Objective To understand the surveillance situation of poliovirus in Guangzhou from 2011 to 2024, and to further strengthen polio surveillance and ensure the continued maintenance of a polio-free status. Methods An analysis was conducted on the discovery and investigation results of six cases of vaccine-derived poliovirus (VDPV) detected in Guangzhou. Results A total of 6 VDPV incidents were reported in Guangzhou from 2011 to June 2024, among which 5 incidents were from sewage sample testing in the Liede Sewage Treatment Plant in Guangzhou, all of which were confirmed as VDPV, with 1 for type I, 1 for type II, and 3 for type III. In addition, one confirmed HFMD case was identified as a type VDPV II carrier. No presence of any wild poliovirus (WPV), VDPV cases, or circulating VDPV (cVDPV) was reported. Conclusion Guangzhou City has maintained a high level of vigilance and effectiveness in the monitoring and prevention of polio. Continuously strengthening the construction of the polio monitoring network, optimizing vaccination strategies, and comprehensively improving public health awareness are still the focus of the prevention and control work in the future.

An ideal dermal filler should integrate filling, repair, and anti-aging effects, with immediate tissue augmentation, slow degradation, and progressive stimulation of collagen regeneration. However, commonly used hyaluronic acid (HA) hydrogels, while effective for rapid filling, suffer from limited duration of support, weak cell adhesion, and an inability to promote collagen regeneration. Silk fibroin (SF), a natural protein from silkworm cocoons, is known for its excellent cell adhesion and collagen-stimulating abilities. However, its limited gelation capability restricts its potential application as a standalone injectable hydrogel. Based on a complementary strategy, this study combines the rapid gelling properties of HA with the collagen regenerative properties of SF to create a co-crosslinked HA-SF hydrogel. The composite hydrogel merges HA's rapid filling effect with SF's strong tissue adhesion and collagen-stimulating abilities. The formulation, physicochemical properties, degradation, biocompatibility, and filling effects of the HA-SF hydrogel were systematically investigated. HA-SF hydrogel exhibits excellent mechanical properties and ensures long-term support while maintaining injectability. Interestingly, after intradermal injection in the UVB-induced photoaging model, HA-SF hydrogel not only enhances hydrogel-cell interaction but also continues to stimulate collagen regeneration, especially type III collagen. This dual action achieves the biological effects of repair and anti-aging while maintaining the filling effect. Proteomic analysis confirms that repair and anti-aging effects are enhanced by the regulation of skin fibroblasts and modulation of amino acid and lipid metabolism. This composite hydrogel holds strong promise for clinical applications, offering a safer, long-lasting, and more natural injectable filler that combines filling, repair, and anti-aging into one system.

Computational approaches, encompassing both physics-based and machine learning (ML) methodologies, have gained substantial traction in drug repurposing efforts targeting specific therapeutic entities. The human dopamine (DA) transporter (hDAT) is the primary therapeutic target of numerous psychiatric medications. However, traditional hDAT-targeting drugs, which interact with the primary binding site, encounter significant limitations, including addictive potential and stimulant effects. In this study, we propose an integrated workflow combining virtual screening based on weighted holistic atom localization and entity shape (WHALES) descriptors with in vitro experimental validation to repurpose novel hDAT-targeting drugs. Initially, WHALES descriptors facilitated a similarity search, employing four benztropine-like atypical inhibitors known to bind hDAT's allosteric site as templates. Consequently, from a compound library of 4,921 marketed and clinically tested drugs, we identified 27 candidate atypical inhibitors. Subsequently, ADMETlab was employed to predict the pharmacokinetic and toxicological properties of these candidates, while induced-fit docking (IFD) was performed to estimate their binding affinities. Six compounds were selected for in vitro assessments of neurotransmitter reuptake inhibitory activities. Among these, three exhibited significant inhibitory potency, with half maximal inhibitory concentration (IC₅₀) values of 0.753 μM, 0.542 μM, and 1.210 μM, respectively. Finally, molecular dynamics (MD) simulations and end-point binding free energy analyses were conducted to elucidate and confirm the inhibitory mechanisms of the repurposed drugs against hDAT in its inward-open conformation. In conclusion, our study not only identifies promising active compounds as potential atypical inhibitors for novel therapeutic drug development targeting hDAT but also validates the effectiveness of our integrated computational and experimental workflow for drug repurposing.

Objective To explore the genotoxicity of lead on DNA damage and the repair role of homologous recombination repair protein RAD51 in lead-induced DNA double-strand breaks in TK6 cells. Methods i) TK6 cells in the logarithmic growth phase were divided into five groups: blank control group, low-dose group, medium-dose group, high-dose group, and positive control group. The first four groups were treated with lead acetate at concentrations of 0, 120, 240 and 480 μmol/L, respectively. The positive control group was treated with 100 μmol/L hydrogen peroxide solution incubated on ice for 24 hours. After the positive rate of phosphorylated histone H2AX (γ-H2AX) was detected by immunofluorescence. Cell proliferation was detected by 5-ethynyl-2'-deoxyuridine (EDU) method. Cell cycle and apoptosis were detected by flow cytometry, and the relative expression of RAD51 protein was detected by Western blotting. ii) A short hairpin RNA (shRNA) silencing RAD51 model was constructed in TK6 cells, and the cells were divided into untreated group (normal TK6 cells), negative control group (sh-NC), and RAD51 silencing group (sh-RAD51). The mRNA expression of RAD51 was detected by real-time fluorescence quantitative polymerase chain reaction, and the protein expression of RAD51 was detected by Western blotting to verify the interference effect. iii) Normal TK6 cells, sh-NC, and sh-RAD51 were treated with 480 μmol/L lead acetate for 24 hours, and were divided into lead treatment group, lead+negative control group, and lead + RAD51 silencing group, respectively. Untreated normal TK6 cells was served as the control group. The positive rate of γ-H2AX and the expression of RAD51 protein in each group was detected by immunofluorescence and Western blotting, respectively. Results i) With the increase of lead acetate treatment concentration in TK6 cells, the positive rate of γ-H2AX increased (all P<0.05), the proportion of EDU positive cells decreased (all P<0.05), and the proportion of S-phase cells decreased (all P<0.05). The proportion of G1-phase cells in the high-dose group and the positive control group was higher than those in the low- and medium-dose groups (all P<0.05). The proportion of G2-phase cells in the medium-dose group, high-dose group, and positive control group increased compared with the blank control group (all P<0.05), although no significant differences were observed among these three dosing groups (all P>0.05). The apoptosis rate and the relative expression of RAD51 protein of TK6 cells in each group increased with the increase of lead acetate concentration (all P<0.05). ii) The relative expression levels of RAD51 mRNA and protein in the RAD51 silencing group were lower than those in the untreated group and the negative control group (all P<0.05) after RAD51 silencing. iii) The positive rate of γ-H2AX in the lead + RAD51 silencing group increased (all P<0.05), and the relative expression of RAD51 protein decreased (all P<0.05),compared with the control group, lead treatment group, and lead + negative control group. Conclusion Lead exposure induces DNA double-strand breaks in TK6 cells, inhibits cell proliferation, and causes cell cycle arrest and apoptosis in a dose-effect manner. Downregulation of the RAD51 gene can lead to inhibition of the homologous recombination repair pathway, thereby increasing the TK6 cell sensitivity to lead-induced DNA damage.

Objective To evaluate the accuracy of selective laser melting of cobalt-chromium(CoCr)clasps with different build angles and support densities.Methods The 3D software constructed a sample clasp(reference object)with an undercut depth of 0.50 mm,which was then imported to a metal 3D printer to form CoCr clasps at different build angles(0°,45°,and 90°)and support densities(0.50,0.70,0.90,and 1.10 mm).A model scanner was used to obtain scans of all clasps(test objects);the test objects were aligned with the reference object and test subjects were aligned with each other through a best-fit alignment method using Geomagic software to obtain root mean square error(RMSE)values for the accuracy of the clasps.The data were statistically analyzed using one-way analysis of variance or non-parametric rank sum test(α=0.05).Results In terms of trueness,the different build angle groups with support density of 0.50 mm were ranked by RMSE values as follows:90°group>0°group>45°group.For the different build angle groups with support densities of 0.70,0.90,and 1.10 mm,the RMSE values ranked as follows:45°group>90°group>0°group.In terms of precision,the different build angle groups with support density of 0.50 mm were ranked by RMSE values as follows:90°group>0°group>45°group.For support density of 0.70 mm,the ranking was 90°group>45°group>0°group,while for support densities of 0.90 and 1.10 mm,the ranking was 45°group>90°group>0°group.Conclusion The accuracy of CoCr clasps varies with the build angle and support density.However,clasps produced at a build angle of 0°and a support density of 0.90 mm exhibit higher accuracy and are recommended for use in clinical and technical laboratories.

Osteosarcoma is the most common primary malignant bone tumor in children and adoles-cents.The current treatment methods include immunotherapy,gene therapy,targeted therapy and chemotherapy,but the prognosis is poor and prone to recurrence and metastasis.There is increasing evidence that the Wnt signaling pathway is involved in the entire process of osteosarcoma occurrence,development,metastasis,and prognosis,making it an attractive target.Current research on small molecule compounds related to the Wnt signaling pathway is making progress and attracting more attention so that targeting the Wnt signaling pathway with small molecule compounds has become a promising therapeutic strategy for osteosarcoma.This review focused on the Wnt signaling pathway and introduced the relationship between the Wnt signaling pathway and osteosarcoma,targeting small molecule compounds upstream and downstream of Wnt signaling,analyzed the classification and mechanism of action of related small molecule compounds,and summarized research progress.Target-ing the Wnt signaling pathway,clarifying the specific mechanism,and an intimate knowledge of the complexity of Wnt signaling will help improve the formulation of clinical treatment plans for osteosarcoma,providing references and ideas for the development of anti-tumor drugs related to Wnt regulation.

Objective:To explore the age of onset and consultation, the main clinical manifestations, common types of combined malformations, the relationship of endometriosis, surgical prognosis and different types of proportion of adolescent female reproductive system dysplasia.Methods:The medical records of 356 patients (aged 10-19) with female reproductive system dysplasia in Women′s Hospital, School of Medicine, Zhejiang University from January 2003 to August 2018 were collected and retrospectively analyzed.Results:(1) Among the 356 adolescent dysplasia patients, uterine dysplasia (23.6%, 84/356), oblique vaginal septum syndrome (OVSS; 22.5%, 80/356) and vaginal dysplasia (21.6%, 77/356) were the most frequent ones, followed by multi-sectional dysplasia (16.0%, 57/356), other types of developmental abnormalities like external genitaliaand urogenital fistula (13.5%, 48/356) and Mayer-Rokitansky-Küster-Hauser syndrome (MRKH syndrome; 2.8%, 10/356). (2) There were significant differences between the median age of onset and the age of consultation of patients with OVSS and other types of abnormalities except hymen atresia (both P<0.05). In contrast, there were no significant differences between the age of onset and the age of consultation of the patients of uterine dysplasia, vaginal dysplasia, hymen atresia, MRKH syndrome and multi-sectional dysplasia (all P>0.05). (3) The clinical manifestations were lack of specificity, and mainly abnormal finding was lower abdominal pain. (4) After admission, the majority of patients underwent comprehensive cardiopulmonary examination (71.3%, 254/356) and urinary system examination (63.5%, 226/356). Only 18.3% (65/356) of patients had completed abdominal organ examination, and 5.9% (21/356) skeletal system examination. About other systemic malformations, urological malformations were the most common (27.5%, 98/356), followed by anorectal malformation (0.6%, 2/356), heart malformations (0.3%, 1/356), and spinal malformations (0.3%, 1/356). 46.4% (84/181) of the surgical patients were diagnosed with combined endometriosis. Patients with obstructive genital tract malformations were more likely to combine with endometriosis than non-obstructive ones [50.3% (74/147) vs 29.4% (10/34); P<0.05]. However, there was no significant difference between the severity of endometriosis of those two kinds ( P>0.05). (5) Totally 308 patients were followed up successfully with a median of 25.0 years old, and 20 cases were treated again; 12.0% (37/308) of them were suffering from menstrual disorder and 33.1% (102/308) of them with dysmenorrhea. Totally 130 patients had sexually active reported no sexual problems. Conclusions:Uterine dysplasia, OVSS and vaginal dysplasia are the most common syndromes in adolescent female reproductive system dysplasia along with frequent cases of coexisting urinary malformations and increasing risks of endometriosis. Meanwhile, the lack of specificity of clinical manifestations might delay the timely diagnosis and treatment after the onset of symptoms. Nonetheless, most patients could achieve good surgical outcomes.

One case of COVID-19 infection secondary to pulmonary mucormycosis in a recipient of simultaneous pancreas-kidney transplantation was described. Early identification of the pathogen was achieved by metagenomic next-generation sequencing. On the basis of disease status and liver function changes, targeted treatments included intravenous amphotericin B liposome, amphotericin B nebulization& gargling and subsequently a maintenance therapy of oral posaconazole. This regimen resulted in the absorption of lung infection, stabilization of transplanted pancreas function and reduced levels of creatinine and urea as compared to pre-infection period. The therapeutic efficacy was decent.

Objective:To summarize the distributional characteristics of postoperative occurrence of multi-drug resistant organism (MDRO) infections and their risk factors in simultaneous pancreas-kidney transplantation (SPK) recipients and examine the impact of MDRO infections on the survival of SPK recipients.Method:From January 2016 to December 2022, the relevant clinical data were retrospectively reviewed for 218 SPK recipients. The source of donor-recipient specimens and the composition percentage of MDRO pathogens were examined. According to whether or not MDRO infection occurred post-transplantation, they were assigned into two groups of MDRO (98 cases) and non-MDRO (120 cases). The clinical data of two groups of donors and recipients were analyzed. And the risk factors for an onset of MDRO infection were examined by binary Logistic regression. The survival rate of two recipient groups was compared by Kaplan-Meier method.Result:A total of 98/218 recipients (45%) developed MDRO infections. And 46 (46.9%) of sputum and 34 (34.7%) of urine were cultured positively and 49 (50%) pathogens expressed extended spectrum beta-lactamase. There were pneumonia (46 cases, 46.9%), urinary tract infections (34 cases, 34.7%), abdominal infections (16 cases, 16.3%) and bloodstream infections (2 cases, 2.0%). Univariate regression analysis revealed that length of renal failure ( P=0.037), length of hospitalization ( P<0.001), length of antibiotic use ( P<0.001), novel antibiotics ( P=0.014), albumin ( P<0.001) and leukocyte count ( P<0.001) were risk factors for an onset of MDRO infections. The results of multifactorial regression indicated that low albumin ( OR=0.855, 95% CI: 0.790~0.925, P<0.001) and leukopenia ( OR=0.656, 95% CI: 0.550~0.783, P<0.001) were independent risk factors for an onset of MDRO infections. The survival rates of recipients in MDRO group at Year 1/3 post-operation were 92.9% (91/98) and 89.8% (88/98). And the survival rate of recipients in non-MDRO group was 96.7% (116/120) at Year 1/3 post-operation. Inter-group difference was not statistically significant in 1-year survival rate of two recipient groups ( P=0.201); statistically significant inter-group difference in 3-year survival rate between two recipient groups ( P=0.041) . Conclusion:Low albumin and leukopenia are risk factors for MDRO infection. Infection with MDRO has some impact on the survival of recipients.

Objective:To analyze the clinical features and risk factors of chest tightness variant asthma (CTVA) in children, so as to provide basis for the prevention and management of the disease.Methods:A cross-sectional study was conducted to analyze 178 children aged 6-17 years old who were admitted to the Department of Allergy, Capital Institute of Pediatrics Affiliated Children′s Hospital from January 2021 to January 2023 due to chest tightness. The age was 8.83(7.50, 11.58) years old, with 89 males (50%) and 89 females (50%). According to the diagnosis of CTVA, 130 cases were divided into CTVA group and 48 non-CTVA cases were divided into control group. Demographic data, personal history, family history, clinical features, auxiliary examination results and other data were collected. The clinical characteristics, allergens, FeNO level and pulmonary function parameters of the two groups were analyzed. Logistic regression analysis was used to explore the risk factors of the disease.Results:The proportion of school-age children (6-11 years old) in CTVA group was higher than that of adolescent children (≥12 years old) [(113/130,86.9%) vs (26/48,54.2%), Z=21.985, P<0.01]. The proportion of CTVA combined with eczema [(74/130,56.9%) vs (19/48,39.6%), χ2=4.225, P<0.05] and rhinitis symptoms [(98/130,75.4%) vs (27/48,56.2%), χ2=6.138, P<0.05] was higher. The positive rates of mold sensitization [(52/130,40.0%) vs (11/48,22.9%), χ2=4.474, P<0.05] and multiple sensitization [(71/130,54.6%) vs (18/48,37.5%), χ2=4.108, P<0.05] in inhaled allergens were significantly higher than those of control group. The proportion of elevated FeNO (>20 ppb) in CTVA children was 20.8% (27/130), which was significantly higher than that in control group 4.2%(2/48)( χ2=7.086 ,P<0.01). There were no statistical differences in spirometry parameters FEV 1 and FVC between CTVA group and control group ( P both>0.05). FEV 1/FVC, PEF, FEF 25, FEF 50, FEF 75 and MMEF were significantly lower than those in control group ( P all<0.05). Logistic regression analysis showed that rhinitis symptoms ( OR=2.351, 95% CI 1.105-5.002, P=0.026), multiple sensitizations ( OR=2.184, 95% CI 1.046-4.557, P=0.038), tIgE>60 kU/L( OR=3.080, 95% CI 1.239-7.654, P=0.015), FeNO>20 ppb ( OR=6.734, 95% CI 1.473-30.796, P=0.014) and small airway dysfunction ( OR=3.164, 95% CI 1.089-9.194, P=0.034) were risk factors for chest tightness variant asthma. FeNO combined with FEF 50 has the largest area under the curve ( Z=2.744, P<0.01) in diagnosing CTVA. Conclusion:CTVA is more common in school-age children than in adolescent children. Rhinitis symptoms, multiple sensitization, tIgE>60 kU/L, FeNO>20 ppb and small airway dysfunction are risk factors for chest tightness variant asthma. FeNO combined with small airway indexes can improve the diagnostic value of CTVA.