Background Work-related musculoskeletal disorders (WMSDs) are a major occupational health concern, particularly among workers exposed to adverse ergonomic conditions. Manganese production involves heavy physical demands, yet research on WMSDs among manganese workers remains limited. Objective To investigate the prevalence and influencing factors of WMSDs among manganese workers in a manganese enterprise in Guangxi. Methods A cross-sectional survey was conducted from May to June 2024 on workers at a manganese factory in Guangxi. The Chinese Musculoskeletal Disorders Questionnaire was used to collect information on demographic characteristics, distribution of musculoskeletal symptoms, and work-related exposures. χ² test was applied to compare differences in positive WMSDs rates across groups, and logistic regression analysis was performed to identify associated factors. Results A total of 1476 workers were enrolled in the study after pre-determined inclusion and exclusion criteria. The overall prevalence of WMSDs was 34.15%. The most commonly affected body regions were the lower back (17.28%), neck (16.67%), and shoulders (13.82%). The results of logistic regression analysis indicated that female, older age, and education level of college or above were associated with a higher risk of WMSDs (P<0.05). Awkward working postures were significantly associated with WMSDs in corresponding body regions; in particular, awkward postures of the neck, upper limbs, trunk, and lower limbs were related to an increased risk of WMSDs in multiple body sites (P<0.05). In addition, poor lighting conditions, high workplace temperature, frequent or sustained arm support during work, and high job demands were associated with an increased risk of overall or site-specific WMSDs (P<0.05). Conclusion The high prevalence of WMSDs among manganese workers is closely associated with demographic characteristics, working postures, and work environment and organizational factors. Targeted ergonomic interventions focusing on high-risk body regions and key ergonomic exposures are warranted to reduce the risk of WMSDs among manganese workers.

Objective To optimize the animal-free fermentation medium and fermentation conditions of pneumococcus, and make it suitable for fermentation production.MethodsThe orthogonal method was used to optimize the carbon source(glucose)(12. 5, 18. 75, 25 g/L), nitrogen source(soybean peptone)(30, 40, 50 g/L) and uracil(10, 20, 30 mg/L) concentrations of fermentation medium for type 1, 3, 5, 9N and 33F pneumococci, as well as fermentation culture conditions such as strain concentration(A_(694))(0. 2, 0. 4, 0. 6), fermentation temperature(35, 36, 37 ℃) and pH(6. 8, 7. 2, 7. 6).ResultsThe optimal fermentation medium compositions for pneumococcus were as follows: for type 1, soybean peptone at 50 g/L, initial glucose concentration at 18. 75 g/L, and uracil at 30 mg/L; the optimal fermentation conditions were A_(694)at 0. 6, temperature at 35 ℃,and pH at 7. 6. For type 3, the optimal medium consisted of soybean peptone at 30 g/L, initial glucose concentration at 12. 5 g/L,and uracil at 10 mg/L; the optimal fermentation conditions were A_(694)at 0. 6, temperature at 35 ℃, and pH at 7. 2. For type 5,the optimal medium comprised soybean peptone at 50 g/L, initial glucose concentration at 12. 5 g/L, and uracil at 20 mg/L;the optimal conditions were A_(694)at 0. 6, temperature at 36 ℃, and pH at 6. 8. For type 9N, the optimal medium consisted of soybean peptone at 50 g/L, initial glucose concentration at 18. 75 g/L, and uracil at 10 mg/L; the optimal conditions were A_(694)at 0. 6, temperature at 36 ℃, and pH at 7. 2. For type 33F, the optimal medium comprised soybean peptone at 50 g/L, initial glucose concentration at 12. 5 g/L, and uracil at 30 mg/L; the optimal conditions were A_(694)at 0. 4, temperature at 37 ℃, and pH at 6. 8.ConclusionThe optimized fermentation medium and fermentation conditions can be applied to the research and production of 24-valent pneumococcal polysaccharide vaccine.

OBJECTIVE: To investigate the prenatal manifestation and genetic basis for two fetuses suspected for Osteocraniostenosis (OCS). METHODS: Two fetuses undergoing invasive prenatal diagnosis at Cangzhou People's Hospital in April and August 2021 for short long bones and abnormal skull morphology were selected as the study subjects. Clinical data were collected and analyzed. Genomic DNA was extracted from amniotic fluid and peripheral blood samples of the two couples. Candidate variants were validated by Sanger sequencing. Literature was retrieved from CNKI, Wanfang Data Knowledge Service Platform and PubMed using keywords including "FAM111A gene", "gracile bone dysplasia", "FAM111A" and "osteocraniostenosis" from January 1, 2000 to June 30, 2025. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: K2020-049). RESULTS: Fetus 1 was found to have short limbs, abnormal skull morphology and shallow cerebral sulci. Fetus 2 showed short limbs, irregular skull halo, prominent forehead and bilateral frontal narrowing. Trio-WES revealed that fetus 1 has carried a heterozygous missense variant c.1582G>C (p.Asp528His) in exon 4 of the FAM111A gene, which was unreported previously. Fetus 2 has harbored a heterozygous in-frame deletion c.1020_1022delTTC (p.Ser343del) in exon 6 of the FAM111A gene, which has been recorded as likely pathogenic by the ClinVar and HGMD databases. Sanger sequencing confirmed that the parents of both fetuses were wild-type for the variant sites. A total of 9 previously reported patients with FAM111A-related gracile bone dysplasia/OCS from 4 publications were retrieved. The main clinical features included intrauterine growth restriction, hypomineralized skull, gracile long bones with narrow medullary cavities and characteristic facial anomalies, which were in large in keeping with the prenatal features of the two fetuses. CONCLUSION Both fetuses were diagnosed with FAM111A-related OCS based on the characteristic prenatal findings and identification of the FAM111A variants. Above finding expanded the phenotypic spectrum of FAM111A-associated disorders and provided clues for the prenatal diagnosis and genetic counseling.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis ; Phenotype ; Fetus ; Male ; Bone Diseases, Developmental/genetics* ; Adult

ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

Objective:To learn about the current situation of organizational management and inter-departmental coordination and provide a basis for optimization the national joint prevention and control strategy of endemic fluorosis and arsenicosis.Methods:The staff engaged in prevention and control of endemic fluorosis and arsenicosis at the provincial, municipal, county, township, and village levels were selected as the investigation subjects. An online questionnaire survey was conducted to collect relevant information on organizational management and departmental coordination. SAS 9.4 software was used for data statistical analysis.Results:A total of 3 107 valid questionnaires were collected, covering 25 provinces, distributed in 6 regions including Northeast China, North China, East China, Central China, Northwest China, and Southwest China. Totally 92.52% (1 088/1 176) of the respondents believed that a leading group for prevention and control of endemic diseases had been established in their localities, there were statistically significant differences among different regions (χ 2 = 17.18, P = 0.004). However, the highest proportion of those who believed that no leading group had been established was in the Southwest China (14.09%, 21/149). Totally 83.97% (906/1 079) of the respondents believed that the coordination role of the leading group for endemic disease prevention and control was very good or relatively good. The proportion of survey respondents who believed that the local water resources department had a good/relatively good main responsibility in implementation of water improvement measures in drinking-water-borne fluorosis and arsenic poisoning areas, as well as in management of fluoride and arsenic reduction water improvement projects, were 90.51% (2 203/2 434) and 89.37% (2 143/2 398), respectively. The differences between different regions were statistically significant (χ 2 = 70.90, 57.40, P < 0.001). The highest proportion of general/poor cases was believed to be in the southwest region [25.14% (46/183), 24.58% (44/179)]. Totally 71.37% (187/262) of the respondents believed that the supply and distribution of low-fluorine brick tea in tea-drinking-borne endemic fluorosis areas were very good or good. Totally 90.55% (1 447/1 598) of the respondents believed that local medical insurance departments had included skeletal fluorosis patients who were covered by medical insurance. Totally 90.71% (1 474/1 625) of the respondents believed that social assistance departments had included eligible patients with skeletal fluorosis in the scope of social assistance. There were significant differences in the inclusion rate among different regions (χ 2 = 50.45, 46.22, P < 0.001). North China [18.99% (30/158), 21.43% (33/154)] and Southwest China [18.64% (33/177), 15.22% (28/184)] were the two regions with the highest percentage of respondents who believed that the above two were not included. Totally 83.19% (1 425/1 713) of the respondents believed that the local designated hospital for treatment of skeletal fluorosis had been established, there were statistically significant differences among different regions (χ 2 = 31.54, P < 0.001). North China (26.40%, 47/178) and Northwest China (24.56%, 42/171) had the highest proportion of those who believed that there were no designated treatment hospitals for skeletal fluorosis. Totally 83.58% (1 502/1 797) of the respondents believed that the utilization of medical insurance and other policy assistance was very good or good by skeletal fluorosis patients. In Northeast China (30.34%, 27/89), North China (28.41%, 50/176), Southwest China (24.00%, 48/200), and Northwest China (21.43%, 39/182), the proportion of those who believed that the utilization was average and poor were significantly lower than those in East China (11.57%, 96/180) and Central China (10.94%, 35/320, Pcorrect < 0.05). Totally 92.96% (2 747/2 955) of the respondents believed that the cooperation degree of education departments in school monitoring and health education was very good or good, and there were significant differences between different regions (χ 2 = 26.11, P < 0.001), and the highest proportion of respondents who believed that the degree of cooperation was average and poor was in Southwest China (12.63%, 37/293). Conclusions:Except for the East China and Central China, there are different degrees of problems in the organization management and/or departmental coordination and cooperation between departments of endemic fluorosis and arsenicosis prevention and control, especially in the Southwest region. All regions should raise awareness of risk prevention and control, strengthen joint prevention and control, and integrate medical and prevention mechanisms, and consolidate and improve the achievements of endemic fluorosis and arsenicosis prevention and control.

Objective To search,evaluate and summarise the best evidence on non-drug intervention for nipple pain or injury in breastfeeding mothers.Methods Based on the"6S pyramid"evidence model,desktop searches were conducted on databases of UpToDate,Joanna Briggs Institute evidence-based practice database(JBI),National Guideline Clearinghouse(NGC),National Institute for health and Care Excellence(NICE),Guidelines International Network(GIN),Registered Nurses'Association of Ontario(RNAO),American College of Obstetricians and Gynecologists(ACOG),Medlive,Chinese Medical Association(CMA)website,Breastfeeding Medical Association(BMA),CNKI,Wanfang Data,SinoMed,Cochrance Library,PubMed,Embase,Web of Science,and CINAHL for literature in non-drug interventions for nipple pain or injury in breastfeeding women.The literature included clinical guidelines,decisions,recommended practices,evidence summaries,expert consensus,systematic reviews and randomized controlled trials(RCTs).The searched databases spanned from 1st January,2013 to 30th April,2024.Two researchers who were trained in evidence-based nursing independently evaluated the methodological quality,extracted and integrated evidence from eligible literature.Results A total of 15 documents were included,consisting of 5 clinical guidelines,2 clinical decisions,1 expert consensus,6 systematic evaluations and 1 RCT.Thirty-one pieces of evidence were summarised across 4 categories:accurate perinatal assessment,feeding guidance,non-drug intervention and health education.Conclusion The summarised best evidence on non-drug intervention for nipple pain or injury in breastfeeding women provides an evidence-based basis for clinical healthcare professionals.

Objective:To assess the nutritional status and risk of children with cyclic vomiting syndrome（CVS）and to provide a clinical evidence for nutritional support.Methods:A total of 160 children diagnosed with CVS and 160 healthy controls were prospectively enrolled in the study，who were admitted to Beijing Tsinghua Changgung Hospital from April 2021 to February 2024.Nutritional status was assessed by anthropometric indices（height，weight，and body mass index），and it was expressed in standard deviation score（Z score）.Nutritional risk screening tool STRONGkids was applied to nutritional risk screening，and the laboratory assessment（albumin，pre-albumin，hemoglobin，urea nitrogen and creatinine）were measured.Results:Among the 160 cases，there were 73 males and 87 females，including 18 cases of mild seizures and 142 cases of moderate and severe seizures，with the average onset age of（47.54±2.96）months and an average diagnosis age of（74.89±3.68）months.The average duration from the first attack to diagnosis was（27.35±2.36）months，and the average course of the disease was（41.35±2.63）months.The malnutrition rate of children in CVS was 36.9%（59/160），of which 18.1%（29/160）was severely malnourished.There was a statistically significant difference in the weight-for-age Z-score（WAZ），height-for-age Z-score（HAZ），and body mass index-for-age Z-score（BAZ）between the CVS group and the control group（ P<0.001）.We found a statistically significant difference in laboratory indicators（albumin，pre-albumin，hemoglobin，urea nitrogen and creatinine）between the two groups（all P<0.001）and hemoglobin was positively correlated with WAZ，HAZ and BAZ（ r=0.346,0.250,0.277，all P<0.01）.Using the STRONGkids nutritional risk screening tool，there were 43 cases with moderate nutritional risk and 117 cases with high nutritional risk，and children with high nutritional risk were likely to have lower WAZ，HAZ and BAZ than the children with moderate nutritional risk，and there was a significant difference in WAZ，HAZ，BAZ，hemoglobin，and creatinine between the two groups（ P<0.05）.And there was a correlation between the degree of CVS attack and nutritional risk grouping（ r=0.543， P<0.001）. Conclusion:Children with CVS have a high incidence of malnutrition，and the serum albumin，prealbumin，hemoglobin，urea nitrogen and creatinine levels are of great value for nutritional assessment.The STRONGkids score method helps to evaluate nutritional risk in children with CVS.

Objective:To investigate the characteristics of gut microbiota distribution in children with cyclic vomiting syndrome（CVS）complicated by constipation.Methods:The children with CVS, aged from 1 to 16 years, who were admitted to Beijing Tsinghua Changgung Hospital from June 2022 to January 2024, were divided into constipation group and normal group(non-constipation group) according to whether they were complicated with constipation or not.The clinical data and stool samples of children were collect. The abundance, diversity and composition of intestinal flora in fecal samples of two groups were detected by metagenomics sequencing.Results:A total of 20 children with CVS were collected, including 10 patients in constipation group and 10 patients in normal group.There were no significant differences in general demographic data between the two groups, including age at admission, age at first onset, body mass index, gender distribution, disease severity, endoscopic findings, and abdominal pain patterns.Microbiome analysis yielded 470 operational taxonomic units (OTUs), with 414 OTUs identified in normal group and 56 OTUs in constipation group. The abundance and diversity of intestinal flora in constipation group were significantly lower than those in normal group. Principal coordinate analysis and principal component analysis indicated significant structural differences in gut microbiota composition between the two groups. LEfSe analysis revealed distinct taxonomic patterns between the two groups, with the normal group demonstrating predominant representation of Firmicutes at the phylum level, while the constipation group showed higher relative abundance of Bacteroidetes and Actinobacteria. KEGG pathway analysis revealed that the carbon metabolism pathways was significantly enriched in the constipation group.Conclusion:There are significant differences in intestinal flora between CVS children with and without comorbid constipation.Bacteroides and Actinomycetes play an important role in constipation of children with CVS. The diversity and metabolic function of intestinal flora may be one of the pathological mechanisms of CVS complicated with constipation.

Objectives:To explore the predictive value of residual Murray's law-based quantitative flow ratio(μQFR)on long-term vessel-oriented composite endpoints(VoCE).Methods:This retrospective study included 3 510 patients from the FAVOR Ⅲ China trial.Offline residual μQFR analysis was performed on all vessels(diameter≥2.5 mm)with 50%-90%stenotic lesions.Patients were stratified into high-,intermediate-,and low-risk groups based on residual μQFR tertiles.The primary endpoint was 3-year VoCE,defined as a composite of cardiac death related to the target vessel,target vessel-related spontaneous myocardial infarction,and ischemia-driven target vessel revascularization.Results:Offline analysis was performed on 5 256 vessels from 3 510 patients.The mean residual μQFR was 0.92±0.75.The high-risk group(residual μQFR≤0.91)with 1 554 patients(1 958 vessels);the intermediate-risk group(residual μQFR 0.92-0.96)with 1 211 patients(1 906 vessels);and the low-risk group(residual μQFR>0.96)with 745 patients(1 392 vessels).Over 3-year follow-up,VoCE occurred in 227 vessels(4.3%).The 3-year VoCE incidence was significantly higher in the high-risk group compared to the intermediate-and low-risk groups(6.2%vs.4.1%vs.2.5%,log-rank P<0.001),primarily driven by ischemia-driven target vessel revascularization(5.0%vs.3.0%vs.1.6%,log-rank P<0.001).Hypertension(OR=0.83,95%CI:0.72-0.96),hypercholesterolemia(OR=0.84,95%CI:0.73-0.97),bifurcation lesions(OR=0.72,95%CI:0.63-0.83),moderate/severe calcification(OR=0.70,95%CI:0.57-0.84),and tandem lesions(OR=0.59,95%CI:0.47-0.75)were independent predictors of lower residual μQFR values.Conclusions:Lower residual μQFR is significantly associated with increased VoCE risk during the 3-year follow up period.