Background Protein tyrosine phosphatase non-receptor type II (PTPN2) is essential for the regulation of inflammation and immunity, but the specific mechanism of action of Ptpn2 in silicosis is unknown. Objective To investigate the regulatory role of overexpression of Ptpn2 in SiO₂-mediated inflammatory response in alveolar type II epithelial cells based on transcriptome sequencing. Methods This study was an in vitro study. A negative control group (vector transferred) and an overexpression of Ptpn2 group of mouse lung epithelial cell line MLE-12 cells were firstly constructed. Transcriptome sequencing was performed to detect differentially expressed genes (DEGs), differentially expressed mRNAs, and differentially expressed ncRNAs in the two groups of MLE-12 cells, and then the DEGs were analyzed by the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Constructed MLE-12 cells and A549 cells were stimulated using SiO₂ suspension, and divided into a negative control group (vector transferred), an overexpression of Ptpn2 group, a negative control + SiO₂ group, and an overexpression of Ptpn2 + SiO₂ group, respectively. Protein expressions of tumor necrosis factor-α (TNF-α) and interleukin (IL)-17A, IL-2, IL-1β were detected by Western blot. Positive TNF-α expression was detected by immunofluorescence staining. Results The results of Western blot showed that the protein expression level of PTPN2 was up-regulated in the overexpressed Ptpn2 group compared with the negative control group (P < 0.05). The volcano plot and clustering heat map showed that there were 1122 DEGs, 3681 differentially expressed mRNAs, and 474 differentially expressed ncRNAs in the overexpressed Ptpn2 group compared with the negative control group. The results of GO enrichment showed that, in terms of the biological process, the DEGs were mainly related to the regulation of metal ion transport, extracellular matrix organization, and extracellular structural organization; in terms of cellular composition, the DEGs were mainly related to collagen-containing extracellular matrix, receptor complexes, and basement membranes; in terms of molecular function, the DEGs were mainly related to the extracellular matrix structural constituents, glycosaminoglycan binding, and semaphorin receptor binding. The results of KEGG enrichment showed that the DEGs were closely related to cytokin-cytokine receptor interaction, IL-17 signaling pathway, TNF signaling pathway, and chemokine signaling pathway. In MLE-12 and A549 cells, the results of Western blot showed that the protein expression levels of TNF-α , IL-17A, IL-2, and IL-1β were up-regulated in the negative control + SiO₂ group compared with the negative control group (P < 0.05), and the protein expression levels of TNF-α, IL-17A, IL-2, and IL-1β were down-regulated in the overexpression of Ptpn2 + SiO₂ group compared with the negative control + SiO₂ group (P < 0.05). The immunofluorescence staining showed that the expression of TNF-α was increased in the negative control + SiO₂ group compared with the negative control group, and decreased in the overexpression of Ptpn2 + SiO₂ group compared with the negative control + SiO₂ group. Conclusion Overexpression of Ptpn2 inhibits SiO₂-mediated inflammatory response in MLE-12 cells and A549 cells.

ObjectiveTo examine the protective mechanism of wogonin in SH-SY5Y cells cultured in the conditioned media with lipopolysaccharide （LPS）-induced BV-2 microglia. MethodBV-2 microglia were divided into the blank group， LPS group， low concentration group of wogonin （4 μmol∙L^-1）， medium concentration group of wogonin （8 μmol∙L^-1）， and high concentration group of wogonin （16 μmol∙L^-1）. The LPS group was given 1 mg·L^-1 LPS， and the other three groups were treated with the corresponding concentration of wogonin for 4 h and then given 1 mg·L^-1 LPS. The conditioned media from these groups were used to cultivate SH-SY5Y cells. Cell counting kit-8 （CCK-8） was used to assess the vitality of BV-2 cells in the above groups. The contents of interleukin-6 （IL-6） and tumor necrosis factor-alpha （TNF-α） in the supernatant of BV-2 cells were determined by enzyme-linked immunosorbent assay （ELISA）. The expression of tyrosine hydroxylase （TH） and α-Synuclein （α-Syn） in SH-SY5Y cells was detected by immunohistochemical staining （IHC）. The nuclear transfer and fluorescence expression intensity of nuclear transcription factor-κB p65 （NF-κB p65） protein in SH-SY5Y cells were detected by immunofluorescence staining （IF）. Western blot was used to detect the expression of Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/NF-κB pathway-related proteins in SH-SY5Y cells. ResultThe levels of IL-6 and TNF-α in the supernatant of BV-2 cells in the LPS group were significantly higher than those in the blank group （P<0.01）. Compared with those in the LPS group， the IL-6 content of BV-2 cells in the low concentration group of wogonin was statistically significantly lower （P<0.05）， whereas the IL-6 and TNF-α contents of the medium and high concentration groups of wogonin were statistically lower （P<0.05，P<0.01）. The IL-6 and TNF-α contents in the high concentration group of wogonin decreased most significantly （P<0.01）， and the intervention effect was the best. Compared with that in the blank group， the expression of α-Syn protein in SH-SY5Y cells cultured with conditioned media in the LPS group was significantly increased， and the expression of TH protein was significantly decreased （P<0.05）. Compared with that in the LPS group， α-Syn protein expression in the medium and high concentration groups of wogonin showed a decreasing trend （P<0.05， P<0.01）. TH protein expression was increased in the low， medium， and high concentration groups of wogonin （P<0.05， P<0.01）. Compared with the blank group， NF-κB p65 protein gradually accumulated into the nucleus， and the fluorescence expression intensity was significantly enhanced （P<0.01）. Compared with the LPS group， the NF-κB p65 protein was gradually dispersed outside the nucleus， and the fluorescence expression intensity was gradually weakened in all concentration groups of wogonin. The fluorescence intensity in the high concentration group of wogonin was significantly reduced （P<0.01）. Compared with those in the blank group， the expression levels of TLR4 protein， phosphorylated（p）-NF-κB p65 protein， and MyD88 protein in the LPS group were significantly increased （P<0.05， P<0.01）. Compared with those in the LPS group， the expressions of TLR4 protein， p-NF-κB p65 protein， and MyD88 protein in the medium concentration group of wogonin were all significantly decreased （P<0.05， P<0.01）. The expressions of TLR4 protein， and MyD88 protein in the high concentration group of wogonin were significantly decreased （P<0.05， P<0.01）. ConclusionWogonin may regulate the TLR4/MyD88/NF-κB signaling pathway to inhibit the release of LPS-induced inflammatory factors in BV-2 microglia and protect SH-SY5Y cells， thereby reducing inflammation and achieving neuroprotective effects.

Objective To investigate th effect of PCSK9 inhibitors on early intensive lipid-lowering therapy in patients with symptomatic intracranial atherosclerotic stenosis(ICAS).Method One hundred and thirty-nine symptomatic ICAS patients who attended the Xuzhou Central Hospital from October 2022 to August 2023 were collected.According to the choice of lipid-lowering regimen,they were divided into statin drug group(n=54),PCSK9 inhibitor group(n=42)and combination drug group(n=43).Baseline data,laboratory indices,adverse drug reactions,clinical neurological function scores and endpoint events of the three groups were collected and analyzed.Results There was no statistically significant difference in the clinical data among the three groups before treatment.Compared with pre-treatment,total cholesterol(TC)and low-density lipoprotein cholesterol(LDL-C)levels were significantly lower in the three groups after treatment(all P＜0.01),and peripheral blood leukocyte counts were significantly lower in the PCSK9 inhibitor group after treatment(P＜0.05).After treatment,the differences in TC and LDL-C levels and the proportions of LDL-C＜1.8 mmol/L after 2 weeks of medication and LDL-C＜1.4 mmol/L on the 90th day were statistically significant among the three groups(all P＜0.01).Compared with the statin drug group,the differences in TC and LDL-C levels and the proportions of LDL-C＜1.8 mmol/L after 2 weeks and LDL-C＜1.4 mmol/L on the 90th day in the PCSK9 inhibitor group and the combination drug group were statistically significant(all P＜0.05).The differences in the occurrence of endpoint events,the proportion of recurrent AIS or TIA,cardiovascular events,and the time to endpoint events among the three groups were statistically significant on the 180th day after treatment(all P＜0.05).Differences in the occurrence of endpoint events,proportion of cardiovascular sexual events,and time to endpoint events on day 180 after treatment were statistically different in the PCSK9 inhibitor group and the combination drug group compared with the statin drug group(all P＜0.05).There was a statistically significant difference among the survival analysis curves of the three groups,with higher event-free survival in both groups with PCSK9 inhibitors alone or in combination(Log-Rank=13.95,P=0.0009).Conclusion Early intensive lipid lowering with PCSK9 inhibitors is effective and safe in patients with symptomatic ICAS,and can further reduce LDL-C,TC,and white blood cell counts,as well as improve lipid compliance,and significantly reduce the rate of end-point events with a significantly prolonged time to occurrence.

Important anatomical structures such as mandibular incisive canal,tongue foramen,and mouth floor vessels may be damaged during implant surgery in the mandibular anterior region,which may lead to mouth floor hematoma,asphyxia,pain,paresthesia and other symptoms.In severe cases,this can be life-threatening.The insufficient alveolar bone space and the anatomical variation of blood vessels and nerves in the mandibular anterior region increase the risk of blood vessel and nerve injury during implant surgery.In case of vascular injury,airway control and hemostasis should be performed,and in case of nerve injury,implant removal and early medical treatment should be performed.To avoid vascular and nerve injury during implant surgery in the mandibular anterior region,it is necessary to be familiar with the anatomical structure,take cone-beam computed tomography,design properly before surgery,and use digital technology during surgery to achieve accurate implant placement.This article summarizes the anatomical structure of the mandibular anterior region,discusses the prevention strategies of vascular and nerve injuries in this region,and discusses the treatment methods after the occurrence of vascular and nerve injuries,to provide clinical reference.

The canalis sinuosus,a canal containing the anterior superior alveolar nerve bundle,originates from the infraorbital canal and extends along the maxillary sinus and nasal cavity edges to the anterior maxilla.It was once regarded as an anatomical variation.However,with the widespread application of cone beam computed tomography(CBCT),the detection rate of canalis sinuosus in the population has increased.The canalis sinuosus exhibits diverse courses,branching into multiple accessory canals and terminating at the nasal floor or the anterior tooth region,with the majority traversing the palatal side of the central incisor.The anterior superior alveolar nerve bundle within the canalis sinuosus not only innervates and nourishes the maxillary anterior teeth and the corresponding soft tissues,and the maxillary sinus mucosa,but also relates to the nasal septum,lateral nasal wall,and parts of the palatal mucosa.To minimize surgical complications,strategies for preventing and treating canalis sinuosus injuries need to be investigated.Preoperatively,CBCT is used to identify the canalis sinuosus and to virtually design implant placement at a distance of more than 2 mm from the canalis sinuosus.Intraoperatively,assessing bleeding and patient comfort,complemented by precision surgical techniques such as the use of implant surgical guide plates.Postoperatively,CBCT is used to examine the relationship between the implant and the canalis sinuosus,and treatment of canalis sinuosus injuries can be tailored based on the patient's symptoms.This review summarizes the detection of canalis sinuosus in the population,its anatomical characteristics,and the physiological functions in the anterior maxilla,and discusses strategies for avoiding canalis sinuosus injuries during implant surgery,thereby enhancing clinical awareness and providing references for clinical decision-making.

Objective To investigate the impact of femoral prosthesis malposition on internal structural strain in unicompartmental knee arthroplasty for osteoporotic knees. Methods A normal bone knee joint model was constructed based on imaging studies (CT, magnetic resonance imaging) of healthy volunteers, and an osteoporotic knee joint model was constructed by altering the elastic modulus. Finite element models of femoral prosthesis malposition in unicompartmental knee arthroplasty were then established for both normal bone and osteoporotic groups. A vertical static load of 1, 000 N was applied to both models, and the peak strain values and distributions were observed in the medial compartment structures (polyethylene gasket, cancellous bone under tibial prosthesis) and lateral compartment structures (meniscus, tibial cartilage) at various malposition angles of the femoral prosthesis. Results The peak strain values of the polyethylene gasket, cancellous bone under tibial prosthesis, meniscus, and tibial cartilage in the osteoporotic group were higher than those in the normal bone group at different varus and valgus angles. In the osteoporotic group, the peak strain values of the polyethylene gasket and cancellous bone under tibial prosthesis increased with the increase in femoral prosthesis malposition angle, with a greater increase at valgus angles than at varus angles. Similarly, the peak strain values of the meniscus and tibial cartilage increased with the increase in femoral prosthesis malposition angle, but the increase was greater at varus angles than at valgus angles. The strain concentration area of the polyethylene gasket was located in a circular-like area where the femoral prosthesis contacted the gasket, the strain concentration area of the cancellous bone was mainly located in the posterolateral region, the strain concentration area of the meniscus was located near the anterior horn, and the strain concentration area of the tibial cartilage was mainly located in the middle near the intercondylar eminence. Conclusion Osteoporosis may adversely affect the strain on internal structures of the knee joint after unicompartmental knee arthroplasty. Varus malposition of the femoral prosthesis may exacerbate the progression of osteoarthritis in the contralateral compartment (lateral compartment), while valgus malposition may increase the risk of prosthesis loosening and revision surgery.

As the National Health Commission changes the management of novel corona virus infection, the situation and preventive policies for controlling the epidemic have also entered a new stage in China. Perioperative care strategies for orthopedic trauma such as designated isolation and nucleic acid test screening have also been adjusted in the new stage. Based on the perioperative work experiences in the new stage of epidemic from the frontline anti-epidemic staff of orthopedics in domestic hospitals and combined with the literature and relevant evidence-based medical data in perioperative care of orthopedic trauma patients under the current anti-epidemic policies at home and abroad, Chinese Orthopedic Association and Chinese Society of Traumatology organized relevant experts to formulate the Guideline for clinical perioperative care of orthopedic trauma patients in the new stage of novel corona virus infection ( version 2023). The guideline summarized 16 recommendations from the aspects of preoperative diagnosis and treatment, infection prevention, emergency operation and postoperative management to systematically standardize the perioperative clinical pathways, diagnosis and treatment processes of orthopedic trauma in the new stage of novel corona virus infection, so as to provide a guidance and reference for hospitals at all levels to carry out relevant work in current epidemic control policies.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

ObjectiveTo investigate the effect of baicalein （BAI） on SH-SY5Y cell injury in lipopolysaccharide （LPS）-activated BV-2 cells conditioned medium and its mechanism. MethodThe BV-2 cells were activated with 1 mg∙L^-1 of LPS to establish the conditioned medium of the LPS group， and a blank group and groups of BAI with low， medium， and high concentrations （4， 8， 16 μmol∙L^-1） were established. SH-SY5Y cells were cultured with the conditioned medium of each group. The cell viability of BV-2 cells in each group after the intervention was determined by cell counting kit-8 （CCK-8）. The content of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in the supernatant of BV-2 cells in each group was determined by enzyme-linked immunosorbent assay （ELISA）. The protein expression of α-synuclein （α-syn） and tyrosine hydroxylase （TH） in SH-SY5Y cells was observed by immunohistochemical （IHC） staining， and the nuclear transfer of nuclear factor kappa-B p65 protein （NF-κB p65， p65） in SH-SY5Y cells was observed by immunofluorescence （IF）. The protein expression of Toll-like receptor 4（TLR4）， p65， phosphorylated p65 （p-p65）， and Myeloid differentiation factor 88 （MyD88） in SH-SY5Y cells was observed by Western blot. ResultAs compared with the blank group， the viability of BV-2 cells in the LPS group was significantly decreased （P<0.01）， and the content of TNF-α， IL-6， and IL-1β in the cell supernatant was significantly increased （P<0.01）. As compared with the LPS group， the cell viability was significantly increased in groups of BAI with low， medium， and high concentrations （P<0.01）， and TNF-α in the cell supernatant was significantly decreased （P<0.01）. The content of IL-6 in the cell supernatant was decreased in the BAI group with high concentration （P<0.05）， and the content of IL-1β in the cell supernatant was significantly decreased in the BAI groups with medium and high concentrations （P<0.01）. The results of conditioned medium cultured SH-SY5Y cells showed that as compared with the blank group， the protein expression of p65 in the LPS group entered into the nucleus and accumulated， and the protein expression of TH was significantly decreased （P<0.01）， while that of α-syn， TLR4， MyD88， and p-p65 was increased （P<0.05， P<0.01）. Compared with the LPS group， the protein expression of p65 in SH-SY5Y cells in BAI groups with low， medium， and high concentrations gradually dispersed into the cytoplasm and had the enhanced protein expression of TH （P<0.01） but the lowered protein expression of α-syn （P<0.01）. The protein expression of TLR4， MyD88， and p-p65 was decreased in the BAI group with high concentration （P<0.05， P<0.01）， the protein expression of p-p65 and MyD88 was decreased in the BAI group with medium concentration， and the protein expression of MyD88 was decreased in the BAI group with low concentration （P<0.05）. There was no significant difference in the protein expression of p65 among groups. ConclusionBAI can inhibit the activation of BV-2 cells， thereby inhibiting the inflammatory response caused by LPS and further inhibiting the damage of inflammation to SH-SY5Y cells. The mechanism may be related to the regulation of the TLR4/MyD88/NF-κB signaling pathway and reduction of the inflammatory response， thus playing a neuroprotective role.

Objective To investigate the expression of Specific protein1(SP1)in esophageal squamous cell carci-noma(ESCC)and adjacent normal tissues and its effect on the proliferation and apoptosis of ESCC cells.Methods The expression of SP1 protein in 121 ESCC tissues and 74 adjacent normal tissues was detected by immunohisto-chemistry.Chi-square test and Cox regression analysis were used to analyze the relationship between SP1 and clini-copathological parameters and survival prognosis of ESCC patients.SP1 siRNA(small interfering RNA)was con-structed and transfected into esophageal squamous cell carcinoma Eca1 09 and EC9706 cell lines.Western blot was used to detect the expression of SP1 after transfection.The effects of SP1 on the proliferation and apoptosis of e-sophageal squamous cell carcinoma cells were detected by cloning assay,CCK-8 cell proliferation assay and flow cytometry.Results SP1 protein was expressed in the nucleus of esophageal squamous cell carcinoma tissues,and the expression rate of SP1 protein in esophageal squamous cell carcinoma tissues was significantly higher than that in adjacent normal tissues(x2=20.568,P＜0.01).Comparison between groups showed that the high expression rate of SP1 was higher in female(P=0.041),moderately or poorly differentiated(P=0.038)and T3-T4 inva-sion depth(P=0.041)ESCC(esophageal squamous cell carcinoma)patients.Log-rank test showed that the sur-vival time of patients with high expression of SP1 was shorter than that of patients with low expression of SP1(P=0.048).Multivariate Cox regression analysis showed that TNM(tumor node metastasis classification)stage(Ⅲ+Ⅳ)was a potential risk factor for shorter survival time in patients with esophageal squamous cell carcinoma(P＜0.001).Cell biological experiments showed that compared with the control group,the proliferation ability of esoph-ageal squamous cell carcinoma cell lines decreased(P＜0.05)and the apoptosis index increased(P＜0.05)after silencing SP1.Conclusion SP1 protein is highly expressed in human esophageal squamous cell carcinoma tissues and is associated with poor prognosis in patients.Silencing SP1 can inhibit the proliferation of esophageal squamous cell carcinoma cells and promote their apoptosis.