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.

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

Since December 2019, the corona virus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (2019-nCoV) has been reported in Wuhan, Hubei Province. Almost 70% of patients susceptible to 2019-nCoV are over age of 50 years, with extremely large proportion of critical illness and death of the elderly patients. Meanwhile, the elderly patients are at high risk of osteoporotic fractures especially osteoporotic vertebral compression fractures (OVCF). During the prevention and control of COVID-19 epidemic, orthopedists are confronted with the following difficulties including how to screen and protect OVCF patients, how to accurately diagnose and assess the condition of OVCF patients with suspected or confirmed COVID-19, and how to develop reasonable treatment plans and comprehensive protective measures in emergency and outpatient clinics. In order to standardize the diagnosis and treatment of patients with OVCF diagnosed with COVID-19, the authors jointly develop this expert consensus. The consensus systematically recommends the standardized emergency and outpatient screening and confirmation procedures for OVCF patients with suspected or confirmed COVID-19 and protective measures for emergency and outpatient clinics. Moreover, the consensus describes the grading and classification of OVCF patients diagnosed with COVID-19 according to the severity of illness and recommends different treatment plans and corresponding protective measures based on the different types and epidemic prevention and control requirements.

Objective:To explore the genetic characteristics, clinical features, and prognostic values of RAS mutations in patients with myelofibrosis (MF) .Methods:We analyzed 112-gene targeted sequencing data from 226 patients who had a diagnosis of either primary myelofibrosis (PMF) or post-polycythemia vera/post-essential thrombocythemia (post-PV MF and post-ET MF) from December 2011 to December 2019. A retrospective analysis of the genetic characteristics, clinical features, and prognosis of RAS mutations was performed.Results:Among 266 patients diagnosed PMF or post-PV/ET MF, RAS mutations were found in 14 (6.2%) cases, including 9 (4.0%) cases of NRAS mutations, 8 (3.5%) cases of KRAS mutations, and 3 (1.3%) cases of both NRAS and KRAS mutations. All of the NRAS mutations were located in codons 12 and 13. The median VAFs of RAS mutations were significantly lower than those of the driver mutations, confirming that they represent sub-clonal events that are acquired during the disease course. SETBP1, SRSF2, and MPL tended to be clustered with RAS mutations. Patients with RAS mutations had a higher number of additional oncogenic mutations (median, 3.36 vs 1.17, P<0.001) . RAS mutations had a statistically significant association with elevated monocyte cell counts ( P=0.003) , lower platelet counts ( P=0.026) , higher bone marrow blasts ( P=0.022) , splenomegaly ( P=0.005) , and very high-risk (VHR) karyotype abnormality percentage ( P=0.031) . In univariate analysis, the OS of patients with NRAS mutations were significantly inferior in the entire MF and PMF cohorts ( P=0.001, P=0.008) . In a multivariate model, NRAS retained an independent negative prognostic factor in PMF. Conclusion:RAS gene mutations were constantly related to elevated monocyte cell counts, lower platelet counts, higher bone marrow blasts, and VHR karyotype abnormality percentage that usually defined high-risk disease and often occurred as sub-clonal events. NRAS mutation is an independent poor prognostic factor in PMF.

Rhodiolae Crenulatae Radix et Rhizoma is a precious traditional Chinese medicine and has extensive pharmacological effects, such as anti-hypoxic, anti-fatigue, anti-aging, anti-inflammatory, anti-tumor, lowing blood sugar, heart and brain protection. It has been applied to the treatment of cardiovascular diseases, nervous diseases, respiratory diseases, endocrine diseases, fracture problems, emotional stress, and skin diseases. The present review summarized the literature about its clinical use, which would provide a reference for further utilization.

Objective To explore effect of Yiqi-Huoxue decoction in combination with exercise rehabilitation therapy on functional recovery of hemiplegic limbs and surface electromyography (Surface electromyography,sEMG) during cerebral infarction convalescence.Methods According to random number table,80 cerebral infarction patients in convalescence stage who met the inclusion criteria were divided into the combination therapy group and rehabilitation therapy group,40 in each group.Rehabilitation therapy group received hemiplegia rehabilitation therapy;combination therapy group took Yiqi-Huoxue decoction on the basis of rehabilitation treatment.The 2 groups were treated for 3 months.In hemiplegic upper limb,Fugl-Meyer Assessment (FMA) was scored and Root Mean Square (RMS) and Median Frequency (MDF) of sEMG on biceps brachii were tested before and after each course of treatment respectively.Results After 1-,2-,or 3-month treatment,FMA score of combination therapy group was significantly higher than that of rehabilitation therapy group (t=2.702,4.595,4.444,respectively;all P＜0.01).At 2 or 3 months after treatment,the RMS of combination therapy group (t=7.188,5.405,respectively;all P＜0.01) and the MDF (t=3.336,4.584,respectively;all P＜0.01) were significantly higher than that of rehabilitation therapy group.Conclusions The Yiqi-Huoxue decoction in combination with exercise rehabilitation therapy can improve motor function and muscle tension of hemiplegic limbs during cerebral infarction convalescence.

Objective To evaluate the application value of the blastocysts derived from non-pronucleus (0PN) zygotes by the good quality blastocyst formation rate and the clinical outcomes of frozen-thawed blastocyst transfers. Methods The good quality blastocyst formation rate derived from 0PN zygotes was compared with that derived from2 pronucleus(2PN)zygotes in in vitro fertilization(IVF)or intracytoplasmic sperm injection (ICSI) cycles from January 2015 to December 2016. In addition, the clinical pregnancy, embryo implantation and live birth rates of frozen-thawed blastocyst transfers with blastocysts derived from 0PN and 2PN zygotes were analyzed on corresponding dates. Results (1)In IVF cycles, the high quality blastocysts formation rate of 2PN embryos was significantly higher than that of 0PN (46.64% versus 42.42%, P<0.01). In ICSI cycles, the high quality blastocysts formation rate of 2PN embryos was markedly higher than that of 0PN(41.96% versus 21.73%, P<0.01).(2)In frozen-thawed embryo transfer cycles for IVF, the clinical pregnancy, implantation and live birth rates of D5 0PN blastocysts were significantly higher than those of D6 2PN(52.64% versus 46.78%, 49.91% versus 41.20%, 46.54% versus 39.56%, all P<0.05), however, the abortion and newborn abnormal rates of D5 0PN blastocysts were lower than those of D6 2PN blastocysts(17.37% versus 23.36%, 1.31% versus 4.21%, both P<0.05); the clinical pregnancy, implantation and livebirth rates of D5 2PN blastocysts were significantly higher than those of D5 0PN(59.73% versus 52.64%, 55.95% versus 49.91%, 53.03% versus 46.54%, all P<0.05), but newborn abnormal rate was a little higher than that of D5 0PN(3.90% versus 1.31%, P<0.05);the clinical pregnancy, implantation and live birth rates of D5 2PN blastocysts were significantly higher than those of D6 2PN(59.73% versus 46.78%, 55.95% versus 41.20%, 53.03% versus 39.56%, all P<0.05), and the abortion rate of D5 2PN blastocysts was lower than that of D6 2PN blastocysts(18.23% versus 23.36%, P<0.05). Conclusions Although the blastocysts derived from 0PN could be transffered, the blastocysts derived from 2PN zygotes are preferred in all cycles. In IVF cycles, the good quality blastocysts derived from 2PN or 0PN zygotes will be transferred.