0.01). Conclusions: The serum osteoprotegerin, RANKL, RANKL/osteoprotegerin ratio, and PTH are increased, and the serum 25 hydroxyvitamin D, albumin, and calcium are decreased in the early stage of severe burn patients, which may be the mechanism leading to bone loss in patients.

[Analysis of causes of death and etiological characteristics of skin tissue donors].

Objective: To investigate the causes of death and etiological characteristics of skin tissue donors, and to provide reference for allogeneic skin transplantation. Methods: From October 2008 to October 2018, 49 skin tissue donors accepted by the Burn Department of Wuhan Third Hospital met the inclusion criteria of this study, and a cross-sectional study was conducted. According to the cause of death, the donors were divided into accidental death group (19 cases) and non-accidental death group (30 cases). The sex and death age of 49 donors were recorded, and the death age between different sex donors and that of donors between accidental death group and non-accidental death group were compared. Diseases or circumstances that caused the death of donors, hepatitis B, hepatitis C, acquired immunodeficiency syndrome, syphilis virus carrying status, and peripheral blood microbial culture results of 49 donors were recorded, and the detection of blood-borne infectious risk factors of donors between accidental death group and non-accidental death group was compared. Abnormal skin tissue was also selected during allogenic skin graft preparing for pathological examination. Data were statistically analyzed with Mann-Whitney U test and continuity correction chi-square test. Results: (1) Out of the 49 donors in this group, 38 were male (77.55%) and 11 were female (22.45%). The death age was 42.00 (24.00, 55.00) years, and the death age of male donors was similar to that of female donors (Z=0.120, P>0.05). The death age of donors in accidental death group was lower than that in non-accidental death group, but the difference was not statistically significant (Z=-1.581, P>0.05). (2) Among the causes and circumstances of the 49 donors in this group, there were 19 cases (38.78%) of injury, poisoning, and some other consequences of external causes, 11 cases (22.45%) of circulatory system diseases, 9 cases (18.37%) of tumors, 3 cases (6.12%) of nervous system diseases, 2 cases (4.08%) of respiratory system diseases, and 2 cases (4.08%) of congenital malformation, deformation, and chromosome abnormality, 1 case (2.04%) of blood and hematopoietic organ diseases and some diseases related to immune mechanism, 1 case (2.04%) of digestive system disease, and 1 case (2.04%) of genitourinary system disease. (3) There were 9 donors (18.37%) with blood-borne infectious risk factors among the 49 donors in this group, including 8 cases (16.33%) of blood-borne infectious diseases, which were 5 cases (10.20%) of hepatitis B, 2 cases (4.08%) of syphilis, and 1 case (2.04%) of hepatitis C, respectively. Blood microorganism culture was positive in 1 case (2.04%), in which multi-drug resistant Pseudomonas aeruginosa was detected. Risk factors of blood-borne infection were detected in 2 donors in accidental death group, with detection ratio lower than that in non-accidental death group (7 cases), but the difference was not statistically significant (χ(2)=0.562, P>0.05). (4) A total of 8 donors' abnormal skin tissue were selected, including 4 cases of intradermal pigmented nevus, 1 case of scar, 1 case of pseudoepithelioma hyperplasia, 1 case of epidermal verrucous hyperplasia, and 1 case of large amount of pigment granules in dermis. Conclusions: Non-accidental death caused by diseases is the main cause of death of skin tissue donors, and the risk of donor-derived infection of non-accidentally dead donors is slightly higher than that of accidentally dead donors. Before the allogeneic skin is obtained and transplanted, the cause of death of the donor should be carefully investigated, and the health status should be evaluated, so as to avoid the occurrence of donor-derived infection.

[Histopathological and genetical diagnosis of one case of neonatal ectodermal dysplasia/skin fragility syndrome].

On August 6, 2015, a male infant with ectodermal dysplasia/skin fragility syndrome at 6 hours of birth was admitted to the Burn Department of Tongren Hospital of Wuhan University & Wuhan Third Hospital. The ulcerous skin tissue in thoracic area was harvested. The histopathological change of wound tissue was observed with hematoxylin-eosin staining. The result showed that the epidermal muscle cell layer was slightly released, there were bullae under the epidermis, the dermal papilla layer disappeared, and a small amount of inflammatory cells infiltrated in the dermis. The expression of plakophilin 1 (PKP1) in wound tissue was observed with immunohistochemical staining. The result showed that the PKP1 expression was completely absent. The PKP1 gene mutation site was identified by target sequencing. The result showed that the PKP1 gene had a homozygous mutation at intron (PKP1: c.203-1G>A). Most of the wounds of the pediatric patient healed after 35 days of treatment, with many scattered residual wounds visible, and new blisters and skin lesions continue to appear.

Associations of Preoperative Irisin Levels of Paired Cerebrospinal Fluid and Plasma with Physical Dysfunction and Muscle Wasting Severity in Residents of Surgery Wards.

BACKGROUND: Myokine Irisin has been proposed to regulate metabolic homeostasis, which is related to chronic diseases or physical activity. However, whether irisin levels in paired cerebrospinal fruid (CSF), plasma and their ratio of inpatients, could use as biomarkers, and be independently related to the varying physical dysfunction, muscle wasting severity and chronic diseases with varying severe degrees, remain largely elusive. METHODS: We conducted an observational study to assess the independent associations between irisin levels in paired cerebrospinal fruid (CSF), plasma and their ratio, and the independence in activities of daily life (ADLs), muscle wasting severity and chronic diseases with varying severe degrees among elderly Chinese in-patient subjects. RESULTS: Among 217 inpatients in surgery wards with a mean age of 68.07 years (±15.94years), 31.3% of women and 68.7% of men were included in the study. Bivariate correlation analysis showed that Log transformed CSF and plasma irisin levels and their ratio were potential associated with age, fat%, muscle wasting time, ADLs, number of multimorbidity, the severity of bone mass loss and anemia. Regression models analysis indicated that CSF and plasma irisin levels and their ratio in inpatient individuals were independently associated with the independence in ADLs. Plasma irisin levels were independently related to the change of muscle wasting use. CONCLUSIONS: Collectively, the evaluation of paired plasma and CSF irisin levels, and their ratio in in-patient individuals is intriguing candidates for the susceptibility of the independence in ADLs. Plasma irisin levels were positively associated with indepedence in ADLs, negatively related to muscle wasting severity, and could use as biomarkers for muscle wasting severity.

Prevalence of Cognitive Frailty Phenotypes and Associated Factors in a Community-Dwelling Elderly Population.

OBJECTIVES: Cognitive frailty was notable target for the prevention of adverse health outcomes in future. The goal of this study was to use a population-based survey to investigate cognitive frailty phenotypes and potentially sociodemographic factors in elderly Chinese individuals. DESIGN: Cross-sectional study. SETTING: General community. PARTICIPANTS: A total of 5328 elderly adults (aged 60 years or older, mean age 71.36 years) enrolled in the Shanghai study of health promotion for elderly individuals with frailty. MEASUREMENTS: The 5-item FRAIL scale and the 3-item Rapid Cognitive Screen tools were used to assess physical frailty and cognitive impairment, including dementia or mild cognitive impairment (MCI). Physical frailty was diagnosed by limitations in 3 or more of the FRAIL scale domains and pre-physical frailty by 1-2 limitations. Subjective cognitive decline (SCD) and pre-MCI SCD, was diagnosed with two self-report measures based on memory and other cognitive domains in elderly adults. RESULTS: Of the participating individuals, 97.17% (n= 5177, female 53.4%) were eligible. Notably, 9.67%, 41.61% and 35.20% of participants were MCI, SCD and pre-MCI SCD; 35.86% and 4.41% exhibited physical pre-frailty and frailty; and 19.86% and 6.30% exhibited reversible and potential reversible cognitive frailty. Logistic regression analyses indicated that physical frailty phenotypes were significantly associated with MCI with SCD, and pre-MCI with SCD. Older single females with a high education level were more likely to exhibit the reversible cognitive frailty; and younger elderly individuals with a middle education level were at lower risk for potentially reversible cognitive frailty. CONCLUSIONS: The prevalence of pre-physical and reversible cognitive frailty was high in elderly individuals and age was the most significant risk factor for all types of frailty phenotypes. To promote the rapid screening protocol of cognitive frailty in community-dwelling elderly is important to find high-risk population, implement effective intervention, and decrease adverse prognosis.

Serial T-SPOT.TB in household contacts of tuberculosis patients: a 6-year observational study in China.

BACKGROUND: Screening tuberculosis (TB) contacts is a priority for TB control; however, it remains inadequate in most regions of China.OBJECTIVE: To investigate the progression of latent TB infection (LTBI) using the interferon-gamma release assay (IGRA) in contacts of active TB patients.DESIGN: This longitudinal prospective observational study included 159 household contacts aged ≥14 years without preventive treatment who were followed up for 6 years to compare their conversion and reversion rates using the T-SPOT®.TB IGRA to diagnose LTBI.RESULTS: Among the 159 household contacts, LTBI positivity was 47.5%. Age was independently associated with LTBI (OR 3.6, 95%CI 1.81-7.14; P = 0.00). T-SPOT.TB conversion rates were respectively 29.4% and 18.8% at 3- and 6-year follow-up. The reversion rates were 9.4% of contacts during the 3-year follow-up period, which increased to 38.2% at the 6-year follow-up. A decreasing trend in spot-forming cells on T-SPOT.TB was observed in most patients at the 6-year follow-up.CONCLUSION: LTBI prevalence among household contacts was relatively high, particularly in elderly patients. Furthermore, serial IGRA testing was highly dynamic; however, this overall trend gradually decreased over time, even if preventive therapy was not prescribed.

Dosimetry study of 18F-FMISO + PET/CT hypoxia imaging guidance on intensity-modulated radiation therapy for non-small cell lung cancer

Objectives: This study was to evaluate the feasibility of simultaneous integrated boost on tumor hypoxia area by studying the dosimetric change of hypoxia imaging guidance on intensity-modulated radiation therapy for non-small cell lung cancer (NSCLC). Methods: Five NSCLC patients with large hypoxic volume participated in this study. FDG PET/CT images were fused with CT localization images to delineate gross tumor volume. FMISO PET/CT images were fused with CT localization images to delineate hypoxic biological target volume (BTV) (tissue maximum ratio ≥ 1.3) by threshold. BTV was irradiated with 72, 78 and 84 Gy, respectively, 30 times. The dosimetry differences were compared in target volume and organ at risk between simultaneous integrated boost plans and conventional radiotherapy plans. Results: Dosages on BTV of NSCLC hypoxic area were increased to 72, 78 and 84 Gy, respectively, by simultaneous integrated boost intensity-modulated radiation therapy. There was no obvious difference in dosage distributions on original target volume compared with those in conventional radiotherapy. Dosages on main organ at risk in chest met the dosimetric constraint, and there was no significant difference compared with those in conventional radiotherapy. Conclusion: It is feasible in dosiology that the dosages in NSCLC hypoxic area were added to 72, 78 and 84 Gy by simultaneous integrated boost with the guidance of 18F-FMISO PET/CT

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[Observation on clinical effects of recombinant human growth hormone on the treatment of children with severe burn].

Objective: To observe the clinical effects of recombinant human growth hormone (rhGH) on children with severe burn. Methods: Clinical data of 94 children with severe burn, hospitalized in our burn unit from April 2012 to December 2016, conforming to the study criteria, were retrospectively analyzed. According to the use of rhGH, children were divided into rhGH group (n=50) and control group (n=44). Children in control group received conventional treatment, while children in rhGH group received both conventional and rhGH treatment. The rhGH treatment was started 3 to 5 days post injury in dosage of 0.2-0.4 U·kg(-1)·d(-1,) by way of subcutaneous injection, and the course of treatment was (11±5) d. The plasma albumin and prealbumin levels, heart rate, alanine aminotransferase (ALT), and serum creatinine level in 2 weeks post injury, times of skin grafting operation, hospitalization time, total hospitalization treatment cost, and sepsis and death of children were compared between the 2 groups. Data were processed with independent sample t test, Mann-Whitney U test, and Fisher's exact test. Results: (1) In 2 weeks post injury, the plasma albumin level [(36±4) g/L] and prealbumin level [(94±34) g/L] of children in rhGH group were significantly higher than those in control group [(33±4) and (73±20) g/L, t=3.666, 3.401, P<0.05]. (2) In 2 weeks post injury, the heart rate of children in rhGH group was (123±11) times per minute, which was slower than (130±14) times per minute of children in control group (t=2.839, P<0.05). There was no significant difference in ALT level of children between the 2 groups (Z=0.868, P>0.05). The blood creatinine levels of children in the 2 groups were within normal range. (3) The times of skin grafting operation of children in rhGH group was 0.3±0.5, which was significantly less than 0.5±0.6 in control group (Z=2.234, P<0.05). The hospitalization time of children in rhGH group was (22±8) days, which was shorter than (28±10) days in control group (t=2.837, P<0.05). The total hospitalization treatment cost of children in rhGH group was (41±15) thousand yuan, which was significantly less than (53±25) thousand yuan in control group (t=2.878, P<0.05). (4) There were 2 cases of sepsis in control group and 1 case of sepsis in rhGH group, with no significant difference between the 2 groups (P>0.05). No children died in the 2 groups. Conclusions: rhGH treatment of children with severe burn can correct post-injury hypoproteinemia, improve cardiac function, reduce the times of skin grafting operation and hospitalization treatment cost, shorten hospitalization time, with no significant effect on kidney and liver function, sepsis, and death.

Dosimetry study of 18F-FMISO + PET/CT hypoxia imaging guidance on intensity-modulated radiation therapy for non-small cell lung cancer.

OBJECTIVES: This study was to evaluate the feasibility of simultaneous integrated boost on tumor hypoxia area by studying the dosimetric change of hypoxia imaging guidance on intensity-modulated radiation therapy for non-small cell lung cancer (NSCLC). METHODS: Five NSCLC patients with large hypoxic volume participated in this study. FDG PET/CT images were fused with CT localization images to delineate gross tumor volume. FMISO PET/CT images were fused with CT localization images to delineate hypoxic biological target volume (BTV) (tissue maximum ratio ≥ 1.3) by threshold. BTV was irradiated with 72, 78 and 84 Gy, respectively, 30 times. The dosimetry differences were compared in target volume and organ at risk between simultaneous integrated boost plans and conventional radiotherapy plans. RESULTS: Dosages on BTV of NSCLC hypoxic area were increased to 72, 78 and 84 Gy, respectively, by simultaneous integrated boost intensity-modulated radiation therapy. There was no obvious difference in dosage distributions on original target volume compared with those in conventional radiotherapy. Dosages on main organ at risk in chest met the dosimetric constraint, and there was no significant difference compared with those in conventional radiotherapy. CONCLUSION: It is feasible in dosiology that the dosages in NSCLC hypoxic area were added to 72, 78 and 84 Gy by simultaneous integrated boost with the guidance of 18F-FMISO PET/CT.

The Presence of MMP-20 Reinforces Biomimetic Enamel Regrowth.

Biomimetic synthesis of artificial enamel is a promising strategy for the prevention and restoration of defective enamel. We have recently reported that a hydrogel system composed of chitosan-amelogenin (CS-AMEL) and calcium phosphate is effective in forming an enamel-like layer that has a seamless interface with natural tooth surfaces. Here, to improve the mechanical system function and to facilitate the biomimetic enamel regrowth, matrix metalloproteinase-20 (MMP-20) was introduced into the CS-AMEL hydrogel. Inspired by our recent finding that MMP-20 prevents protein occlusion inside enamel crystals, we hypothesized that addition of MMP-20 to CS-AMEL hydrogel could reinforce the newly grown layer. Recombinant human MMP-20 was added to the CS-AMEL hydrogel to cleave full-length amelogenin during the growth of enamel-like crystals on an etched enamel surface. The MMP-20 proteolysis of amelogenin was studied, and the morphology, composition, and mechanical properties of the newly grown layer were characterized. We found that amelogenin was gradually degraded by MMP-20 in the presence of chitosan. The newly grown crystals in the sample treated with MMP-20-CS-AMEL hydrogel showed more uniform orientation and greater crystallinity than the samples treated with CS-AMEL hydrogel without MMP-20. Stepwise processing of amelogenin by MMP-20 in the CS-AMEL hydrogel prevented undesirable protein occlusion within the newly formed crystals. As a result, both the modulus and hardness of the repaired enamel were significantly increased (1.8- and 2.4-fold, respectively) by the MMP-20-CS-AMEL hydrogel. Although future work is needed to further incorporate other enamel matrix proteins into the system, this study brings us one step closer to biomimetic enamel regrowth.

[Differential expression of microRNAs in serum of severe burn patients and analysis of the signaling pathway at early stage].

Objective: To explore differential expression of microRNAs in serum of patients with severe burn and analysis of the signaling pathway at early stage. Methods: In this study, we included three healthy adult volunteers and three patients with severe burn, conforming to the inclusion criteria and hospitalized in Tongren Hospital of Wuhan University & Wuhan Third Hospital in July 2015. Venous whole blood of 6 mL of each burn patient and healthy volunteer was collected at 24 to 48 h post injury of burn patients. The whole blood was divided into burn group and healthy control group. Whole blood of 2 mL of each one was used to determine white blood cell count and neutrophile granulocyte content. Serum was separated from the other whole blood of 4 mL of each one. Half of serum was used to determine content of blood glucose, total protein, and albumin; another half of serum was used to extract total RNA with Trizol method. The differentially expressed microRNA, with differential expression ratio larger than or equal to 1.500 between 2 groups, were screened by microRNA chip technique. Then cluster analysis and functional enrichment analysis of Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway were performed on the differentially expressed microRNAs. Data were processed with t test. Results: (1) Content of white blood cell count, neutrophile granulocyte of whole blood, and blood glucose of serum of patients in burn group was obviously higher than that in healthy control group (with t values from 4.27 to 7.83, P<0.05 or P<0.01). Content of total protein and albumin of serum of patients in burn group was significantly lower than that in healthy control group (with t values respectively -12.80 and -12.36, P values below 0.01). (2)Compared with those in serum of healthy control group, differential expression ratios of 48 microRNAs in serum of burn group were larger than 1.500, with 22 up-regulated microRNAs and 26 down-regulated microRNAs. MicroRNA expression profile in serum of burn group was different from that of healthy control group. (3)Functional enrichment analysis of KEGG signaling pathway showed that compared with those in serum of healthy control group, microRNAs of differential expression in serum of burn group took part in tumor transcription misregulation signaling pathway, tumor proteoglycan signaling pathway, long-term potentiation signaling pathway, tumor associated microRNAs signaling pathway, citrate cycle signaling pathway, tumor necrosis factor signaling pathway, focal adhesion signaling pathway, endocytosis signaling pathway, insulin secretion signaling pathway, and estrogen signaling pathway. Conclusions: MicroRNA expression profile in serum of patients with severe burn is different from that in serum of healthy adults. MicroRNAs of differential expression may take part in important pathophysiological process of energy metabolism, inflammatory response, and regulation of blood glucose at early stage of severe burn.

[Analysis of microRNA expression profile in serum of patients with electrical burn or thermal burn].

Objective: To explore the differential expression of microRNAs in the serum among patients with electrical burn or thermal burn and healthy persons and to explore the significance. Methods: In this study we included three patients with electrical burn and three patients with thermal burn, conforming to the inclusion criteria and hospitalized in our burn ward from June to August 2015, and three healthy adult volunteers. Their serum samples were separated from whole blood and divided into electrical burn group, thermal burn group, and normal control group. Total RNA was extracted from their serum samples using Trizol method. The differentially expressed microRNAs (with differential ratio larger than or equal to 2.000, less than or equal to 0.500) among the three groups were screened by microRNA chip technique. Then cluster and Venn diagram analysis of the differentially expressed microRNAs were performed. Enrichment analysis of Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway was performed on the distinctly changed microRNAs (with differential ratio larger than or equal to 5.000, less than or equal to 0.500). Results: There were 220 differentially expressed microRNAs among serum of the three groups. MicroRNA expression profiles in serum of electrical burn and thermal burn groups were different from that in serum of normal control group. Compared with those in serum of normal control group, the expressions of 59 microRNAs changed more than 2.000 times in serum of electrical burn group, with 50 up-regulated microRNAs and 9 down-regulated microRNAs; the expressions of 40 microRNAs changed more than 2.000 times in serum of thermal burn group, with 21 up-regulated microRNAs and 19 down-regulated microRNAs. Compared with those in serum of thermal burn group, the expressions of 167 microRNAs changed more than 2.000 times in serum of electrical burn group. There were 17 exclusively expressed microRNAs in serum of thermal burn group and 26 exclusively expressed microRNAs in serum of electrical burn group, compared with those in serum of normal control group. Enrichment analysis of KEGG signaling pathway showed that compared with those in serum of normal control group, microRNAs which changed distinctly in serum of electrical burn group took part in the insulin secretion signaling pathway, arrhythmogenic right ventricular cardiomyopathy signaling pathway, hypertrophic cardiomyopathy signaling pathway, glutamatergic synapse signaling pathway, calcium signaling pathway, cyclic adenosine monophosphate signaling pathway, glycerophospholipid metabolism, pyrimidine metabolism, serotonergic synapse signaling pathway, etc, while microRNAs which changed distinctly in serum of thermal burn group took part in the tumor transcription misregulation signaling pathway, proteoglycans in tumor signaling pathway, microRNAs in tumor signaling pathway, long-term potentiation signaling pathway, citrate cycle signaling pathway, tumor necrosis factor signaling pathway, focal adhesion signaling pathway, endocytosis signaling pathway, insulin secretion signaling pathway, p53 signaling pathway, and estrogen signaling pathway, etc. Conclusions: MicroRNA expression profiles in serum of electrical and thermal burn are different from that in serum of healthy adult. The signaling pathways enriched with target genes which are regulated by the differentially expressed microRNAs are related to the pathological changes and clinical manifestations after electrical or thermal burn.

Effect of acute/subchronic samarium exposure on the concentration, motility, and morphology of sperm in male mice.

Male ICR mice were orally administered samarium nitrate [Sm(NO3)3] to investigate its effects on sperm concentration and sperm quality. After acute exposure to ≥2880.00 mg/kg Sm(NO3)3 via intragastric gavage, sperm motility and acrosome integrity were decreased, and the sperm malformation percentage was increased (P < 0.05). After subchronic exposure to ≥500.00 mg/L Sm(NO3)3 administered via drinking water for 90 days, relative gonad weight, sperm concentration, and sperm quality significantly decreased (P < 0.05). Sperm malformation also increased after subchronic exposure to Sm, which was found to be the most sensitive index. Sperm head malformation accounted for the largest proportion of all types of sperm malformations evaluated. Of the six different subtypes of head malformation, irregular shape accounted for the largest proportion.