Genetic association of COVID-19 severe versus non-severe cases by RNA sequencing in patients hospitalised in Hong Kong.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has caused extensive disruption of public health worldwide. There were reports of COVID-19 patients having multiple complications. This study investigated COVID-19 from a genetic perspective. METHODS: We conducted RNA sequencing (RNA-Seq) analysis of respiratory tract samples from 24 patients with COVID-19. Eight patients receiving mechanical ventilation or extracorporeal membrane oxygenation were regarded as severe cases; the remaining 16 patients were regarded as non-severe cases. After quality control, statistical analyses were performed by logistic regression and the Kolmogorov-Smirnov test to identify genes associated with disease severity. RESULTS: Six genes were associated with COVID-19 severity in both statistical tests, namely RPL15, BACE1-AS, CEPT1, EIF4G1, TMEM91, and TBCK. Among these genes, RPL15 and EIF4G1 played roles in the regulation of mRNA translation. Gene ontology analysis showed that the differentially expressed genes were mainly involved in nervous system diseases. CONCLUSION: RNA sequencing analysis showed that severe acute respiratory syndrome coronavirus 2 infection is associated with the overexpression of genes involved in nervous system disorders.

[Epidemic trends and prevention and control of seasonal influenza in China after the COVID-19 pandemic].

During the COVID-19 pandemic, a series of non-pharmaceutical interventions, which were implemented to curb the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), significantly modified the seasonal pattern of influenza. The intensity of influenza activity markedly decreased and B/Yamagata lineage was no longer detected. As the national influenza sentinel surveillance data shown, clear seasonal patterns were observed for influenza between 2012-2019, annually with an average of 14.57% of specimens tested positive for influenza virus. However, the seasonal pattern of influenza was disrupted after the outbreak of COVID-19. In the 2020-2021 season, influenza demonstrated an extremely low activity (yearly positivity rate<1.0%), followed by a resurgence of winter peak in the 2021-2022 season. Following the downgrade of management of COVID-19 to Class B in China in December 26, 2022, social activities gradually resumed, leading to the rebound of influenza activity with an out-of-season ciculation. After COVID-19 pademic, other respiratory infectious diseases caused by SARS-CoV-2, respiratory syncytial virus, and mycoplasma pneumonia were alternatively or concurrently circulated with influenza. The prevention and control of influenza and other respiratory infectious diseases emphasizes a multi-disease prevention strategy, including long-term and continuous monitoring the epidemic trends in influenza virus and SARS-CoV-2, promoting influenza and COVID-19 vaccination among key populations, and strengthening the knowledge and public awareness of prevention and control for respiratory infectious diseases, etc.

[Analysis on the implementation of payment policies for four non-national immunization program vaccines in China].

This study systematically retrieved information on the payment policy of vaccination fees for pneumococcal vaccines, human papillomavirus vaccines, haemophilus influenzae type b vaccines and rotavirus vaccines using a Python-based crawler. The proportion of the population covered by policies among the total applicable population was estimated based on the medical insurance coverage ratio and population data in 2020. This study showed that the payment policies included two categories, government-funded free vaccination policies and medical insurance payment policies. Among the four non-national immunization program vaccines, the free vaccination policies only involved pneumococcal vaccines and human papillomavirus vaccines. Among them, the 13-valent pneumococcal conjugate vaccine, the 23-valent pneumococcal polysaccharide vaccine, and the human papillomavirus vaccine were provided free of charge in 1, 10 and 15 provinces, respectively. For these policies, the corresponding covered population and the proportion among the total applicable population were children aged 6 months to 2 years old (2.5%), older people (1.2% to 21.5%) and middle school girls (1.1% to 12.2%). Medical insurance payment policies were implemented in 14 provinces, and nearly covered the four types of vaccines in the policy implementation areas, with the proportion of the covered population about 10.9% to 41.5% among the total applicable population.

[Advances in clinical significance and detection methods research of high density lipoprotein subfractions].

High density lipoprotein (HDL) is an important biochemical index of clinical cardiovascular disease. Many new studies have demonstrated abnormalities of plasma HDL subfractions in patients with this disease,and their clinical significance is greater than the overall abnormalities of HDL. Therefore,the HDL subfraction as an important factor in cardiovascular disease has attracted extensive research and attention. This article summarizes current research on HDL subfractions,their measurements and their relationships with atherosclerosis and coronary artery disease.

[Evaluation of clinical outcomes of allogeneic hematopoietic stem cell transplantation for relapsed/refractory peripheral T-cell lymphoma with chemoresistance].

Objective: To evaluate the clinical outcomes in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) who had undergone allogeneic hematological stem cell transplantation (allo-HSCT). Methods: From June 2007 to June 2017, the clinical data of PTCL patients who underwent HSCT from eight hospitals were assessed retrospectively. Results: There were 23 patients diagnosed as relapsed or refractory PTCL with chemoresistance who underwent allo-HSCT. Among these patients, 18 were identified as progressive disease (PD) status and 5 patients as stable disease (SD) status before allo-HSCT. Seventeen patients received allo-HSCT from matched sibling donor (MSD),2 patients from matched unrelated donor and 4 patients from related haplo-identical donor (HD). After a median follow-up of 29 months, 21 patients survived longer than 28 days after allo-HSCT. Hematopoietic reconstitution was achieved in 20 of the 21 patients. The median time of myeloid and platelet engraftment were+13 (9-22) d and+16(10-38) d, respectively. The 100-d treatment-related mortality rate was 13.1%. Acute GVHD occurred in 11(47.8%) patients at a median time of 22(6-82) d after transplantation. Grade Ⅱ~Ⅳ aGVHD occurred in 6 patients. Chronic GVHD occurred in 10 patients at a median of 7.9 (3.5-27) months. After a median follow-up of 29 months, 13 patients died after HSCT. Four of them died of complications associated with allo-HSCT, and other 9 patients died of the primary lymphoma. The 3-years cumulative overall survival (OS) and progress-free survival (PFS) were 43.03% (95%CI: 29.79-69.16) and 39.13% (95%CI: 23.50-65.14), respectively. No significant difference was found in the 3-year PFS between patients with PD status and SD status before allo-HSCT (P=0.133). Conclusion: Allo-HSCT can be a promising treatment for relapsed or refractory PTCL with chemoresistance.

Oncogenes expand during evolution to withstand somatic amplification.

Background: Cancer-related genes are under intense evolutionary pressure. We conjectured that gene size is an important determinant of amplification propensity for oncogenes and thus cancer susceptibility and therefore could be subject to natural selection. Patients and methods: Gene information, including size and genomic locations, of all protein-coding genes were downloaded from Ensembl (release 87). Quantification of gene amplification was based on Genomic Identification of Significant Targets in Cancer scores obtained from available The Cancer Genome Atlas studies. Results: Oncogenes are larger in size as compared with non-cancer genes (mean size: 92.1 kb versus 61.4 kb; P < 0.0001) in the human genome, which is contributed by both increased total exon size (mean size: 4.6 kb versus 3.4 kb; P < 0.0001) and higher intronic content (mean %: 84.8 versus 78.0; P < 0.01). Such non-random size distribution and intronic composition are conserved in mouse and Drosophila (all P < 0.0001). Stratification by gene age indicated that young oncogenes have been subject to a stronger evolutionary pressure for gene expansion than their non-cancer counterparts. Pan-cancer analysis demonstrated that larger oncogenes were amplified to a lesser extent. Tumor-suppressor genes also moved toward small oncogenes in the course of evolution. Conclusions: Oncogenes expand in size whereas tumor-suppressor genes move closer to small oncogenes in the course of evolution to withstand oncogenic somatic amplification. Our findings have shed new light on the previously unappreciated influence of gene size on oncogene amplification and elucidated how cancers have shaped our genome to its present configuration.

[Various choices of reconstructing the left subclavicular artery to extend the proximal landing zone thoracic endovascular aortic repair].

Thoracic endovascular aortic repair (TEVAR) has become the preferred treatment for Stanford type B aortic dissection. Covered the left subclavian artery (LSA) directly may cause corresponding complications in Stanford type B aortic dissection with unfavourable proximal landing zone. TEVAR can be successfully implemented by reconstructing LSA to expand the proximal landing zone. Currently, the methods of reconstructing LSA mainly include hybridization technology (carotid-subclavian artery transposition), chimney technology (including branch stent technology) and fenestration (or slot technology), etc. These techniques are all valid for aortic dissection that needs to reconstructing LSA. The choices and applications of these techniques should follow the individualized principles.

[Efficacy and safety analysis of ivabradine hydrochloride treatment of Chinese patients with chronic heart failure: subgroup analysis of Chinese patients in the SHIFT study].

Objective: To evaluate the efficacy and safety of ivabradine for the treatment of Chinese patients with chronic heart failure based on the Chinese subgroup data of the systolic heart failure treatment with the I(f) inhibitor ivabradine trial (SHIFT). Method: A total of 6 558 stable outpatients who presented symptoms of heart failure, with a left ventricular ejection fraction (LVEF) ≤35%, sinus rhythms with a heart rate ≥70 bpm participated in the randomized, double-blind, placebo-controlled, international multicenter clinical study.The subset of Chinese patients with heart rate ≥75 bpm was enrolled in the post-hoc subgroup analyses.Patients were randomly allocated by computer-generated assignment through a telephone interactive voice response system to ivabradine group (starting dose 5 mg bid, which was then uptitrated to the maximum 7.5 mg bid) or matched placebo group.The clinical baseline characteristics of participants were obtained and analyzed.The primary outcome endpoint was a composite endpoint of cardiovascular death or hospitalization resulting from worsening HF.The primary safety endpoint included total incidence of adverse events during the study, bradycardia, and adverse visual reaction (phosphenes). Results: A total of 49 Chinese centers enrolled a total of 225 patients with chronic heart failure, of whom, 106 patients were randomized to the ivabradine group and the other 119 patients to the placebo group, and the mean follow-up time was (15.6±5.1) months.By the end of the study, mean heart rate (71.0 bpm vs. 80.3 bpm, P<0.05) and incidence of the primary endpoint events (18.9% (20/106) vs. 31.9%(38/119), HR=0.56, 95%CI 0.33-0.97, P=0.039) were significantly lower, while the percentage of patients with improvement in heart functional class NYHA (53.8% (56/106) vs. 34.5% (41/119), P=0.006 1) was significantly higher in the ivabradine group than in the placebo group.The total number of adverse events (129 events, 49.6% PY) in the ivabradine group was lower than that in the placebo group (203 events, 50.8% PY). In the ivabradine group and the placebo group, there were respectively 2 patients (1.9%) and 0 patients experienced bradycardia, 3 patients (2.9%) and 1 patient (0.8%) experienced adverse visual reaction (phosphenes). Conclusions: Ivabradine significantly reduced heart rate and improved the clinical outcomes and NYHA function class in Chinese patients with chronic heart failure, these beneficial effects are achieved without inducing remarkable adverse reactions.The results of Chinese subgroup analysis were thus consistent with the overall results of the SHIFT study. Clinical Trial Registry: International standard randomized controlled trials registry, ISRCTN 70429960.

Interpreting the transmissibility of the avian influenza A(H7N9) infection from 2013 to 2015 in Zhejiang Province, China.

Three epidemic waves of human influenza A(H7N9) were documented in several different provinces in China between 2013 and 2015. With limited understanding of the potential for human-to-human transmission, it was difficult to implement control measures efficiently or to inform the public adequately about the application of interventions. In this study, the human-to-human transmission rate for the epidemics that occurred between 2013 and 2015 in Zhejiang Province, China, was analysed. The reproduction number (R), a key indicator of transmission intensity, was estimated by fitting the number of infections from poultry to humans and from humans to humans into a mathematical model. The posterior mean R for human-to-human transmission was estimated to be 0·27, with a 95% credible interval of 0·14-0·44 for the first wave, whereas the posterior mean Rs decreased to 0·15 in the second and third waves. Overall, these estimates indicate that a human H7N9 pandemic is unlikely to occur in Zhejiang. The reductions in the viral transmissibility and the number of poultry-transmitted infections after the first epidemic may be attributable to the various intervention measures taken, including changes in the extent of closures of live poultry markets.

Outbreak of primary inoculation tuberculosis in an acupuncture clinic in southeastern China.

Outbreak of Mycobacterium tuberculosis infections associated with acupuncture has not been reported. Thirteen patients with a painful swollen lump were referred to our hospital. The index patient received acupuncture and paraspinal muscular injection at a local acupuncture clinic in April 2011 and was diagnosed with M. tuberculosis 1 month later. From May 2011 to August 2011, 12 more patients with a swollen lump on the nuchal region or in the lower back or the buttocks region were referred to our hospital. Tuberculin skin test (TST), T-SPOT.TB, acid-fast stain, M. tuberculosis culture, chest radiograph, and lump magnetic resonance imaging (MRI) were performed and the patients were diagnosed with tuberculous abscess of the lump. All 13 patients received intramuscular injection at the paraspinal muscle by two acupuncturists at a local clinic and reported a swollen lump at the injection site. The needles and syringes were reused after autoclave sterilization. The TST was positive in all patients. Twelve patients had positive acid-fast stains. Mycobacterial cultures of abscess specimens were positive in all 13 patients. T-SPOT.TB tests were positive in all patients who underwent the test. The lesions and biopsies were subjected to polymerase chain reaction (PCR) and gene sequencing by the Disease Control Center of Zhejiang Province, China and the causative agent was identified as M. tuberculosis, Beijing type. In conclusion, physicians should consider the possibility of mycobacterial infections, apart from other bacterial agents, in patients with a swollen paraspinal lump following intramuscular injection.

A higher anti-Müllerian hormone level is associated with an increased chance of pregnancy in patients undergoing controlled ovarian stimulation and intrauterine insemination.

Anti-Müllerian hormone (AMH) level has been found to be a useful marker of ovarian reserve, and a predictor of poor and hyper-responses in patients undergoing controlled ovarian stimulation (COS). The study aimed to determine the association of serum AMH level with achieving pregnancy in patients undergoing COS with intrauterine insemination. The cross-sectional study investigated 204 patients who underwent COS with intrauterine insemination at the Obstetrics and Gynecology Department of Taipei Medical University Hospital, from January 2011 to March 2012. The medical records of these patients were reviewed, and serum AMH levels were evaluated for association with successful clinical pregnancy. The AMH level in the patients who achieved clinical pregnancy was significantly higher than in patients who did not (median 2.7 vs 2.0 ng/ml, p = 0.005). Controlling for factors affecting infertility, AMH level had a significant independent influence on outcome; a higher AMH level was associated with a decreased risk of a non-pregnant outcome (odds ratio, OR = 0.895, p = 0.026). In patients undergoing COS and intrauterine insemination, a low AMH level is associated with a decreased chance of a clinical pregnancy, and this association remains irrespective of the presence or absence of endometriosis.

Defective bone repair in mast cell deficient mice with c-Kit loss of function.

KitW-sh mice carry an inactivating mutation in the gene encoding the receptor for stem cell factor, which is expressed at high levels on the surface of haematopoietic precursor cells. The mutation results in mast cell deficiency, a variety of defects in innate immunity and poorly defined abnormalities in bone. The present study was designed to characterise healing of a cortical window defect in skeletally mature KitW-sh mice using high-resolution micro computed tomographic imaging and histological analyses. The cortical bone defect healed completely in all wild type mice but failed to heal in about half of the KitW-sh mice by 12 weeks post-operative. Defective healing was associated with premature and excessive expression of TRAP positive cells embedded in fibrous marrow but with little change in ALP activity. Immuno-histochemical analyses revealed reduced CD34 positive vascular endothelial cells and F4/80 positive macrophages at 1 and 2 weeks post-operative. Impaired bone healing in the KitW-sh mice was therefore attributed to altered catabolic activity, impaired re-vascularisation and compromised replacement of woven with compact bone.

[Standardized diagnosis and treatment of colorectal polyps].

This article explores the standardized management of colorectal polyps, including classification, treatment, follow-up, and preventive control. Corresponding treatment strategies, including endoscopic resection and surgical intervention, are employed for different types of polyps. Currently, there is debate over whether to choose endoscopic resection or surgical intervention for malignant polyps at pT1 stage. Drawing on the latest literature and guidelines, the article elaborates on polyp classification, treatment modalities, follow-up, and preventive measures. Standardized management of colorectal polyps is important for reducing the incidence of colorectal cancer and improving the cure rate of early-stage colorectal cancer.

Validation of the Chinese version of the Halitosis Associated Life-quality Test (HALT) questionnaire.

OBJECTIVE: This study aimed to evaluate the reliability and validity of the Chinese version of the Halitosis Associated Life-quality Test (HALT) questionnaire. METHODS: A total of 106 patients with oral malodour were recruited to complete the questionnaire after its translation and cross-cultural adaptation. The reliability of the Chinese version of the HALT was evaluated using internal consistency and test-retest methods. Both construct validity and discriminative validity were adopted to evaluate the validity of the HALT. RESULTS: The Cronbach's alpha value (internal reliability) for the total HALT score was 0.95, and the intraclass correlation coefficient (ICC) value (test-retest reliability) was 0.89 (95% CI = 0.74-0.98). The construct validity was determined by exploratory factor analysis. Four factors were extracted, which accounted for 85.18% of the variance. All items had factor loadings above 0.40, ranging from 0.53 to 0.94. In addition, the Chinese version of the HALT was found to be valid for distinguishing patients with different degrees of oral malodour. CONCLUSION: The results suggest that the Chinese version of the HALT has satisfactory psychometric properties and is applicable to patients with oral malodour in Chinese-speaking populations.

Exosome-mediated delivery of SCD-1 siRNA promoted the death of anaplastic thyroid carcinoma cells via regulating ROS level.

PURPOSE: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers in the world. Stearoyl-CoA desaturase-1 (SCD-1) is one of major enzymes in the de novo synthesis of fatty acids and is related to cancer aggressiveness and poor patient prognosis. The study aimed to construct exosomes loaded SCD-1 interference, investigate its effects and mechanisms on the cell proliferation and apoptosis of ATC cells. METHODS: The expressions of SCD-1 in normal thyroid cell line and ATC cell lines were determined by qRT-PCR and western blotting, respectively. Exosomes were prepared and purification then loaded with SCD-1 siRNA by electroporation and observed by transmission electron microscopy. Higher SCD-1 mRNA and protein levels were found in ATC cell lines compared than normal thyroid cell line (P < 0.05), and both Hth-7 and FRO cells could uptake PKH67-labeled exosomes. The effects of exosomes loaded SCD-1 siRNA on ATC cells were measured by CCK8 assay and apoptosis detection kit. RESULTS: When compared with control group, the cell viability significantly decreased in both two ATC cell lines taken up exosomes loaded SCD-1 siRNA (P < 0.001), and apoptotic and necrotic cells obviously increased (P < 0.05). In order to explore the mechanism of exosomes loaded SCD-1 on ATC, the ROS level was detected by fluorescence reagent. It was found that exosomes loaded SCD-1 siRNA significantly increased intracellular ROS level of ATC cells (P < 0.05). CONCLUSIONS: Exosomes loaded SCD-1 siRNA inhibited ATC cellular proliferation and promoted cellular apoptosis, and the mechanisms involved maybe the regulation of fatty acids metabolism and ROS level. Our study provides a promising therapeutic strategy for ATC.

Interaction between synchronous bilateral prophylactic oophorectomy and adjuvant chemotherapy in female patients with locally advanced colorectal cancer.

AIM: In this study we explored the prognostic impact of synchronous bilateral prophylactic oophorectomy in female patients with primary colorectal cancer undergoing radical surgery. METHOD: From 1991 to 2000, 267 female patients with stage II or stage III colorectal cancer, who had undergone curative resection, were retrospectively reviewed. In 224 patients, the ovaries were preserved. The other 43 patients underwent synchronous bilateral prophylactic oophorectomy. Univariate and multivariate analyses (Kaplan-Meier and Cox regression, respectively) were used to evaluate the effect of prophylactic oophorectomy and other clinical factors on the prognosis of patients. RESULTS: Both univariate and multivariate analyses showed that tumor stage and adjuvant chemotherapy were the only two significant clinical factors that affected the 5-year overall survival of patients (P < 0.01). There was no significant difference in the 5-year overall survival between patients who had, or had not, undergone prophylactic oophorectomy (75%vs 73%, P > 0.05). In the subgroup analysis by adjuvant chemotherapy, the 5-year overall survival in patients receiving adjuvant chemotherapy was similar between nonoophorectomy and oophorectomy groups. However, in patients without adjuvant chemotherapy, the oophorectomy group was shown to have a significantly better 5-year overall survival than the nonoophorectomy group (76%vs 51%, P = 0.047). CONCLUSION: Prophylactic oophorectomy may improve the overall survival of female patients with locally advanced colorectal cancer without adjuvant chemotherapy, but its survival benefit vanished in patients receiving adjuvant chemotherapy. The role of prophylactic oophorectomy may be substituted by adjuvant chemotherapy, which makes prophylactic oophorectomy unnecessary during surgery for locally advanced colorectal cancer.