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Abstract Biallelic pathogenic variants in TARS2 lead to combined oxidative phosphorylation deficiency, subtype 21 (COXPD21, MIM #615918), which is a rare mitochondrial encephalomyopathy (ME) characterized by early-onset severe axial hypotonia, limb hypertonia, psychomotor developmental delay, epilepsy and brain anomalies. To date, approximately 28 individuals with COXPD21 and 28 TARS2 variants have been identified. In this study, we reported additional four individuals from three unrelated Chinese families with mitochondrial encephalomyopathy caused by pathogenic variants in TARS2, and described the novel clinical phenotypes and genotypic information. In addition to two novel variants (c.512G > A, p.Arg171Lys; c.988dup, p.Arg330Lysfs*4), one previously reported variant (c.470 C > G, p.Thr157Arg) recurred in six Chinese individuals with COXPD21 but was not present in populations of other races. Our findings expanded the mutation spectrum of TARS2 and confirmed that c.470 C > G is a Chinese-specific founder mutation. The novel phenotypes, including reduced fetal movement, eye anomalies and sleep irregularities, observed in our patients enriched the clinical characteristics of COXPD21.

Objective To obtain the monitoring measurement range of quality indicators of red blood cells, plasma and derivatives and leukocyte-reduced apheresis platelets provided by blood stations in Hebei province, explore the distribution of monitoring values and the change of monitoring level, so as to further strengthen the homogenization construction of quality control laboratories in blood stations in Hebei. Methods In 2023, the sampling data of 12 blood stations in Hebei from 2015 to 2022 were collected, scatter plots were made and the range markers were set, and the "mean±SD" line was taken as the upper limit and lower limit of the measurement range. In 2024, the monitoring values in 2023 were added, and the changes of two measurement ranges were compared to analyze the stability and overall level. Results Comparison of the measurement range from 2015 to 2022 and the measurement range from 2015 to 2023 showed that the standard deviation of the content of deleukocyte suspension of red blood cells-hemoglobin, washed erythrocyte-hemoglobin, washed erythrocyte-supernatant protein, cryoprecipitate coagulation factor-FⅧ, fresh frozen plasma-FⅧ, leukocyte-reduced apheresis platelets-leukocyte residue and leukocyte-reduced apheresis platelet-red blood cell concentration decreased from 8.132 to 7.993, 6.252 to 6.104, 0.273 to 0.267, 57.506 to 56.276, 0.920 to 0.892, 0.653 to 0.644 and 2.653 to 2.603, respectively.The narrowing of the standard deviation range of the above items led to more concentrated monitoring values and reduced dispersion. Comparison of the measurement range from 2015 to 2022 and the measurement range from 2015 to 2023 showed that the mean value of leukocyte residue of the deleukocyte suspension of red blood cells, hemoglobin content of the wash erythrocyte, protein content of supernatant of the wash erythrocyte, hemolysis rate of the wash erythrocyte, FⅧ content of the cryoprecipitate coagulation factor, plasma protein content of the fresh frozen plasma, FⅧ content of the fresh frozen plasma, platelet content of the leukocyte-reduced apheresis platelets changed from 0.362 to 0.476, 44.915 to 44.861, 0.280 to 0.283, 0.137 to 0.142, 133.989 to 133.271, 60.262 to 60.208, 1.301 to 1.277 and 3.036 to 3.033, respectively, and was closer to the national standard line, which reflects an increase in the number of unqualified monitoring values or values close to the national standard line in 2023. The long-term qualified rate of coagulation items was low, and no improvement has been observed. The stability of biochemical items has been enhanced but overall deviation has occurred, with the average value close to the national standard line. The possibility of subsequent testing failure has increased. The counting items showed no obvious common characteristics. Conclusion The use of "mean±SD" in the analysis can visually display the distribution of monitoring values of different items in Hebei, forming an indicator measurement range covering the past nine years. It shows the characteristics of each item, and provides reference for subsequent quality control laboratory data analysis of each blood stations to takes active measures to improve the monitoring level.

Abstract Background Transient receptor potential (TRP) channels are involved in the development and progression of tumors. However, their role in colorectal cancer (CRC) remains unclear, and this study aims to investigate the role of TRP-related genes in CRC. Methods Data was obtained from The Cancer Genome Atlas (TCGA) database, and analyses were conducted on the GSE14333 and GSE38832 datasets to assess the prognosis and mark TRP-related genes (TRGs). Subsequently, clustering analysis and immune infiltration analysis were performed to explore the relevant TRGs. In vitro validation of key TRGs’ gene and protein expression was conducted using human colon cancer cells. Results Compared to normal tissues, 8 TRGs were significantly upregulated in CRC, while 11 were downregulated. TRPA1 was identified as a protective prognostic factor, whereas TRPM5 (HR = 1.349), TRPV4 (HR = 1.289), and TRPV3 (HR = 1.442) were identified as prognostic risk factors. Receiver operating characteristic (ROC) curves and Kaplan-Meier (KM) analyses yielded similar results. Additionally, lower expression of TRPA1 and higher expression of TRPV4 and TRPM5 were negatively correlated with patient prognosis, and experimental validation confirmed the underexpression of TRPA1 and overexpression of TRPV4 and TRPM5 in CRC cell lines. Conclusion This study identifies a TRP channel-related prognosis in CRC, providing a novel approach to stratifying CRC prognosis.

BackgroundChimeric antigen receptor (CAR) T-cell therapy (CAR-T therapy) has demonstrated significant efficacy in the ZUMA-2 study. After regulatory approvals, several clinical trials and real-world studies on CAR-T therapy for relapsed or refractory mantle cell lymphoma (R/R MCL) were conducted. However, data on clinical safety and efficacy are inconsistent. In this study, we aimed to conduct a systematic analysis of the effectiveness and safety of CAR-T therapy across a wider and more representative cohort of patients with R/R MCL.MethodsWe performed a systematic review and meta-analysis of studies on patients with R/R MCL who received CAR-T cell therapy. Data were extracted and consolidated, with primary focus on the evaluation of safety and efficacy outcome measures. This study has not been registered with PROSPERO.ResultsThis meta-analysis identified and included 16 studies with 984 patients. The pooled estimate for overall response rate (ORR) was 89%; complete remission (CR) rate was 74%. The 6-month and 12-month progression-free survival (PFS) rates were 69% and 53%, respectively, while the overall survival (OS) rates were 80% and 69%, respectively. Cytokine release syndrome (CRS) of grade 3 or higher was observed in 8% of patients, whereas neurotoxicity of grade 3 or higher was observed in 22% of patients. The risk of bias was assessed as low in 9 studies and moderate in 7 studies.ConclusionCAR-T therapy exhibited promising efficacy and manageable adverse reactions in patients with R/R MCL.

Abstract Background Biallelic pathogenic variants in PIP5K1C (MIM #606,102) lead to lethal congenital contractural syndrome 3 (LCCS3, MIM #611,369), a rare autosomal recessive genetic disorder characterized by small gestational age, severe multiple joint contractures and muscle atrophy, early death due to respiratory failure. Currently, 5 individuals with LCCS3 were reported and 5 pathogenic variants in PIP5K1C were identified. Here, we reported the two fetuses in a Chinese pedigree who displayed multiple joint contractures and other congenital anomalies. Methods Trio-based whole-exome sequencing (WES) was performed for the parents and the recent fetus to detect the genetic cause for fetus phenotype. Results A novel variant, NM_012398.3: c.949_952dup, p.S318Ifs*28 and a previously reported variant, c.688_689del, p.G230Qfs*114 (ClinVar database) in PIP5K1C, were detected in the individuals, and these variants were inherited from the mother and father, respectively. We described the features of multiple joint contractures in our fetuses, including bilateral talipes equinovarus, stiffness in the limbs, extended knees, persistently closed hands and overlapping fingers, which have not been delineated detailedly in previously reported LCCS3 individuals. Furthermore, novel phenotype, bilateral dilated lateral ventricles, was revealed in one fetus. Conclusions These findings expanded the genetic variant spectrum of PIP5K1C and enriched the clinical features of LCCS3, which will help with the prenatal diagnosis and genetic counseling for this family.

Objectives This study aims to assess the impact of the nationwide Omicron outbreak in December 2022 on Chinese patients with plasma cell disorders (PCD), focusing on the clinical characteristics of PCD patients with COVID-19 and the risk factors contributing to adverse clinical courses (severity and hospitalization) and outcomes.Methods A multicenter retrospective study was performed from December 1, 2022, to January 19, 2023. The study population includes 404 PCD patients, divided into a COVID-19 group (n = 342) and an uninfected group (n = 62).Results The frequency of COVID-19 infection was 84.7% (342/404), and 16.4% (56/342) were severe COVID-19. Among the 277 patients with complete follow-up, 2 deaths (0.7%) were reported, while 231 (83.4%) recovered from COVID-19. Age > 65 (P = 0.02) and prior anti-CD38 monoclonal antibody (mAb) treatment within six months (P = 0.03) were independent risk factors for severe infection. Additionally, previous chimeric antigen receptor T-cell (CAR-T) therapy within six months was correlated with a higher risk of hospitalization (P = 0.04) and prolonged recovery time (P = 0.03). No significant protective effect of vaccination on infection or severe infection was observed (P > 0.05).Conclusions The latest Omicron outbreak results in higher rates of severe infection and mortality in PCD patients compared with the general population in China, highlighting the need to protect this vulnerable population during the pandemic. Recent use of anti-CD38 mAb and CAR-T therapy are associated with poorer clinical courses and outcomes of PCD patients with COVID-19.

Background: High horseshoe-shaped anal fistula (HHAF) is a complex disease that manifests in the perianal region and typically requires surgical intervention for treatment. However, the current therapeutic approaches are limited by the high rates of postoperative recurrence and anal incontinence. To overcome the limitations of traditional surgical approaches, we introduce the bared external anal sphincter (BEAS) technique. Our study aims to compare the clinical efficacy of BEAS surgery with that of the modified Hanley procedure in a real-world setting. Materials and methods: This single-centre, prospective cohort study will be conducted in a tertiary hospital in China and aims to evaluate the short-term clinical efficacy and safety of BEAS surgery and modified Hanley surgery in HHAF patients from March 2024 to March 2026. Data from the prospective database of this tertiary referral hospital will be used to obtain insights into the clinical outcomes of these surgical treatments. The primary outcome of this study will be the wound healing rate within six months, while the secondary outcomes will include the time to return to work, the maximum visual analogue scale pain score (VAS-PS) within 1–5 days postsurgery, and the Cleveland Clinic Florida Incontinence Score (CCF-IS) and Quality of Life in Anal Fistula Questionnaire Score (QoLAF-QS) at 1, 3, and 6 months postsurgery. Moreover, logistic regression analysis will be used to explore the risk factors for anal fistula recurrence after the BEAS procedure. Discussion: This will be the first cohort study to evaluate the differences in therapeutic outcomes between patients who undergo BEAS surgery and patients who undergo surgery via the modified Hanley procedure. By conducting a detailed observation of the efficacy and treatment results of these two surgical methods, this study aims to reveal the differences the clinical effectiveness of these approaches and to provide evidence-based support for future randomized controlled trials (RCTs).

BackgroundSignificant evidence has been documented regarding the intricate connection between the development of anal fistula (AF) and the composition of Body Mass Index (BMI). Nevertheless, due to the inherent limitations of reverse causality and confounders inherent in observational studies, this relationship remains unclarified. Our study aims to reveal the causal impact between BMI and AF, as well as identify its associated risk factors, thereby providing a more comprehensive understanding of this complex interaction.MethodsSingle nucleotide polymorphisms (SNPs) identified through genome-wide association study (GWAS) databases were used as instrumental variables for analysis. BMI served as the exposure variable, with six pooled GWAS datasets included. AF was the outcome variable. The Inverse Variance Weighted (IVW) method was used as the primary analytical technique, with MR-Egger regression, Weighted Median (WME) estimation, and Multiplicity Residual Sum and Outlier (MR-PRESSO) tests serving as secondary validations of the IVW results. Odds ratios (OR) were utilized as indicators to evaluate the causal relationship between BMI and AF.ResultsA total of 738 SNPs strongly associated with the exposure were identified as instrumental variables. The IVW results demonstrated a positive correlation between BMI and the risk of AF. The MR-Egger analysis yielded p-values greater than 0.05, indicating no pleiotropic effects among the selected SNPs. Cochran’s Q test also resulted in p-values greater than 0.05, suggesting no significant heterogeneity among the instrumental variables. The MR-PRESSO analysis revealed no horizontal pleiotropy or outliers potentially violating the causal assumption (p > 0.05).ConclusionHigh BMI is positively associated with the risk of AF, and correcting BMI levels may have a preventive effect on the incidence of AF.

Clonal cytopenia of undetermined significance (CCUS) has the characteristics of high-risk transformation into myelodysplastic syndromes. At present, there are few effective treatments for CCUS, and there is no consensus or evidence-based recommendation. We present a case demonstrating a rapid, significant and sustained response to combined treatment with luspatercept and eltrombopag, following the failure of cyclosporin and androgen therapy. Even after discontinuing luspatercept for 10 months, trilineage haematopoiesis remained normal with the use of cyclosporin and other haematopoietic stimulants. This case suggests that the inhibition of transforming growth factor-β could potentially have an immunomodulatory effect, thereby promoting the recovery of haematopoietic function. Luspatercept, along with Acalabrutinib or Cyclosporine, may synergistically stimulate haematopoiesis.

Study region: The Yangtze−Huang−Huai−Hai River basin (3.19 million km2) in China, which is vital for China's economic development. Study focus: We employed the Eulerian method to identify the primary water vapor channels from 2005 to 2020, and the water vapor net budget over the basin was calculated. Additionally, the Lagrangian method was utilized to simulate water vapor transport trajectories across four seasons, with the aim of investigating the influence of changes in water vapor on precipitation. New hydrological insights for the region: Utilizing both Eulerian and Lagrangian methods, the findings indicate that: (1) Precipitation in the basin experienced a downward trend of −3.5 mm·a−1 during 2005−2020, mainly in spring (−1.4 mm·a−1) and summer (−1.7 mm·a−1); (2) The water vapor net budget has a substantial downward trend (−0.9 kg·m−1·s−1·a−1), mainly in spring (−0.4 kg·m−1·s−1·a−1) and summer (−0.3 kg·m−1·s−1·a−1), which aligns with the declining trend of precipitation. (3) The Hybrid Single Particle Lagrangian Integrated Trajectory Model demonstrates that the decrease in long−distance water vapor transport trajectories impacts the basin’s water vapor channels. The decline in spring is predominantly influenced by the water vapor transport trajectories from Asia, Europe, and Africa−Arctic Ocean (−0.7 %·a−1), while the summer is mainly driven by the water vapor transport trajectory from the Indian Ocean−South China Sea (−0.3 %·a−1). This study improves the existing understanding of the hydrological cycle in the context of the basin, and offers a crucial scientific basis for water resource management and regulation.

Abstract Background The aim of this study is to investigate the profiles of gut microbiota and metabolites in acute myelocytic leukemia (AML) patients treated with/without chemotherapy. Methods Herein, high‐throughput 16S rRNA gene sequencing was performed to analysis gut microbiota profiles, and liquid chromatography and mass spectrometry were performed to analysis metabolites profiles. The correlation between gut microbiota biomarkers identified by LEfSe and differentially expressed metabolites were determined by spearman association analysis. Results The results showed the distinguished gut microbiota and metabolites profiles between AML patients and control individuals or AML patients treated with chemotherapy. Compared to normal populations, the ratio of Firmicutes to Bacteroidetes was increased at the phylum level than that in AML patients, and LEfSe analysis identified Collinsella and Coriobacteriaceae as biomarkers of AML patients. Differential metabolite analysis indicated that, compared to AML patients, numerous differential amino acids and analogs could be observed in control individuals and AML patients treated with chemotherapy. Interestingly, spearman association analysis demonstrated that plenty of bacteria biomarkers shows statistical correlations with differentially expressed amino acid metabolites. In addition, we found that both Collinsella and Coriobacteriaceae demonstrate remarkable positive correlation with hydroxyprolyl‐hydroxyproline, prolyl‐tyrosine, and tyrosyl‐proline. Conclusion In conclusion, our present study investigated the role of the gut‐microbiome–metabolome axis in AML and revealed the possibility of AML treatment by gut‐microbiome–metabolome axis in the further.

Abstract Climate warming leads to frequent extreme precipitation events, which is a prominent manifestation of the variation of the global water cycle. In this study, data from 1842 meteorological stations in the Huang–Huai–Hai–Yangtze River Basin and 7 climate models of CMIP6 were used to obtain the historical and future precipitation data using the Anusplin interpolation, BMA method, and a non-stationary deviation correction technique. The temporal and spatial variations of extreme precipitation in the four basins were analysed from 1960 to 2100. The correlation between extreme precipitation indices and their relationship with geographical factors was also analysed. The result of the study indicates that: (1) in the historical period, CDD and R99pTOT showed an upward trend, with growth rates of 14.14% and 4.78%, respectively. PRCPTOT showed a downward trend, with a decreasing rate of 9.72%. Other indices showed minimal change. (2) Based on SSP1-2.6, the intensity, frequency, and duration of extreme precipitation changed by approximately 5% at SSP3-7.0 and 10% at SSP5-8.5. The sensitivity to climate change was found to be highest in spring and autumn. The drought risk decreased, while the flood risk increased in spring. The drought risk increased in autumn and winter, and the flood risk increased in the alpine climate area of the plateau in summer. (3) Extreme precipitation index is significantly correlated with PRCPTOT in the future period. Different atmospheric circulation factors significantly affected different extreme precipitation indices of FMB. (4) CDD, CWD, R95pD, R99pD, and PRCPTOT are affected by latitude. On the other hand, RX1day and RX5day are affected by longitude. The extreme precipitation index is significantly correlated with geographical factors, and areas above 3000 m above sea level are more sensitive to climate change.

Increasing yield is an important goal of barley breeding. In this study, 54 papers published from 2001-2022 on QTL mapping for yield and yield-related traits in barley were collected, which contained 1080 QTLs mapped to the barley high-density consensus map for QTL meta-analysis. These initial QTLs were integrated into 85 meta-QTLs (MQTL) with a mean confidence interval (CI) of 2.76 cM, which was 7.86-fold narrower than the CI of the initial QTL. Among these 85 MQTLs, 68 MQTLs were validated in GWAS studies, and 25 breeder's MQTLs were screened from them. Seventeen barley orthologs of yield-related genes in rice and maize were identified within the hcMQTL region based on comparative genomics strategy and were presumed to be reliable candidates for controlling yield-related traits. The results of this study provide useful information for molecular marker-assisted breeding and candidate gene mining of yield-related traits in barley.

Abstract The aim of this study was to introduce a new technique, the bared external anal sphincter technique, and to evaluate its effectiveness and safety for primary or recurrent high horseshoe anal fistula (HHAF). We used data from a tertiary referral hospital’s prospective database of a hospital-based cohort. All the patients underwent the bared external anal sphincter procedure. The main outcomes were short‐term clinical outcomes including the 6-month cure rate, Visual Analog Scale pain score (VAS-PS) and Cleveland Clinic Florida incontinence score (CCF-IS). The secondary outcomes included the Quality of Life in Patients with Anal Fistula Questionnaire score (QoLAF-QS), Bristol stool chart and postoperative complications. A total of 48 HHAF patients (39 males) with a mean age of 34.2 years (SD 9.04; range, 21–54) were analyzed in this retrospective study. At the 6-month follow-up, the average VAS-PS and CCF-IS were 0.81 (SD 2.28; range, 0–10) and 1.29 (SD 2.87; range, 0–13), respectively. QoLAF-QS showed that the bared external anal sphincter procedure had no impact over their quality of life in 45 patients (93.75%), limited impact in 2 patients (4.16%), and moderate impact in one patient (2.08%). The Bristol stool scale showed that all patients had normal stool characteristics. The 6-month cure rate was 93.75%. Three patients (6.25%) experienced recurrent symptoms but recovered after surgical management. Urinary retention occurred in 1 case (2.78%). No other postoperative complications were reported. No patient had anal incontinence. The bared external anal sphincter procedure is a safe, effective and sphincter-sparing approach for patients with primary or recurrent HHAF in terms of short‐term results.

The study employed the PML (Penman–Monteith–Leuning) model to simulate the evolution law of long-sequence evapotranspiration in the mountainous region of the Luan River basin. Additionally, this study conducted a quantitative analysis to determine the effect of restoration on evapotranspiration water consumption. From 1981 to 2020, the results indicated that there were significantly less fluctuations in precipitation in the mountainous region of the Luan River basin than there were fluctuations in discharge. The restoration of vegetation in the mountainous region of the Luan River basin caused a mean annual growth rate of 3.47 mm in evapotranspiration. A linear positive correlation was observed between the evapotranspiration and vegetation NDVIs (normalized difference vegetation indexes) in mountainous regions. Specifically, for each 0.01 increase in the NDVI, there was an approximate 8.3 mm increase in evapotranspiration. When comparing the time periods of 1995–2001 and 2002–2020, it was observed that evapotranspiration increased by 70 mm. Furthermore, the evapotranspiration rate in the southeastern region exhibits significant variation, peaking at over 50 mm per year. In contrast, the northwest experiences variations of less than 10 mm per year. A quantitative analysis of the relationship between the evolution of mountain evapotranspiration and the response law of vegetation restoration is presented in this study; this information can be used as a guide when developing practical vegetation restoration strategies.

AimThere is accumulating evidence indicating that ASS1 is closely related to tumors. No pan-cancer analysis of ASS1 was available.MethodsHere we explored the gene expression and survival analysis of ASS1 across thirty-three tumors based on the datasets of the TCGA (Cancer Genome Atlas), the GEO (Gene Expression Omnibus), and the GEPIA2 (Gene Expression Profiling Interactive Analysis, version 2).ResultsASS1 is highly expressed in most normal tissues and is related to the progression of some tumors. We also report ASS1 genetic alteration and their association with tumor prognosis and report differences in ASS1 phosphorylation sites between tumors and control normal tissues. ASS1 expression was associated with the infiltration of cancer-associated fibroblasts (CAFs) for the TCGA tumors of BRCA (Breast invasive carcinoma), CESC (Cervical squamous cell carcinoma and endocervical adenocarcinoma), COAD (Colon adenocarcinoma), ESCA (Esophageal carcinoma), SKCM (Skin cutaneous melanoma), SKCM-Metastasis, TGCT (Testicular germ cell tumors), and endothelial cell for the tumors of BRCA, BRCA-Basal, CESC, ESCA, KIRC (Kidney renal clear cell carcinoma), LUAD (Lung adenocarcinoma), LUSC (Lung squamous cell carcinoma), SKCM, SKCM-Metastasis, SKCM-Primary, STAD (Stomach adenocarcinoma), and TGCT. The KEGG and GO analysis were used to analyze ASS1-related signaling pathways. Finally, we used Huh7 cell line to verify the function of ASS1 in vitro. After ASS1 knockdown using small interfering RNA (siRNA), the proliferation and invasion of Huh7 were enhanced, cyclin D1 was up-regulated, and anti-apoptotic protein bax was down-regulated, suggesting that ASS1 is a tumor suppressor gene in hepatocellular carcinoma.ConclusionOur first pan-cancer study offers a relatively comprehensive understanding of the roles of ASS1 in different tumors.

Abstract Background Biallelic pathogenic variants in the KCNJ16 gene result in hypokalemic tubulopathy and deafness (HKTD) (MIM #619406), which is a rare autosomal recessive disease characterized by hypokalemic tubulopathy with renal salt wasting, disturbed acid–base homeostasis, and sensorineural deafness. Currently, nine individuals with HKTD have been reported, and seven pathogenic variants in KCNJ16 have been revealed. Methods A 5‐year‐6‐month‐old Chinese female patient displayed hypokalemic metabolic acidosis, salt wasting, renin‐angiotensin‐aldosterone system (RAAS) activation, arrhythmia, myocardial damage, cardiogenic shock and secondary diffuse brain oedema. Trio‐based whole‐exome sequencing (WES) was applied to detect the genetic cause. Results Novel compound heterozygous variants, c.190A>C (p.Thr64Pro) and c.628C>G (p.His210Asp), in KCNJ16 were detected in the patient, and these variants were inherited from the patient's mother and father, respectively. Then, we systematically reviewed the available clinical manifestations of individuals with HKTD. We found that HKTD patients are at risk of cardiogenic shock and secondary diffuse brain oedema, which urges clinicians to make early diagnoses with prompt treatments. Conclusion These findings expand the variant spectrum of KCNJ16, enrich the clinical characteristics of HKTD, and provide a solid base for the genetic counseling, diagnosis and treatment of this condition.

Abstract More and more evidence show that HK2 is closely related to tumors. But no pan-cancer analysis is available. This paper aimed to explore the potential roles of HK2 across thirty-three tumors based on the datasets of the cancer genome Atlas (TCGA) and gene expression omnibus. HK2 is highly expressed in most tumors and related to the progression of some tumors. HK2 expression was associated with the infiltration of T follicular helper cells for the TCGA tumors of uveal melanoma, breast invasive carcinoma (BRCA), breast invasive carcinoma-luminalA (BRCA-LumA), head and neck squamous cell carcinoma (HNSC), head and neck squamous cell carcinoma with HPV positive (HNSC-HPV+), and cancer-associated fibroblasts for the tumors of brain lower grade glioma and stomach adenocarcinoma. Our first pan-cancer study offers a relatively comprehensive understanding of the roles of HK2 in different tumors.

The purpose of this study is to assess effects of two different simulation methods (i.e., interfaces with a single spring-slider system and interfaces with double spring-slider systems) for interactions between reinforcement and the surrounding medium on the performances of geosynthetic-reinforced soil (GRS) structures when conducting numerical analyses. The fundamental difference between these two methods is the number of the spring-slider systems used to connect the nodes of structural elements simulating the geosynthetic reinforcement and the points of solid grids simulating the surrounding medium. Numerical simulation results of pull-out tests show that both methods reasonably predicted the pullout failure mode of the reinforcement embedded in the surrounding medium. However, the method using the interfaces with a single spring-slider system could not correctly predict the interface shear failure mode between the geosynthetics and surrounding medium. Further research shows that these two methods resulted in different predictions of the performance of GRS piers as compared with results of a laboratory load test. Numerical analyses show that a combination of interfaces with double spring-slider systems for reinforcement between facing blocks and interfaces with a single spring-slider system for reinforcement in soil resulted in the best performance prediction of the GRS structures as compared with the test results. This study also proposes and verifies an equivalent method for determining/converting the interface stiffness and strength parameters for these two methods.

Understanding developments in the trunk sap flow of prevalent tree species within the hilly areas of the Haihe River basin is imperative for ecosystem conservation. Nevertheless, the changes in sap flow of local trees and their response to environmental factors remain elusive. This study focuses on seven dominant tree species in the hilly area of the Haihe River basin and analyzed the relationship between tree sap flow rate and environmental factors at different time scales (hourly and daily). Our findings suggested: (1) Regardless of the time scale, total solar irradiance played a primary role in influencing sap flow rate. Conversely, as the time scale grew, the associations between most soil factors and sap flow rate enhanced, while those with meteorological factors declined. Notably, soil temperature exerted a more profound influence on sap flow rate than soil moisture and conductivity. (2) At the hourly scale, the sap flow rate of each species had a lag effect of 1–2 h with vapour pressure deficit, relative humidity and temperature, and 1 h or no lag effect with total solar irradiance and wind speed. (3) The response model of sap flow rate and environmental factors showed that, except for Pinus tabuliformis Carr., other tree species fit well at various time scales (R2 ≥ 0.59). As the time scale of most tree species increased from hourly scale to daily scale, the fit gradually weakened. Concurrently, considering the time-lag effect, the accuracy of the model has been improved, and the fitting accuracy of Koelreuteria paniculata Laxm. and Pinus tabuliformis Carr. has been significantly improved.

An accurate assessment of sediment transport can assist land and resource managers in any region. The primary objective of this study was to develop a distributed hydrological model for calculating rainfall-runoff coupled with sediment transport to provide a practical method for estimating sediment transport in western Heilongjiang Province, China. The Alun River Basin, which has typical meteorological and hydrological characteristics of western Heilongjiang Province, was chosen as the study area. A sediment transport calculation module was developed based on physically based formulas for the suspended load and bedload, which was coupled with a numerical model of the physical distributed rainfall-runoff process. The model’s ability was validated by comparing the sediment sampling survey results of the particle size group distribution (PSGD) in the flow and the corresponding value of the model calculation results for a control case. The root mean square error ( RMSE ) and the mean absolute error ( MAE ) were mostly 15%. The results provide a basis for the assessment of sediment transport and the development of a numerical platform for modeling hydrological processes coupled with land surface processes in western Heilongjiang Province, China.

Objective To perform quantitative analysis on the sample provincial laws and regulations for voluntary blood donation, and provide reference for further revision of laws and regulations. Methods 31 study samples were current provincial laws and regulations for voluntary blood donation that can be collected from open sources. The issue date and the revision date of each sample were recorded. With "The Blood Donation Law of the People’s Republic of China" as reference, 5 categories were formed and additional clauses in samples were coded and rated following content analysis procedures. Sample provinces were divided into two groups based on donation rate and their differences in evaluation scores of categories were examined using rank sum test. Results Until December, 2021, 31 sample provinces had issued and implemented provincial laws and regulation for voluntary blood donation, and 14 of which had been revised. Many detailed clauses (total score 9.32±3.09) were added in sample provincial laws and regulations, more clauses were added in the categories of 'related government agencies and their responsibilities’, 'management of clinical blood use’ and 'rewards and punishment’. Sample provinces were divided into two groups according to the donation rate per 1 000 people recommended by World Health Organization(10‰). Compared to lower donation rate group, the total score and sub score in the categories of 'basic principles’, 'management of blood collection and supply’ were significantly higher in higher donation rate group. Conclusion In revision and improvement of provincial laws and regulations, 'basic principles’ and 'management of blood collection and supply’ could be considered. This assay mainly tries to provide a new research perspective and perform quantitative analysis on content of sample provincial laws and regulation for voluntary blood donation, the actual effect of the results in this study need longer time to be examined, and we will keep following its new advances.

Abstract Background Homozygous or compound heterozygous variants in the KLHL40 gene cause nemaline myopathy 8 (NEM8), a severe autosomal recessive muscle disorder characterized by prenatal polyhydramnios, fetal akinesia or hypokinesia, joint contractures, fractures, respiratory failure and dysphagia. Currently, 46 individuals with NEM8 have been described in the literature, and 30 variants in KLHL40 have been identified. Results Here, we reported five individuals from four unrelated Chinese families who presented common features of nemaline myopathy and infrequent clinical characteristics. Whole-exome sequencing (WES) was used to identify the causative gene. WES identified a recurrent missense variant c.1516A>C (p.Thr506Pro) and a novel frameshift variant c.543del (p.Ser182Profs*17) in KLHL40 in patient 1, a nonsense variant c.602G>A (p.Trp201*) and a missense variant c.1516A>C (p.Thr506Pro) in KLHL40 in patient 2, and homozygous variant c.1516A>C (p.Thr506Pro) in KLHL40 in patient 3 and both siblings (patients 4 and 5), all of which were confirmed by Sanger sequencing. Next, we estimated the incidence of this disorder in the southern and northern Chinese population to be 4.59/106 and 2.95/106, respectively, based on the cumulative allele frequency of pathogenic variants in internal database. Conclusion The results of our study expand the mutation spectrum of KLHL40 and enrich our understanding of the clinical characteristics of NEM8. Genetic counseling was provided for the four families involved in this study. Given the severity and the relatively high incidence of this condition, we strongly suggest that KLHL40 be incorporated into a carrier screening panel for the Chinese population.

With the update of the power transaction mode and the access of increasing electric vehicles with high randomness to the power grid, the existing carbon emission flow calculation method cannot consider the influence of carbon emission due to the fluctuation in electric vehicle charging and various transaction modes. Given the above shortcomings, this paper proposes an improved carbon emission flow model considering electric vehicle charging fluctuations and hybrid power transactions. The model first considers different transaction modes, allocates the network loss to both sides of power generation, and forms a lossless network, realizing the decoupling of the bilateral transaction mode, pool transaction mode, and network loss and then calculating the day-ahead network’s carbon emission. Then, the changes in different transaction modes caused by the fluctuation in electric vehicle charging under different transaction modes are analyzed and the nodes of ‘spontaneous change’ are found to form a day-ahead intra-day deviation network and calculate its carbon emission flow. Finally, the calculation results are combined to obtain an improved power system carbon emission flow considering electric vehicle charging fluctuations and transaction modes. In this paper, the 33-node system is used for verification.

IntroductionAnal fistula is the natural evolution of perianal abscess and one of the most common perianal diseases for adults. For complex fistula, it is still very challenging for anorectal surgeons to manage. With the introduction of laser technique in surgery, it is becoming more and more widely used for the treatment of cryptoglandular anal fistula. During the past decade, numerous studies have reported the clinical effectiveness and postoperative outcomes of different forms of laser treatment for anal fistula. However, as these studies were varied in terms of baseline characteristics, the evidence for the true clinical effectiveness of laser treatment for anal fistula need further critical appraisal. Therefore, the purpose of this study is to evaluate the outcomes of surgical laser therapy for cryptoglandular anal fistula stratified by laser type and Parks' classification through a synthesis of quantitative and qualitative evidence.Methods and analysisThis study will be carried out with adherence to the Cochrane Handbook. We will search PubMed, Cochrane Library, and Embase until June, 2022 to identify all relevant interventional and observational studies examining the effects of laser therapy on the clinical outcomes for cryptoglandular anal fistula. Data extraction from eligible studies will be performed independently by two unblinded authors using standardized extraction forms. Risk of bias assessment for each study will be conducted using Cochrane tool for randomized controlled trials (RCTs) and the Newcastle-Ottawa scale (NOS) tool for observational studies. The DerSimonian-Laird random-effects model will be used to calculate the pooled estimates. Heterogeneity will be examined by subgroup analysis stratified by laser type and Parks' classification and other study characteristics. Potential publication bias will be assessed by funnel plot symmetrical and Egger's regression tests.ConclusionsThe synthesis of quantitative and qualitative evidence of this systemic review will yield updated and comprehensive evidence of laser treatment on specific outcomes, which can provide anorectal surgeons with high level evidence-based recommendations to improve patient care and clinical outcomes. OSF registration number: DOI 10.17605/OSF.IO/36ADW.

ObjectiveThe diagnosis of prostate cancer has been a challenging task. Compared with traditional diagnosis methods, the radiofrequency (RF) signal is not only non-invasive but also rich in microscopic lesion information. This paper proposes a novel and accurate method for detecting prostate cancer based on the ultrasound RF signal.MethodOur approach is based on low-dimensional features in the frequency domain and high-throughput features in the spatial domain. The whole process could be divided into two parts: first, we calculate three feature maps from the ultrasound original RF signal, and 1,050 radiomics features are extracted from the three feature maps; second, we extracted 37 spectral features from the normalized frequency spectrum after Fourier transform.ResultsWe use LASSO regression as the method for feature selection; moreover, we use support vector machine (SVM) for classification 10-fold cross-validation for examining the classification performance of the SVM. An AUC (area under the receiver operating characteristic curve) of 0.84 was obtained on 71 subjects.ConclusionsOur method is feasible to detect prostate cancer based on the ultrasound RF signal with superior classification performance.

Pathogenic variants in the RASopathy-causing SHOC2 gene have been suggested to cause Noonan syndrome-like with loose anagen hair (NS/LAH). This condition is characterized by facial features resembling Noonan syndrome (NS), short stature, growth hormone deficiency (GHD), cognitive deficits, cardiac defects, and ectodermal abnormalities, including easily pluckable, sparse, thin, slow-growing hair, hyperpigmented skin and hypernasal voice. The mutation spectrum of SHOC2 is narrow, and only 8 pathogenic variants have been identified. Here, we report a 5-year-3-month-old Chinese female who displays characteristics typical of NS and has normal neurodevelopment. Trio-based whole-exome sequencing (WES) revealed a de novo variant (c.1231A>G, p.Thr411Ala) in SHOC2. This variant has been recently reported in one subject in the literature who displayed facial features typical of NS and also presented with significant speech delays, moderate intellectual disabilities, epilepsy, bilateral sensorineural deafness and renal dysplasia. The differential phenotypes between these subjects deserve to be further investigated. Next, we reviewed the clinical pictures of NS/LAH and noticed that a recurrent SHOC2 Ser2Gly variant was more likely to result in delayed neurodevelopment and short stature, compared to other SHOC2 variants. And growth hormone (GH) therapy could improve height prognosis. It was noticed that the slight sleep problems and friendly and relatively mature personality observed in our patient may be a novel phenotype of NS/LAH. Our study reconfirms the pathogenic nature of the SHOC2 Thr411Ala variant. It also provides insights into the genotype-phenotype relationship in NS/LAH and a foundation for its genetic counseling, diagnosis and treatment.

Study region: The study area was the Cangzhou area in the central-eastern North China Plain (NCP). Study focus: Compaction of the aquifer system leads to a change in hydraulic parameters, including the storage coefficient and hydraulic conductivity. This further reduces its groundwater storage and supply capacity. This study aimed to evaluate the non-linear variation in hydraulic parameters and feedback to the aquifer system during land subsidence. The aquifer system in Cangzhou has suffered severe land subsidence caused by groundwater overexploitation and was chosen to demonstrate this effect. A one-dimensional non-linear compaction and water drainage model was developed considering the changes in the storage coefficient and hydraulic conductivity. New hydrological insights: Based on the physical characteristics of the Cangzhou aquifer system, a compaction model was applied to establish a quantitative relationship between deep groundwater abstraction, hydraulic parameter change, groundwater storage, and supply capacity change during land subsidence. Results show that the inelastic storage coefficient was reduced by 0.005–0.032 for the deep aquifer system in the subsiding area. This represents a reduction of 220 million m3 of groundwater that can be exploited per meter decline in the confined water level. The permanent loss of groundwater storage capacity is estimated to be 9.41 billion m3. These research results have important reference significance for the scientific evaluation of aquifer water supply capacity change in subsiding regions.

This study conducted plane-strain scaled model tests to investigate the deformation characteristics of geosynthetic reinforced soil (GRS) abutments subjected to vertical loads. Setback distance, i.e., the distance between the back of the abutment facing and the front of the loading plate, was chosen as the investigated influencing factor since it is one of the most frequently used variables by engineers for the design of GRS abutments. This study analyzed the settlements at the top of the abutment, the lateral displacements of the abutment facing, and the volumetric deformations of the abutment under the applied vertical loads. Test results showed that increasing the setback distance could effectively reduce the deformations of the GRS abutment. There existed an optimum setback distance and further increasing the setback distance beyond this optimum value did not have a significant effect on reducing the abutment deformations. The vertical, lateral, and total volumetric deformations of the GRS abutment showed an approximately linear increase with the increase of the applied vertical loads. The lateral volumetric deformations of the GRS abutment were larger than its vertical volumetric deformations and therefore the total volumetric strains of the GRS abutment were not zero based on the test results. However, the theory of zero volume change may still be suitable for the deformation calculation of the GRS abutment since the values of the volumetric strains were minimal. The measured maximum lateral facing displacements were compared with the calculated values using the US Federal Highway Administration (FHWA) method, which assumes zero volume change of the GRS abutment under vertical loads. Comparison results indicated that the FHWA method overestimated the maximum lateral facing displacements of the GRS abutment under vertical loads. An improved method was proposed in this study to calculate the maximum lateral facing displacements under vertical loads based on the theory of zero volume change and a revised distribution of the settlements at the top of the GRS abutment. Results showed that the improved method could better predict the maximum lateral facing displacements as compared to the FHWA method.

This study aimed to assess the effects of insoluble dietary fiber (IDF) from feijoa supplementation on the physicochemical and functional properties of wheat bread. The results showed that feijoa IDF (FJI) had the typical structures of hydrolysis fiber, polysaccharide functional groups, and crystal structure of cellulose. The gradual increase of FJI levels (from 2 to 8%) in wheat bread resulted in increased total DF, ash, and protein contents, accompanied by a reduction in moisture, carbohydrates, and energy value. The inclusion of FJI in the bread crumb caused a rise in both redness (a*) and yellowness (b*) values while decreasing the brightness (L*) relative to the control specimen. In addition, adding FJI up to 2% significantly increased total phenolic and flavonoid contents and antioxidant activity, as well as flavor score of supplemented bread samples, while additions above 2% resulted in undesirable taste and texture. FJI addition caused higher bile acid, NO2−, and cholesterol adsorption capacities. Moreover, FJI addition up to 4% significantly reduced glucose adsorption capacities at different in vitro starch digestion intervals. The findings revealed that FJI offers great potential as an ideal functional ingredient in food processing.

Background:ZEB2 gene mutations or deletions cause Mowat-Wilson syndrome (MWS), which is characterized by distinctive facial features, global developmental delay, intellectual disability, epilepsy, friendly and happy personalities, congenital heart disease, Hirschsprung disease and multiple congenital anomalies. Currently, more than 300 MWS patients have been described in the literature, and nearly 280 variants in ZEB2 have been identified.Methods: In this study, we report three unrelated Chinese patients presenting multiple congenital anomalies that were consistent with those of MWS. Whole-exome sequencing (WES) was used to identify the causative variants.Results: WES identified two novel de novo frameshift variants in ZEB2 (NM_014795.4:c.2136delC, p. Lys713Serfs*3 and c.2740delG, p. Gln914Argfs*16) in patients 1 and 2, respectively, and a novel de novo splicing variant in ZEB2 (NM_014795.4:c.808-2delA) in patient 3, all of which were confirmed by Sanger sequencing. Next, we systematically reviewed the clinical characteristics of Chinese and Caucasian MWS patients. We revealed a higher incidence of constipation in Chinese MWS patients compared to that previously reported in Caucasian cohorts, while the incidence of Hirschsprung disease and happy demeanor was lower in Chinese MWS patients and that epilepsy in Chinese MWS patients could be well-controlled compared to that in Caucasian MWS individuals.Conclusion: Our study expanded the mutation spectrum of ZEB2 and enriched our understanding of the clinical characteristics of MWS. Definitive genetic diagnosis is beneficial for the genetic counseling and clinical management of individuals with MWS.

Abstract Background Haemorrhoids occur commonly and frequently in the human digestive system. There are diverse causes of haemorrhoids and their in-depth pathogenesis is still currently unclear. Methods In this study, we explored haemorrhoids from an epigenetics perspective by employing RNA-Seq for comprehensive and in-depth analysis of the differences in microRNA (miRNA) transcripts between haemorrhoidal tissue and normal tissue in 48 patients with Grade II and above haemorrhoids. Results The results showed that 9 miRNAs were significantly upregulated (ratio > 3.5 and P-value 0.6 and P-value

Abstract Background Xp11.22 duplications have been reported to contribute to nonsyndromic intellectual disability (ID). The HUWE1 gene has been identified in all male Xp11.22 duplication patients and is associated with nonsyndromic ID. Currently, few Xp11.22 duplication cases have been reported in the Chinese population, with limited knowledge regarding the role of other genes in this interval. Case presentation We investigated four unrelated Chinese male Xp11.22 duplication patients, performed a comprehensive clinical evaluation for the patients and discussed the role of other genes in this interval. All patients presented with similar clinical features, including ID, speech impairments and motor delay, which were mostly consistent with those of the Xp11.22 duplication described previously. We searched and compared all cases and noted that one of the probands (Family 1) and DECIPHER case 263,219, who carried small overlapping duplications at Xp11.22 that only covered the entire HSD17B10 gene, also suffered from ID, suggesting the important role of HSD17B10 in this interval. Furthermore, three patients (two probands in Families 3 and 4 and DECIPHER case 249,490) had strikingly similar hypogonadism phenotypes, including micropenis, small testes and cryptorchidism, which have not been previously described in Xp11.22 duplication patients. Interestingly, the FGD1 gene was duplicated only in these three patients. Sufficient evidence has suggested that haploinsufficiency of the FGD1 gene causes Aarskog-Scott syndrome, which is characterized by hypogonadism and other abnormalities. Given that, we are the first group to propose that FGD1 may be a potential dosage-sensitive gene responsible for the hypogonadism observed in our patients. Conclusion We reported novel genotypes and phenotypes in Chinese male Xp11.22 duplication patients, and the HSD17B10 and FGD1 genes may be involved.

Abstract Background Pathogenic SLC6A1 variants have been reported in patients with myoclonic-atonic epilepsy (MAE). NOTCH1, encoding a member of the Notch family of proteins, is known to be associated with aortic valve disease. The PRIMPOL variant has only been identified in Chinese patients with high myopia. Exome sequencing analysis now allows the simultaneous detection of multiple genetic etiologies for patients with complicated clinical features. However, the presence of three Mendelian disorders in one patient supported by their respective pathogenic variants and clinical phenotypes is very rare. Case presentation Here, we report a 4-year-old Chinese boy who presented with MAE, delayed language, borderline intellectual disability (ID), mildly impaired social skills and attention deficit hyperactivity disorder (ADHD). He also had mild aortic valve stenosis and high myopia. Using whole-exome sequencing (WES), we identified three variants: (1) SLC6A1, NM_003042.4: c.881-883del (p.Phe294del), (2) NOTCH1, NM_017617.5:c.1100-2A > G and (3) PRIMPOL, NM_152683.4:c.265 T > G (p.Tyr89Asp). Parental Sanger sequencing confirmed that SLC6A1 and NOTCH1 variants were de novo, whereas the PRIMPOL variant was inherited from the father who also had high myopia. Furthermore, the PRIMPOL variant was absent from the genomes of the paternal grandparents, and thus was also a de novo event in the family. All three variants are classified as pathogenic. Conclusion The SLC6A1 variant could explain the features of MAE, delayed language, borderline ID, impaired social skills and ADHD in this patient, whereas the features of aortic valve stenosis and high myopia of the patient may be explained by variants in NOTCH1 and PRIMPOL, respectively. This case demonstrated the utility of exome sequencing in uncovering the multiple pathogenic variants in a patient with complicated phenotypes due to the blending of three Mendelian disorders.

With the intensification of human activities, the natural water cycle has a significant nature-society dual feature, and identifying the mutual feedback mechanism between natural and social water cycles is an important basis for a more accurate simulation of the dualistic water cycle. In this study, two indexes of cumulative runoff change rate and social water cycle feedback rate are put forward, representing the degree of change in socio-hydrological unit runoff under the mutual feedback of the natural social water cycle in all upstream regions, and the degree influence of the water intake, consumption, and discharge process of the social water cycle on the natural water cycle in the socio-hydrological unit, respectively. Taking the Beijing–Tianjin–Hebei region, which is marked by strong human activities, as the study area, the 2035 natural-social dualistic water cycles were simulated by a water allocation and simulation (WAS) model. Different water supply types and use structures cause the social water cycle to increase or decrease local runoff in different areas. The social water cycle feedback rate is greater than 1 in Beijing and Tianjin, and less than 0.25 in the mountainous areas and the Hebei plain, indicating that the social water cycle of each unit in the Beijing–Tianjin–Hebei region increases or decreases local runoff due to different water supply types and use structures. The cumulative runoff change rate in this region was 0.66, indicating that the overall runoff was attenuated due to the social water cycle, and runoff attenuation was greater in the south than the north.

Studies on human activities and the natural water cycle as a coupled system are essential for effective water resource management in river basins. However, existing calculation methods based solely on the natural water cycle do not meet the accuracy requirements of natural society dualistic water cycle simulations. Therefore, it is necessary to establish a more scientific and reasonable calculation unit division method and river confluence relationship determination method. This paper presents a socio-hydrological unit with natural society dual characteristics based on both the hydrological characteristics and the social administrative characteristics of the river basin. According to the elevation of the river buffer zone, river confluence relationships among socio-hydrological units are determined, and upstream and downstream confluence of the human–water system is obtained. Finally, a case study of the Jing-Jin-Ji region in China, an area of intensive human activities, was performed. A reliability of 94.3% was reached using the proposed socio-hydrological unit division and river confluence calculation method, suggesting that the approach is highly applicable. Thus, the proposed method for generating socio-hydrological units and determining river confluence relationships can be applied to study the mutual influence and spatial distribution characteristics of natural society dualistic water cycles. The data requirement is minimal, and the approach can provide benefits in research on human water systems.

IntroductionA high prevalence of cryptoglandular and Crohn's perianal fistulas has been reported worldwide, and several surgical options are available for the management of anal fistula, with varying clinical efficacy. However, currently, the available evidence for the effectiveness of these surgical approaches are lacking and of concern in terms of the credibility and strength. The purpose of this study is to evaluate the credibility of the published systematic reviews and meta-analyses that assess the efficacy and safety of the surgical options for cryptoglandular and Crohn's perianal fistulas through an umbrella review.Methods and analysisA systematic search in PubMed, Embase and Cochrane library will be performed from inception to December 2020 without any language restriction. We will include systematic reviews and meta-analyses that investigate the efficacy and safety of surgical approaches in the management of cryptoglandular and Crohn's perianal fistulas. Two reviewers will independently screen search results through reading the titles or abstracts. Relevant information will be extracted from each eligible systematic review or meta-analysis. Based on random effects model summary estimates along with their p values, 95% prediction intervals, between-study heterogeneity, small-study effects and excess significance, we will classify the evidence from convincing (class I) to weak (class IV). Findings will be summarized using quantitative synthesis combined with a narrative approach. Cryptoglandular and Crohn's perianal fistulas will be summarized separately. Two authors will independently perform the literature search, data extraction, and quality assessment of each included systematic review and meta-analysis. Any unresolved conflicts or doubts will be resolved by discussion or by consulting a senior author. The risk of bias of the systematic reviews will be assessed using a 16-item Assessment of Multiple Systematic Reviews 2 (AMSTAR2) checklist. The strength of evidence for the included systematic reviews will be classified as "high", "moderate", "low", or "critically low" quality.Ethics and disseminationEthics approval is not required as we will collect data from the published systematic reviews and meta-analyses without using individual patient data. The results of this umbrella review will be published in a peer-reviewed journal and will be presented at an anorectal disease conference.Prospero registration numberCRD42020200754.

Abstract Background Pathogenic KCNA1 variants have been linked to episodic ataxia type 1 (EA1), a rare neurological syndrome characterized by continuous myokymia and attacks of generalized ataxia that can be triggered by fever, abrupt movements, emotional stress, and fatigue. Currently, over 40 KCNA1 variants have been identified in individuals with EA1. Methods A male patient displayed partial seizures in addition to EA1 symptoms, often triggered by fever. A sibling presented with typical EA1 symptoms, seizures, and learning difficulties. In addition, the older brother displayed cognitive impairment, developmental delay, and slurred speech, which were absent in his younger sister. Whole‐exome sequencing was performed for the patients. Results A novel de novo missense variant in KCNA1 (p.Ala261Thr) was identified in the male patient, which is located in a base of the 3rd transmembrane domain (S3). The other novel KCNA1 variant (p.Gly376Ser) was identified in the sibling and was inherited from an unaffected father with low‐level mosaicism. The variant was located in the S5–S6 extracellular linker of the voltage sensor domain of the Kv channel. Next, we systematically reviewed the available clinical phenotypes of individuals with EA1 and observed that individuals with KCNA1 variants at the C‐terminus were more likely to suffer from seizures and neurodevelopmental disorders than those with variants at the N‐terminus. Conclusion Our study expands the mutation spectrum of KCNA1 and improves our understanding of the genotype–phenotype correlations of KCNA1. Definitive genetic diagnosis is beneficial for the genetic counseling and clinical management of individuals with EA1.

IntroductionPostoperative recurrence and related complications are common and related to poor outcomes in patients with anal fistula (AF). Due to being associated with short-term and long-term cure rates, perioperative complications have received widespread attention following AF surgery. This study aims to identify a set of predictive factors to develop risk prediction models for recurrence and related complications following AF surgery. We plan to develop and validate risk prediction models, using information collected through a WeChat patient-reported questionnaire system combined with clinical, laboratory and imaging findings from the perioperative period until 3–6 months following AF surgery.Methods and analysisThis is a prospective hospital-based cohort study using a linked database of collected health data as well as the follow-up outcomes for all adult patients who suffered from AF at a tertiary referral hospital in Shanghai, China. We will perform logistic regression models to predict anal fistula recurrence (AFR) as well as related complications (eg, wound haemorrhage, faecal impaction, urinary retention, delayed wound healing and unplanned hospitalisation) during and after AF surgery, and machine learning approaches will also be applied to develop risk prediction models. This prospective study aims to develop the first risk prediction models for AFR and related complications using multidimensional variables. These tools can be used to warn, motivate and empower patients to avoid some modifiable risk factors to prevent postoperative complications early. This study will also provide alternative tools for the early screening of high-risk patients with AFR and related complications, helping surgeons better understand the aetiology and outcomes of AF in an earlier stage.Ethics and disseminationThe study was approved by the Institutional Review Board of Shuguang Hospital affiliated with Shanghai University of Traditional Chinese Medicine (approval number: 2019-699-54-01). The results of this study will be submitted to international scientific peer-reviewed journals or conferences in surgery, anorectal surgery or anorectal diseases.Trial registration numberChiCTR1900025069; Pre-results.

Vegetation regulates the exchange of terrestrial carbon and water fluxes and connects the biosphere, hydrosphere, and atmosphere. Over the last four decades, vegetation greening has been observed worldwide using satellite technology. China has also experienced a notably widespread greening trend. However, the responsiveness of vegetation dynamics to elevated CO2 concentration, climate change, and human activities remains unclear. In this study, we attempted to explore the impact of natural (precipitation, air temperature), biogeochemical (CO2), and anthropogenic drivers (nighttime light, afforestation area) on changes in vegetation greenness in the Haihe River Basin (HRB) during 2002–2018 at the county-level. We further determined the major factors affecting the variation in satellite-derived normalized difference vegetation index (NDVI) from moderate resolution imaging spectroradiometer (MODIS) for each county. The results indicated that over 85% of the counties had a significantly increased NDVI trend, and the average linear trend of annual NDVI across the study region was 0.0037 per year. The largest contributor to the NDVI trend was CO2 (mean contribution 45%), followed by human activities (mean contribution of 27%). Additionally, afforestation was a pronounced driving force for NDVI changes in mountainous areas, resulting from ecosystem restoration efforts. Our findings emphasize the crucial role of CO2 fertilization in vegetation cover change, while considering CO2 concentration, climate change, and human activities, and shed light on the significant influences of afforestation programs on water resources, especially in mountainous areas.

It is of significance to examine the factors impacting individual water-saving behavior and their mechanism of action for water demand management, especially for domestic water demand management. To provide a solution to the issues of individual water-saving behavior research with unclear influence mechanisms and subjective modeling decisions, this study provides a novel idea of combining social survey and model study for research on domestic water conservation, introduces complex adaptive system theory to describe the mechanism of action between individuals as well as between individuals and external stimuli, and proposes a general framework for the model establishment and analysis of individual water-saving response research under external stimuli. This study uses Beijing as an empirical city. Based on the analysis results of the survey on Beijing residents’ domestic water use combined with the problems in Beijing’s domestic water-saving efforts, this study constructs water-saving regulation scenarios and corresponding individual water-saving response rules; systematically simulates the change process of individual water use considering the aspects of water price formulation, water use information, and water-saving publicity and education; quantitatively analyzes the influence of these three types of external stimuli on individual water saving; proposes individual water-saving promotion measures; and suggests the three aspects of water price formulation, water use information feedback, water-saving publicity and education.

With the intensification of global warming, spatiotemporal variations in the climate and their mechanisms have received increasing attention. Currently, the relationship between regional precipitation regime, large-scale circulation, and topography, particularly in high-altitude areas such as the Qinghai–Tibet Plateau, are not well understood. Herein, the spatial and temporal variability in the annual and intra-annual (wet and dry periods) precipitation at 33 stations in the Three-River Headwaters (TRH) region from 1967 to 2016 are analysed. Moreover, the empirical orthogonal function and wavelet transform coherence methods are used to analyse the relationships between the different modes of precipitation change and 14 atmospheric circulation indices. The following results were obtained. (1) The mean annual precipitation and mean dry period precipitation significantly increased over the studied period. Annual and intra-annual precipitation showed a spatial southeast-to-northwest decreasing trend. (2) Two main patterns of precipitation were observed during the studied period: a dominant pattern with high- and low-value centres located in southeast and northwest TRH, respectively, and a dipole pattern with more precipitation over southwest TRH and less precipitation over northeast TRH. (3) Precipitation had a negative correlation with latitude, positive correlation with longitude, and nonlinear relationship with elevation. (4) Precipitation changes over various parts of the studied domain were determined based on changes in the weather systems affecting the area, with different indices being correlated with different components during different times of the year.

Water-rights trade has proved to be an effective method for coping with water shortages through the transfer of water resources between users. The water allocation system is classified into two categories based on information transparency and water rights transaction goals: administered system (AS) and market-based system (MS). A multi-agent and multi-objective optimal allocation model, built on a complex adaptive system, was introduced to direct the distribution of water resources under an AS in the Shiyang River Basin; it was compared with a market-based water rights transaction model using the bulletin-board approach. Ideal economic agent equations played a dominant role in both models. The government and different water users were conceptualized as agents with different behaviors and goals in water allocation. The impact of water-saving cost on optimal water allocation was also considered. The results showed that an agent’s water-saving behavior was incentivized by high transaction prices in the water market. Under the MS, the highest bid in the quotation set had a dominant influence on how trade was conducted. A higher transaction price will, thus, result in a better benefit ratio, and a lower one will result in inactivity in terms of water rights trade. This will significantly impact the economic benefit to the basin.

In water shortage regions, water rights trading would be much useful for increasing water use inefficiency through changing users’ water demand. In this study, a water optimal allocation modelling system is proposed by considering water rights trading and other governmental policies such as water prices, water savings and industrial policies. An agent-based model was developed to describe the behaviors and goals of individual agents using complex adaptive system theory, information transfers, and functional mechanisms between agents. The developed model was applied to Bayannur City, which suffers from severe water shortages. The water prices for different industries, the water rights transaction price, and the behaviors of various agents in 2020 were forecasted. The results reveal that the water resources optimal allocation model applied in this study can help realize the reasonable allocation of regional water resources under limited water supply. It is also valuable to guide the government in making water resources allocation policies and provide a practical reference for the formulation and adjustment of a water market transaction price.

The performances of hydrological simulations for the Pearl River Basin in China were analysed using the Coupled Land Surface and Hydrological Model System (CLHMS). Three datasets, including East Asia (EA), high-resolution gauge satellite-merged China Merged Precipitation Analysis (CMPA)-Daily, and the Asian Precipitation Highly-Resolved Observational Data Integration Towards Evaluation (APHRODITE) daily precipitation were used to drive the CLHMS model to simulate daily hydrological processes from 1998 to 2006. The results indicate that the precipitation data was the most important source of uncertainty in the hydrological simulation. The simulated streamflow driven by the CMPA-Daily agreed well with observations, with a Pearson correlation coefficient (PMC) greater than 0.70 and an index of agreement (IOA) similarity coefficient greater than 0.82 at Liuzhou, Shijiao, and Wuzhou Stations. Comparison of the Nash-Sutcliffe efficiency coefficient (NSE) shows that the peak flow simulation ability of CLHMS driven with the CMPA-Daily rainfall is relatively superior to that with the EA and APHRODITE datasets. The simulation results for the high-flow periods in 1998 and 2005 indicate that the CLHMS is promising for its future application in the flood simulation and prediction.

In the title compound, C17H21N2O6P·CH3OH, the planes of the 4-nitroaniline and 2-hydroxyphenyl groups form a dihedral angle of 84.04 (8)°. The P atom exhibits tetrahedral geometry involving two O-ethyl groups, a Cα atom and a double-bonded O atom. In the crystal, O—H...O, N—H...O and C—H...O hydrogen bonds link the α-aminophosphonic acid and methanol molecules into chains that propagate parallel to the a axis.

As the debates surrounding the negative influences of flood control using dams or reservoirs on the eco-environment become fierce, non-structural flood control measures like land use change gain more attention. This study researched the effect of integrated and single land use changes on three floods at small, medium and large scales, respectively, in Yongding River basin. A SWAT (Soil and Water Assessment Tool) model was used to simulate the effect of integrated and single land use changes on floods of different scales. The single land uses were set as S1, S2, S3 to represent the agricultural, grass and construction land changes. The results showed that: (1) the integrated land use changes reduced the small flood, the medium flood and the large flood by 14%, 13% and 5%; (2) the land use management functioned most effectively on medium-scale floods and least effectively on large-scale floods; (3) S1 decreased the medium floods optimally by 24% with a 7-day maximum runoff volume as the indicator and by 29% with a 1-day maximum flood discharge; (4) S2 reduced the medium floods optimally by 21% with runoff depth volume as the indicator; (5) S3 increased the medium floods optimally by 15% with a 1-day maximum flood discharge as the indicator.