Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.

Objective To predict the potential suitable habitat of Haemaphysalis concinna in Heilongjiang Province under different climatic scenarios. Methods The geographic locations of ticks in Heilongjiang Province from 1980 to 2022 were captured from literature review and field ticks monitoring data from Harbin Center for Disease Control and Prevention in Heilongjiang Province, and the tick distribution sites with spatial correlations were removed using the software ArcGIS 10.2. The environment data under historical climatic scenarios from 1970 to 2000 and the climatic shared socioeconomic pathways (SSP) 126 scenario model from 2021 to 2040 and from 2041 to 2060 were downloaded from the WorldClim website, and the elevation (1 km, 2010), population (1 km grid population dataset of China, 2010) and annual vegetation index (1 km, 2010) data were downloaded from the Resource and Environmental Science and Data Center, Institute of Geographical Sciences and Natural Resources, Chinese Academy of Sciences. The contribution of environmental factors to H. concinna distribution was evaluated and environmental variables were screened using the software MaxEnt 3.4.1 and R package 4.1.0, and the areas of suitable habitats of H. concinna and changes in center of gravity were analyzed using the maximum entropy model in Heilongjiang Province under different climatic scenarios. In addition, the accuracy of the maximum entropy model for prediction of H. concinna distribution was assessed using the area under curve (AUC) of the receiver operating characteristic curve. Results A total of 79 H. concinna distribution sites and 24 environmental variables were collected, and 70 H. concinna distribution sites and 9 environmental factors that contributed to distribution of the potential suitable habitats of H. concinna in Heilongjiang Province were screened. The three most significant contributing factors included precipitation seasonality, annual precipitation, and mean temperature of the driest quarter, with cumulative contributions of 60.7%. The total area of suitable habitats of H. concinna was 29.05 × 10⁴ km² in Heilongjiang Province under historical climatic scenarios, with the center of gravity of suitable habitats located at (47.31° N, 129.16° E), while the total area of suitable habitats of H. concinna reduced by 0.97 × 10⁴ km² in Heilongjiang Province under the climatic SSP126 scenario from 2041 to 2060, with the center of gravity shifting to (47.70° N, 129.28° E). Conclusions The distribution of suitable habitats of H. concinna strongly correlates with temperature and humidity in Heilongjiang Province. The total area of potential suitable habitats of H. concinna may appear a tendency towards a decline with climatic changes in Heilongjiang Province, and high-, medium- and low-suitable habitats may shift.

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE^-/-LDLR^-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

ObjectiveTo investigate an outbreak of norovirus diarrhea in a welfare home for the elderly in Shanghai， and to analyze the epidemiology and virus genotype characteristics of the epidemic， thus providing a scientific basis for the prevention and control of norovirus epidemic. MethodsCase definition was clarified. After case definition， a standardized questionnaire was used to carry out case investigation to make comprehensive analysis in combination with field epidemiological investigation and laboratory tests results. ResultsThe epidemic lasted for 14 days， and 23 cases were reported with an incidence rate of 12.37% （23/186）， including 3 males and 20 females. There were more cases on the 1st， 4th and 6th floor of the main building in the welfare home， accounting for 52.17% （12/23） of total cases. 19 cases were reported in the main building， with an incidence rate of 11.59% （19/164）； 4 cases were reported in the auxiliary building， with an incidence rate of 18.18% （4/22）. There was no significant difference in the morbidity between the main building and the auxiliary building （χ²=0.779，P>0.05）. The main clinical manifestations were vomiting and diarrhea. There was a significant difference in the incidence of vomiting symptoms among the elderly， nursing staff and other staff in the welfare home （χ²=10.216， P<0.05）. But there was no significant difference in the incidence of diarrhea among the elderly， nursing staff and other staff （χ²=1.218， P>0.05）. Fecal samples were collected from 23 cases， 1 case family member， 68 risk personnel and 14 environmental surface swab samples. Norovirus GⅡ was detected in stool samples of 19 cases， 1 family member and 36 risk personnel. ConclusionOutbreak of norovirus infection is reported in a welfare home in Shanghai. The close contact between the elderly and health workers might lead to the outbreak.

Animals ; Antibodies, Neutralizing/biosynthesis* ; Antibodies, Viral/biosynthesis* ; Body Weight/immunology* ; COVID-19/virology* ; Disease Models, Animal ; Disease Progression ; Humans ; Immunohistochemistry ; Lung/virology* ; Male ; Mesocricetus ; Nasal Cavity/virology* ; RNA, Viral/immunology* ; SARS-CoV-2/pathogenicity* ; Severity of Illness Index ; Viral Load

Objective:To explore the effect of posture management combined with incentive nursing in patients with esophageal cancer surgery.Methods:From February 2019 to February 2021, convenience sampling was used to select 90 patients with esophageal cancer who received radical surgery for esophageal cancer in a ClassⅢ Grade A hospital in Nanjing as the research object. According to the random number table method, the patients were divided into the observation group and the control group with 45 cases each. The control group conducted conventional nursing, and the observation group carried out incentive nursing combined posture management. The quality of life, sleep quality, hope level, postoperative recovery and nursing satisfaction of the two groups of patients before and after the intervention were compared.Results:After the intervention, the total score of the Quality of Life Index (QL-Index) , total score and dimension scores of Herth Hope Index (HHI) , and the score of nursing satisfaction in the observation group were all higher than those in the control group, and the differences were statistically significant ( P<0.05) . After the intervention, the total score of the Pittsburgh Sleep Quality Index (PSQI) of the observation group was lower than that of the control group, and the differences were statistically significant ( P<0.05) . After the intervention, the hospital stay, first exhaust time, and first defecation time of the observation group were lower than those of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Posture management combined with incentive nursing is applied to patients with esophageal cancer surgery, which can effectively improve the patient's quality of life, sleep quality, level of hope and nursing satisfaction, and promote the patient's postoperative recovery.

Objective:To analyze the epidemiological characteristics related to Norovirus-associated infectious diarrhea bud events in Shanghai, and to discuss the value of bud events surveillance, so as to help Norovirus-associated infectious diarrhea control, prevention and to improve the surveillance system on bud events.Methods:Data related to 142 Norovirus-associated infectious diarrhea bud events were gathered from 16 districts of Shanghai areas in 2018 and were analyzed.Results:There were 2 peaks, April and November for 142 Norovirus-associated infectious diarrhea bud events reported in 2018. 98.59 % (140/142) of the bud events occurred in schools and kindergartens. 80.28 % (114/142) of the bud events would involve 6-19 cases per each event. The median time duration between the onset date of the first case and the reporting date of the event was 2 days and the median event duration was 7 days. The bud event scale and regional incidence of bud events as well as the reporting timelines were influential factors on the duration of the bud events. Conclusions:Two peaks, spring and winter bud events of the Norovirus-associated infectious diarrhea were seen in Shanghai in 2018. Schools and kindergartens were to be prioritized locations for control and prevention of Norovirus-associated infectious diarrhea bud events. Surveillance system was proved to have contributed to the early detection, reporting and control of bud events.

Objective: To understand the seasonality and etiological characteristics of infectious diarrhea in adults from Shanghai. Methods: Adult patients with diarrhea who had visited the enteric disease clinics in 22 hospitals that carrying on the Diarrhea Comprehensive Surveillance sentinel programs in Shanghai during 2014-2017, were surveyed. Stool specimens were collected according to the different intervals of sampling and detected for 12 bacteria and 5 viruses. Concentration ratio and circular distribution method were used for data analysis. Results: From 2014 to 2017, a total of 9 573 stool specimens were collected from the targeted diarrhea patients ≥18 years old (n=96 067), through the Shanghai Diarrhea Comprehensive Surveillance program. The positive rate of detection was 46.44%. Seasonal peaks of infectious diarrhea were both seen in summer (bacteria peak, diarrheagenic Escherichia coli and Vibrio parahaemolyticus, etc.) and in winter (virus peak, Norovirus, etc.). Both bacterial and viral infections presented seasonal concentration (Raleigh’s test P<0.001) but more obvious with bacterial infection. Viral infection accounted for 60.19% of the cause of infectious diarrhea. The top five predominant pathogens appeared as Norovirus, Rotavirus, diarrheagenic Escherichia coli, Vibrio parahaemolyticus, and Salmonella spp.. Conclusions Among the adult outpatients with infectious diarrhea in Shanghai, obvious seasonality was seen, with peaks in both summer and winter. Viral infection with Norovirus in particular, appeared as the predominant source of infection. Active, continuous and comprehensive diarrhea-related surveillance programs would be able to monitor the changing dynamic of pathogen spectrum, and lead to the adoption of targeted preventive measures.

Objective: To conduct a viral pathogen surveillance program on pediatric inpatients less than five years old with acute gastroenteritis in Shanghai and to better understand the pathogenic spectrum and molecular features in the target population, for setting up programs on control, prevention, medication and vaccine applications of the diseases. Methods: Fecal samples were collected from inpatients less than 5 years old who were admitted to a pediatric hospital for having acute gastroenteritis. Information related to demographic, clinical and epidemiological features of the patients was also collected. Laboratory assays including ELISA, real-time PCR and nested PCR, were performed to detect the presence of pathogens as rotavirus, calicivirus, astrovirus and adenovirus. Results: A total of 1 018 samples were collected (male 671 and 347 female), with the positive detection rate as 40.57% which peaked from autumn till winter, annually. Calicivirus and rotavirus A presented with the highest detection rates (24.75% and 13.95% respectively). The lowest detection rate was found in the 0-6 month-olds (32.20%). 65% of the patients with positive virus had received antibiotic treatment prior to the hospitalization. However, no statistically significant difference was seen, regarding the rates of antibiotic medication in the virus positive or negative populations (P>0.05). Data from the Rotavirus genotype analysis revealed that G9P[8] genotype was the predominant strain, and causing majority of rotavirus infections in all the age groups. Conclusions Among the inpatients under 5 years of age in Shanghai, the positive detection rate for Calicivirus was higher than that for rotavirus group A, suggesting the necessity to carefully monitor the changes regarding the pathogenic spectrum and subtypes of the virus. Antibiotics should also be attentively administered, together with the development of suitable vaccine.

Objective To explore the application value of cone-shaped gastric tube combined with cervical end-to-end anastomosis in thoracoscopic and laparoscopic esophagectomy for esophageal cancer.Methods The retrospective and descriptive study was conducted.The clinical data of 122 patients with esophageal cancer who were admitted to West China Hospital of Sichuan University from December 2016 to December 2017 were collected.There were 89 males and 33 females,aged (61±8)years,with a range from 48 to 81 years.McKeowntype three-incision esophagectomy was performed,and the cone-shaped gastric tube was pulled up to esophagus in left neck for hand-sewn end-to-end anastomosis after the dissection of esophagus and stomach under total thoracoscopy and laparoscopy.Observation indicators:(1) surgical treatment situations;(2) postoperative complications;(3) follow-up.Follow-up using outpatient examination was performed to detect postoperative gastroesophageal reflux,anastomotic stenosis and evaluate anastomotic width at 1,3,6 months and one year postoperatively up to December 2018.Measurement data with normal distribution were represented by Mean±SD.Measurement data with skewed distribution were described by M (P25,P75) or M (range).Count data were expressed by absolute number.Results (1) Surgical treatment situations:122 patients underwent laparocopic McKeown-type three-incision esophagectomy successfully,using cone-shaped gastric tube combined with cervical hand-sewn end-to-end anastomosis as digestive tract reconstruction,with no intraoperative conversion to open surgery.The operation time,cervical anastomosis time,and volume of intraoperative blood loss were (229 ± 49) minutes,(27± 1) minutes,and 50 mL (40 mL,60 mL),respectively.There were 6-8 stations of lymph node dissected,and the number of lymph node dissected were 19 (15,25).Duration of postoperative hospital stay was 10 days (9 days,11 days) in the 122 patients.(2) Postoperative complications:31 of 122 patients had postoperative complications.The primary complications:3 patients with anastomotic fistula were cured by conservative treatment including enteral nutrition through placement of nutritional tube under gastroscope,closed thoracic drainage and anti-infection;6 cases with severe thoracic gastric dilation were cured after gastrointestinal decompression.The secondary complications of 22 patients included 8 cases with hoarseness caused by recurrent laryngeal never injury,5 with arrhythmia,9 with pulmonary infection.They were cured after symptomatic and supportive treatment.No chylothorax occured,and there was no perioperative death.(3) Follow-up:all the 122 patients were followed up for 10-24 months,with a median time of 19 months.During the follow-up,7 cases with anastomotic stenosis including 4 scoring less than grade 2 and 3 scoring more than grade 3 were relieved after dilation through gastroscope.There were 33 of 122 patients without any reflux symptoms,and 89 with reflux symptoms,among which 52 were scored 1,25 were scored 2 and 12 were scored 3.The width of gastroesophageal anastomosis measured by barium radiography at 1 month after operation was (1.2±0.4) cm.Conclusion Coneshaped gastric tube combined with cervical end-to-end anastomosis in digestive tract reconstruction of thoracoscopic and laparoscopic esophagectomy can reduce the incidence of postoperative anastomotic complications and thoracic gastric dilation,and nasogastric tube placement could be abandoned,which demonstrates good safety and universality.