Objective To construct an index system for assessment of schistosomiasis transmission risk following natural disasters such as rainstorms, floods, earthquakes, mudslides, and landslides, so as to provide insights into rapid identification of schistosomiasis transmission risk post-disasters and formulation of targeted schistosomiasis control strategies. Methods An initial framework for the index system for assessment of schistosomiasis transmission risk following natural disasters was drafted through literature review, brainstorming, and focus group discussions. Two rounds of expert correspondence consultations were conducted using the Delphi method to refine and finalize the system, and the degrees of expert activeness, authority and endorse ment, and consensus were evaluated. In addition, the weights of each index were calculated using the analytic hierarchy process. Results A total of 18 experts participated in the consultation. The expert positive coefficients were 100.00% and 94.44% for two rounds of consultations, with authority coefficients of 0.92 and 0.94, respectively. The coefficients of coordination on the index importance, rationality and operability were 0.209, 0.185, 0.222 and 0.407, 0.214, 0.257 for two rounds of consultations, respectively, and all consistency tests were statistically significant (χ² = 246.771 to 505.278, all P values < 0.001). Following two rounds of expert consultations, an index system consisting of 6 first-level indicators, 15 second-level indicators, and 49 third-level indicators was ultimately constructed. In terms of first-level indicators, “disaster situation”, “previous epidemics”, “healthcare guarantee”, “response capacity” and “emergency recovery” had the highest weights, each at 18.18%. Regarding second-level indicators, “Schistosoma japonicum infections in animals”, “S. japonicum infections in snails” and “medical treatment” had the highest weights, each at 7.35%. In terms of third-level indicators, ten items had the highest weights, including “identification of schistosomiasis cases”, “detection of S. japonicum infections in wild feces”, “detection of S. japonicum infections in snails”, “reserves of schistosomiasis diagnostic/testing reagents and consumables”, “reserves of chemotherapy agents for human and animal schistosomiasis”, “reserves of cercariacides”, “periodical surveillance on schistosomiasis”, “identification of schistosomiasis transmission risk and timely response”, “normal provision of diagnosis and treatment services” and “post-disaster schistosomiasis surveillance”, each at 2.40%. Conclusion A scientific, systematic, and practical index system has been constructed for assessment of schistosomiasis transmission risk following natural disasters, which may provide insights into rapid post-disaster identification of schistosomiasis transmission risk, formulation of targeted schistosomiasis control strategies and optimization of resource allocation.

Sichuan Province is a hilly schistosomiasis-endemic province in China with the highest endemicity and largest coverage. During the period of more than 70 years of integrated control, there are five distinct phases of schistosomiasis control in Sichuan Province, including baseline investigation, Oncomelania hupensis snail control, chemotherapy for both humans and livestock, management of source of Schistosoma japonicum infections, and sustained control and intensified surveillance and early warning, and a package of key interventions are implemented, including environmental modification, snail control with chemical treatment, large-scale chemotherapy for humans and livestock, management of source of S. japonicum infections, intensified integrated control, establishment of an early warning and surveillance system. As a result, schistosomiasis has been eliminated across all 63 disease-endemic counties (cities, districts) in Sichuan Province by June 2025. Government-led multi-sectoral collaborations, science and technology-supported precision control strategies, and a sustainable control model tailored to the ecological and socio-economic conditions in endemic regions are essential to achieving the target of schistosomiasis elimination in Sichuan Province.

Objective To investigate the effectiveness of the integrated schistosomiasis control programme in Sichuan Province during the stage moving from transmission interruption to elimination (2015—2023), so as to provide insights into formulation of the schistosomiasis control measures during the post-elimination stage. Methods Schistosomiasis control data were retrospectively collected from departments of health, agriculture and rural affairs, forestry and grassland, water resources, and natural resources in Sichuan Province from 2015 to 2023, and a database was created to document examinations and treatments of human and livestock schistosomiasis, and snail survey and control, conversion of paddy fields to dry fields, ditch hardening, rivers and lakes management and building of forests for snail control and schistosomiasis prevention. The completion of schistosomiasis control measures was investigated, and the effectiveness was evaluated. Results A total of 20 545 155 person-times received human schistosomiasis examinations in Sichuan Province during the period from 2015 to 2023, and 232 157 person-times were seropositive, with a reduction in the seroprevalence from 2.10% (44 299/2 107 003) in 2015 to 1.12% (9 361/837 896) in 2023 (χ² = 7.68, P < 0.001). The seroprevalence of human schistosomiasis appeared a tendency towards a decline in Sichuan Province over years from 2015 to 2023 (b = −8.375, t = −10.052, P < 0.001); however, no egg positive individuals were identified during the period from 2018 to 2023, with the prevalence of human Schistosoma japonicum infections maintained at 0. Expanded chemotherapy was administered to 2 754 515 person-times, and medical assistance of advanced schistosomiasis was given to 6 436 persontimes, with the treatment coverage increasing from 46.80% (827/1 767) in 2015 to 64.87% (868/1 338) in 2023. Parasitological tests for livestock schistosomiasis were performed in 35 113 herd-times, and expanded chemotherapy was administered to 513 043 herd-times, while the number of fenced livestock decreased from 121 631 in 2015 to 103 489 in 2023, with a reduction of 14.92%. Snail survey covered 433 621.80 hm² in Sichuan Province from 2015 to 2023, with 204 602.81 hm² treated by chemical control and 4 637.74 hm² by environmental modifications. The area of snail habitats decreased from the peak of 5 029.80 hm² in 2016 to 3 709.72 hm² in 2023, and the actual area of snail habitats decreased from the peak of 8 585.48 hm² in 2016 to 473.09 hm² in 2023. The mean density of living snails remained low across the study period except in 2017 (0.62 snails/0.1 m²). Schistosomiasis control efforts by departments of agriculture and rural affairs in Sichuan Province included conversion of paddy fields to dry fields covering 153 346.93 hm², hardening of 6 110.31 km ditches, building of 70 356 biogas digesters, replacement of cattle with 227 161 sets of machines, and captive breeding of 21 161 070 livestock from 2015 to 2023, and the control efforts by departments of water resources included rivers and lakes management measuring 5 676.92 km and renovation of 2 331 irrigation areas, while the control efforts by departments of forestry and grassland included building of forests for snail control and schistosomiasis prevention covering 23 913.33 hm², renovation of snail control forests covering 8 720 hm² and newly building of shelterbelts covering 764 686.67 hm². All 63 endemic counties (cities and districts) had achieved the criterion for schistosomiasis elimination criteria in Sichuan Province by the end of 2023. Conclusion Following the integrated control efforts from 2015 to 2023, remarkable achievements have been obtained in the schistosomiasis control programme in Sichuan Province, with all endemic counties successfully attaining the schistosomiasis elimination target at the county level.

Objective:Molecular mechanisms underlying compound heterozygous mutations in a patient with inherited antithrombin (AT) deficiency.Methods:The proband was admitted to the First Affiliated Hospital of Wenzhou Medical University in November 2018 with a one-day history of sudden syncope and limb twitching. Peripheral venous blood was collected from the proband and members of his lineages, totaling nine persons across three generations, and a family lineage survey was conducted. AT activity (AT:A) was measured using a chromogenic substrate assay, while AT antigen (AT:Ag) was detected through an immunoturbidimetric assay. Mutation sites were identified by means of Sanger sequencing of the SERPINC1 gene, and silico tools were applied to predict the mutational conservation and hydrophobicity changes. Recombinant plasmid expression vectors were constructed and transfected into HEK293T cells for in vitro overexpression studies. The recombinant AT protein was characterized using Western Blotting, ELISA, and cellular immunofluorescence assays.Results:The proband was a 21-year-old man with type Ⅰ AT deficiency. His AT:A was 33%, along with a corresponding reduction in AT:Ag. The genetic analysis revealed there was a heterozygous insertion mutation at c.318_319insT (p.Asn107*) and a heterozygous missense mutation at c.922G>T (p.Gly308Cys) in exons 2 and 5, respectively. These mutation sites were entirely conserved among the homologous species. Additionally, hydrophobicity studies showed that the p.Gly308Cys mutation will decrease the hydrophilicity of amino acid residues 307-313. The in vitro expression studies indicated a reduction of approximately 46.98%±2.94% and 41.35%±1.48% in the amount of recombinant protein AT-G308C in transfected cell lysates and culture supernatants, respectively. Treatment with the proteasome inhibitor (MG132) restored the cytoplasmic levels of AT-G308C protein to a level similar to that of wild-type protein. However, neither cell lysate nor culture supernatant demonstrated the presence of the recombinant protein AT-N107*. Conclusions:The heterozygous insertion mutation of p.Asn107* and the heterozygous missense mutation of p.Gly308Cys have been associated with reduced AT levels in proband. The p.Asn107* heterozygous insertion mutation may initiate the degradation of mRNA via nonsense mutation-mediated mechanisms, which would remove the defective transcripts, as well as the p.The Gly308Cys heterozygous missense mutation may cause the AT protein to undergo proteasome-dependent degradation by modifying the hydrophobicity of nearby residues in the cytoplasm.

An ambitious goal has been set for elimination of schistosomiasis in all endemic counties (districts) in Sichuan Province by 2023. To achieve this goal, and to continue to consolidate the control achievements, it is necessary to understand the current endemic status of schistosomiasis, identify the challenges and analyze the experiences and lessons from the schistosomiasis control program, and develop targeted control strategies and interventions in the province. This paper reviews the progress of schistosomiasis control in Sichuan Province since the 12th Five-Year Plan period, analyzes the challenges in the schistosomiasis elimination program, and proposes recommendations for future directions and priorities.

Neonatal persistent pulmonary hypertension refers to the continuous increase of pulmonary artery pressure, right heart pressure, right-to-left shunt at foramen ovale and ductus arteriosus level, severe hypoxemia and even respiratory failure after birth.At present, the drug treatments of neonatal persistent pulmonary hypertension include inhaling nitric oxide, sildenafil, milrinone, endothelin receptor antagonists bosentan, prostaglandins and their analogs.This review briefly summarized the progress on the treatment of neonatal persistent pulmonary hypertension.

OBJECTIVE: To explore the molecular pathogenesis for a pedigree affected with hereditary coagulation factor XII (FXII) deficiency. METHODS: Potential variant of the F12 gene was analyzed by PCR and Sanger sequencing. Expression plasmids were constructed by site-directed mutagenesis based on the wild-type and transiently transfected into 293T cells. FXII:C and FXII:Ag of the expression products were determined in the supernatant and cell lysate. Western blotting was used to verify the identify of the protein. RESULTS: Gene sequencing revealed that the proband has carried 46TT genetype and heterozygous p.Glu502Lys variants in exon 13, and a heterozygous p.Gly542Ser variant in exon 14 of the F12 gene. Transfection experiment suggested that the FXII:C and FXII:Ag of p.Glu502Lys variant in the supernatant were 28% and 24%, compared with the wild-type (100%) and FXII:Ag of cell lysates was 39% compared to the wild-type (100%). The FXII:C and FXII:Ag of p. Gly542Ser variant in the supernatant were 32% and 17% and the FXII:Ag of cell lysates was 59%. CONCLUSION The 46TT genetype, p.Glu502Lys and p.Gly542Ser variants of the F12 gene probably underlie the low FXII level in the proband. As shown by in vitro experiment, the p.Glu502Lys and p.Gly542Ser variants can both inhibit the synthesis and secrection of the FXII protein.
Exons ; Factor XII ; genetics ; Factor XII Deficiency ; genetics ; Heterozygote ; Humans ; Pedigree

OBJECTIVE: To analyze the phenotype and genetic basis for a pedigree affected with hereditary coagulation factor XI deficiency. METHODS: Activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), FXI activity (FXI:C) and the antigen of FXI (FXI:Ag) were determined for the proband and members from his pedigree. Sanger sequencing was used to analyze all exons, exon-intronic boundaries, as well as the 5'- and 3'- untranslated regions of the F11 gene. Suspected variants were verified in her family members and confirmed by reverse sequencing. The impact of the variants on the protein function was predicted by using PolyPhen-2 and SIFT software. The protein structure and amino acid interaction were analyzed by using Swiss-PdbViewer. RESULTS: The APTT, FXI:C and FXI:Ag of the proband and her sister were significantly reduced to 73.0 s, 10.0%, 15.0% and 87.1 s, 2.0% and 11.5%, respectively. APTT of some family members was slightly prolonged, and FXI:C and FXI:Ag also decreased to various extents. DNA sequencing revealed that the proband and her sister have carried compound heterozygous variants of c.738G>A (p.Trp228stop) and c.938G>T (p.Ser295Ile) respectively in exons 7 and 9 of the F11 gene. Her father, sister and daughter were heterozygous for the c.738G>A (p.Trp228stop) variant, while her mother and nephew were heterozygous for the c.938G>T (p.Ser295Ile). Both PolyPhen-2 and SIFT predicted that the p.Ser295Ile variant is likely to be deleterious and can affect the protein function. Modeling analysis indicated that the p.Ser295Ile variant may lead to disruption of a hydrogen bond, resulting in alteration of protein structure and instability. CONCLUSION The compound heterozygous c.738G>A (p.Trp228stop) and c.938G>T (p.Ser295Ile) variants of the F11 gene probably underlie the decreased FXI level in this pedigree.
Factor XI Deficiency ; genetics ; Female ; Genetic Variation ; Heterozygote ; Humans ; Mutation ; Pedigree

Bronchopulmonary dysplasia(BPD)is the most common chronic respiratory disease in premature and low birth weight infants, characterized by alveolar and pulmonary vascular dysplasia.This article reviews the factors related to the pathogenesis of BPD, with the aim of providing new ideas for the research of pathogenesis of BPD and its prevention and treatment.Among them, immature lung development, acute lung injury, and abnormal repair after injury are the key links of BPD.Other influencing factors include oxygen poisoning, barotrauma, infection, lack of nutritional support, patent ductus arteriosus, blood transfusion, gastroesophageal reflux, pulmonary interstitial edema, abnormal coagulation function, cholestasis and so on.

Objective To evaluate the effects of serum procalcitonin (PCT)-guided antibiotic therapy in elderly patients with early-onset stroke-associated pneumonia (EOP).Methods Totally 179 eligible elderly patients with EOP were randomly devided into 2 groups:standard therapy group (standard group,n=88) and PCT-guided group (PCT group,n=91).Patients in standard group received antibiotics according to antibiotics guidelines in China by the treating physicians.Patients in PCT group were treated with antibiotics for 5 days,then the antibiotic treatment was based on serum PCT levels as follows:discouraged if PCT＜0.25 μg/L and encouraged if PCT≥0.25 μg/L.Length of hospitalization,duration of antibiotics,costs of hospitalization and antibiotics,clinical efficacy,andmortality,National Institutes of Health Stroke Scale (NIHSS) score and Barthel index (BI) on the 28th day were observed.Results There were no significant differences in clinical efficacy,mortality,NIHSS score and BI between the two groups on the 28th day [(85.7％ vs.86.3％),(8.8％ vs.7.9％),10.1 (7.8,16.2) vs.9.8 (6.0,15.5),60.1(42.5,82.3) vs.57.9 (39.2,84.8),respectively,all P＞ 0.05].The length of hospitalization,antibiotic duration,costs of hospitalization and antibiotics were lower in PCT group than in standard group [19 (10,38) d vs.26(17,42) d,10 (7,14) dvs.15 (6,21) d,3350 (2052,6163) yuanvs.10355 (6877,15421) yuan,7532 (4810,12116) yuan vs.5358 (3089,8144) yuan,respectively,all P＜0.05].Conclusions PCT guidance of antibiotic therapy is effective and safe for the treatment of early-onset stroke associated pneumonia in elderly patients.It can reduce the antibiotic duration and costs of hospitalization.