Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Objective: To evaluate the efficacy of supraclavicular fasciocutaneous island flap (SIF) for repairing the defect of parotid or auricle regions after tumor resection. Methods: From February 2019 to June 2021, 12 patients (11 males and 1 female, aged 54-77 years old), of whom 4 with parotid adenoid cystic carcinoma and 8 with auricular basal cell carcinoma underwent reconstruction surgery for postoperative defects in the parotid gland area and auricular area with SIF in the Department of Otorhinolaryngology Head and Neck Surgery, the Second Xiangya Hospital of Central South University and their clinical data were retrospectively analyzed. Size of the SIF, time for harvesting SIF, neck lymph node dissection and postoperative complications were recorded. Results: The flap areas were (6-9) cm × (8-13) cm, and the harvesting time for SIF ranged from 40 to 80 min, averaging 51.7 min. The donor sites were directly closed. All patients underwent ipsilateral levels Ⅰ-Ⅲ neck dissection, with 4 cases undergoing additional level Ⅳ neck dissection and 2 cases undergoing level Ⅳ-Ⅴ neck dissection. Of the 12 SIF, 10 were completely survival and 2 had flap arterial crisis with partial flap necrosis, in addition, 1 had donor site wound dehiscence. With follow-up of 10-42 months, there were no tumor recurrences in 10 patients, 1 patient was lost to follow-up at 10 months postoperatively, and 1 patient experienced local tumor recurrence at 11 months after surgery and died 15 months later. Conclusion: SIF is an easily harvested flap with good skin features matching the skin in parotid and auricle regions and less damage to donor site, and this flap has no need for microvascular anastomosis technique. SIF is feasible and effective for repairing defects in parotid and auricle area.
Male ; Humans ; Female ; Middle Aged ; Aged ; Plastic Surgery Procedures ; Parotid Gland/surgery* ; Retrospective Studies ; Neoplasm Recurrence, Local ; Surgical Flaps/blood supply* ; Skin Transplantation/methods* ; Postoperative Complications ; Treatment Outcome

Objective:To analyze measurement results of serum allergen-specific immunoglobulin E (IgE) in patients with eczema/dermatitis.Methods:A retrospective analysis was conducted on serum allergen-specific immunoglobulin E (IgE) levels in 3 051 patients with eczema/dermatitis, who visited the allergy clinic of Huashan Hospital from April 1, 2021 to March 31, 2022. The serum allergen-specific IgE level was detected by using the Phadia allergen detection system, and positive rates of allergens were calculated to determine common inhaled allergens and food allergens in patients with eczema/dermatitis. Comparisons of enumeration data between groups were performed by chi-square test.Results:Among the 3 051 patients with eczema/dermatitis, there were 1 412 with atopic dermatitis and 1 639 were other eczema/dermatitis. Detection of serum allergen-specific IgE showed that 1 629 (53%) patients were positive for allergens, and the number of positive allergen-specific IgEs in each patient was 3.0 ± 1.6. The top 3 common inhaled allergens in patients with eczema/dermatitis were Dermatophagoides farinae (904/1 522, 59%) , Dermatophagoides pteronyssinus (891/1 513, 59%) and Alternaria alternata (206/1 068, 19%) , and the top 3 common food allergens were shrimps (251/1 432, 18%) , egg white (165/992, 17%) and cow milk (149/994, 15%) . Among the 3 051 patients, 25 (1%) were aged < 2 years, 571 (19%) aged 2 - 12 years, 285 (9%) aged 12 - 18 years, and 2 170 (71%) were aged > 18 years. The most common food allergens were both egg white in the age groups of < 2 years and 2 -12 years (77%, 37%, respectively) , and were both shrimps in the age groups of 12 - 18 years and > 18 years (31%, 17%, respectively) . Dermatophagoides pteronyssinus and Dermatophagoides farina were the top 2 common inhaled allergens in all age groups, with the positive rate ranging from 36% to 84%; in addition, the positive rate of molds was relatively high in the age group of 2 - 12 years (mold mixture: 37%; Alternaria alternata: 27%) . From April 2021 to March 2022, the positive rate of outdoor allergens ranged from 10% to 15% among outpatients in every month; the positive rates of tree pollen and grass pollen increased from April 2021, and peaked in October 2021. The patients with atopic dermatitis showed a significantly increased positive rate of allergens (73%) compared with those with other eczema/dermatitis (37%, χ2 = 389.36, P<0.001) , and the rank of common allergens in the patients with atopic dermatitis was basically the same as that in those with eczema/dermatitis. Conclusions:The common allergens were Dermatophagoides farina, Dermatophagoides pteronyssinus and Alternaria alternata in the patients with eczema/dermatitis. Food allergy was more common in infant patients, and inhalation allergy was more common in child, adolescent and adult patients. The positive rate of allergen-specific IgEs was markedly higher in the patients with atopic dermatitis than in those with other eczema/dermatitis.

Objective To observe the potential mechanism of electroacupuncture regulating the erythropoietin-producing hepatocellular receptor B2/erythropoietin-producing hepatocellular receptor-interacting B2/big mitogen-activated protein kinase 1(EphB2/EphrinB2/BMK1) signaling pathway to improve neural damage in vascular dementia rats. Methods Eighty SD male adult rats were randomly divided into a sham surgery group, a model group, a non acupoint electroacupuncture group, a nimodipine group, and an electroacupuncture three needle group. The vascular dementia rat model was made by the modified Pulsinelli four vessel occlusion method. After grouping, the rats in each group were subjected to water maze test, HE staining, Nissl staining, and transmission electron microscopy(TEM) to observe the pathological changes in the hippocampal CA1 area, and the expression of EphB2 and BMK1 in the hippocampal CA1 area was detected by immunohistochemistry; Detection of EphB2 and BMK1 protein expression in rat hippocampal CA1 region was detected by Western blotting. Results Compared with the model group, the escape latency of vascular dementia rats treated with electroacupuncture and nimodipine decreased (P<0.05), while the number of crossing platforms significantly increased (P<0.05); The result of HE staining, Nissl staining and TEM showed that compared with the model group, the neurons in hippocampal CA1 area of rats in the EA Zhisanzhen group and nimodipine group were arranged orderly, and the morphology and structure of cells and organelle were complete; Immunohistochemical method and Western blotting showed that the expression of EphB2 and BMK1 in the CA1 region of hippocampus in the model group was significantly lower than that in the sham surgery group (P<0.05); Compared with the model group, the expression of EphB2 and BMK1 in the hippocampal CA1 region of rats in the electroacupuncture Zhisanzhen group significantly increased (P<0.05), while the expression of EphB2 and BMK1 in the hippocampal CA1 region of rats in the non acupoint electroacupuncture group was not statistically significant (P>0.05). Compared with the nimodipine group, the expression of EphB2 and BMK1 in the hippocampal CA1 region of rats in the electroacupuncture Zhisanzhen group significantly increased (P<0.05). Conclusion Electroacupuncture may improve the damage of hippocampal neurons in vascular dementia rats by increasing the expression of EphB2 and BMK1 in the CA1 region of the hippocampus, thereby improving the learning and memory of vascular dementia rats.

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

Objective To investigate the serum C-type lectin domain family 4 member G(CLEC4G)level and its clinical value in patients with Atopic Dermatitis(AD).Methods The blood samples of 60 AD patients and 29 control patients were collected,and CLEC4G,Interleukin-33(IL-33),total immunoglobulin E(tIgE),specific IgE(specific IgE),and eosinophil levels were detected.The correlation between CLEC4G level and clinical data of AD patients and IL-33 was analyzed.The risk of AD was evaluated by Logistic regression analysis of CLEC4G,IL-33 and other indicators.Results Compared with the control group,the serum CLEC4G level in AD patients was significantly decreased(359.4±57.3 vs.521.8±48.1)pg/mL.There was no significant difference in CLEC4G level between child-hood,adolescent and adult,male and female AD patients.Compared with tIgE≤100 kU/L group,CLEC4G level was significantly decreased in 100～200 kU/L group and tIgE≥200 kU/L group,but there was no significant difference between 100～200 kU/L group and tIgE≥200 kU/L group.Serum CLEC4G level decreased significantly only in the moderate AD group,but had no significant difference among the other groups.The serum level of IL-33 was increased in AD patients,but there was no significant correlation between CLEC4G and IL-33(r = 0.090,P = 0.495).Age less than 14 years old and IL-33 were risk factors for the incidence of AD,with OR values of 2.756 and 1.241,95%CI of 1.076～7.060 and 1.030～1.495,respectively.CLEC4G was a protective factor for AD(OR = 0.890,95%CI:0.809～0.979).Conclusion CLEC4G may be a protective factor independent of IL-33 mediated AD pathogenesis.

OBJECTIVE: To explore the design points of a three-dimensional (3D) printed customized cementless intercalary endoprosthesis with an intra-neck curved stem and to evaluate the key points and mid-term effectiveness of its application in the reconstruction of ultrashort bone segments in the proximal femur. METHODS: Between October 2015 and January 2021, 17 patients underwent reconstruction with a 3D printed-customized cementless intercalary endoprosthesis with an intra-neck curved stem. There were 11 males and 6 females, the age ranged from 10 to 76 years, with an average of 30.1 years. There were 9 cases of osteosarcoma, 4 cases of Ewing sarcoma, 2 cases of chondrosarcoma, 1 case of liposarcoma, and 1 case of myofibroblastoma. The disease duration was 5-14 months, with an average of 9.5 months. Enneking staging included 16 cases of stage ⅡB and 1 case of stage ⅢB. The distances from the center of the femoral head to the body midline and the acetabular apex were measured preoperatively on X-ray images. Additionally, the distances from the tip of the intra-neck curved stem to the body midline and the acetabular apex were measured at immediate postoperatively and last follow-up. The neck-shaft angle was also measured preoperatively, at immediate postoperatively, and at last follow-up. The status of osseointegration at the bone-prosthesis interface and bone growth into the prosthesis surface were assessed by X-ray films, CT, and Tomosynthesis-Shimadzu metal artefact reduction technology (T-SMART). The survival status of the patients, presence of local recurrence or distant metastasis, and occurrence of postoperative complications were assessed. The recovery of lower limb function was evaluated pre- and post-operatively using the Musculoskeletal Tumor Society (MSTS) scoring system, and pain relief was evaluated using the visual analogue scale (VAS) scores. RESULTS: The patient's femoral resection length was (163.1±57.5) mm, the remaining proximal femoral length was (69.6±9.3) mm, and the percentage of femoral resection length/total femoral length was 38.7%±14.6%. All 17 patients were followed up 25-86 months with an average of 58.1 months. During the follow-up, 1 patient died of lung metastasis at 46 months postoperatively, and the remaining 16 patients survived tumor-free. There was no complication such as periprosthetic infection, delayed incision healing, aseptic loosening, prosthesis fracture, or periprosthetic fracture. No evidence of micromotion or wear around the implanted stem of the prosthesis was detected in X-ray and T-SMART evaluations. There was no significant radiolucent lines, and radiographic evidence of bone ingrowth into the bone-prosthesis interface was observed in all stems. There was no significant difference in the distance from the tip of the curved stem to the body midline and the apex of the acetabulum at immediate postoperatively and last follow-up compared with the distance from the center of the femoral head to the body midline and the apex of the acetabulum before operation, respectively (P>0.05), and there was no significant difference in the above indexes between immediate postoperatively and last follow-up (P>0.05). The differences in the neck-shaft angle at various time points before and after operation were also not significant (P>0.05). At last follow-up, the MSTS score was 26.1±1.2 and the VAS score was 0.1±0.5, which were significantly improved when compared with those before operation [19.4±2.1 and 5.7±1.0, respectively] (t=14.735, P<0.001; t=21.301, P<0.001). At last follow-up, none of the patients walked with the aid of crutches or other walkers. CONCLUSION The 3D printed customized cementless intercalary endoprosthesis with an intra-neck curved stem is an effective method for reconstructing ultrashort bone segments in the proximal femur following malignant tumor resection. The operation is reliable, the postoperative lower limb function is satisfactory, and the incidence of complications is low.
Female ; Male ; Humans ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Femur/surgery* ; Lower Extremity ; Bone-Implant Interface ; Femur Head ; Artificial Limbs

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment

OBJECTIVE: To identify new biomarkers and molecular pathogenesis of Down syndrome (DS) by analyzing differentially expressed miRNAs in the placentas and their biological pathways. METHODS: Whole transcriptome sequencing was used to identify the differentially expressed miRNAs in DS (n=3) and normal placental samples (n=3) diagnosed by prenatal diagnosis. The target genes were predicted using miRWalk, Targetscan and miRDB, and GO and KEGG pathway analyses were performed for gene enrichment studies. RESULTS: We identified a total of 82 differentially expressed miRNAs in the placental tissues of DS, including 29 up-regulated miRNAs (fold change ≥2, P < 0.05) and 15 down-regulated miRNAs (fold change ≥2, P < 0.05), among which 10 miRNAs with relatively high expression abundance were selected for further analysis, including 4 up-regulated and 6 down-regulated miRNAs. These selected miRNAs shared the common target genes BTBD3 and AUTS2, both of which were associated with neurodevelopment. GO analysis showed that the target genes of the selected miRNAs were mainly enriched in protein binding, hydrolytic enzymes, metal ion binding protein combining, transferase activity, nucleotide, cytoplasmic constituents, nucleus composition, transcriptional regulation, RNA metabolism regulation, DNA-dependent RNA polymerase Ⅱ promoter transcriptional regulation, eye development, and sensory organ development. KEGG enrichment analysis showed that the target genes of these differentially expressed miRNAs were involved in the signaling pathways including tumor-related signaling pathway, PI3K-Akt signaling pathway, Ras signaling pathway, Rap1 signaling pathway, cytoskeletal regulatory signaling pathway, purine metabolization-related signaling pathway and P53 signaling pathway. CONCLUSION The differentially expressed miRNAs may play important roles in placental damage and pregnancy pathology in DS and provide clues for the prevention and treatment of mental retardation-related diseases.
Cytoskeletal Proteins/metabolism* ; Down Syndrome/metabolism* ; Female ; Gene Expression Profiling ; Humans ; MicroRNAs/metabolism* ; Nerve Tissue Proteins ; Phosphatidylinositol 3-Kinases/metabolism* ; Placenta/metabolism* ; Pregnancy ; Transcription Factors/metabolism* ; Transcriptome ; Whole Exome Sequencing

Objective: To observe the clinical efficacy of sinew-bone balancing manipulation in treating lumbar disc herniation (LDH) and offer clinical evidence to support the concept of paying equal attention to sinew and bone. Methods: Sixty LDH patients were randomized into an observation group and a control group, with 30 cases in each group. The observation group was treated with the sinew-bone balancing manipulation, and the control group received conventional Tuina (Chinese therapeutic massage) manipulation. The clinical efficacy and posterior muscle chain tone effect were compared between the two groups by observing the visual analog scale (VAS) score, Japanese Orthopaedic Association (JOA) score, and posture-associated indicators. Results: The total effective rate was 86.7％ in the observation group, higher than 76.7％ in the control group, but the between-group difference in efficacy was statistically insignificant (P>0.05). After treatment, the VAS and JOA scores, angle-dependent muscle tone indicator of the posterior muscle chain, and lumbar posture symmetry showed significant changes in both groups (P<0.05). The VAS and JOA scores, angle-dependent muscle tone indicator of the posterior muscle chain, and lumbar posture symmetry in the observation group were significantly different from those in the control group after treatment (P<0.05), but the between-group difference in the general posture symmetry was statistically insignificant (P>0.05). Conclusion: Both the sinew-bone balancing and conventional Tuina manipulations can reduce pain in LDH patients, improve lumbar function, and adjust the angle-dependent muscle tone coefficient of the posterior muscle chain and lumbar posture symmetry; except for the general posture symmetry of the posterior muscle chain, the sinew-bone balancing manipulation wins out over the conventional Tuina manipulation.