Evaluation of factors associated with high advanced HIV disease and mortality in Southwestern China: a retrospective cohort study, 2005-2020.

OBJECTIVES: To assess the prevalence, all-cause mortality and determinants of advanced HIV disease (AHD) or severe immunosuppression (SIS) in the rural-urban communities of Southwestern China. STUDY DESIGN: Retrospective cohort study. METHOD: Data on HIV/AIDS cases reported in 2005-20 were collected from Case Report System. A binary logistic regression model assessed the risk factors of AHD/SIS prevalence. Survival curves across rural-urban regions were compared using Kaplan-Meier estimates and log-rank tests. Determinants of all-cause mortality were identified using the Cox proportional hazard model. RESULTS: Among 14,533 newly diagnosed HIV/AIDS patients, 7497 (51.6%) presented with AHD and 2564 (17.6%) with SIS. Compared with urban patients, rural patients had a higher prevalence of AHD (56.7% vs 40.7%) and SIS (20.1% vs 12.4%), all-cause mortality (AHD 12.3 vs 5.6, SIS 16.3 vs 5.5, per 100 person-years). Their 5-year survival probability (AHD 59.5% vs 77.1%; SIS 54.4% vs 76.3%) and mean survival time (AHD 106.5 vs 140.6 months, SIS 95.3 vs 144.2 months, p < 0.0001) were lower. Rural patients had an increased risk of SIS prevalence (adjusted odds ratios 1.45, 95% confidence interval [CI] 1.28-1.64; p < 0.0001) and mortality of the total cohort (adjusted hazard ratios 1.41, 95% CI 1.29-1.55; p < 0.0001), AHD cohort (1.38, 1.24-1.54; p < 0.0001), and SIS cohort (1.49, 1.23-1.81; p < 0.0001). CONCLUSIONS: A high prevalence of AHD/SIS was a severe phenomenon that caused high mortality in rural areas. A regional point-of-care strategy targeting AHD/SIS detection and management is essential for reducing the mortality risk.

[Advances in the co-signal molecular function of Mtb-specific T lymphocytes].

Costimulatory and co-inhibitory receptors on T lymphocytes play an essential role in the immune response. There is increasing evidence that the expression of co-signal molecules on T cells is altered in infection, tumor, autoimmunity, and other diseases, and that intervention of co-signal molecules can be used in the immunotherapy. This paper reviewed the costimulatory and coinhibitory receptors on Mtb-specific T lymphocytes and further explained the mechanism of co-signal molecules in the progression of tuberculosis, to provide a reference for future research and clinical application.

[Epidemiological characteristics of inpatients with liver failure at the Beijing You'an Hospital from 2012 to 2021].

Objective: To elucidate the epidemiological characteristics and changing trends of liver failure in order to provide evidence-based strategies for prevention and treatment. Methods: The epidemiological information of inpatients with liver failure admitted and treated at Beijing You'an Hospital from 2012 to 2021 was retrospectively collected. The trend test was used to analyze age, gender, as well as the year-by-year changes in the underlying acute and chronic etiology of acute liver failure (ALF), sub-acute liver failure (SALF), acute-on-chronic liver failure (ACLF), and chronic liver failure (CLF). Results: During the study period, information on a total of 8512 inpatients, aged 51.3±13.5 years and mainly male (71.9%) with liver failure, was collected. The highest to lowest proportions of liver failure types were ACLF 4 023 (47.3%), CLF 3 571(42.0%), SALF 670 (7.9%), and ALF 248 (2.9%). The top five causes of liver failure in the overall population, accounting for 87.6% of the total, were hepatitis B 3 199 (37.58%), alcoholic liver disease 2 237 (26.28%), cryptogenic liver disease 906(10.61%), hepatitis B + alcoholic liver disease 603 (7.08%), drugs 488 (5.73%), The top three etiologies of patients with different types of liver failure were acute etiologies for acute liver failure (ALF), followed by drugs 107 (43.1%), hepatitis B 47(19.0%), and unknown etiology 36 (14.5%); sub-acute liver failure (SALF), followed by drugs 381(56.9%), unknown etiology 106 (15.8%), and sepsis 56 (8.4%); and acute-on-chronic liver failure (ACLF), followed by drugs 2 092(52.0%), alcoholic liver disease 813(20.2%), and cryptogenic liver disease 398(9.9%); and chronic etiologies for chronic liver failure (CLF), followed by alcoholic liver disease 1 410(39.5%), hepatitis B 1 028(28.8%), and cryptogenic liver disease 364(10.2%). Longitudinal analysis showed that the average age of patients with liver failure increased year by year, but the sex ratio trend did not change significantly, with male patients predominating throughout. The proportion of drug-induced liver failure in patients with ALF and SALF increased year by year, and the difference in the trend test was statistically significant (P < 0.05). The proportion of patients with chronic etiologies of ACLF and CLF decreased year by year among hepatitis B, while the proportion of alcoholic liver disease, autoimmune liver disease, and cryptogenic liver disease increased year by year (the difference was statistically significant, P < 0.05). Conclusion: The etiological spectrum of liver failure is changing in our country. Although hepatitis B is still the main cause of liver failure, its proportion shows a decreasing trend year by year, with the exception of ACLF, which is no longer the primary etiology of other types of liver failure, while drug-induced liver disease, alcoholic liver disease, autoimmune liver disease, and cryptogenic liver disease are increasing year by year and will become the focus of liver disease prevention and treatment in the future.

[A preliminary study on the characteristics of refractive parameters and retinal blood flow in dominant eyes].

Objective: To explore the characteristics of refractive parameters and retinal and choroidal blood flow in dominant and non-dominant eyes. Methods: A cross-sectional study. Students who were 18 to 32 years old and had emmetropia or myopia but no systemic diseases were recruited from universities in Wuhu, Anhui Province from April 2019 to August 2023. They were divided into 4 groups based on the difference in spherical equivalent between two eyes:<0.50 D (group A), 0.50 to 1.74 D (group B), 1.75 to 2.49 D (group C), and≥2.50 D (group D). The card hole method was used to determine the dominant eye. The refractive parameters of both eyes were recorded, including spherical equivalent, myopia degree, astigmatism degree, axial length, and corneal curvature difference (K2-K1). Optical coherence tomography angiography was performed to measure the blood flow density of the superficial retinal capillaries, deep retinal capillaries (DVC), avascular layer (AC), entire retina, choroidal capillaries, and choroidal vessels, as well as the retina and choroid as a whole. Statistical analysis was conducted using the paired sample t-test, chi square test, and variance analysis. Results: A total of 78 eligible subjects, aged (24.50±2.36) years old, 28 males and 50 females, were included. Fifty subjects had the right eye and 28 had the left eye as the dominant eye. Forty-two subjects had high myopia in the dominant eye, and 30 had high myopia in the non-dominant eye. There were statistically significant differences (all P<0.05) in the spherical equivalent [(-4.588±2.534) D vs. (-4.058±2.453) D], myopic spherical power [(-4.253±2.504) D vs. (-3.779±2.425) D], and axial length [(25.531±1.212) mm vs. (25.256±1.238) mm] between dominant and non-dominant eyes among all subjects, as well as in the astigmatism degree of groups A and C, spherical power of groups B to D, and spherical power and axial length of groups C and D. There were also statistically significant differences (all P<0.05) in the blood flow density of the DVC [(0.291±0.130) vs. (0.257±0.148)], AC [(0.347±0.118) vs. (0.326±0.126)], and overall retina and choroid [(0.385±0.102) vs. (0.349±0.084)] between dominant and non-dominant eyes among all subjects, as well as in the blood flow density of the superficial retinal capillaries, DVC, AC, choroidal capillaries, and overall retina and choroid of groups C and D, density of the choroidal vessels of group C, and density of the entire retina of group D. Conclusions: In young individuals with emmetropia or near vision, the degree of myopia in dominant eyes is higher than that in non-dominant eyes. When the difference in the spherical equivalent between two eyes is ≥1.75 D, the blood flow density of the retina and choroid in the dominant eye is greater than that in the non-dominant eye.

[Application of different prognostic scores in liver transplantation decision-making for acute-on-chronic liver failure].

Objective: To compare the impact of different prognostic scores in patients with acute-on-chronic liver failure (ACLF) in order to provide treatment guidance for liver transplantation. Methods: The information on inpatients with ACLF admitted at Beijing You'an Hospital Affiliated to Capital Medical University and the First Affiliated Hospital of Zhejiang University School of Medicine from January 2015 to October 2022 was collected retrospectively. ACLF patients were divided into liver transplantation and non-liver transplantation groups, and the two groups prognostic conditions were followed-up. Propensity score matching was carried out between the two groups on the basis of liver disease (non-cirrhosis, compensated cirrhosis, and decompensated cirrhosis), the model for end-stage liver disease incorporating serum sodium (MELD-Na), and ACLF classification as matching factors. The prognostic condition of the two groups after matching was compared. The difference in 1-year survival rate between the two groups was analyzed under different ACLF grades and MELD-Na scores. The independent sample t-test or rank sum test was used for inter-group comparison, and the χ (2) test was used for the comparison of count data between groups. Results: In total, 865 ACLF inpatients were collected over the study period. Of these, 291 had liver transplantation and 574 did not. The overall survival rates at 28, 90, and 360 days were 78%, 66%, and 62%, respectively. There were 270 cases of matched ACLF post-liver transplantation and 270 cases without ACLF, in accordance with a ratio of 1:1. At 28, 90, and 360 days, patients with non-liver transplantation had significantly lower survival rates (68%, 53%, and 49%) than patients with liver transplantation (87%, 87%, and 78%, respectively; P < 0.001). Patients were classified into four groups according to the ACLF classification criteria. Kaplan-Meier survival analysis showed that the survival rates of liver transplantation and non-liver transplantation patients in ACLF grade 0 were 77.2% and 69.4%, respectively, with no statistically significant difference (P = 0.168). The survival rate with an ACLF 1-3 grade was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.05). Patients with ACLF grades 1, 2, and 3 had higher 1-year survival rates compared to non-liver transplant patients by 50.6%, 43.6%, and 61.7%, respectively. Patients were divided into four groups according to the MELD-Na score. Among the patients with a MELD-Na score of < 25, the 1-year survival rates for liver transplantation and non-liver transplantation were 78.2% and 74.0%, respectively, and the difference was not statistically significant (P = 0.149). However, among patients with MELD-Na scores of 25-30, 30-35, and≥35, the survival rate was significantly higher in liver transplantation than that of non-liver transplantation, and the 1-year survival rate increased by 36.4%, 54.9%, and 62.5%, respectively (P < 0.001). Further analysis of the prognosis of patients with different ACLF grades and MELD-Na scores showed that ACLF grades 0 or 1 and MELD-Na score of < 30 had no statistically significant difference in the 1-year survival rate between liver transplantation and non-liver transplantation (P > 0.05), but in patients with MELD-Na score≥30, the 1-year survival rate of liver transplantation was higher than that of non-liver transplantation patients (P < 0.05). In the ACLF grade 0 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 77.8% and 25.0% respectively (P < 0.05); while in the ACLF grade 1 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 100% and 20.0%, respectively (P < 0.01). Among patients with ACLF grade 2, the 1-year survival rate with MELD-Na score of < 25 in patients with liver transplantation was 73.9% and 61.6%, respectively, and the difference was not statistically significant (P > 0.05); while in the liver transplantation patients group with MELD-Na score of ≥25, the 1-year survival rate was 79.5%, 80.8%, and 75%, respectively, which was significantly higher than that of non-liver transplantation patients (36.6%, 27.6%, 15.0%) (P < 0.001). Among patients with ACLF grade 3, regardless of the MELD-Na score, the 1-year survival rate was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.01). Additionally, among patients with non-liver transplantation with an ACLF grade 0~1 and a MELD-Na score of < 30 at admission, 99.4% survived 1 year and still had an ACLF grade 0-1 at discharge, while 70% of deaths progressed to ACLF grade 2-3. Conclusion: Both the MELD-Na score and the EASL-CLIF C ACLF classification are capable of guiding liver transplantation; however, no single model possesses a consistent and precise prediction ability. Therefore, the combined application of the two models is necessary for comprehensive and dynamic evaluation, but the clinical application is relatively complex. A simplified prognostic model and a risk assessment model will be required in the future to improve patient prognosis as well as the effectiveness and efficiency of liver transplantation.

[Impact of different diagnostic criteria for assessing mild micro-hepatic encephalopathy in liver cirrhosis: an analysis based on a prospective, multicenter, real-world study].

Objective: To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test. Methods: This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ (2) test. A kappa test was used to compare the consistency between groups. Results: After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea (Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences (P < 0.001). Conclusion: The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Accurate elemental analysis with variant one-point calibration laser-induced breakdown spectroscopy capable of using analytical lines with unknown transition probabilities.

Calibration-free laser-induced breakdown spectroscopy (CF-LIBS) is a very useful elemental analysis technique. However, it requires knowledge of transition probabilities of the analytical lines. To solve this problem, a variant one-point calibration (OPC) LIBS method was proposed. Quantitative elemental analysis on Cu-Zn-Ag-Au alloys was realized with this method capable of using zinc analytical lines with unknown transition probabilities. The relative error was demonstrated to be less than 3.3%. This variant OPC method will be helpful for quantitative elemental analysis of different samples using CF-LIBS, no matter whether the transition probabilities of the observed lines are known or unknown.

[Inhibition of GAS5 promoted invasion, migration and epithelial-mesenchymal transition of colorectal cancer cells via miR-21/PTEN/Akt axis].

Objective: To explore the effect of growth arrest-specific5 (GAS5) inhibition on the proliferation, colony formation, invasion, migration andepithelial-mesenchymal transition(EMT), cancer cell stem of HCT-116 and its mechanism. Methods: The colorectal carcinoma (CRC) cell HCT116 was divided into blank control, negative control (NC), si-GAS5 and si-GAS5+ miR-21 inhibitor groups. The quantitative real-time polymerase chain reaction (qRT-PCR) was used to test the expressions of miR-21 and GAS5 at 48 h after transfection. The binding site of GAS5 and miR-21 was determined by luciferase reporter array. Cell proliferation ability was detected by CCK-8 assay. Cell colony ability was detected by colony formation assay. Cell invasion and migration abilities were detected by Transwell assay. Cell cycle and apoptosis were examined by flow cytometer (FCM). The protein levels of EMT associated factors including Snail, N-cadherin, vimentin, E-cadherin, stem cell related factors including CD44, SOX2, Oct2, and PTEN/Akt signal pathway associated factors were examined by western blotting. Results: The expression levels of miR-21 in blank, NC, si-GAS5 group were 1.00±0.10, 1.00±0.10, 1.80±0.20, the absorbance values were 0.51±0.02, 0.50±0.01 and 0.65±0.01, the cell clones were 90±4, 91±5, 200±8, the invaded cells were 118±3, 119±3, 150±4, the migrated cells were 110±2, 108±2, 127±2, the cell ratios in G(1) phase were (49.3±2.1)%, (50.1±2.0)% and (42.2±1.1)%, the cell ratios in S phase were (19.2±1.2)%, (20.2±1.1)% and (28.3±2.2)%, the cell apoptotic ratios were (14.4±2.2)%, (14.5±2.1)% and (7.2±1.3)%. These results indicated that inhibition of GAS5 up regulated the expression level of miR-21, promoted cell proliferation, invasion and migration, decreased G(1)-phase cells and increased S-phase cells, and suppressed cell apoptosis (P<0.05). Moreover, inhibition of GAS5 up regulated the expressions of Snail, N-cadherin, vimentin, Sox2, CD44, Oct2 and p-Akt in HCT-116 cells (P<0.05), while down regulated the expressions of E-cadherin and PTEN (P<0.05). Inhibition of miR-21 reversed the impact of GAS5 knockdown on PTEN/Akt signaling pathway (P<0.05). Conclusion: GAS5 can act as a competing endogenous RNA for miR-21, and down regulation of GAS5 can promote the development of CRC by activating the miR-21/PTEN/Akt signaling pathway and promoting the acquisition of EMT and tumor cell stemness.

[Progress of regulatory T cells in the regulation of anti-tuberculosis immunity].

Mycobacterium tuberculosis (MTB), as an intracellular parasitic bacterium, invades the human body mainly through droplets, which can lead to multiple organ infection, causing the body to produce T cell-dominated immunity to tuberculosis (TB). Regulatory T cells (Tregs), as a class of T lymphocyte subsets that negatively regulate the immune response of the body, play an important role in regulating immune balance in host anti-tuberculosis immunity. A large number of studies have shown that MTB-specific Tregs affects the occurrence and development of tuberculosis and the efficacy of the vaccine. Therefore, elucidating the role and regulatory mechanism underlying anti-MTB immune response of MTB-specific Tregs will help to further understanding of the decrease of host anti-MTB immune cell function, and provide a basis for the study of immunotherapy of TB. This paper briefly introduces the subtypes and functions of Tregs, and systematically reviews the research progress of Tregs in many fields of TB.

[Quantitative evaluation of global left ventricular myocardial work in patients with hepatitis B cirrhosis by pressure-strain loop].

Objective: To quantitatively evaluate myocardial work in patients with hepatitis B cirrhosis by using left ventricular pressure-strain loop. Methods: 70 cases with hepatitis B cirrhosis who were hospitalized in Henan Provincial People's Hospital from March to December 2020 were selected as the study group. Patients were divided into three subgroups according to the Child-Pugh score of liver cirrhosis (Child-Pugh class A, B, and C groups: 25, 25, and 20 patients, respectively). At the same time, 25 healthy volunteers were included as the control group. Global longitudinal strain (GLS), global myocardial work index (GWI), global work efficiency (GWE), global constructive work (GCW), and global wasted work (GWW) were obtained by applying pressure-strain loops. The differences were analyzed and compared among the four groups parameters. Results: Compared with the control group, the Child-Pugh class A group had decreased GLS, while Child-Pugh class B and C had decreased GLS, GWI, GWE, GCW, and increased GWW, and the differences were statistically significant (P<0.05). Compared with Child-Pugh class A group, Child-Pugh class B group had decreased GLS, GWE, and increased GWW, while Child-Pugh class C group had decreased GLS,GWI, GWE, GCW, and increased GWW, and the differences were statistically significant (P<0.05). Compared with Child-Pugh class B group, Child-Pugh class C group had decreased GLS, GWI, GWE, GCW, and increased GWW, and the differences were statistically significant (P<0.05). Conclusion: The pressure-strain loop can detect early myocardial dysfunction, and has a certain value in the diagnosis, treatment and prognosis evaluation of myocardial function changes in patients with hepatitis B cirrhosis.

[Comparative study of ultrasound-guided percutaneous microwave ablation and surgical resection for colorectal cancer with liver metastasis].

Objective: To study the clinical efficacy of ultrasound-guided percutaneous microwave ablation and surgical resection for liver metastases from colorectal cancer. Methods: Retrospective analysis of 184 patients with liver metastases from colorectal cancer in Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology from January 2012 to June 2017.Percutaneous microwave ablation or surgical resection for liver metastases were selected under ultrasound guidance. Subgroup analysis was performed according to the treatment of liver metastases. There were 98 patients in the microwave-only group (56 males and 42 females, aged (59±11) years) and 86 cases in the surgery-only group (56 males and 30 females, aged (56±11) years). The baseline data of the two groups were compared, and the results showed that the size of the metastatic lesions in the microwave-only group was smaller than that in the surgery-only group, and the remaining data didn't had statistical differences.The survival time of the two groups of patients was analyzed separately.According to the size of the metastases, the metastases were divided into groups with a diameter of<3 cm and a group of ≥3 cm. The survival time of patients in the microwave-only group and the surgery-only group were analyzed respectively.According to the different primary tumor grades of colorectal cancer, the survival time of patients in the simple microwave-only group and the surgery-only group in the primary tumors Duck A, Duck B, and Duck C were analyzed. Results: In the microwave-only group, the overall survival rates at 1, 3, and 5 years were 100%, 50.9%, and 20.9%; in the surgery-only group, the overall survival rates at 1, 3, and 5 years were 100%, 42.8%, and 20.8%, respectively. There was no significant difference in overall survival between the groups (P=0.972).Metastatic focus diameter ≥3 cm: the overall survival rates of 1, 3, and 5 years with microwave-only were 100%, 65.4%, and 12.1%; the overall survival rates of 1, 3, and 5 years with surgery-only were 100%, 59.5%, and 30.9%. There was no significant difference in overall survival between the groups (P=0.067). The long-term survival rate of the surgery-only group was greater than that of the microwave-only group (P=0.018).Metastasis diameter<3 cm: there was no significant difference in overall survival between the surgery-only group and the microwave-only group (P=0.103).In the treatment of Duck B and C liver metastases of primary colorectal cancer, there was no significant difference in overall survival between microwave alone and surgery alone (P=0.376, P=0.385).Multivariate analysis showed that the size of colorectal cancer metastases was an independent risk factor affecting the prognosis of patients with colorectal cancer liver metastases. Conclusions: Percutaneous microwave ablation has a good effect on colorectal cancer liver metastases and has a similar survival prognosis as surgery.For livers with color ≥ 3 cm in colorectal cancer, the long-term survival rate of the surgery-only group is greater than that of the microwave-only group.

[Impact of complicated myocardial injury on the clinical outcome of severe or critically ill COVID-19 patients].

Objective: To analyze the clinical characteristics of the severe or critically ill patients with novel coronavirus pneumonia (COVID-19), and evaluate the impact of complicated myocardial injury on the prognosis of these patients. Methods: A retrospective study was conducted in 54 patients who admitted to Tongji hospital from February 3, 2020 to February 24, 2020 and met the criteria of severe or critical conditions of COVID-19. The clinical characteristics and hospital mortality rate were analyzed and compared between the patients with or without myocardial injury, which was defined with 3 times higher serum cardiac troponin value. Results: The age of the 54 patients was 68.0(59.8, 74.3) years. Among all the patients, 24 (44.4%) patients were complicated with hypertension, 13 (24.1%) with diabetes, 8 (14.8%) with coronary heart disease, and 3 (5.6%) with previous cerebral infarction. During hospitalization, 24 (44.4%) of the patients were complicated with myocardial injury and 26 (48.1%) patients died in hospital. In-hospital mortality was significantly higher in patients with myocardial injury than in patients without myocardial injury (14 (60.9%) vs. 8 (25.8%), P=0.013). Moreover, the levels of C-reactive protein (153.6 (80.3, 240.7) ng/L vs. 49.8 (15.9, 101.9) ng/L) and N-terminal pro-B-type natriuretic peptide (852.0 (400.0, 2 315.3) ng/L vs. 197.0 (115.3, 631.0) ng/L) were significantly higher than patients without myocardial injury (all P<0.01). Conclusions: Prevalence of myocardial injury is high among severe or critically ill COVID-19 patients. Severe or critically ill COVID-19 patients with myocardial injury face a significantly higher risk of in-hospital mortality. The study suggests that it is important to monitor and manage the myocardial injury during hospitalization for severe or critically ill COVID-19 patients.

Vasoactive intestinal peptide is required in the maintenance of immune regulatory competency of immune regulatory monocytes.

Dysfunction of the immune regulatory system plays an important role in the pathogenesis of rheumatoid arthritis (RA). Vasoactive intestinal peptide (VIP) has multiple bioactivities. This study aims to investigate the role of VIP in the maintenance of the immune regulatory capacity of monocytes (Mos). Human peripheral blood samples were collected from RA patients and healthy control (HC) subjects. Mos and CD14+ CD71- CD73+ CD25+ regulatory Mos (RegMos) were isolated from the blood samples and characterized by flow cytometry. A rat RA model was developed to test the role of VIP in the maintenance of the immune regulatory function of Mos. The results showed that RegMos of HC subjects had immune suppressive functions. RegMos of RA patients expressed less interleukin (IL)-10 and showed an incompetent immune regulatory capacity. Serum levels of VIP were lower in RA patients, which were positively correlated with the expression of IL-10 in RegMos. In-vitro experiments showed that the IL-10 mRNA decayed spontaneously in RegMos, which could be prevented by the presence of VIP in the culture. VIP suppressed the effects of tristetraprolin (TTP) on inducing IL-10 mRNA decay in RegMos. Administration of VIP inhibited experimental RA in rats through restoring the IL-10 expression in RegMos. RegMos have immune suppressive functions. VIP is required in maintaining IL-10 expression in RegMos. The data suggest that VIP has translational potential in the treatment of immune disorders such as RA.

[Progress in research on tumor immune PD-1/PD-L1 signaling pathway in malignant bone tumors].

Programmed death receptor 1 (PD-1) and its ligand PD-L1 have been shown to play an important role in evading the immune system. In recent years, PD-1/PD-L1 blockade has shown significant clinical effects in many malignancies, including malignant melanoma, renal cell carcinoma, classic Hodgkin lymphoma, non-small cell lung cancer and so on. PD-1/PD-L1 signaling pathway has become a new target of immunotherapy in patients with malignant tumors. However, there are few researches on immunotherapy in malignant bone tumors, and the progress of clinical research on PD-1/PD-L1 remains to be elucidated. This review started from the mechanism of PD-1/PD-L1 signaling in tumor immunity, and analyzed the application prospect of PD-1/PD-L1 antibodies in malignant bone tumors. We hope to provide a theoretical basis for the treatment of malignant bone tumors based on PD-1/PD-L1 signaling pathway in China.

[Association of ICOS and CD28 single nucleotide polymorphisms with pulmonary tuberculosis susceptibility].

Objective: To investigate the association of inducible co-stimulator (ICOS) and CD28 gene polymorphisms with pulmonary tuberculosis susceptibility. Methods: In this case-control study, from Mar 2015 to Sep 2016, peripheral venous blood of 100 pulmonary tuberculosis patients (pulmonary tuberculosis group) in the Jintan People's Hospital of Changzhou and 100 community physical examination volunteers (health control group) were collected. A total of 56 single nucleotide polymorphisms (SNP) in ICOS and CD28 sequences were selected and SNP genotype and allele frequency were analyzed using the next-generation sequencing technology. Association of these SNP with pulmonary tuberculosis susceptibility was investigated using linkage disequilibrium (LD) analysis and genetic models. Results: Among these 56 SNP, 23 SNP with Hardy-Weinberg equilibrium P (HWE-P) value<0.001 or minimum allele frequency<0.05 were kicked out. The frequencies of T allele and TT genotype of ICOS gene SNP locus (rs55663036), and GG genotype of CD28 gene locus (rs45620941) in tuberculosis group were significantly higher than those in healthy control group (all P<0.05). There was a strong linkage imbalance between rs45620941 at CD28 locus and rs56262258 (r(2)=0.757). Conclusion: The polymorphisms of rs55663036 of ICOS gene and rs45620941 of CD28 gene are significantly associated with the risk of pulmonary tuberculosis.

[The association between the whole blood riboflavin level and the occurrence, development and prognosis of esophageal squamous cell carcinoma].

Objective: To investigate the association between the whole blood riboflavin level and the occurrence, development and prognosis of esophageal squamous cell carcinoma (ESCC) in China. Methods: From March 2014 to September 2018, ESCC patients from three hospitals (the Affiliated Hospital of Medical College of Shantou University, Shantou Central Hospital in Southern Chaoshan area and First Affiliated Hospital of Zhengzhou University in Northern Taihang Mountain) were selected as a case group; non-esophageal patients who had a physical examination were selected as a control group. The case and control group were paired by age (±5 years) and a 1:1 ration. A total of 1 528 subjects were enrolled including 764 patients in the case group and 764 patients in the control group. About 3-5 ml venous blood samples were collected, and the erythrocyte glutathione reductase activity coefficient (GRAC) was measured to assess the whole blood riboflavin level. A multivariate conditional logistic regression model was used to analyze the association between the GRAC and the risk of ESCC. The association between the GRAC and the prognosis of ESCC was analyzed by using Cox proportional risk regression model based on 288 patients with complete survival data. They were divided into two groups, the high GRAC group (GRAC≥7.87) group and the low GRAC group (GRAC<7.87) according to the strongest correlation between the total survival time, survival outcome and GRAC (GRAC=7.87). Results: Among the 1 528 patients, 958 patients were from Southern Chaoshan area, including 479 patients in the case group with an average age about (59.90±9.34) years and 479 patients in the control group with an average age about (59.55±8.77) years. Other 570 patients were from Northern Taihang Mountain area, including 285 patients in the case group with an average age (58.39±5.19) years and 285 patients in the control group with an average age about (58.74±4.57) years. The multivariate conditional logistic regression showed that the OR (95%CI) of the GRAC and the risk of ESCC was 1.009 (0.998-1.019). The Cox proportional hazard regression model analysis showed that the HR (95%CI) of the high GRAC group was 1.712 (1.034-2.824) compared with the low GRAC group in the 50-70 years group. Conclusion: The whole blood riboflavin level might not be associated with the occurrence of ESCC. The high whole blood riboflavin level would be more beneficial to the prognosis of ESCC patients aged 50-70 years.

[Effect of microRNA-27a-3p on proliferation, apoptosis and cell cycle of hepatoma cells].

Objective: To investigate the effect of miR-27a-3p on proliferation, apoptosis and cell cycle of hepatoma cells. Methods: A quantitative real-time polymerase chain reaction (qPCR) was used to detect differential expression of miR-27a-3p in normal hepatic epithelial cells (L02) and hepatoma cells (HepG2 and PLC). Cell experiment was divided into four groups: HepG2 overexpression cells, Mi-27a-3p overexpression group (Mi-27a) and negative control group (Mi-Con); PLC knockdown cells, Mi-27a-3p knockdown group (Mi-inhibitor-27a) and negative control group (Mi-inhibitor-Con). The expression of microRNA-27a-3p in each group after transfection was detected by qPCR analysis. MTT assay was used to detect the cell proliferation. Flow cytometry was used to detect the apoptosis and cell cycle. One-way ANOVA was used for multiple comparisons, and t-test was used to compare two groups. Results: qPCR results showed that the expression levels of miR-27a-3p in L02, HepG2 and PLC increased sequentially, and the relative expression levels were 1.07 ± 0.04, 4.81 ± 0.64 and 11.31 ± 0.92, respectively (P < 0.05). MTT assay showed that the cell viability of HepG2 cells transfected with miR-27a-3p overexpression plasmid was significantly decreased compared with the negative control group (P < 0.05). The apoptosis assay showed that the apoptosis rate of miR-27a-3p overexpression group was higher than the negative control group (P < 0.05). The cell cycle results showed that the proportion of S phase cells in the miR-27a-3p overexpression cell group was significantly lower than the negative control group (P < 0.05). Furthermore, microRNA-27a-3p knockdown validation in PLC cells showed that MTT, apoptosis and cell cycle tests results were opposite to the results of HepG2 overexpression cells, and the differences were statistically significant (P < 0.05). Conclusion: miR-27a-3p can significantly inhibit the proliferation of hepatoma cells, promote cell apoptosis, alter the cell cycle distribution, and may become a potential target in hepatocellular carcinoma therapy.

[Helical tomotherapy using simultaneously integrated boost and simultaneous integrated protection technique for unresectable biliary tract cancer].

Objective: To evaluate the safety and efficacy of helical tomotherapy using simultaneously integrated boost and simultaneous integrated protection technique in the treatment of unresectable biliary tract cancers. Methods: The data of 23 patients with unresectable biliary tract cancer who received tomotherapy-based hypofractionated radiotherapy at Comprehensive Cancer Centre of Drum Tower Hospital,the Affiliated Drum Tower Clinical College of Nanjing Medical University between February 2015 and October 2017 were analyzed. There were 10 males and 13 females, aged from 40 to 85 years(median:58 years). Pathological type included intrahepatic cholangiocarcinomas(n=11), gallbladder cancers(n=6),extrahepatic cholangiocarcinomas(n=6). The irradiated sites covered primary tumors and areas of local invasion,including metastatic lymph nodes which were confined to the abdominal or retroperitoneal space. Dose escalation was achieved using simultaneously integrated boost(SIB) technique, and simultaneous integrated protection(SIP)technique was used to protect gastrointestinal tracts and other adjacent organs. Cox regression modal and Kaplan-Meier analysis were used to analyze the associations between patients' characteristics and overall survival(OS). Results: The median total radiation dose was 54 Gy(range: 28-72 Gy)and median biologically effective dose(BED)was 74.4 Gy(range: 37.8-115.2 Gy).The median planning target volume(PTV)was 445.79 cm(3)(range:126.02-950.12 cm(3)). Based on the various PTV,patients received 2.4-6.0 Gy/fraction with 8-28 fractions. The local control rate was 65.2% and the median OS was 11.3 months(range:2.1-31.9 months).The most common cause of death was out-field failure and only 3 patients died of in-field failures. The longest survival was 31.9 months. BED≥70 Gy significantly improved OS,compared to BED<70 Gy(16.8 months vs.5.1 months)(HR=0.146, 95%CI:0.028-0.762, P=0.022). No patients developed grade ≥4 toxicities. Conclusions: Helical tomotherapy-based hypofractionated radiotherapy is effective and well tolerated for patients with unresectable biliary tract cancer. The dose escalation with higher BED could improve the survival for such patients.

Analysis of Characteristics and Relevant Factors of 1 340 Cases of Intentional Injury Cases in Southwest China.

ABSTRACT: Objective To investigate the characteristics and patterns of factors such as victims' information, injury tools and time of occurrence of intentional injury cases in southwest China. Methods One thousand three hundred and forty intentional injury cases from several places in southwest China from 2014 to 2016 assessed as minor injury level Ⅱ and above had been randomly selected. Data on victims' information, motives, injury tools, sites of occurrence, time of occurrence, injured parts and degrees of injury were classified and gathered, and then association analyses of motives and types of injury tools as well as degrees of injury and injury tools were made. Results Most of the victims were young adults between 20-50 years （65.2%）, male （82.3%）, rural household registration （62.8%）; the motives were mainly dispute （45.8%）. Injury tools were mostly blunt （54.6%） or sharp （36.0%）. Specifically, injuries were mostly made bare-handed （36.9%） and by cutting tools （33.2%）; the cases mainly occurred in public areas （59.0%）. Cases occurred more frequently in January （11.3%）, February （13.1%）, March （11.6%） and from 22：00 to 01：00 every night. Injuries mainly involved the craniofacial region. The wounds were mainly assessed as minor injury level Ⅱ （61.6%）. There was statistical significance in the difference of types of injury tools among cases with different motives （P<0.05）. There was statistical significance in the difference of the distribution of injury tools among cases with different degrees of injury （P<0.05）. Conclusion The occurrence of intentional injury cases in southwest China has potential patterns and relevant influencing factors. Prevention and analysis of such cases need to be comprehensively considered from the aspects such as victims' information, injury tools and time of occurrence.