ObjectiveTo understand the epidemiological characteristics and post-exposure prophylaxis of rabies exposure cases in Suqian City of Jiangsu Province from 2021 to 2024, providing a reference for optimizing the allocation of health resources and formulating scientific prevention and control measures. MethodsData on individuals exposed to rabies and treated at Suqian’s rabies post-exposure prophylaxis (PEP) clinics from 2021 to 2024 were collected. Descriptive epidemiological methods were used to analyze patient characteristics, exposure classification, animal species responsible for injuries, wound management, and vaccination status. ResultsBetween 2021 and 2024, the number of outpatient visits for rabies PEP clinics in Suqian City totaled 333 450. The median age and the 25th and 75th percentiles of exposed individuals was 23 (9, 47) years. The highest proportion of exposed individuals was recorded in 2023 (27.09%); the majority were female (52.22%), aged 5‒9 years (17.49%), and in other occupations (37.05%). The rabies exposure rate in Suqian City from 2021 to 2024 was 16.75‰. The overall rabies exposure rate showed an upward trend (χtrend2=1 994.80, P<0.001). The exposure rate among males was lower than that among females (χ²=890.43, P<0.001). The highest exposure rate was observed in the 5‒9 age group (χ²=67 063.20, P<0.001). The number of individuals seeking medical care for rabies exposure exhibited a weak bimodal distribution, with the primary peak occurring in August and the secondary peak in January. The primary animal responsible for injuries was the cat (53.70%), and the source of these animals was predominantly domestic pets (88.90%). The proportion of exposed individuals bitten by cats showed an upward trend from 2021 to 2024 (χtrend2=548.44, P<0.001). Grade Ⅲ exposure accounted for the highest proportion (53.53%), and 301 652 cases (90.46%) presented within 24 hours of exposure. The coverage rate of rabies vaccine was 98.18% (13 625/13 877) for those with Grade Ⅰ exposure and 99.95% (319 413/319 573) for those with Grade Ⅱ and Ⅲ exposures; 64 042 individuals received rabies immunoglobulin or anti-rabies serum; 8 360 exposed individuals received tetanus vaccine, with the usage rate of tetanus vaccine among exposed individuals was only 2.51%, though the rate was on the rise (χtrend2=618.26, P<0.001). ConclusionBetween 2021 and 2024, the overall incidence of rabies exposure in Suqian City showed an upward trend, with a higher incidence among women than men. The incidence was particularly high among children and adolescents aged 14 and under, with the majority of injuries caused by cats; most injuries were inflicted by domestic animals. The overall uptake of tetanus vaccines showed an upward trend. Suqian City should step up health education on rabies exposure during January and August each year, with a particular focus on raising awareness of rabies exposure prevention among people aged 14 and under and women. It should also strengthen the management of domestic animals and ensure that they receive regular rabies vaccinations, particularly for pet cats. Preventive measures against tetanus should be strengthened for individuals exposed to rabies. Medical staff at rabies PEP clinics should receive enhanced training on the management of rabies exposures and the completion of information system reports to ensure the standardized operation of these clinics.

ObjectivePeripheral nerve injury is a common clinical condition that can impair the regulatory function of target organs, leading to functional disability; severe injuries may even result in lifelong disability. Therefore, how to effectively promote the morphological and functional reconstruction of injured peripheral nerves has become a critical scientific issue that urgently needs to be addressed. This study biomimicked the highly oriented structure and electrophysiological properties of peripheral nerves and investigated the feasibility and effectiveness of combining electrical stimulation (ES) with oriented conductive substrates for the repair of injured peripheral nerves at the cellular level. MethodsPolydimethylsiloxane (PDMS) substrates with oriented microgroove structures of varying widths (0, 5, 10, and 20 μm) were fabricated using silicon wafers with micropatterned grooves as templates. Graphene-based conductive patterned substrates (GCPSs) with oriented microgrooves were then constructed via soft lithography and designated as GCPS 0, GCPS 5, GCPS 10, and GCPS 20 according to the groove width. The GCPSs were prepared from collagen/polycaprolactone (PCL) matrices containing 1.0 wt% graphene, and their morphology, wettability, and conductivity were characterized. Mesenchymal stem cells (MSCs) viability, proliferation, adhesion, and orientation on the substrates were evaluated before ES treatment. Then, ES at a frequency of 2 Hz and field strengths of 10, 20, or 50 mV/cm were applied to the cells for 10 min daily, over 3 or 7 consecutive days. Neural differentiation was assessed by morphological observation, immunofluorescence staining, and analysis of neural lineage-related markers. ResultsThe oriented microgroove PDMS substrates supported long-term MSCs growth, guided cells to align along the groove direction, and promoted a morphological transition toward neural-like cells, exhibiting the capacity to induce MSCs differentiation toward the neural lineage. Microgroove structures effectively guided the alignment of MSCs and promoted the development of a more elongated, neural-like morphology, with the most pronounced morphological changes observed on grooves of 10 and 20 μm in width. Meanwhile, the incorporation of graphene endowed the GCPSs with favorable electrical conductivity, though the groove width did not significantly affect the conductive performance. The GCPSs showed good cytocompatibility with MSCs, and cell proliferation on these substrates exhibited a time-dependent pattern, with no significant effect observed from groove width. The inductive effect of ES combined with GCPSs on MSCs differentiation toward specific neural lineages was co-regulated by ES intensity (0, 10, 20, and 50 mV/cm) and microgroove width. ES at 10 mV/cm and 20 mV/cm promotes MSCs differentiation toward neurons on microgrooved substrates of various widths (5, 10, and 20 μm); under the same ES intensities, microgrooves with widths of 5 μm and 10 μm are more favorable for MSCs differentiation toward glial cells/SCs. Notably, low-intensity ES (10 or 20 mV/cm) combined with GCPS 10 significantly enhanced the neural differentiation of MSCs. Neurotrophic factor secretion levels by MSCs cultured on various GCPS substrates after 3 d of ES application was further detected. There were no significant differences in nerve growth factor‑β (NGF‑β) and brain-derived neurotrophic factor (BDNF) concentrations among the GCPS 5, GCPS 10, and GCPS 20 substrates, and these levels were not affected by variations in ES intensity. Under ES at 10 mV/cm, the glial cell line-derived neurotrophic factor (GDNF) concentration in each GCPS substrate was higher than that in the corresponding non-ES group on the same substrate. However, as ES intensity increased, the GDNF concentration decreased to varying degrees. ConclusionThis study demonstrates that the combined strategy of “oriented topographical structure+ES” can effectively promote the neural differentiation of MSCs and holds promise for accelerating the repair process of peripheral nerve injuries.

Taxifolin (TAX) is a natural compound known for its liver protection effect, but the mechanism remains unknown. Phosphorylated proteomics analyses discovered that the phosphorylation level of NDRG1 at T328 was a key event of TAX-improved liver fibrosis. We established models with NDRG1 knockout (KO) in vivo and in vitro, demonstrating that NDRG1 KO attenuated the development of hepatocyte injury, and combining NDRG1 KO and TAX administration did not result in a reduction in protection against liver injury. Cellular thermal shift assay and surface plasma resonance analysis showed that TAX directly binds to NDRG1 rather than its upstream kinase, subsequently demonstrating that TAX regulated phosphorylation of NDRG1 at T328 through binding to its C289 site. NDRG1 T328A (phosphorylated mutation) and T328E (mimic phosphorylation) in vivo and in vitro confirmed that pNDRG1_T328 exacerbates hepatocyte injury along with DNA damage, inflammatory response, and apoptosis, thereby contributing to hepatic stellate cells (HSCs) activation. In contrast, TAX can inhibit the above pathological abnormalities and block hepatocyte injury-triggered HSCs activation and fibrosis. Overall, TAX is a potent liver protection drug primarily targeting NDRG1 and inhibiting pNDRG1_T328 in hepatocytes.

Objective To explore the role and mechanism of RNA m6A methyltransferase Wilms'tumor 1-associated protein(WTAP)in epithelial-mesenchymal transition(EMT)of glioblastoma cells and its association with transcription factor JUNB.Methods(1)Based on the Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases,the expression levels of transforming growth factor β(TGF-β),WTAP,and JUNB in glioblastoma multiforme(GBM)and normal brain tissues were analyzed,as well as their diagnostic and prognostic values for GBM.The correlation of TGF-β,WTAP,and JUNB with gliomas of different WHO grades was analyzed using the Chinese Glioma Genome Atlas(CGGA)database.Spearman correlation analysis was performed to assess the correlation between TGF-β and m6A methyltransferases.(2)An EMT model was established in human astrocytoma U87-MG cells through TGF-β1 induction.qRT-PCR and Western blotting were employed to detect the expression levels of WTAP,JUNB,matrix metalloproteinase 2(MMP2),and N-cadherin.The migration capacity of U87-MG cells was evaluated by wound-healing and Transwell assays.An m6A RNA methylation quantification kit(colorimetric)was used to detect RNA m6A methylation modification levels.A stable cell line with low expression of WTAP was constructed to investigate the effects of WTAP knockdown on the migration ability of U87-MG cells,as well as the expression of JUNB.(3)A protein-protein interaction network was constructed using STRING database and GeneMANIA database,followed by gene ontology(GO)and KEGG pathway enrichment analyses to explore the biological processes,molecular functions,cellular components,and signaling pathways potentially involved in TGF-β/WTAP/JUNB.Gene set enrichment analysis(GSEA)was performed on JUNB-related genes to investigate their potential downstream signaling pathways.Results(1)The expression levels of TGF-β,WTAP,and JUNB were significantly higher in GBM(P<0.001),positively correlated with WHO grades of glioma(P<0.001).Glioma patients with high expression of all three genes had shorter overall and disease-free survival(P<0.001).Spearman analysis showed that the expression of TGF-β in GBM was positively correlated with WTAP(r=0.175,P=0.023),but no significant correlation with other m6A methyltransferases(P>0.05).(2)After TGF-β1 treatment,the level of m6A methylation modification of total RNA in U87-MG cells significantly increased(P<0.001).Wound-healing assay and Transwell assay results showed that the migration ability of U87-MG cells was significantly increased after TGF-β1 treatment(P<0.01),while WTAP knockdown significantly reduced the migration ability of U87-MG cells(P<0.01).qRT-PCR and Western blotting results showed that the mRNA and protein expression levels of WTAP,N-Cadherin,MMP2,and JUNB in U87-MG cells were significantly increased after 48 h of TGF-β1 induction(P<0.001),while WTAP knockdown significantly reduced the mRNA and protein expression of JUNB(P<0.001).(3)The TGF-β/WTAP/JUNB-related protein-protein interaction network was constructed,which was primary involved in mRNA modification and EMT.GSEA results showed that JUNB-related signaling pathways were closely associated with glioma malignant progression.Conclusions TGF-β,WTAP,and JUNB are all associated with GBM malignant progression and poor patient prognosis.TGF-β may enhance total RNA m6A modification by promoting the expression of m6A methyltransferase WTAP,and WTAP subsquentaly upregulates transcription factor JUNB,thereby promoting EMT and malignant progression of GBM.

This research aims to construct a stable epithelial cell senescence model for screening and e-valuation of senolytics.We explored the optimal conditions for doxorubicin-induced senescence of non-transformed epithelial cells MCF 10A,including the optimal induction concentration,the optimal inter-vention time,and the optimal senescence duration,and confirmed the feasibility of MCF 10A as an epi-thelial senescence model by multiple ways.The optimal condition for Doxorubicin-induced senescence of MCF 10A cells was treatment with 0.6 μmol/L Doxorubicin for 16 h to achieve the best senescence state on the 8th day.Under the optimal induction conditions,the positive rate of senescence-associated β-gal-actosidase(SA-β-gal)staining in the treated group reached 97％.At the same time,biochemical results of detecting the expression of mRNA,proteins,and immunofluorescence demonstrated that the expression levels of senescence-associated secretory phenotype(SASP),p16,p21 and p53 in the treated group were significantly higher than those in the control cells,and Lamin B1 was significantly decreased(P＜0.001),which were consistent with the specific characteristics of senescence.In summary,an epithelial senescence model was successfully induced in MCF 10A cells by Doxorubicin in this study,which will promote the screening of senolytics for senescent epithelial cells.

Objective:To analyze the efficacy of phantom-less quantitative computer tomography (PL-QCT) for the diagnosis of osteoporosis in patients with lumbar degenerative diseases.Methods:From October 2021 to October 2023, a total of 1 248 patients with lumbar degenerative disease who did not receive anti-osteoporosis treatment in the Department of Spine Surgery, Tianjin Hospital were retrospectively analyzed. There were 520 males and 728 females, aged 62.31±9.37 years (range, 40-87 years), height 1.66±0.08 m (range, 1.43-1.89 m), weight 69.04±8.27 kg (range, 49-93 kg). The mean body mass index was 26.11±3.67 kg/m 2 (range, 14.40-37.11 kg/m 2). Dual-energy X-ray absorptiometry (DXA) and PL-QCT were used to diagnose osteoporosis, and the detection rates of the two diagnostic methods were compared. The receiver operating characteristic (ROC) curve of PL-QCT for the diagnosis of osteoporosis was drawn, the area under the curve (AUC) and 95% confidence interval (CI), sensitivity and specificity were calculated. Results:Among 1 248 patients with lumbar degenerative diseases, 626 (50.2%) were diagnosed as osteoporosis by PL-QCT, 423(33.9%) were diagnosed by spine DXA, 488(39.1%) were diagnosed by hip DXA and 539 patients(43.2%) were diagnosed by dual-site DXA. The detection rate of osteoporosis of PL-QCT was higher than that of spine DXA (χ 2=193.557, P<0.001), hip DXA (χ 2=322.201, P<0.001) and dual-site DXA (χ 2=94.683, P<0.001), and the difference was statistically significant. Taking the diagnostic results of spinal DXA for osteoporosis as a reference, the ROC curve of PL-QCT for the diagnosis of osteoporosis showed a sensitivity of 79%, a specificity of 81%, and an AUC and 95% CI of 0.82(0.79, 0.85). Taking the diagnostic results of hip DXA for osteoporosis as a reference, the ROC curve of PL-QCT for the diagnosis of osteoporosis showed a sensitivity of 85%, a specificity of 55%, and an AUC and 95% CI of 0.75(0.71, 0.78). Taking the diagnostic results of two-site DXA for osteoporosis as a reference, the ROC curve of PL-QCT for the diagnosis of osteoporosis showed a sensitivity of 72%, a specificity of 75%, and an AUC and 95% CI of 0.81(0.78, 0.83). Conclusion:Compared with DXA, PL-QCT has a higher detection rate of osteoporosis in patients with degenerative lumbar spine disease and good diagnostic efficacy.

Objective:To investigate the clinical efficacy of lumbar lateral interbody fusion (LLIF) versus posterior lumbar interbody fusion (PLIF) in the treatment of severe lumbar spinal stenosis.Methods:The data of patients with severe lumbar spinal stenosis who underwent LLIF or PLIF from February 2019 to December 2023 were retrospectively analyzed. There were 30 patients in the LLIF group, 10 males and 20 females, aged 62.7±5.6 years (range, 53-74 years), including 21 cases of single segment and 9 cases of double segment. There were 46 patients in the PLIF group, including 20 males and 26 females, aged 63.2±8.4 years (range, 43-75 years), 40 cases of single segment and 6 cases of double segment. The visual analogue scale (VAS), Oswestry disability index (ODI), intervertebral space height, intervertebral foramen height and postoperative complications were compared between the two groups.Results:All patients were followed up for an average of 21.3±6.4 months (range, 12-32 months). The intraoperative blood loss in the LLIF group was 112.2±76.9 ml, which was significantly lower than 193.9±88.2 ml in the PLIF group ( P<0.05). The VAS scores of back pain and leg pain after operation were significantly lower than those before operation in the two groups ( P<0.05). There was no statistically significant difference between groups in back pain VAS scores at preoperative, 6 months postoperative, and final follow-up ( P>0.05); the back pain VAS score at 1 month postoperatively in the LLIF group was 1.6±1.2, which was less than 2.8±0.7 in the PLIF group ( P<0.05). There was no statistically significant difference between groups in leg pain VAS scores at preoperative, 1 month postoperative, and 6 months postoperative ( P>0.05); the leg pain VAS score at the final follow-up in the LLIF group was 1.2±1.5, which was smaller than 1.8±1.0 in the PLIF group ( P<0.05). The postoperative ODI was smaller than the preoperative one in both groups, and the difference was statistically significant ( P<0.05); the preoperative, 1-month postoperative, 6-month postoperative, and final follow-up ODIs in the LLIF group were 45.7%±16.0%, 17.9%±12.0%, 16.2%±11.6%, and 15.7%±11.7%, and those in the PLIF group were 47.9%±15.4%, 20.1%±9.3%, 16.9%±10.6%, and 14.6%±11.0% in the PLIF group, and the difference between the groups was not statistically significant ( P>0.05). The preoperative intervertebral space height in the LLIF group was 10.6±2.0 mm, which was smaller than that in the PLIF group 11.8±2.2 mm ( P<0.05). The intervertebral space heights in the immediate postoperative period and at the final follow-up were 13.3±2.3 mm and 12.3±2.2 mm in the LLIF group and 13.7±1.7 mm and 13.0±1.9 mm in the PLIF group ( P>0.05). The preoperative intervertebral foraminal height in the LLIF group was 18.0±3.2 mm, which was smaller than that of 19.7±2.4 mm in the PLIF group ( P<0.05); the intervertebral foraminal heights in the immediate postoperative period and at the final follow-up were 21.4±2.5 mm and 20.2±2.4 mm in the LLIF group, and in the PLIF group were 20.7±2.4 mm and 19.7±2.6 mm in the PLIF group ( P>0.05). In the LLIF group, 2 cases had femoral nerve injury and 2 cases had transient back pain after operation. There were 2 cases of cerebrospinal fluid leakage, 1 case of screw loosening, and 2 cases of deep vein thrombosis in the PLIF group. In the PLIF group, 2 patients underwent revision, including 1 case due to cage displacement and 1 case due to screw malposition. The fusion settling rate was 21% (8/39) in the LLIF group and 12% (6/52) in the PLIF group ( P>0.05). Conclusion:Both LLIF and PLIF can effectively restore the intervertebral height, improve the lumbar function and the symptoms of back and leg pain in the treatment of severe lumbar spinal stenosis.

Objective:To investigate the risk factors for complications following lateral lumbar interbody fusion (LLIF) surgery.Methods:A retrospective analysis was conducted on 196 patients who underwent LLIF surgery via the psoas major muscle approach in the Department of Spinal Surgery, Tianjin Hospital, Tianjin University, from October 2018 to July 2024. The age, gender, body mass index (BMI), presence of hypertension, type 2 diabetes, heart disease, osteoporosis, history of lumbar surgery, history of abdominal surgery, history of abdominal inflammation, smoking status, operative time, surgical segments (whether the surgery was single-segment or multi-segments), and use of internal fixation or not were compared between patients with and without postoperative complications, the indicators with P<0.10 were included in the binary variable logistic regression analysis, and determine the independent risk factors for complications after LLIF surgery. Complications included anterior thigh symptoms (pain, numbness, weakness), cage subsidence, surgery-related complications (nerve injury, surgical site infection, postoperative buttock pain, urinary and fecal incontinence, etc.), and medical complications (cerebrovascular accident, deep vein thrombosis, urinary tract infection, etc.). Results:All 196 patients were followed up for 27.02 (12.6, 40.69) months. Postoperative complications occurred in 71 cases (96 times), and no complications occurred in 125 cases. In the complication group, there were 15 males and 56 females with a mean age of 61.82±7.57 years; in the non-complication group, there were 43 males and 82 females with a mean age of 62.00± 8.39 years. In the complication group, there were 43 cases of anterior thigh symptoms, 38 cases of cage subsidence, 11 cases of surgical operation-related complications, and 4 cases of medical complications. There were statistically significant differences in gender (χ 2=3.829, P=0.051), operation time ( t=2.391, P=0.018), and surgical segment (χ 2=4.245, P=0.039) between the complication group and the non-complication group. No statistically significant differences were found in age, gender, BMI, presence of hypertension, type 2 diabetes, heart disease, osteoporosis, history of lumbar surgery, history of abdominal surgery, history of abdominal inflammation, smoking status, or use of internal fixation ( P>0.10). Binary variable logistic regression analysis indicated that prolonged operative time [ OR=1.007, 95% CI(1.001, 1.013), P=0.019] and multilevel surgery [ OR=2.099, 95% CI(1.095, 4.025), P=0.026] were independent risk factors for complications following LLIF. Conclusion:Prolonged operative time and multi-segments surgery are independent risk factors for complications following LLIF.

Objective:To analyze the clinical characteristics and outcomes of Haemophilus influenzae (Hi) meningitis in children. Methods:This is a retrospective case series study. This study included 34 Hi meningitis patients who admitted to Beijing Children′s Hospital, Capital Medical University, from January 1, 2010, to December 31, 2023. Data on clinical presentations, laboratory tests, hearing assessment and outcomes at discharge were collected. Patients were divided into 2 groups according to the outcome at discharge: favorable outcome group and unfavorable outcome group. Mann-Whitney U test and Fisher exact test was used to estimate the risk factors for an unfavorable outcome at discharge. Results:Thirty-four patients were enrolled. There were 16 males and 18 females. The age at onset ranged from 3 months to 12 years. Fever (34 patients (100%)), convulsions (17 patients (50%)), and coma (21 patients (62%)) were the common clinical presentations. Twenty-four patients (71%) developed complications. There were 15 patients (44%) needed treatment in the intensive care unit, 5 patients (15%) received intubation, and 4 patients (12%) had developed shock. The favorable outcome group included 23 patients, and the unfavorable outcome group included 11 patients. Female, patients with limb movement disability, dystonia, ventriculomegaly or hydrocephalus, and a concentration of glucose in the initial cerebrospinal fluid lower than 1 mmol/L were risk factors of unfavorable outcome at discharge (all P<0.05). Among the 23 patients (68%) in favorable outcomes group, 13 patients (57%) had data available on their long-term follow-up results, including 12 patients with favorable long-term outcomes and 1 patient with unfavorable long-term outcome. Among the 11 patients (32%) in unfavorable outcomegroup, 1 patient died, the other 10 patients (91%) had data available on their long-term outcomes. Eight patients had unfavorable long-term outcomes and 2 patients with favorable long-term outcomes. Patients who had unfavorable outcomes at discharge were at a greater risk of experiencing unfavorable long-term outcomes ( P=0.001). Conclusions:It is common for patients with Hi meningitis to have intracranial complications or develop into critical conditions. Patients who have limb movement disability, dystonia, ventriculomegaly or hydrocephalus, and who exhibit a concentration of glucose in the initial cerebrospinal fluid lower than 1 mmol/L tend to have unfavorable outcomes; they need to be assessed for sequelae.

Objective To compare clinical efficacy of combined external fixator and plate fixation in treating throwing fracture of humerus.Methods Sixty-seven male patients with throwing humerus fracture admitted from February 2018 to February 2021 were retrospectively analyzed and divided into external fixator group and plate group according to different treatment methods.There were 32 patients in external fixator group,aged from 18 to 27 years old with an average of(23.6±2.6)years old;19 patients with type A,13 patients with type B according to AO classification;fixed by combined external fixer.There were 35 patients in plate group,aged from 17 to 28 years old with an average of(23.2±2.9)years old;21 patients with type A,14 patients with type B according to AO classification;fixed with steel plate screws.Operation time,intraoperative blood loss,total incision length,fracture healing time and complications were compared between two groups.Clinical effect was evaluated by Mayo elbow performance score(MEPS)and shoulder Neer score at 12 months after operation.Results Patients in both groups were successfully completed operation and followed up for 15 to 21 months with an average of(18.3±3.4)months.In external fixator group,intraoperative blood loss,incision length,fracture healing time and postoperative MEPS of el-bow joint function at 12 months were(68.5±15.7)ml,(4.9±1.2)cm,(10.5±2.9)weeks,(93.6±5.1)min,respectively;which were superior to ml(149.4±38.9)ml,(12.5±2.4)cm,(12.8±2.7)weeks,(85.6±6.8)in plate group(P＜0.05),and had signif-icant differences;there were no significant difference in operative time and postoperative Neer score of shoulder joint function at 12 months between two groups(P＞0.05).There were 6 patients occurred radial nerve injury in plate group and no patient occurred radial nerve injury in external fixator group,and the difference between two groups was statistically significant(x2=6.025,P＜0.05).There were no significant difference in postoperative MEPS grading and Neer shoulder joint grading at 12 months(P＞0.05).Bone healing was achieved in both groups without failure of internal fixation.Conclusion The combined ex-ternal fixator for the treatment of humerus throwing fracture has characteristics of low incidence of radial nerve injury,less bleeding,less complications,fast fracture healing,which is convenient to remove after fracture healing.