Effect of immunotherapy-infusion time of day on survival of patients with advanced cancers: a study-level meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become the standard of care for numerous malignancies. Emerging evidence suggests that the time of day (ToD) of ICI administration could impact the outcomes of patients with cancer. The consistency of ToD effects on ICI efficacy awaits initial evaluation. MATERIALS AND METHODS: This meta-analysis integrates progression-free survival (PFS) and overall survival (OS) data from studies with a defined 'cut-off' ToD. Hazard ratios (HRs) [95% confidence interval (CI)] of an earlier progression or death according to 'early' or 'late' ToD of ICIs were collected from each report and pooled. RESULTS: Thirteen studies involved 1663 patients (Eastern Cooperative Oncology Group performance status 0-1, 83%; males/females, 67%/33%) with non-small-cell lung cancer (47%), renal cell carcinoma (24%), melanoma (20%), urothelial cancer (5%), or esophageal carcinoma (4%). Most patients received anti-programmed cell death protein 1 or anti-programmed death-ligand 1 (98%), and a small proportion also received anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) (18%). ToD cut-offs were 13:00 or 14:00 (i.e. ICI median infusion time), for six studies, and 16:00 or 16:30 (i.e. reported threshold for weaker vaccination responses) for seven studies. Pooled analyses revealed that the early ToD groups had longer OS (HR 0.50, 95% CI 0.42-0.58; P < 0.00001) and PFS (HR 0.51, 95% CI 0.42-0.61; P < 0.00001) compared with the late ToD groups. CONCLUSIONS: Patients with selected metastatic cancers seemed to largely benefit from early ToD ICI infusions, which is consistent with circadian mechanisms in immune-cell functions and trafficking. Prospective randomized trials are needed to establish recommendations for optimal circadian timing of ICI-based cancer therapies.

[Molecular detection and phylogenetic analysis of Wolbachia infection in common mosquito species in Henan Province].

OBJECTIVE: To investigate the infection and genotypes of Wolbachia in common mosquito species in Henan Province, so as to provide insights into management of mosquito-borne diseases. METHODS: Aedes, Culex and Anopheles samples were collected from cowsheds, sheepfolds and human houses in Puyang, Nanyang City and Xuchang cities of Henan Province from July to September, 2022, and the infection of Wolbachia was detected. The 16S rDNA and wsp genes of Wolbachia were amplified and sequenced. Sequence alignment was performed using the BLAST software, and the obtained 16S rDNA gene sequence was compared with the sequence of the 16S rDNA gene in GenBank database. In addition, the phylogenetic trees were created based on 16S rDNA and wsp gene sequences using the software MEGA 11.0. RESULTS: A total 506 female adult mosquitoes were collected from three sampling sites in Nanyang, Xuchang City and Puyang cities from July to September, 2022. The overall detection of Wolbachia was 45.1% (228/506) in mosquitoes, with a higher detection rate in A. albopictus than in Cx. pipiens pallens [97.9% (143/146) vs. 50.6% (85/168); χ2 = 88.064, P < 0.01]. The detection of Wolbachia in Cx. pipiens pallens was higher in Xuchang City (96.8%, 62/64) than in Nanyang (15.6%, 7/45) and Puyang cities (27.1%, 16/59) (χ2 = 89.950, P < 0.01). The homologies of obtained Wolbachia 16S rDNA and wsp gene sequences were 95.3% to 100.0% and 81.7% to 99.8%. Phylogenetic analysis based on wsp gene sequences showed Wolbachia supergroups A and B in mosquito samples, with wAlbA and wMors strains in supergroup A and wPip and wAlbB strains in supergroup B. Wolbachia strain wAlbB infection was detected in A. albopictus in Puyang and Nanyang Cities, while Wolbachia strain wPip infection was identified in A. albopictus in Xuchang City. Wolbachia strain wAlbA infection was detected in Cx. pipiens pallens sampled from three cities, and one Cx. pipiens pallens was found to be infected with Wolbachia strain wMors in Nanyang City. CONCLUSIONS: Wolbachia infection is commonly prevalent in Ae. albopictus and Cx. pipiens pallens from Henan Province, and Wolbachia strains wAlbB and wAlbA are predominant in Ae. albopictus, while wPip strain is predominant in Cx. pipiens pallens. This is the first report to present Wolbachia wMors strain infection in Cx. pipiens pallens in Henan Province.

[Independent and joint effect of chronotype and sleep duration on self-rated health in medical students].

Objective: To investigate the independent and joint effects of chronotype and sleep duration on self-rated health in medical students. Methods: A cross-sectional study was conducted in 1 526 medical students selected through proportional stratified cluster random sampling from a medical university in Zhejiang province. A questionnaire survey was conducted to collect the information about their basic demographic characteristics, chronotype, sleep duration, and other lifestyle factors such as midnight snack, sedentary behavior, physical activity, meal time, and self-rated health. The independent and joint effects of chronotype and sleep duration on self-rated health were assessed by logistic regression model after controlling for confounding variables. Results: The numbers of the students with evening chronotype, neutral chronotype, and morning chronotype were 664 (43.5%), 442 (29.0%), and 420 (27.5%), respectively. Among the medical students, 42.8% (653) had poor self-rated health. Compared with those with the morning chronotype, the adjusted ORs for those with neutral chronotype and evening chronotype were 1.69 (95%CI: 1.23-2.31) and 2.43 (95%CI: 1.81-3.26), respectively, trend test P<0.001. Compared with those with sleep duration of 8 h or above per night, the adjusted ORs for those with sleep duration of 7 and ≤6 h per night were 1.40 (95%CI: 1.07-1.84) and 2.38 (95%CI: 1.69-3.37), respectively, trend test P<0.001. In the joint effect, compared with those with the morning chronotype and sleep duration of 8 h or above per night, the adjusted OR for those with evening chronotype and sleep duration of ≤6 h per night was 6.53 (95%CI: 3.53-12.09). Conclusions: Both evening chronotype and insufficient sleep were associated with increased odds of poor self-rated health in medical students, and they had joint effects. Therefore, it is necessary to promote early to bed, early to rise and adequate sleep in medical student to maintain their health.

[Outcome comparison between LSA complete reconstruction and partial coverage with endovascular technique for patients with Stanford type B aortic dissection].

Objectives: To compare the short-term outcomes of branched stentgrafts for left subclavian artery (LSA) revascularization or partial LSA coverage without reconstruction in the treatment of type B aortic dissection with proximal tear close to LSA. Methods: A total of 125 type B aortic dissection patients were treated with thoracic endovascular aortic repair (TEVAR) in Xinqiao Hospital of the Army Medical University from January 2019 to March 2021. Their medical records were reviewed and the outcomes were followed up. According to the different treatment methodologies, the patients were divided into complete LSA coverage with reconstruction group (n=25) and partial LSA coverage without reconstruction group (n=100). The data of baseline characteristics, clinical outcomes, and incidence of postoperative in-hospital adverse events were collected and compared between the two groups. The adverse events during one-year follow-up were also compared between the two groups. Kaplan-Meier analysis and log-rank test were used to compare the cumulative survival rates between groups. Results: Compared with partial LSA coverage group, distance of proximal tear to LSA((8.69±2.32)mm vs. (13.77±1.71) mm) was shorter, in-hospital expenses[175 400(166 000-189 900) yuan vs. 143 700 (138 100-151 800) yuan] was higher, average length of stent [200.00 mm vs. 150.00 (150.00-150.00) mm] and operation time [155.00 (140.00-170.00) min vs. 95.00 (80.00-100.00) min] were longer, and volumes of contrast agent [300.00 (200.00-300.00) ml vs. 200.00 (200.00-300.00) ml] (P<0.05) were higher for patients in the complete LSA coverage with reconstruction group. The incidence of post-operative fever was significantly higher in complete LSA coverage with revascularization group than that in partial LSA partial coverage with reconstruction group (56% vs. 25%, P=0.003). There was no significant difference in the incidences of all-cause death, stroke, endoleak, paraplegia, and LSA branch vessel occlusion between the two groups during follow-up. Kaplan-Meier analysis showed that there was no significant difference in the cumulative survival rates between the two groups (log-rank test: P=0.572 5). Conclusion: The TEVAR with complete LSA revascularization or partial LSA coverage without reconstruction for type B aortic dissection close to LSA are safe and effective with high success rates. There is no significant difference between these two techniques in short-term outcomes.

[Epidemiological investigation on a visceral leishmaniasis case in Zhengzhou City of Henan Province].

OBJECTIVE: To perform an epidemiological investigation on a case with visceral leishmaniasis in Zhengzhou City, Henan Province, and to identify the source of infection, so as to illustrate the transmission chain and assess the risk of local leishmaniasis transmission. METHODS: The medical data were collected from a case with visceral leishmaniasis in Zhengzhou City, and the patient's bone marrow smears were detected by microscopy. Serum anti-Leishmania antibody test and PCR assay were performed among high-risk residents and all dogs in the village where the patient lived. Sandflies were captured using light traps and artificial traps, and the captured female Phlebotomus chinensis was subjected to PCR assay. The internal transcribed spacer 1 (ITS1) gene was amplified with a nested PCR assay using the genomic DNA extracted from visceral leishmaniasis patients, positive dogs and sandflies, and the sequences were aligned with those download from NCBI. In addition, a phylogenetic tree was created based on the ITS1 gene. RESULTS: The visceral leishmaniasis patient had recurrent irregular fever, reduced complete blood counts, low hemoglobin, and a large number of Leishmania amastigotes in bone marrow smears, and was therefore diagnosed as visceral leishmaniasis. Both rk39 rapid diagnostic test and PCR assay tested negative among 324 residents living neighboring the patient's residence, while 21.39% (43/201) dogs were positive for rk39 rapid diagnostic test and 13.93% (28/201) positive for PCR assay. There were 17 female Ph. chinensis tested positive for Leishmania (0.82%) by PCR assay, and the ITS gene sequences from visceral leishmaniasis patients, positive dogs and sandflies shared a 100% homology with L. infantum. The Leishmania species was therefore characterized as L. infantum. CONCLUSIONS: L. infantum infection occurs in visceral leishmaniasis patients, dogs and sandflies in Zhengzhou City, indicating a complete transmission chain and a high transmission risk of visceral leishmaniasis by L. infantum. Intensified control measures are required to prevent local transmission of leishmaniasis in Zhengzhou City.

[Susceptibility of Anopheles sinensis to insecticides in Puyang City, Henan Province].

OBJECTIVE: To investigate the susceptibility of Anopheles sinensis to malathion, deltamethrin and lambda-cyhalothrin in Puyang City, Henan Province, so as to provide the scientific basis for local malaria vector control. METHODS: An. sinensis was captured from Puyang County, Puyang City of Henan Province in September 2018 and July 2020, and the susceptibility of field captured An. sinensis to malathion, deltamethrin and lambda-cyhalothrin was tested using the filter-paper bioassay recommended by WHO. The insecticide resistance level was assessed based on the WHO criteria. RESULTS: In 2018 and 2010, the half knock-down times (KT50) of malathion were 91.08 min and 40.95 min for An. sinensis, with knock-down rates of 37.50% and 60.87% 60 min post-exposure to malathion and 24-hour mortality rates of 90.91% and 100%, respectively, and the insecticide resistance levels were moderately resistant (M) and susceptible (S). The KT50 of deltamethrin were 415.56 min and 341.19 min for An. sinensis in 2018 and 2020, with knock-down rates of 22.92% and 16.98% 60 min post-exposure to malathion and 24-hour mortality rates of 22.92% and 16.98%, and the insecticide resistance levels were all resistant (R). The KT50 of lambda-cyhalothrin were 164.22 min and 236.22 min for An. sinensis in 2018 and 2020, with knock-down rates of 30.39% and 38.30% 60 min postexposure to malathion and 24 h mortality rates of 19.60% and 21.28%, respectively, and the insecticide resistance levels were all R. CONCLUSIONS: An. sinensis is relatively susceptible to malathion but has developed high-level resistance to deltamethrin and lambda-cyhalothrin in Puyang City, Henan Province..

[Risk factors of perivalvular leakage after transcatheter aortic valve replacement with Venus-A valve].

Objective: To investigate the risk factors of moderate or severe perivalvular leakage (PVL) after transcatheter aortic valve replacement (TAVR) with Veneus-A valve. Methods: This study was a single-center case-control study. The clinical data of patients with severe aortic stenosis, who underwent TAVR in the Department of Cardiology of Second Affiliated Hospital of Army Medical University from October 2017 to January 2021, were analyzed. According to the circumferential extent of prosthetic valve paravalvular regurgitation measured by transthoracic echocardiography before discharge (patients who died in hospital were referred to transesophageal echocardiography results after valve implanted), the patients were divided into moderate or severe PVL group and mild or non-PVL group. The clinical features, CT scan and analysis results of aortic root were compared between the two groups. Multivariate logistic regression analysis was used to identify the independent risk factors of postoperative moderate or severe PVL, and receiver operating characteristic (ROC) curve was used to explore the predictive value of related factors. Results: Eighty-two patients (mean age: (70.9±6.5) years, 46 males) were included in the analysis, there were 16 patients in the moderate or severe PVL group and 66 patients in the mild or non-PVL group. The proportion of male gender, depth of valve implantation, size of valve annulus and left ventricular outflow tract (LVOT), and coverage index of LVOT were significantly higher in moderate or severe PVL group than those in mild or non-PVL group (Pall<0.05). As there was a strong collinearity among the valve annular short diameter, LVOT short diameter and LVOT coverage index (partial correlation coefficient R 0.251-0.779, P<0.05), these parameters were not entered in regression model. Multivariate logistic regression analysis showed that valve implantation depth(OR=1.239,95%CI 1.036-1.442,P=0.023), aortic angulation(OR=1.128, 95%CI 1.044-1.312,P=0.038)and LVOT tract coverage index (OR=1.123, 95%CI1.003-1.315, P=0.032) were independent risk factors for moderate or severe PVL after TAVR. The ROC curve showed that the valve implantation depth could predict the occurrence of moderate or severe PVL after TAVR (area under ROC curve (AUC)=0.697, 95%CI 0.554-0.851, P=0.039). Conclusion: Among patients with severe aortic stenosis who undergo TAVR with Venus-A valve, the implantation depth, aortic angulation and LVOT coverage index are independent risk factors of moderate/severe PVL after TAVR, among which valve implantation depth could be used to predict the occurrence of moderate/severe PVL after TAVR.

[Prevalence of intestinal protozoan infections among rural children in Henan Province from 2014 to 2015].

OBJECTIVE: To investigate the prevalence and influencing factors of intestinal protozoan infections among rural children in Henan Province. METHODS: A total of 104 survey sites were sampled from 35 counties (cities) in Henan Province using the stratified cluster sampling method to investigate the prevalence of intestinal protozoan infections among rural children from 2014 to 2015. The trophozoites and cysts of intestinal protozoa were identified using the iodine staining method and the physiological saline direct smear method (one detection for one stool sample). The prevalence of intestinal protozoan infections was compared among rural children with different characteristics, and the factors affecting intestinal protozoan infections among rural children were identified. RESULTS: The overall prevalence of intestinal protozoan infections was 0.60% (40/6 771) among rural children in Henan Province from 2014 to 2015. There were 7 species of intestinal protozoa identified, and there was no species-specific prevalence (χ2 = 37.732, P = 0.000). No significant differences were found in prevalence of intestinal protozoan infections among rural children in terms of gender (χ2 = 1.793, P = 0.181), age (χ2 = 1.443, P = 0.486), occupation (χ2 = 0.219, P = 0.896) or ecological region (χ2 = 1.700, P = 0.637). In addition, terrain (χ2 = 2.311, P = 0.510), economic level (χ2 = 4.322, P = 0.229), source of drinking water (χ2 = 0.731, P = 0.393), eating raw vegetables (χ2 = 1.134, P = 0.287) and deworming (χ2 = 1.089, P = 0.297) had no remarkable effects on the prevalence of intestinal protozoan infections among rural children in Henan Province; however, the prevalence of intestinal protozoan infections varied significantly among rural children living in regions with different coverage of non-harmless toilets (χ2 = 10.050, P = 0.018). CONCLUSIONS: The prevalence of intestinal protozoan infections is low among rural children in Henan Province.

[Epidemiology and the risk factors of myopia among children and youths in Yunnan province].

Objective: The purpose of the study was to describe the prevalence of myopia and to explore the associated factors of myopia among Han and Yi students aged 5-16 years in Yunnan province, China. Methods: A total of 5 971 Han and Yi students were included in the data analysis from the Yunnan eye study which was conducted from March to August, 2014. Information regarding demographic factors, socioeconomic status and lifestyle-related exposures were collected by per-designed questionnaires. The ophthalmic examinations including distance visual acuity, anterior segment examination, cycloplegic auto-refraction, and ocular motility examination were conducted. Logistic regression models were fitted to estimate the risk factors for myopia. Results: The age of 5 971 subjects was (10.68±2.24)years old, and the total prevalence of myopia and high myopia was 48.05% and 0.59%. Myopia prevalence was found to be higher in Han students compared with Yi ethnicity (50.20% vs. 47.10%,P=0.029). In multivariate analysis, the occurrence of myopia was associated with age (OR=1.28, 95%CI: 1.25-1.31), girls (OR=1.32, 95%CI: 1.18-1.48), increasing reading and writing time per day (OR=1.13, 95%CI: 1.07-1.20), having self-reported myopia among friend(s) (OR=1.15, 95%CI: 1.02-1.29), having myopic father (OR=1.38, 95%CI: 1.06-1.79), having myopic mother (OR=1.43, 95%CI: 1.12-1.83) and higher educated mother (OR=1.24, 95%CI: 1.03-1.51). Conclusions: We observed a high prevalence of myopia among Mangshi students. The presence of myopia was associated with increasing age, girls, increasing reading and writing time per day, having self-reported myopia among friend(s), having myopic father, having myopic and high educated mother.

LncRNA XIST promotes migration of Wilms' tumor cells through modulation of microRNA-193a-5p.

OBJECTIVE: The aim of this study was to investigate long non-coding RNA (lncRNA) XIST expression in Wilms' tumor (WT) and to further explore its relationship with clinical features and prognosis of WT patients. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was carried out to examine the expression level of XIST in tumor tissue samples and paracancerous ones collected from 43 patients with renal cell carcinoma, and the interplay between XIST expression and clinical indicators, as well as prognosis of patients was analyzed. Meanwhile, XIST level in the nephroblast cancer cell line was further confirmed by qRT-PCR. In addition, XIST knockdown model was constructed using lentivirus in the WT cell lines, including HFWT and 17-94, and the influence of XIST on WT cell functions was analyzed through transwell assay. Finally, we investigated whether lncRNA XIST plays a role in the progression of WT by modulating microRNA-193a-5p. RESULTS: In this research, qRT-PCR results revealed a significantly higher expression of lncRNA XIST in tumor tissue specimens of patients with renal cell carcinoma than that in adjacent ones. Compared with patients with low expression of lncRNA XIST, those with high XIST expression had a higher incidence of distant metastasis and a lower overall survival rate. Compared with the negative control group, the metastatic ability of WT cells in the lncRNA XIST knockdown group was markedly weakened. In addition, the results of qPCR showed that mRNA expression of lncRNA XIST and microRNA-193a-5p were negatively correlated in renal cell carcinoma tissue specimens. At the same time, silencing microRNA-193a-5p reversed the reduced metastasis ability of WT cells induced by knockdown of XIST. CONCLUSIONS: LncRNA XIST expression is dramatically enhanced in WT tissues and cell lines, which is closely associated with the incidence of distant metastasis and patients' poor prognosis. In addition, we demonstrated that lncRNA XIST may accelerate the malignant progression of WT via inhibiting microRNA-193a-5p.

[Diagnosis of imported malaria cases in Henan Province from 2015 to 2019].

OBJECTIVE: To analyze the diagnosis of imported malaria cases in Henan Province from 2015 to 2019, so as to provide the evidence for malaria surveillance during the post-elimination stage. METHODS: The data pertaining to malaria cases in Henan Province from 2015 to 2019 were extracted via the web-based Chinese Information System for Infectious Diseases Control and Prevention and the Parasitic Diseases Information Reporting Management System (PDIRMS) of Chinese Center for Disease Control and Prevention, and the diagnostic methods, diagnostic institutions and diagnostic time of imported malaria cases were analyzed. RESULTS: A total of 952 imported malaria cases were reported in Henan Province during the period from 2015 through 2019, and all cases were laboratory-confirmed. The positive rate of malaria rapid diagnostic tests (RDTs) was 98.61% (779/790), which was significantly greater than that (94.22%, 897/952) of microscopic examinations (χ2 = 22.773, P < 0.05). The proportion of imported malaria cases diagnosed in medical institutions increased from 65.22% (120/184) in 2015 to 81.50% (185/227) in 2019. Among the 238 imported malaria cases diagnosed in centers for disease control and prevention (CDC), 71.01% (169/238) were diagnosed in county-level CDC, and among the 704 cases diagnosed in medical institutions, only 8.38% (59/704) were diagnosed at county-level medical institutions. The median time from onset to definitive diagnosis of malaria was 3 days, and the median duration between onset and initial diagnosis of malaria was 1 day. The duration between initial diagnosis and definitive diagnosis of malaria varied significantly among years (χ2 = 24.956, P < 0.05), and the interquartile range from initial diagnosis to definitive diagnosis reduced from 4 days in 2016 to 2 days in 2019. In addition, the median time from initial diagnosis to definitive diagnosis was significantly longer in severe falciparum malaria cases than in non-severe falciparum malaria cases (2 days vs. 1 day; Z = 7.557, P < 0.05). CONCLUSIONS: Medical institutions play a more and more important role in the identification and surveillance of malaria cases; however, the diagnostic capability of malaria remains low in county-level medical institutions. The diagnostic awareness and capability of county-level medical institutions requires to be improved, in order to play their roles as sentinel hospitals in the malaria surveillance during the post-elimination stage.

[Efficacy of esophageal cancer screening program on population at high risk: a survey carried out in people aged 40-69 years in Yangzhong, Jiangsu province].

Objective: To understand the incidence of esophageal cancer in population at high risk in Yangzhong of Jiangsu province. Methods: Cluster random sampling method was conducted to select several natural villages from the high risk area of esophageal cancer in Yangzhong during 2011-2017. Local residents aged 40-69 years were selected as the target population and a total of 14 687 persons were diagnosed esophageal cancer by endoscopy and pathology. Results: Precancerous lesions were detected in 341 persons, with the detection rate as 2.32% (341/14 687). Among them, there were 234 (1.59%) cases with mild and 107 (0.73%) cases with moderate esophageal hyperplasia. There were 77 positive cases with esophageal hyperplasia and the detection rate was 0.52%. Among these positive cases, 41 showed severe esophageal hyperplasia/carcinoma in situ (0.28%), with another 19 as early esophageal cancer (0.13%) and 17 with invasive carcinoma (0.12%). The overall early detection rate of positivity through active screening was 77.92% (60/77), with trends of upwarding and then downwarding. The detection rate of esophageal lesions in men was higher than that in women (P<0.05), but without significant gender specific differences seen in the detection rates of early esophageal cancer or invasive carcinoma (P>0.05). The detection rates of all lesions other than invasive carcinoma, gradually increased with age (P<0.05). The detection rate of invasive carcinoma reached the highest (0.39%, 10/2 547) in the age group of 60-years and slightly decreased in the age group of 65-years old. Conclusions: Considerable numbers of patients with cancer and precancerous lesions in groups at high-risk can be found through the screening program for esophageal cancer, suggesting that the screening program is of great significance in improving the survival rate and quality of life. Attention should be paid to men, with elderly groups in particular, at high-risk in order to increase the detection rate of early cases.

[Epidemic status of malaria and progress of malaria elimination in Henan Province, 2018].

OBJECTIVE: To understand the epidemic status of malaria and progress of malaria elimination in Henan Province in 2018, so as to provide the scientific evidence for formulating the control strategy of malaria. METHODS: All data pertaining to the epidemic status of malaria and malaria case were captured from Henan Province in 2018, and the epidemic status of malaria and the diagnosis and treatment of malaria cases were analyzed using a descriptive epidemiological method. RESULTS: A total of 174 malaria cases were reported in Henan Province in 2018, with a male-to-female ratio of 33.8∶1. The cases were predominantly found at 30- and 40- years, and farmer was the highest-risk population. All cases were imported for overseas countries and 96.55% (168/174) were from Africa. The cases were reported across 17 cities of the province, and 63.22% (110 cases) were detected in 4 cities of Zhengzhou, Luoyang, Xuchang and Puyang. Both the median duration from onset to initial admission and the median time from the initial admission to definitive diagnosis were 1 d. There were 6 cases (3.45%) with more than 7 days to visit a doctor, and there were 13 cases (7.47%) with definitive diagnosis of over 7 days (delay in definitive diagnosis). All malaria cases were reported within 24 h, and 98.28% (171/174) completed case investigations within 3 d. All 18 cities had achieved malaria elimination by December 2018. CONCLUSIONS: All malaria cases reported in Henan Province in 2018 are imported from overseas countries. Intensifying malaria surveillance among returnees from Africa and Southeast Asia and timely identification and treatment of imported malaria cases are required to prevent the development of secondary malaria cases, so as to ensure the achievement of malaria elimination in Henan Province on schedule.

Downregulated long noncoding RNA LUCAT1 inhibited proliferation and promoted apoptosis of cardiomyocyte via miR-612/HOXA13 pathway in chronic heart failure.

OBJECTIVE: Long non-coding RNAs (lncRNAs) have been reported to play important roles in numerous kinds of cardiovascular disease, including chronic heart failure (CHF). In this study, we mainly focused on investigating the potential roles of lncRNA LUCAT1 patients with CHF. PATIENTS AND METHODS: RT-PCR was used to detect the expressions of LUCAT1 and miR-612 in serum samples of CHF patients (n=60) and healthy volunteers. Relationships between the expressions of LUCAT1 and miR-612, LUCAT1 and overall survival (OS) were analyzed using the Kaplan-Meier method. Si-LUCAT1 and miR-612 mimic were constructed and respectively transfected into AC16 cells to explore the functions of LUCAT1 and miR-612. Cell proliferation abilities were detected by CCK-8 assay AC16 cells. Cell apoptotic rates were measured by flow cytometry (FACS) analysis. Western blot (WB) was performed to detect the protein levels of HOXA13, Bcl-2, Bax, Bad and Cleaved Caspase3. In addition, luciferase gene reporter assay was used to prove the relationships between LUCAT1 and miR-612, miR-612 and HOXA13. RESULTS: Firstly, we found that LUCAT1 was decreased for 1.7 folds in CHF patients, which was correlated with poor prognosis patients. LUCAT1 repression inhibited cell proliferation and promoted cell apoptosis in human cardiomyocyte cell line AC16 cells. Furthermore, we found that miR-612 was increased for 2.0 folds in CHF patients, which was negatively interacted with LUCAT1 expression. Luciferase gene reporter assay demonstrated that LUCAT1 could directly bind with miR-612 in AC16 cells. Moreover, miR-612 overexpression also inhibited cell proliferation and promoted cell apoptosis in AC16 cells. Luciferase reporter assay indicated that miR-612 could directly target at HOXA13 in AC16 cells, which was associated with cell proliferation and apoptosis. Finally, miR-612 inhibitor was transfected into AC16 cells with si-LUCAT1. The results showed that the inhibited cell proliferation and promoted cell apoptosis were reversed, which confirmed that LUCAT1 repression inhibited cell proliferation and promoted apoptosis via miR-612/HOXA13 axis in CHF patients. CONCLUSIONS: According to the above results, our study revealed that LUCAT1 was decreased in CHF patients, which was correlated with poor prognosis of CHF patients. Furthermore, the downregulation of LUCAT1 inhibited cell proliferation and promoted cell apoptosis via targeting miR-612/HOXA13 axis. Our results elucidated a potential mechanism underlying cardiomyocyte apoptosis, which might be used as a promising prognostic marker and a potential target for CHF patients.

Genetic variants in the folate metabolic pathway genes predict cutaneous melanoma-specific survival.

BACKGROUND: Folate metabolism plays an important role in DNA methylation and nucleic acid synthesis and thus may function as a regulatory factor in cancer development. Genome-wide association studies (GWASs) have identified some single-nucleotide polymorphisms (SNPs) associated with cutaneous melanoma-specific survival (CMSS), but no SNPs were found in genes involved in the folate metabolic pathway. OBJECTIVES: To examine associations between SNPs in folate metabolic pathway genes and CMSS. METHODS: We comprehensively evaluated 2645 (422 genotyped and 2223 imputed) common SNPs in folate metabolic pathway genes from a published GWAS of 858 patients from The University of Texas MD Anderson Cancer Center and performed the validation in another GWAS of 409 patients from the Nurses' Health Study and Health Professionals Follow-up Study, in which 95/858 (11·1%) and 48/409 (11·7%) patients died of cutaneous melanoma, respectively. RESULTS: We identified two independent SNPs (MTHFD1 rs1950902 G>A and ALPL rs10917006 C>T) to be associated with CMSS in both datasets, and their meta-analysis yielded an allelic hazards ratio of 1·75 (95% confidence interval 1·32-2·32, P = 9·96 × 10-5 ) and 2·05 (1·39-3·01, P = 2·84 × 10-4 ), respectively. The genotype-phenotype correlation analyses provided additional support for the biological plausibility of these two variants' roles in tumour progression, suggesting that variation in SNP-related mRNA expression levels is likely to be the mechanism underlying the observed associations with CMSS. CONCLUSIONS: Two possibly functional genetic variants, MTHFD1 rs1950902 and ALPL rs10917006, were likely to be independently or jointly associated with CMSS, which may add to personalized treatment in the future, once further validated. What is already known about this topic? Existing data show that survival rates vary among patients with melanoma with similar clinical characteristics; therefore, it is necessary to identify additional complementary biomarkers for melanoma-specific prognosis. A hypothesis-driven approach, by pooling the effects of single-nucleotide polymorphisms (SNPs) in a specific biological pathway as genetic risk scores, may provide a prognostic utility, and genetic variants of genes in folate metabolism have been reported to be associated with cancer risk. What does this study add? Two genetic variants in the folate metabolic pathway genes, MTHFD1 rs1950902 and ALPL rs10917006, are significantly associated with cutaneous melanoma-specific survival (CMSS). What is the translational message? The identification of genetic variants will make a risk-prediction model possible for CMSS. The SNPs in the folate metabolic pathway genes, once validated in larger studies, may be useful in the personalized management and treatment of patients with cutaneous melanoma.

[Epidemiological characteristics of malaria in Henan Province from 1950 to 2019].

OBJECTIVE: To analyze the epidemiological characteristics of malaria in Henan Province from 1950 to 2019, so as to provide the scientific evidence for consolidating malaria elimination achievements in the province. METHODS: The epidemiological situation of malaria and demographic data in Henan Province from 1950 to 2019 were collected, and the statistical analyses were performed using a descriptive epidemiological method. The spatial temporal distribution of malaria cases was identified using the software ArcGIS version 10.3. RESULTS: During the period from 1950 through 2019, the progress of malaria elimination was divided into 4 stages in Henan Province, including the baseline-survey and key-control stage, morbidity-control and incidence-reduction stage, basic-eradication and achievement-consolidation stage and elimination stage. The spatial distribution of malaria cases shifted from south of the Huai River and the plain regions between the Yellow River and Taihang Mountain to the Huang-Huai-Hai Plain and Nanyang Basin, then was concentrated in eastern part of southern Huai River where Anopheles anthropophagus was distributed, and finally was gradually under control following malaria outbreak in Eastern Henan Plain. In addition, the species of Plasmodium changed from P. vivax, P. falciparum and P. malariae co-endemics to a single P. vivax infection, and the current co-endemics of 5 invasive malaria parasites, and the malaria vectors shifted from co-existence of Anopheles sinensis and An. anthropophagus to An. sinensis alone. CONCLUSIONS: There has been a large change in the epidemiological characteristics of malaria in Henan Province from 1950 to 2019. Although malaria has been eliminated in Henan Province, the consolidation of the malaria elimination achievements remain a great challenge due to overseas imported malaria.

[Cost-effectiveness and cost-benefit analysis of upper gastrointestinal cancer screening in Yangzhong City, Jiangsu Province, from 2009 to 2015].

Objective: To evaluate the effectiveness and benefit of the upper gastrointestinal cancer screening in Yangzhong city, Jiangsu province, from 2009 to 2015. Methods: From 2009 to 2015, 31 natural villages with high-incidence of upper gastrointestinal cancer were selected from Baqiao town, Youfang town and Xinglong sub-district in Yangzhong city. 13 776 residents aged 40 to 69 years old were recruited and screened for upper gastrointestinal cancer by using endoscopic examination and pathological diagnosis. Two economic evaluation methods, cost-effectiveness analysis and cost-benefit analysis, were performed to evaluate the current screening schemes. Results: The mean age of all respondents were (53.60±8.14) years old and the males accounted for 43.64% (6 012). A total of 502 cases of upper gastrointestinal tract lesions were detected, including 100 cases of cancer (62 cases of esophagus, gastric/cardiac early stage cancer, 38 cases of advanced stage cancer), 38 cases of severe esophageal hyperplasia/carcinoma in situ, and 15 cases of high-grade intraepithelial neoplasia in stomach/cardia, the detection rate was 0.73%, 0.28% and 0.11%, respectively; the early diagnosis rate was 75.16% (115/153). The cost of a precancerous lesion, a case diagnosed at the early stage and a positive case identified through the upper gastrointestinal cancer screening in Yangzhong City was 10 037.17, 30 460.64 and 22 895.25 RMB, respectively. The early detection cost index from 2009 to 2015 was 0.52, 0.56, 0.48, 0.48, 0.21, 0.30, and 0.26, respectively. The effectiveness-cost ratio from 2009 to 2015 was 3.41, 2.77, 2.66, 2.58, 4.99, 3.12, and 3.48, respectively. Conclusions: The project of early diagnosis and treatment of upper gastrointestinal tract cancer in Yangzhong city has achieved good results and benefits.

[Prevalence and influencing factors of intestinal parasitic diseases among rural children in Henan Province].

OBJECTIVE: To understand the epidemic status and influencing factors of intestinal parasitic diseases among rural children in Henan Province. METHODS: According to the Scheme for The National Survey on Current Status of Major Human Parasitic Diseases in China, the survey counties were selected based on the ecological zones and economic levels in Henan Province between 2014 and 2015. Then, the included counties were stratified according to the topography and economic levels. A township was randomly sampled from each stratum, and a village was randomly sampled from each township as the study site. Finally, a total of 104 study sites from 35 counties were enrolled for the survey of intestinal parasitic diseases in children. At least 250 fresh stool samples were collected from each study site for detection of intestinal helminth eggs with the Kato-Katz technique, for the identification of Necator americanus and Ancylostoma duodenale with the fecal culture method, and for the detection of intestinal protozoa trophozoite and cyst with the physiological saline smear and iodine staining techniques. In addition, the Enterobius vermicularis and tapeworm eggs were detected in children aged 3 to 6 years using the adhesive cellophane-tape perianal swab method. RESULTS: The overall prevalence of intestinal parasitic infections was 3.21% (214/6 671) among rural children in Henan Province, and the prevalence of intestinal helminthes (2.62%, 175/6 671) was higher than that of intestinal protozoa (0.60%, 40/6 671). A total of 12 species of intestinal parasites were found, including 4 nematodes species, one trematode species, and 7 protozoa species, and the highest infection was seen in E. vermicularis (2.47%, 161/6 671). Among the four ecological zones in Henan Province, the greatest prevalence of intestinal parasitic infections was detected among children in the Qinba Mountain Ecological Zone (5.85%, 90/1 538). There was no gender-specific difference in the prevalence of intestinal parasitic infections in children (P > 0.05); however, there were age- (χ2 = 32.762, P < 0.05) and education level-specific differences in the prevalence of intestinal parasitic infections in children (χ2 = 67.507, P < 0.05), with the greatest prevalence of E. vermicularis infection seen in all species of intestinal parasites in children at all age groups. Multivariate non-conditional logistic regression analysis showed that high education level, high coverage of harmless toilets, drinking tap water and deworming were protective factors for intestinal parasitic infections in children in Henan Province. The overall prevalence of intestinal parasitic infections appeared a tendency towards a gradual decline among children in Henan Province as compared to the previous two surveys. CONCLUSIONS: The overall prevalence of intestinal parasitic infections shows a tendency towards a remarkable decline among children in Henan Province. E. vermicularis infection should be given a priority for future parasitic disease control activities among rural children in Henan Province.