Background Carbendazim (CBZ), a widely used benzimidazole fungicide, has raised increasing concerns regarding the health risks associated with its residues. However, the toxic effects and associated mechanisms of CBZ on the skeletal system have not been reported. Objective To elucidate the effects of carbendazim on osteogenic differentiation and its underlying mechanisms. Methods MC3T3-E1 mouse pre-osteoblastic cells were treated with 1, 10, and 100 μmol·L⁻¹ CBZ for 24 h to examine cell viability, alkaline phosphatase (ALP) activity, bone nodule formation, reactive oxygen species (ROS) level, malondialdehyde (MDA) content, and nitric oxide synthase (NOS) activity. Transcriptomics was used to identify differentially expressed genes (DEGs) in osteoblasts exposed to CBZ. Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) were employed to analyze the potential biological pathways of DEGs. Real-time polymerase chain reaction (RT-PCR) and Western blot were used to validate changes in gene and protein expression. Results Exposure to 10 and 100 μmol·L⁻¹ CBZ significantly reduced osteoblast viability, ALP activity, bone nodule formation, and NOS activity, while increasing intracellular ROS levels. CBZ at 100 μmol·L⁻¹ concentration significantly elevated MDA level (P < 0.05). The transcriptomic analysis revealed that 1 μmol·L⁻¹ CBZ treatment resulted in 385 significantly DEGs. The KEGG enrichment analysis revealed that CBZ significantly affects hormone regulation pathways (including parathyroid hormone, growth hormone, dopamine, and oxytocin), mitogen-activated protein kinase (MAPK) and cyclic GMP-dependent protein kinase G (cGMP-PKG) signaling pathways, focal adhesion and adherens junction, as well as the NOD-like receptor signaling pathway and the mRNA surveillance (NMD) pathway. The results of GSEA showed that CBZ significantly inhibited the bile acid metabolism and the Wnt/β-catenin pathway in osteoblasts. The validation results demonstrated that CBZ significantly suppressed the mRNA expression of Wnt3a and β-catenin, as well as the protein expression of Runx2 and Osterix in the Wnt/β-catenin pathway. Conclusion CBZ exposure exhibits potential skeletal toxicity, and its mechanism is through promoting oxidative stress, interfering with the Wnt/β-catenin pathway in osteogenic differentiation, thereby inhibiting the bone formation function of osteoblasts.

Background With the progression of industrialization, an increasing number of emerging contaminants are entering aquatic environments, posing significant threats to the safety of drinking water. Therefore, establishing a system for identifying unknown hazardous factors and implementing safety warning mechanisms for drinking water is of paramount importance. Among these efforts, non-target screening plays a critical role, but its effectiveness is largely constrained by the scope of coverage of sample pre-treatment methods. Objective To integrate modern chromatography/mass spectrometry techniques with advanced data mining methods to develop a non-discriminatory sample pre-treatment method for comprehensive enrichment of unknown contaminants in drinking water, laying a technical foundation for the discovery and identification of unknown organic hazardous factors in drinking water. Methods A non-discriminatory pre-treatment method based on supramolecular and solid-phase extraction was developed. The final target compounds including 333 pesticides, 194 pharmaceuticals and personal care products (PPCPs), and 59 per- and polyfluoroalkyl substances (PFASs) were used for optimizing the pre-treatment method, confirming its coverage. The impacts of different eluents on the absolute recovery rates of target compounds were compared to select the conditions with the highest recovery for sample pre-treatment. The effects of different supramolecular solvents and salt concentrations on target compound recovery were also evaluated to determine the most suitable solvent and salt concentration. Results The solid-phase extraction elution solvents, supramolecular extraction solvents, and salt concentrations were optimized based on the target compound recovery rates. The optimal recovery conditions were achieved using 2 mL methanol, 2 mL methanol (containing 1% formic acid), 2 mL ethyl acetate, 2 mL dichloromethane, hexanediol supramolecular solvent, and 426 mg salt. The detection method developed based on these conditions showed a good linear relationship for all target compounds in the range of 0.1-100.0 ng·mL⁻¹, with R² > 0.99. The method’s limit of detection ranged from 0.01 ng⁻¹ to 0.95 ng⁻¹, and 95% of target compounds were recovered in the range of 20%-120%, with relative standard deviation (RSD) less than 30%, indicating good precision. Conclusion The combined pre-treatment method of solid-phase extraction and supramolecular solvent extraction can effectively enrich contaminants in drinking water across low, medium, and high polarities, enabling broad-spectrum enrichment of diverse trace contaminants in drinking water. It provides technical support for broad-spectrum, high-throughput screening and identification of organic pollutants in drinking water, and also serves as a reference for establishing urban drinking water public safety warning systems.

ObjectiveTo explore the biological mechanism of bone loss caused by perfluorooctanoic acid (PFOA) through transcriptomic analysis, and to provide new insights into regulating perfluoroalkyl substances (PFAS) applications and the prevention of hazards affecting bone health. MethodsMouse embryonic osteoblast precursor cells (MC3T3-E1) were exposed to 0.1, 1, 10, and 100 μmol·L^-¹ PFOA for 24 hours to assess the effects on cell viability and alkaline phosphatase (ALP) activity, and to determine the critical concentration of PFOA toxicity. The transcriptome sequencing (RNA-seq) was performed to identify differentially expressed genes (DEGs) induced by PFOA. Gene ontology (GO) analysis and gene set enrichment analysis (GSEA) were conducted to identify significantly affected gene pathways. Additionally, Seahorse XF metabolic phenotyping and reverse transcription polymerase chain reaction (RT-PCR) were used to validate the key pathways. ResultsExposure to 10 and 100 μmol·L^-¹ PFOA significantly reduced the cell viability and ALP activity of MC3T3-E1 cells. Therefore, the results of transcriptomic analysis for 10 μmol‧L^-1 PFOA exposure found that a total of 80 DEGs were identified, including 32 upregulated genes and 48 downregulated genes. According to GO analysis, PFOA mainly affected cellular components such as mitochondrion and nucleus, molecular functions involving GTPase activity and GTP binding, as well as biological process related to mRNA processing. GSEA identified the downregulation of the β-oxidation of fatty acid pathway in mitochondria. Metabolic phenotyping reserches showed that PFOA indeed reduced mitochondrial aerobic respiration capacity and adenosine triphosphate (ATP) production, and the ratio of ATP production from cellular aerobic respiration to glycolysis was significantly decreased as well. The mRNA expression of glucose metabolism-related genes (GK, G6PD, and CS), as well as fatty acid metabolism-related genes (CPT1A and CPT2), were significantly downregulated. ConclusionPFOA reduces bone formation by inhibiting energy metabolism and β-oxidation of fatty acid pathways in osteoblasts, whihc lays the foundation for revealing the mechanism of PFOA exposure induced bone loss.

ObjectiveTo explore the role of flurochloridone (FLC) on osteogenic differentiation and the potential mechanism of inhibiting bone formation, and to provide new insights into bone health risks associated with FLC pesticide exposure. MethodsNeonatal rat skull differentiation primary osteoblast model was used to investigate the effects of 1, 10 and 100 μmol·L^-1 FLC exposure on cell viability, osteogenic differentiation alkaline phosphatase (ALP) activity, and bone mineralization nodule formation, respectively. The potential mechanism underlying the inhibition of FLC on osteoblast differentiation was analyzed using osteogenic differentiation gene chip technique, and the expression of key genes and proteins in the pathway was validated using reverse transcription polymerase chain reaction (RT-PCR) and protein immunoblotting (Western blot) methods. ResultsExposure to FLC at a concentration of 100 μmol·L⁻¹ reduced cell proliferation, ALP activity, and the formation of mineralized nodules in primary osteoblasts. Gene chip analyses revealed that exposure to 10 μmol·L⁻¹ FLC induced 15 differentially expressed genes (DEGs). Among these, MMP9 and Tnf were up-regulated, while Nkx3⁃2, Tuft1, Bmp2, Col12a1, Pparg, Enam, Igf1, Bmp5, Bmp3, Calcr, Egf, Igfbp3, and Col14a1 were down-regulated. Results of protein-protein interaction analyses and gene ontology enrichment analyses indicated that FLC inhibited the BMP/SMAD pathway involved in osteogenic differentiation. FLC suppressed the protein expression of BMP2 and Osterix, as well as the expression of key genes critical for osteogenic differentiation and ossification, such as BMP2, Runx2, SMAD1, and SMAD5 in the BMP/SMAD pathway. ConclusionFLC affects osteogenic differentiation and bone formation potential by regulating the BMP/SMAD axis and the expression of osteogenic genes, suggesting its potential risk in bone metabolism.

BACKGROUND:For elderly patients with traumatic hip fractures,the related factors of prognosis are very complex,and the integrity of the lateral wall is one of the influencing factors.It is of important clinical value to understand the effect of lateral wall injury on the prognosis of femoral intertrochanteric fracture. OBJECTIVE:To evaluate the relationship between the integrity of the lateral wall and hip functional recovery and other outcomes in patients with femoral intertrochanteric fractures. METHODS:Totally 82 patients with femoral intertrochanteric fractures were screened and all patients received proximal femoral nail antirotation fixation.According to the thickness of the lateral wall,the patients were divided into the lateral wall intact group(n=31)and lateral wall risk group(n=51).The perioperative indexes,weight-bearing time,fracture healing time,hip joint function and range of motion,postoperative pain and complications were compared between the two groups. RESULTS AND CONCLUSION:(1)The time of hospitalization and the number of fluoroscopies during operation in the lateral wall intact group were significantly lower than those in the lateral wall risk group(P<0.05),but there was no significant difference in other perioperative indexes.(2)Both groups were able to get down to the ground early after surgery and finally complete weight-bearing,but in the lateral wall risk group,the time of fracture healing was longer;the time of complete weight-bearing was significantly delayed;the Harris score of the last follow-up was lower;the range of motion of hip extension and flexion and neck trunk angle on the affected side were smaller(P<0.05).(3)There was no significant difference in the incidence of postoperative complications between the two groups,but the overall incidence of complications in the lateral wall intact group was significantly lower(P<0.05).(4)In summary,after internal fixation of proximal femoral nail antirotation,patients with the intact lateral wall had a relatively better prognosis than those with risk lateral wall.

Per- and polyfluoroalkyl substances （PFASs） are a new type of persistent organic pollutants with global attention. They have shown multiple toxic effects due to their persistent accumulation in human body through exposure to environmental media such as drinking water， food， atmosphere， and soil. However， the bone toxicity of PFASs has not attracted enough attention. It is believed that the exposure and accumulation of PFASs in human have a significant impact on the bone health， especially hindering the healthy bone development in infants and adolescents， and aggravating the occurrence of bone loss and fracture in the elder populations. This paper will review the research progress of the effects of PFASs exposure on bone health indicators such as bone mineral density， and discuss the mechanisms of PFAS in bone toxicity. This review will provide references for revealing the effects of PFASs exposure on bone health and their toxic mechanisms.

OBJECTIVE: To explore the effectiveness and advantages of using Fastpass Scorpion suture passer to stitch the inferior capsulolabral complex in arthroscopic Bankart repair compared with traditional arthroscopic suture shuttle. METHODS: The clinical data of 41 patients with Bankart lesion, who met the selection criteria and were admitted between August 2019 and October 2021, was retrospectively analyzed. Under arthroscopy, the inferior capsulolabral complex was stitched with Fastpass Scorpion suture passer in 27 patients (FS group) and with arthroscopic suture shuttle in 14 patients (ASS group). There was no significant difference between the two groups ( P>0.05) in gender, age, injured side, frequency of shoulder dislocation, time from first dislocation to operation, and preoperative Rowe score of shoulder. Taking successful suture and pull-tightening as the criteria for completion of repair, the number of patients that were repaired at 5∶00 to 6∶00 (<6:00) and 6∶00 to 7∶00 positions of the glenoid in the two groups was compared. The operation time, and the difference of Rowe shoulder score betwee pre- and post-operation, the occurrence of shoulder joint dislocation, the results of apprehension test, and the constituent ratio of recovery to the pre-injury movement level between the two groups at 1 year after operation. RESULTS: Both groups completed the repair at 5∶00 to 6∶00 (<6∶00), and the constituent ratio of patients completed at 6∶00 to 7∶00 was significantly greater in the FS group than in the ASS group ( P<0.05). The operation time was significantly shorter in the FS group than in the ASS group ( P<0.05). All incisions in the two groups healed by first intention. All patients were followed up 12-36 months (mean, 19.1 months). No anchor displacement or neurovascular injury occurred during follow-up. Rowe score of shoulder in the two groups significantly improved at 1 year after operation than preoperative scores ( P<0.05), and there was no significant difference in the difference of Rowe shoulder score between pre- and post-operation between the two groups ( P>0.05). At 1 year after operation, no re-dislocation occurred, and there was no significant difference in the apprehension test and the constituent ratio of recovery to the pre-injury movement level between the two groups ( P>0.05). CONCLUSION Compared with the arthroscopic suture shuttle, using Fastpass Scorpion suture passer to stitch the inferior capsulolabral complex in arthroscopic Bankart repair is more convenient, saves operation time, and has good effectiveness.
Humans ; Animals ; Arthroscopy/methods* ; Scorpions ; Retrospective Studies ; Treatment Outcome ; Shoulder Dislocation/surgery* ; Sutures ; Equidae ; Shoulder Joint/surgery* ; Joint Instability/surgery* ; Suture Anchors ; Recurrence ; Range of Motion, Articular

Background Parabens, a widely used class of preservatives, are suspected to be potential obesogens as emerging endocrine disrupting chemicals with reproductive and developmental toxicity. Objective To analyze five urinary parabens (PBs) and estimate the associations of exposure to PBs with adiposity measures in 10-year-old school-age children. Methods A total of 471 school-age children aged 10 years from the Sheyang Mini Birth Cohort were enrolled in this study. A questionnaire survey was conducted to collect socio-demographic information, physical activity, and dietary intake. Weight, height, and waist circumference of children were measured, and age- and sex-adjusted body mass index (BMI-Z score) was calculated. Spot urine samples were collected during the follow-up visits. Urinary concentrations of five PBs including methyl-paraben (MeP), ethyl-paraben (EtP), propyl-paraben (PrP), butyl-paraben (BuP), and benzyl-paraben (BzP) were detected by gas chromatography-tandem mass spectrometry (GC-MS/MS). Generalized linear models (GLMs) and Bayesian kernel machine regression (BKMR) models were applied to estimate associations of individual/overall urinary PBs concentrations with BMI Z-score and waist circumference. Results The positive rates of selected five urinary PBs were in the range from 78.98% to 98.94%. The urinary PBs concentrations (geometric mean) were in the range of 0.31-5.43 μg·L⁻¹. The children's BMI Z-score and waist circumference (mean ± standard deviation) were (0.56±1.40) and (67.62±10.07) cm respectively. The GLMs results showed that the urinary BzP concentration was negatively associated with waist circumference (b=−0.08, 95%CI: −0.14, −0.02; P=0.01). In sex-stratified analysis, the urinary concentration of BzP was negatively associated with BMI-Z score (b=−0.59, 95%CI: −0.88, −0.30; P<0.001) and waist circumference (b=−0.80, 95%CI: −1.23, −0.37; P<0.001) in boys, but not in girls. The BKMR results also found significant negative correlations of urinary BzP concentrations with BMI-Z score and waist circumference, which were consistent with the GLM results. Conclusion The selected 10-year-old children are extensively exposed to PBs in the study area. Furthermore, childhood PBs exposure may have potential impacts on childhood adiposity measures with sex-specific effects.

The epidemic of 2019 novel coronavirus, later named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still gradually spreading worldwide. The nucleic acid test or genetic sequencing serves as the gold standard method for confirmation of infection, yet several recent studies have reported false-negative results of real-time reverse-transcriptase polymerase chain reaction (rRT-PCR). Here, we report two representative false-negative cases and discuss the supplementary role of clinical data with rRT-PCR, including laboratory examination results and computed tomography features. Coinfection with SARS-COV-2 and other viruses has been discussed as well.

A 25-year-old man with extensive burn due to industrial dust explosion was admitted to the First Affiliated Hospital of Naval Medical University on 16th October, 2018. Four days after the first skin grafting and vacuum sealing drainage surgery, the patient developed signs of uncontrolled severe inflammation and shock. However, several atypical manifestations interfered the diagnosis of septic shock. After giving emergency treatment including fluid resuscitation, broad-spectrum antibiotics, and administration of vasopressor agents, the patient′s condition was alleviated, but quickly relapsed and deteriorated, with acute pulmonary edema appeared in the evening of the same day. Finally, the condition was reversed by completely removing the negative pressure devices on upper limbs and thorough dressing change. This case suggests that the diagnosis and treatment of infection in patients with extensive burn need comprehensive analysis. Timely intervention of the wound is the key to control the exacerbation of sepsis. In addition, the possibility of pulmonary edema in patients with sepsis should be on high alert.