Objective To describe and analyze the epidemiological characteristics of scrub typhus in Huai'an, Jiangsu Province from 2006 to 2024 and explore the long-term incidence trend and distribution of high-risk areas, and to formulate targeted prevention and control strategies. Methods The scrub typhus case report data of Huai'an from 2006 to 2024 in the Chinese Disease Prevention and Control Information System were extracted for descriptive analysis. Results A total of 898 cases of scrub typhus were reported in Huai'an, with an average annual incidence rate of 0.96 per 100 000 from 2006 to 2024. There was a turning point in the incidence trend of scrub typhus in 2011. From 2006 to 2011, the annual percentage change (APC) was 47.09% (95% CI: 7.53 - 859.39), and the upward trend was statistically significant (P < 0.05). From 2012 to 2024, the APC was -2.12% (95% CI: -29.09 - 3.75), and the downward trend was not statistically significant. October and November were the high-incidence months, and the total concentration from 2006 to 2024 was 0.93, indicating that scrub typhus had strict seasonality. The circular distribution method estimated that the peak period of the epidemic was from October 11th to November 25th, and the peak day of incidence was November 3rd. Jinhu County was a high-incidence area. The ratio of male to female cases was 1.03. The age group with the highest reported incidence was 40 to < 80 years old. The occupation with the highest proportion was farmers, accounting for 78.03%. Conclusion From 2006 to 2024, scrub typhus in Huai'an shows a peak every 3 - 4 years. Middle-aged and elderly farmers are the key population at risk, and Jinhu County is a key area. In the future, targeted health education should be carried out to effectively control the prevalence of scrub typhus.

The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL⁺ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL⁺ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.

Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug delivery. However, it remains a challenge to localize and control drug release while retaining macrophage activity and exerting its immunotherapeutic effect. Herein, a localized light-triggered release macrophage cytopharmaceutical (USIP@M) was proposed, which could utilize the tumor targeting and immunotherapy effects of macrophages to reverse the immune suppression of tumor microenvironment (TME). Amphiphilic block copolymers with ultraviolet (UV)-responsive o-nitrobenzyl groups were synthesized and co-loaded with sorafenib (SF), IMD-0354 (IMD), and upconverting nanoparticles (UCNPs), which were then taken up by macrophages, and the targeted delivery of drugs was realized by using the tumor tropism of macrophages. UCNPs converted near-infrared light with strong penetrability and high safety into UV light, which promoted the photoresponsive depolymerization of block copolymers and production of exosomes from USIP@M, accelerated drug efflux and maintained the activity of macrophages. IMD simultaneously polarized carrier macrophages and tumor-associated macrophages to exert the antitumor effect of macrophages, enhance T cell immunity, and alleviate the immunosuppressive state of TME. Synergistically with the chemotherapeutic effect of SF, it could effectively kill tumors. In conclusion, based on the localized light-triggered release strategy, this study constructed a novel macrophage cytopharmaceutical that could localize and control drug release while retaining the activity of macrophages and exerting its immunotherapeutic effect, which could effectively treat solid tumors.

Background The human body is usually exposed to a variety of heavy metals at the same time, and different types and concentrations of heavy metals may have complex interactions during their absorption and metabolism in the human body. Seminal fructose is an important energy source for sperm movement. A large number of studies have shown that metal exposure may impair semen quality, and seminal fructose is an important factor affecting male reproduction, so it is necessary to investigate the relationship between mixed heavy metal exposure and seminal fructose to explore the mechanism of semen quality damage caused by metal exposure. Objective To understand the status of common heavy metal exposure in men of childbearing age in Puyang City, Henan Province, and to study the relationship between mixed exposure to heavy metals and seminal fructose, as well as potential interactions among heavy metals. Methods Volunteers were recruited from the Puyang Maternal and Child Health Hospital Reproductive Center for a cross-sectional survey on general demographic characteristics, smoking, alcohol consumption, and other information. Semen samples were collected to detect 12 metals such as vanadium (V), manganese (Mn), cobalt (Co), nickel (Ni), zinc (Zn), selenium (Se), silver (Ag), cadmium (Cd), barium (Ba), thallium (Tl), iron (Fe), and lead (Pb) in seminal plasma and seminal fructose. After correcting for selected confounding factors, a Bayesian kernel machine regression (BKMR) model was used to evaluate the impact of seminal plasma heavy metal mixed exposure and its interactions on seminal fructose. Results A total of 825 adult males were enrolled. The concentrations in M (P₂₅, P₇₅) of V, Mn, Co, Ni, Zn, Se, Ag, Cd, Ba, Tl, Fe, and Pb in seminal plasma were 0.39 (0.28, 0.54), 12.31 (8.92, 17.52), 0.26 (0.18, 0.38), 5.15 (3.32, 8.64), 182159.80 (121847.80, 199144.50), 13.61 (10.55, 17.68), 0.03 (0.02, 0.04), 0.34 (0.27, 0.46), 8.64 (5.94, 13.43), 0.06 (0.05, 0.08), 168.74 (114.17, 259.45), and 1.69 (1.15, 2.36) μg·L⁻¹ respectively. The Spearman correlation results indicated that there was a negative correlation between V, Mn, Co, Zn, Se, Ba, Tl, or Fe in seminal plasma and seminal fructose (P<0.05), and the values of r (95%CI) were −0.044 (−0.087, −0.001), −0.129 (−0.171, −0.087), −0.055 (−0.099, −0.012), −0.099 (−0.143, −0.056), −0.053 (−0.097, −0.010), −0.068 (−0.111, −0.025), −0.095 (−0.138, −0.052), and −0.082 (−0.125, −0.039), respectively. The results of multiple linear regression indicated that there was a negative correlation between the exposure level of Cd, Mn, Zn, Ag, Ba, Tl, or Fe in seminal plasma and seminal fructose (P<0.05), the values of associated β (95%CI) were −0.551 (−0.956, −0.147), −0.315 (−0.419, −0.212), −0.187 (−0.272, −0.103), −0.161 (−0.301, −0.021), −0.188 (−0.314, −0.062), −1.159 (−2.170, −0.147), and −0.153 (−0.230, −0.076), respectively. The BKMR model analysis showed that seminal fructose level decreased with the increase of plasma metal mixed exposure concentration. Compared with all metal exposure at P₅₀, the seminal fructose level decreased by 0.2374 units when all metal exposure was at P₇₅. Seminal plasma Zn [posterior inclusion probabilities (PIPs)=1.0000] had the strongest effect on seminal fructose, followed by Mn (PIPs=0.5872), Se (PIPs=0.5656), and Ba (PIPs=0.5398). The univariate exposure-response curve showed a negative approximate linear correlations between Ba or Mn and seminal fructose, a positive linear correlation between Se and seminal fructose, and an approximate inverted U-shaped association between Zn and seminal fructose. No significant interaction between studied metals was found. Conclusion Mixed metal exposure may lead to decrease of seminal fructose, in which Zn, Mn, Se, and Ba may play an important role. Mn and Zn exposure may reduce the level of seminal fructose, Se may increase the level of seminal fructose, and there may be a threshold effect between Zn exposure and seminal fructose level. No interaction between different metals on seminal fructose is found.

One of the distinct hallmarks of cancer cells is aerobic glycolysis (Warburg effect). Lactate dehydrogenase A (LDHA) is thought to play a key role in aerobic glycolysis and has been extensively studied, while lactate dehydrogenase C (LDHC), an isoform of LDHA, has received much less attention. Here we showed that human LDHC was significantly expressed in lung cancer tissues, overexpression of Ldhc in mice could promote tumor growth, and knock-down of LDHC could inhibit the proliferation of lung cancer A549 cells. We solved the first crystal structure of human LDHC4 and found that the active-site loop of LDHC4 adopted a distinct conformation compared to LDHA4 and lactate dehydrogenase B4 (LDHB4). Moreover, we found that (ethylamino) (oxo)acetic acid shows about 10 times selective inhibition against LDHC4 over LDHA4 and LDHB4. Our studies suggest that LDHC4 is a potential target for anticancer drug discovery and (ethylamino) (oxo)acetic acid provides a good start to develop lead compounds for selective drugs targeting LDHC4.

Esophageal cancer (EC) is one of the most fatal cancers worldwide. According to GLOBOCAN 2020, it was estimated that there were 600, 000 new EC cases and 540 000 EC deaths, while nearly half of all newly diagnosed cases of EC and associated deaths worldwide occurred in China. The annual incidence and mortality of EC have been reduced in the last 20 years in China. However, the early symptoms and signs of EC are not easily distinguished and the disease tends to be within the middle and late stage of pathogenesis when identified, leading to its low 5-year survival rate. Therefore, it could help effectively reduce the burden of EC by clarifying its etiology and risk factors, as well as taking preventive and early diagnosis measures. This article reviews the epidemiology, etiology, screening and early diagnosis of EC in China, to provide systematic references for EC prevention and control.

Objective To study patient delay and the influencing factors of the elderly patients with pulmonary tuberculosis（PTB），so as to provide evidence for developing effective prevention and control strategies. Methods Derived the information from PTB management information system in 2010-2019 of the tuberculosis patients who were aged 60 years or older in Huai'an City, described and analyzed the influencing factors of patient delay. Results The median time of PTB patients delay in Huaian was 21 day, while the rate was 65.91%. Multivariate logistic regression analysis results showed that compared with permanent residents, city dwellers, the first diagnosis unit specialized hospital, and the patient source referral, the patient delay risks of the floating residents（OR = 2.942 , 95% CI: 2.461-3.518）, the country dwellers（OR = 1.528,95% CI :1.377-1.697）, the first diagnosis unit general hospital（OR = 1.203,95% CI: 1.087-1.333）, and the patient source recommendation （OR = 2.395,95% CI: 1.960-2.928）were higher, Compared with the peasants（OR = 0.315 , 95% CI : 0.213-0.512）, new patients（OR = 0.812 , 95% CI : 0.689-0.974） and sputum smear positive patients（OR = 0.866 , 95% CI : 0.780-0.962）, the patient delay risks of the non-peasants, recurrent patients, and sputum negative patients were lower. Conclusion The patient delay of the elderly patients with pulmonary tuberculosis（PTB）in Huaian was serious, the influencing factors of patient delay were type of household registration, current residence, occupation, type of first-time unit, source of patient , classification of treatment, and the sputum test results.

Mycoplasma pneumoniae pneumonia (MPP) complicated with cerebral venous sinus thrombosis (CVST) is rare.We retrospectively analyzed the clinical data of two patients with refractory mycoplasma pneumoniae pneumonia (RMPP) complicated with CVST who were hospitalized in Xi′an children′s Hospital from December 2018 to April 2019, inquired the relevant literature, analyzed the clinical diagnosis and treatment characteristics, and discussed the diagnosis and treatment measures of RMPP complicated with CVST.Two cases were 6-year-old girls with fever and cough as the main symptoms.After physical examination, the respiratory sounds of the affected lung decreased, and the sounds of phlegm and dampness could be heard in both lungs.Mycoplasma pneumoniae (MP) antibody and RNA were positive.Chest CT showed lobar pneumonia with a large number of pleural effusion.The effect of macrolide antibiotics anti infection treatment was not good.Headache symptoms occurred during the course of the disease, and serum D-dimer increased significantly.Brain MRI showed CVST, including 1 case with lower extremity pain, and B-ultrasound showed right lower extremity arterial embolism.After anti infection, thrombectomy, anticoagulation and symptomatic treatment, 2 cases were discharged.When children with MPP, especially those with RMPP, have extracranial thrombosis and/or neurological symptoms, accompanied by elevated serum D-dimer, the possibility of CVST should be considered, and brain MRI examination should be performed in time to confirm and actively treat, which can reduce or avoid the occurrence of sequelae.Thrombosis may be related to excessive inflammatory reaction and vascular endothelial injury caused by MP infection.

Objective:To understand the infection and distribution of syphilis in hospitalized patients, thus to provide reference for syphilis prevention and control.Methods:TP-ELISA test was used to examine early syphilis antibody, and adopted the TPPA test to validation syphilis antibody, and TRUST was used to determine the titer of syphilis antibody in 80 478 hospitalized patients from January 2015 to November 2017, then the results were retrospectively analyzed.Results:Among 80 478 inpatients, 1 326 cases were positive by TP-ELISA test(1 223 cases positive, 101 cases weak positive and 2 cases negative by TPPA confirmed). The positive rates of TP-ELISA in different years were 1.62%(445/27 394), 1.72%(490/28 412) and 1.58%(389/24 672), respectively, and the difference was not statistically significant( P>0.05). The positive rates of male and female patients were 2.02%(689/33 985) and 1.37%(635/46 479), and the difference was statistically significant(χ 2=52.91, P=0.00). The positive rates of ≤18 years old, >18-59 years old, >59-79 years old and>79 years old were 0.32%(7/2 161), 1.44%(765/53 001), 2.31%(488/21 163) and 1.50%(62/4 153), respectively.The highest proportion of syphilis patients was in the group of >59-79 years old, and the differences were statistically significant compared with the other groups(χ 2=37.08, 67.05, 10.80, all P<0.01). Among the TP-ELISA positive patients, 54.90%(728/1 326) had TRUST titer negative, 36.50%(484/1 326) had titer less than 1∶8, and the others had 8.44%(112/1 326). Conclusion:The incidence of syphilis was higher in males than in females in 80 478 hospitalized patients.The highest positive rate was found in >59-79 years old group, and the number of elderly cases increased rapidly.Therefore, the effective interventions should be developed to control the transmission of syphilis according to the epidemiological features.

Objective To understand the strategy of schistosomiasis elimination and its effects in Jinhu County, Jiangsu Province. Methods The data of schistosomiasis control in Jinhu County at different stages from 1970 to 2017 were collected and analyzed. Results From 1970 to 2017, there were three stages of schistosomiasis control, including transmission control, transmission interruption, and monitoring and elimination stages in Jinhu County. The main measures included Oncomelania hupensis snail control, infectious source control, and health education. A total of area of 290 691.78 hm² was detected in Jinhu County, and the area with snails was 3 420.98 hm². There were 8 729.37 hm² area with snails was controlled. Since 2014, no O. hupensis snails were found. A total of 525 377 person-times were examined for schistosomiasis, with 2 815 schistosomiasis patients identified, and 2 844 person-times were treated by chemotherapy. In addition, 977 cases received the expand chemotherapy. Since 1990, no local schistosome-infected persons were found. In 2017, the awareness rate of schistosomiasis control knowledge and the correct rate of health behavior were increased by 54.59% and 14.23% respectively compared with those in 1992. Conclusions The comprehensive schistosomiasis control measures implemented in Jinhu County at different periods have achieved remarkable outputs and accelerated the schistosomiasis elimination process. However, the precise control measures should be implemented in the future to consolidate the prevention and control achievements.