Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Objective:The epidemiological and host animal pathogen data of leptospirosis in the population of Zhejiang Province in 2023 were analyzed, providing scientific basis for formulating prevention and control strategies of leptospirosis.Methods:The data of human leptospirosis in the population were collected from the China Information System for Disease Control and Prevention, and analyzed using descriptive epidemiological methods. The data on isolation, culture, and nucleic acid testing of Leptospira pathogens from mouse kidneys, frog kidneys, pig kidneys, and duck kidneys as well as duck serum antibody data were collected from Zhejiang Provincial Center for Disease Control and Prevention "Leptospirosis Surveillance Project of Zhejiang Province". The carrying and changing status of Leptospira epidemic microbiota in populations and host animals were analyzed. Results:In 2023, a total of 83 cases of leptospirosis were reported in Zhejiang Province, with a incidence rate of 0.126 2/ 100 000, aged (62.66 ± 11.31) years, including 68 males and 15 females. Leptospirosis cases were reported in 11 cities, mainly concentrated in the southern cities of Wenzhou City, Lishui City and Taizhou City(a total of 68 cases), accounting for 81.93% of the total number of cases. August to October were high incidence months for leptospirosis (a total of 70 cases), accounting for 84.34% of the total number cases. The male to female ratio of patients was 4.53 ∶ 1.00, and all were adults ≥20 years old, the middle and old people aged 45 - 79 years were the high-risk population (a total of 77 cases), accounting for 92.77% of the total number of cases. The patient's occupation was mainly farmers, with a total of 54 cases, accounting for 65.06% of the total number cases. The shortest time from onset to initial diagnosis for patients with leptospirosis was 0 day, and the longest was 13 days. The shortest time from initial diagnosis to confirmed diagnosis was 0 day, and the longest was 16 days. The 72.29% of the leptospirosis cases (60 cases) had a history of field labor or suspected contact with contaminated water within one month before the onset of the disease, and 18.07% of the leptospirosis cases (15 cases) had a history of contact with animals such as mice, frogs, pigs, cows, dogs, fish or ducks, or their excreta within one month before the onset of the disease. The average nucleic acid positive rate of host animals with leptospirosis was 5.92% (31/524) in mouse kidney, 6.74% (36/534) in frog kidney, and 0.66% (1/151) in pig kidney. The isolation and culture of leptospirosis from duck kidney, nucleic acid detection, and antibody detection in duck blood were all negative. The leptospirosis bacteria detected in human population were serogroup Icterohaemorrhagiae (3 samples) and Hebdomadis (4 samples), and the bacteria group detected in host animals was serogroup Icterohaemorrhagiae (3 samples). Conclusions:The outbreak of leptospirosis in Zhejiang Province mainly occurs in the summer and autumn, with the affected areas mainly concentrated in the southern region of Zhejiang Province. The affected population is mainly middle-aged and elderly males, and the population carrying Leptospira is still mainly composed of the serogroup Icterohaemorrhagiae and the Hebdomadis, with the host animal being the serogroup Icterohaemorrhagiae.

Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

Objective: To evaluate the effectiveness for the construction of "mosquito-free village" in Xuejia Village, Pujiang County, Zhejiang Province, so as to provide the guidance for the construction of "mosquito-free village" in other rural areas. Methods: Density of adult mosquitoes in Xuejia Village was investigated using light trap method and density of larval mosquitoes was investigated using larval straw method from April to November each year. Totally 30 households of villagers were randomly selected, and their awareness rates of mosquito control knowledge, mosquito control behavior forming rates and satisfaction rates were surveyed through questionnaires. Investment during construction (from August 2016 to December 2018) and maintenance period (from 2019 to 2023) of "mosquito-free village" were investigated through data review and interviews. Long-term effects of "mosquito-free village" construction in Xuejia Village were evaluated in terms of mosquito density from 2016 to 2023, effectiveness of health education for villagers, satisfaction and investment. Results: Compared with the year 2016, the densities of adult and larval mosquitoes in Xuejia Village were significantly decreased from 2017 to 2023. The average monthly density of adult mosquitoes in 2023 decreased by 98.34%, and the average monthly 100 household index of larval mosquitoes decreased by 98.45% compared to 2016. The average monthly density of adult mosquitoes from 2019 to 2023 was less than or equal to one mosquito per light trap in a night, and the average monthly 100 household index of larval mosquitoes was less than or equal to five places per 100 households. The awareness rate of mosquito control knowledge was 93.33%, the behavior forming rate was 86.67%, and the satisfaction rate was 90.00%. By December 2023, the total investment during construction and maintenance period was 450 thousand Yuan, with an average annual investment of 60.7 thousand Yuan and average annual investment of 206.61 Yuan per household. The average annual investment during maintenance period was 36.2 thousand Yuan, and the average annual investment per household was 109.70 Yuan. Conclusion The mosquito density, effectiveness of health education for villagers and satisfaction of "mosquito-free village" in Xuejia Village all meet the evaluation criteria of "mosquito-free village", and the investment is reasonable, making it suitable for promotion to other rural areas.

BACKGROUND:Cardiac hypertrophy is an adaptive response of the heart to physiological and pathological stimuli such as pressure overload.It is of compensatory significance in the early stage,but if the stimulation continues,it can cause cardiomyopathy leading to heart failure.MicroRNAs are involved in the regulation of cardiac hypertrophy.However,the role of miR-20a in pressure overload-induced cardiac hypertrophy has not been reported. OBJECTIVE:To investigate the role of miR-20a in pressure overload-induced cardiac hypertrophy and the underlying mechanisms. METHODS:Transverse aortic constriction was used to induce cardiac hypertrophy in vivo and angiotensin Ⅱ was used to induce H9c2 cell models of cardiac hypertrophy in vitro.MiR-20a was overexpressed in vivo by intramyocardial injection of miR-20a overexpressing adenovirus and in vitro by transfecting miR-20a mimic into H9c2 cells.Cardiac hypertrophy was assessed by measuring heart weight/body weight ratio,cell surface area,and myocardial fibrosis.The expression levels of atrial natriuretic peptide,brain natriuretic peptide,β-myosin heavy chain and miR-20a were detected by real-time fluorescence quantitative PCR.Mitochondrial fission was detected by MitoTracker.The downstream target genes of miR-20a were predicted by RNAhybrid software. RESULTS AND CONCLUSION:(1)The expression level of miR-20a was significantly decreased in both hypertrophic cardiomyocytes and hearts(P<0.05).(2)At the animal level,overexpression of miR-20a significantly inhibited transverse aortic constriction-induced cardiac hypertrophy,including decreasing the upregulated expression level of hypertrophic marker genes(P<0.05),reduced the enlarged heart volume,reducing the increased heart weight/body weight ratio(P<0.01),reducing the increased myocardial cross-sectional area(P<0.05),and attenuating fibrosis(P<0.01).(3)At the cellular level,overexpression of miR-20a significantly inhibited angiotensin Ⅱ-induced cardiomyocyte hypertrophy,including decreasing the upregulated expression levels of atrial natriuretic peptide(P<0.05),brain natriuretic peptide(P<0.01)and β-myosin heavy chain(P<0.05),reducing the increased protein/DNA ratio(P<0.01),and suppressing the increased cell surface area(P<0.05).(4)Overexpression of miR-20a significantly inhibited angiotensin Ⅱ-induced mitochondrial fission(P<0.05).(5)The results of RNAhybrid software analysis showed that miR-20a and the mRNA 3'untranslated region of cAMP-dependent protein kinase inhibitor alpha were well complementary and the predicted binding sites were highly conserved.(6)In conclusion,miR-20a is significantly down-regulated in pressure overload-induced cardiac hypertrophy.Overexpression of miR-20a inhibits cardiac hypertrophy at both the cellular level and animal level and attenuates angiotensin Ⅱ-induced mitochondrial fission.

Objective: To estimate the epidemic threshold and graded intensity thresholds of influenza in Zhejiang Province from 2012 to 2023 using the moving epidemic method (MEM), and evaluate the intensity of influenza epidemics, so as to provide the reference for influenza prevention and control in Zhejiang Province. Methods: The positive rates of influenza virus per week during the influenza epidemic seasons (from 40th week to 20th week of the following year) in Zhejiang Province from 2012 to 2022 were collected through the Chinese Influenza Surveillance Information System. A MEM model was established and optimized using cross-validation. The maximum accumulated rates percentage was used to divide the epidemic into pre-epidemic, epidemic, and post-epidemic periods, and to estimate the epidemic thresholds and graded intensity thresholds. The intensity of influenza epidemics in Zhejiang Province during the 2022-2023 epidemic season were assessed. Results: The positive rates of influenza virus in five epidemic seasons from 2012 to 2022 were included in the model. The MEM model performed best when the parameter δ was set to 1.5, with a sensitivity of 0.971, a specificity of 0.745, and a Youden's index of 0.716. According to the model analysis, the epidemic beginning and ending thresholds of influenza in Zhejiang Province during the 2022-2023 epidemic season were 19.32% and 10.92%, respectively, and the medium, high, and extremely high intensity thresholds were 48.65%, 63.49%, and 68.47%, respectively. During 2022-2023, the influenza epidemic was in the pre-epidemic period from the 40th week in 2022 to the 7th week in 2023; the epidemic period was from the 8th to the 18th week, the epidemic intensity was low in the 8th week and increased to a high level in the 9th week, and reached to a extremely high level from the 10th to the 13th week, then fell to the high and the medium level in the 14th week and 15th week, respectively, and fell to a low level from the 16th to the 18th week; the influenza epidemic entered the post-epidemic period since the 19th week. Conclusion MEM could be applied for evaluation of influenza epidemic intensity, providing the reference for early identification and taking graded preventive and control measures.

A gossypiboma is an inflammatory pseudotumor that forms when a surgical sponge or gauze is accidentally left behind during surgery, triggering a foreign body reaction. This condition can lead to complications in nearby tissues. Gossypibomas are most commonly found in the abdomen, pelvis, or thorax. However, they are extremely rare in the extremities, making them difficult to diagnose. As a result, they can be mistaken for soft tissue tumors in these areas. This paper presents the case of a 12-year-old boy with a solid mass in his right anterior thigh, later identified as a gossypiboma with characteristic magnetic resonance imaging findings. When evaluating patients with a soft tissue mass and a history of surgery, gossypiboma should be included in the differential diagnosis.

Objective: To investigate the epidemiological characteristics of rabies-exposed populations in Anji County, Zhejiang Province from 2017 to 2021, so as to provide insights into rabies control in the county. Methods: All data pertaining to rabies were captured from Monthly Report of Rabies-exposed Populations in Huzhou City and Investigation Form of Multiple Dog Injuries reported by dog injury clinics in Anji County from 2017 to 2021, and the species of animals causing dog injuries, duration, degree and site of exposure, and post-exposure treatment of rabies-exposed populations were descriptively analyzed. Results: Totally 46 186 cases with rabies exposure were reported in dog injury clinics in Anji County from 2017 to 2021, and the rate of exposure appeared a tendency towards a decline year by year (Z=-23.249, P<0.001), with an annual mean exposure rate of 1 739.59/105. The number of cases with exposure to rabies peaked in July and August (10 066 cases, 21.79%). Dogs were predominant animals causing injuries (31 732 cases, 68.70%), and the rate of exposure to dog bites appeared a tendency towards a decline year by year (Z=-35.541, P<0.001). There were 11 350 cases with cat-causing injuries (24.57%), and the rate of exposure to cat bites appeared a tendency towards a rise (Z=14.834, P<0.001). Lower extremity was the main site of exposure (22 364 cases, 48.42%), and the proportions of grade Ⅱ and Ⅲ exposure to rabies were 72.85% and 25.23%, the rates of exposure both appeared a tendency towards a decline (Z=-14.522, P<0.001; Z=-21.820, P<0.001). The proportion of using human rabies immune globulin was 25.72% among populations with grade Ⅲ exposure, which appeared a tendency towards a rise (Z=6.636, P<0.001). Conclusions The rate of exposure to rabies appeared a tendency towards a decline in Anji County from 2017 to 2021. Dogs were predominant animals causing injuries, and the rate of cat bites appeared a tendency towards a rise from 2017 to 2021; however, the proportion of using human rabies immune globulin remains to be improved among populations with grade Ⅲ exposure.

Objective: To investigate the seroprevalence and influencing factors of serum neutralizing antibodies among SARS-CoV-2 infected individuals, so as to provide the evidence for developing the health management and COVID-19 vaccination strategy among SARS-CoV-2 infected individuals. Methods: Recovered SARS-CoV-2 infected individuals from January 1st, 2020 to February 10th, 2021 in Zhejiang Province were recruited in March 2021. Participants' demographics, underlying diseases, date of definitive diagnosis and severity of clinical symptoms were collected using questionnaire surveys, and serum neutralizing antibody against SARS-CoV-2 was detected using a fluorescent immunoassay. In addition, factors affecting the seropositivity of neutralizing antibody against SARS-CoV-2 were identified using a multivariable logistic regression model. Results: A total of 559 SARS-CoV-2 infected individuals were enrolled, including 480 confirmed cases and 79 asymptomatic carriers, with an median (interquartile range) age of 47.00 (22.00) years, and all participants had never received COVID-19 vaccination. The median (interquartile range) duration from diagnosis to serum sampling was 387.00 (11.00) days, and the seroprevalence of neutralizing antibody against SARS-CoV-2 was 83.90%. The serum neutralizing antibody against SARS-CoV-2 was all positive 9 months after diagnosis, and the seroprevalence of neutralizing antibody against SARS-CoV-2 appeared no tendency towards a decline with time within 14 months after diagnosis (P>0.05). Multivariable logistic regression analysis showed that women were 1.892 times (95%CI: 1.169-3.064) more likely to produce serum neutralizing antibodies against SARS-CoV-2 than men, and mild, common and severe/critically ill SARS-CoV-2 infected cases were 2.438 (95%CI: 1.305-4.557), 4.481 (95%CI: 2.318-8.663), and 23.525 (95%CI: 2.990-185.068) times more likely to produce serum neutralizing antibodies against SARS-CoV-2 than asymptomatic carrier, respectively. Conclusions The seroprevalence of neutralizing antibody was 100.00% among SARS-CoV-2 infected individuals within 9 months after diagnosis. Individuals' gender and severity of clinical symptoms correlate with the seroprevalence of neutralizing antibody against SARS-CoV-2.

Traditionally, Tripterygium hypoglaucum (Levl.) Hutch (THH) are widely used in Chinese folk to treat rheumatoid arthritis (RA). This study aimed to investigate whether the anti-RA effect of THH is related with the gut microbiota. The main components of prepared THH extract were identified by HPLC-MS. C57BL/6 mice with adjuvant-induced arthritis (AIA) were treated with THH extract by gavage for one month. THH extract significantly alleviated swollen ankle, joint cavity exudation, and articular cartilage destruction in AIA mice. The mRNA and protein levels of inflammatory mediators in muscles and plasma indicated that THH extract attenuated inflammatory responses in the joint by blocking TLR4/MyD88/MAPK signaling pathways. THH extract remarkably restored the dysbiosis of the gut microbiota in AIA mice, featuring the increases of Bifidobacterium, Akkermansia, and Lactobacillus and the decreases of Butyricimonas, Parabacteroides, and Anaeroplasma. Furthermore, the altered bacteria were closely correlated with physiological indices and drove metabolic changes of the intestinal microbiota. In addition, antibiotic-induced pseudo germ-free mice were employed to verify the role of the intestinal flora. Strikingly, THH treatment failed to ameliorate the arthritis symptoms and signaling pathways in pseudo germ-free mice, which validates the indispensable role of the intestinal flora. For the first time, we demonstrated that THH extract protects joint inflammation by manipulating the intestinal flora and regulating the TLR4/MyD88/MAPK signaling pathway. Therefore, THH extract may serve as a microbial modulator to recover RA in clincial practice.ver RA in clincial practice.
Mice ; Animals ; Gastrointestinal Microbiome ; Tripterygium ; Myeloid Differentiation Factor 88/genetics* ; Toll-Like Receptor 4/genetics* ; Mice, Inbred C57BL ; Arthritis, Experimental/drug therapy*