BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

ObjectiveTo construct an animal model of respiratory syncytial virus（RSV）-infected pneumonia suitable for preclinical studies. MethodsThe virulence of RSV to the four cell lines was observed by cytopathic effect （CPE）， and 50% tissue culture infective dose（TCID₅₀） was calculated. Twenty BALB/c mice were randomly divided into a normal group and a model group. Six BALB/c-hIGF1R mice served as the humanized IGF1R model group. Except for the normal group， the other groups received intranasal RSV infection on days 1 and 3 to establish a viral pneumonia model. The efficacy of establishing an RSV-induced pneumonia animal model based on humanized insulin-like growth factor 1 receptor （IGF1R） mice was evaluated by measuring organ indices， peripheral blood lymphocyte percentages， pulmonary pathology and imaging， and pulmonary viral load. Additionally， ten BALB/c mice served as normal group， and thirty-two BALB/c-hIGF1R mice were randomly assigned to humanized IGF1R model group， ribavirin group （82.5 mg·kg^-¹·d^-¹）， and high and low dose groups of Lianhua Qingwen （3.3 mg·kg^-¹·d^-¹ ， 1.65 mg·kg^-¹·d^-¹）， with 8 mice per group. The viral load in lung tissue was measured after ribavirin and Lianhua Qingwen intervention， and the model was applied to the evaluation of anti-RSV drugs. ResultsIn the lungs of the humanized IGF1R model group， large solid and diffuse ground-glass shadows were seen， and the lung volume was significantly increased （P<0.01）. The lung index was significantly increased （P<0.01）， and both the spleen index and thymus index were significantly decreased （P<0.01）. The percentages of CD3⁺ and CD4⁺T cells were significantly decreased （P<0.05）， and there was a large amount of inflammation and stasis in the perivascular area of the lung tissue， which was predominantly characterized by lymphocytes. The endothelium of blood vessels was partially detached， with a small number of eosinophils. After infecting BALB/c-hIGF1R mice with RSV， the expression of viral nucleic acids in the lung tissue of the mice was significantly increased， with significant differences compared with the normal group （P<0.01）. The expression of viral nucleic acids in the ribavirin group and the high and low dose groups of Lianhua Qingwen was significantly reduced， with significant differences compared with the normal group （P<0.01）. ConclusionHumanized IGF1R mice are more susceptible to respiratory SVC， and the animal model of RSV-infected pneumonia based on humanized IGF1R mice was successfully constructed， which is suitable for the evaluation of anti-RSV drugs.

ObjectiveTo construct an animal model of respiratory syncytial virus（RSV）-infected pneumonia suitable for preclinical studies. MethodsThe virulence of RSV to the four cell lines was observed by cytopathic effect （CPE）， and 50% tissue culture infective dose（TCID₅₀） was calculated. Twenty BALB/c mice were randomly divided into a normal group and a model group. Six BALB/c-hIGF1R mice served as the humanized IGF1R model group. Except for the normal group， the other groups received intranasal RSV infection on days 1 and 3 to establish a viral pneumonia model. The efficacy of establishing an RSV-induced pneumonia animal model based on humanized insulin-like growth factor 1 receptor （IGF1R） mice was evaluated by measuring organ indices， peripheral blood lymphocyte percentages， pulmonary pathology and imaging， and pulmonary viral load. Additionally， ten BALB/c mice served as normal group， and thirty-two BALB/c-hIGF1R mice were randomly assigned to humanized IGF1R model group， ribavirin group （82.5 mg·kg^-¹·d^-¹）， and high and low dose groups of Lianhua Qingwen （3.3 mg·kg^-¹·d^-¹ ， 1.65 mg·kg^-¹·d^-¹）， with 8 mice per group. The viral load in lung tissue was measured after ribavirin and Lianhua Qingwen intervention， and the model was applied to the evaluation of anti-RSV drugs. ResultsIn the lungs of the humanized IGF1R model group， large solid and diffuse ground-glass shadows were seen， and the lung volume was significantly increased （P<0.01）. The lung index was significantly increased （P<0.01）， and both the spleen index and thymus index were significantly decreased （P<0.01）. The percentages of CD3⁺ and CD4⁺T cells were significantly decreased （P<0.05）， and there was a large amount of inflammation and stasis in the perivascular area of the lung tissue， which was predominantly characterized by lymphocytes. The endothelium of blood vessels was partially detached， with a small number of eosinophils. After infecting BALB/c-hIGF1R mice with RSV， the expression of viral nucleic acids in the lung tissue of the mice was significantly increased， with significant differences compared with the normal group （P<0.01）. The expression of viral nucleic acids in the ribavirin group and the high and low dose groups of Lianhua Qingwen was significantly reduced， with significant differences compared with the normal group （P<0.01）. ConclusionHumanized IGF1R mice are more susceptible to respiratory SVC， and the animal model of RSV-infected pneumonia based on humanized IGF1R mice was successfully constructed， which is suitable for the evaluation of anti-RSV drugs.

ObjectiveTo investigate the possible mechanism of Shufeng Jiedu capsules （SFJD） in alleviating influenza A （H1N1） virus pneumonia and focus on its effect on Toll-like receptor （TLR） signaling pathway in respiratory epithelial cells. MethodsA mouse model of viral pneumonia was established via the A/PR/8/34 （PR8） strain of influenza A virus. Mice were randomly divided into a normal group， a PR8 infection （PR8） group， and an SFJD group （8.4 g·kg^-1）， with 10 mice in each group. The day of infection was designated as day 1. The SFJD group was administered intragastrically at a volume of 20 mL·kg^-1 daily， while the normal and PR8 groups were given an equal volume of deionized water. Micro-computed tomography （Micro-CT） was performed on day 5， and the mice were dissected to collect their lungs， after which the lung index was calculated to verify the therapeutic effect of SFJD. Single-cell sequencing was used to analyze the differentially expressed genes in respiratory epithelial cells. Multiplex fluorescence immunohistochemistry was employed to detect the expression of TLR， tumor necrosis factor receptor-associated factor 6 （TRAF6）， and myeloid differentiation factor 88 （MyD88） proteins in epithelial cell adhesion molecule （EpCAM）-positive cells， and the proportion of respiratory epithelial cells expressing TLR pathway proteins was calculated. Respiratory epithelial cells were then sorted by flow cytometry， and Western blot was used to detect the expression of TLR， MyD88， TRAF6， Toll-interleukin receptor domain-containing adaptor inducing interferon-β （TRIF）， inhibitor of κB kinase α （IKKα）， and nuclear factor-κB （NF-κB） in the sorted epithelial cells. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in lung tissue. ResultsAt the transcriptional level， SFJD reversed the expression of TLR signaling pathway genes in respiratory epithelial cells， downregulating multiple TLR signaling pathway-related genes （P<0.01）. At the protein level， SFJD significantly reduced the proportion of respiratory epithelial cells expressing TLR3 （P<0.05）， the expression levels of TLR2， TLR3， TLR4， TRIF， TRAF6， IKKα， and NF-κB in epithelial cells（P<0.05， P<0.01）， as well as the levels of pro-inflammatory cytokines IL-1β and TNF-α in lung tissue （P<0.01）. ConclusionSFJD may alleviate viral pneumonia by suppressing the expression of TLR in respiratory epithelial cells and their subsequent signaling cascades.

ObjectiveTo analyze the adverse reactions associated with the clinical use of Banxia （Rhizoma Pinelliae）- Wutou （Aconitum） in the same formula， with the aim of providing a reference for the safety of their clinical application. MethodsLiterature on the clinical application of antagonistic herbs "Banxia-Wutou" used in the same formula， published from January 1st， 2014， to June 30th， 2023， was retrieved from databases including CNKI， VIP， Wanfang， SinoMed， PubMed， Cochrane Library， and Embase. A database was established， and information related to adverse reactions was extracted， including descriptions， classifications， specific manifestations， management and outcomes， patients' primary diseases （western medicine diseases and traditional Chinese medicine diagnoses and syndromes）， and medication information （dosage， ratio， administration routes， and dosage forms）. ResultsA total of 79 researches simultaneously used antagonistic herbs Banxia-Wutou in the same formula and reported associated advers reactions. Gastrointestinal adverse reactions were the most common， with 8 studies reporting management of adverse reactions and 3 studies reporting improvement with no intervention. Among the 11 researches， the adverse reaction relieved to extant， while other 69 researches didn't report the managment of adverse reaction and its prognosis. For the primary disease in western medicine system， chronic bronchitis and chronic obstructive pulmonary disease （COPD） were most common， while gastric pain was the most common symptom in traditional Chinese medicine with spleen and kidney deficiency and spleen stomach cold deficiency being the most frequent syndromes. The most common Banxia dosage was 10 g， while for the Wutou， Fuzi （Radix Aconiti Lateralis Praeparata） was predominant with the highest dose at 15 g. The most frequent herbal combination was Banxia-fuzi， with a 1∶1 ratio. The main administration route was oral， and the primary dosage form was decoction. ConclusionGastrointestinal adverse reactions are the most common in the clinical use of Banxia-Wutou antagonistic herb combinations. Research on the safety of "Banxia-Wutou" combinations should focus on respiratory system diseases and spleen-stomach related conditions.

Objective:To compare the anterior long-segment fixation, posterior long-segment fixation, and combined anterior-posterior fixation in the treatment of ankylosing spondylitis with cervical fracture (ASCF).Methods:A retrospective study was conducted to analyze the 153 patients with ASCF who had been treated at Department of Orthopaedics, Peking University Third Hospital and Department of Orthopedics, Luoche Central Hospital between January 2014 and December 2023. The cohort included 86 males and 67 females, with an age of (41.6±11.5) years, a disease duration of (10.0±3.9) years, and an interval from injury to surgery of (3.3±1.4) d. By Frankel's classification for preoperative nerve injury, 57 cases were grade B, 51 grade C, and 45 grade D. Based on the surgical approaches, the patients were divided into 3 groups: an anterior group ( n=63) undergoing the anterior cervical long-segment fixation, a posterior group ( n=51) undergoing the posterior cervical long-segment fixation, and a combination group ( n=39) undergoing combined anterior-posterior cervical fixation. Surgical time, intraoperative blood loss, fracture healing, complications, and changes in Frankel grading for spinal cord injury were compared among the 3 groups. Results:There was no statistically significant difference in the preoperative general data among the 3 groups, indicating comparability ( P > 0.05). All patients were followed up for (33.5±12.0) months after surgery. In the anterior group, the surgical time [(103.0±16.8) min] was significantly shorter than that in the posterior group [(148.4±17.7) min] and that in the combination group [(228.5±23.9) min], the intraoperative blood loss [(92.8±27.8) mL] was significantly less than that in the posterior group [(477.5±109.5) mL] and that in the combination group [(769.5±136.9) mL], and the incidence of complications [9.5% (6/63)] was significantly lower than that in the posterior group [41.2% (21/51)] and that in the combination group [53.8% (21/39)] (all P<0.05). There was no statistically significant difference in the fracture healing time among the 3 groups ( P=0.111). At the last follow-up, X-ray and CT scans showed no loosening or breakage of internal fixation in all the 3 groups. The Frankel grading at the last follow-up: 12 cases of grade C, 15 cases of grade D, and 36 cases of grade E in the anterior group; 3 cases of grade B, 12 cases of grade C, 12 cases of grade D, and 24 cases of grade E in the posterior group; 6 cases of grade C, 12 cases of grade D, and 21 cases of grade E in the combination group. At the last follow-up, all patients showed a significant improvement compared to their Frankel grades before surgery ( P<0.001), but there was no statistically significant difference between the 3 groups ( H=2.238, P=0.327). Conclusions:In the treatment of ASCF, anterior long-segment fixation is advantageous over posterior long-segment fixation and combined anteri-or-posterior fixation due to its shorter surgical time, reduced intraoperative blood loss, and a lower complication incidence. All the 3 surgical approaches demonstrate comparable outcomes in terms of fracture healing time, radiographic stability, and final neurological recovery.

Purpose To investigate the expression of SNRPA in gastric cancer and its effect on the proliferation,migration and invasion of gastric cancer cells.Methods The expression of SNRPA in gastric cancer tissues was ana-lyzed using The Cancer Genome Atlas(TCGA)database.The level of SNRPA was detected by immunohistochemistry(EnVision method),and its relationship with clinicopathological parameters was analyzed.Western blot was used to detect the expression of SNRPA in 15 cases of fresh gastric cancer and paracancerous tissues.The expression of SNRPA in MGC-803 and GES-1 cells was detected by immunofluorescence staining.The effects of SNRPA expression on the proliferation,migration and invasion of gastric cancer cell lines were determined by RNA interference technology and cell function assays,and the expression levels of Cyclin D1 protein and EMT-related proteins(E-cadherin,N-cadher-in)were detected by Western blot.Results The expression level of SNRPA in gastric cancer tissues was significantly higher than that in normal gastric mucosal tissues(P＜0.05),with an area under the curve(AUC)of 0.902 for diag-nostic accuracy.The Kaplan-Meier survival curves showed that the survival time of the group with high expression of SNRPA was shorter.SNRPA expression correlated with tumor size,Ki67,infiltration depth,and p53 status(P＜0.05).Compared with the corresponding control group,SNRPA silencing inhibited the proliferation,migration and in-vasion ability of gastric cancer cells,accompanied by decreased Cyclin D1 and N-cadherin expression and increased E-cadherin expression(P＜0.05).Conclusion SNRPA expression is upregulated in gastric cancer tissues and cell lines,promoting the proliferation,migration,and invasion of gastric cancer cells,and may be a potential molecular marker for gastric cancer.

Objective:This study aimed to clarify clinicopathologic characteristics, postoperative complications, and related risk factors of elderly patients with gastric cancer.Methods:A total of 395 patients(≥65 years old)who underwent radical gastrectomy for gastric cancer in Beijing Hospital from January 2014 to December 2021 were enrolled in this study.The patients were divided into the common elderly group(age<80 years, n=340)and the high-age group(age ≥ 80 years, n=55). Postoperative complications were classified into medical and surgical types.The clinicopathological characteristics and complications were compared between the two groups.Logistic regression models(univariate and multivariate)were used to identify the risk factors for postoperative complications.Results:The common elderly group was 65-79 years old(mean age: 71.5±4.3 years), with 263 male(77.4%); The high-age group was 80-89 years old(mean age: 82.6±2.6 years), with 42 male(76.4%). The comorbidity rate and the number of comorbidities in the high-age group were significantly higher than those in the common elderly group.The American Society of Anesthesiologists(ASA)scores and nutritional risk screening(NRS)2002 scores in the high-age group were significantly higher than those in the common elderly group(both P<0.05), and the activities of daily living(ADL)scores in the high-age group were significantly lower than that in the common elderly group( P<0.001). There were no statistically significant differences in tumor location, degree of differentiation, pathological type, T stage, and N stage between the two groups(all P>0.05). The overall postoperative complication rate in the high-age group was significantly higher than that in the common elderly group(38.2% vs.24.7%, P=0.036); the medical complications were significantly increased in the high-age group(21.8% vs.10.9%, P=0.022), whereas the surgical complications did not increase significantly(25.5% vs.17.1%, P=0.135). Multivariate analysis revealed that the number of comorbidities ≥2( HR=2.502, 95% CI: 1.275-4.911, P=0.008), preoperative NRS 2002 scores ≥5( HR=2.714, 95% CI1.294-5.693, P=0.008), and preoperative ADL scores<100( HR=2.012, 95% CI1.010-4.009, P=0.047)were independent risk factors for medical complications.Additionally, ASA grade ≥ 3( HR=2.586, 95% CI: 1.444-4.632, P=0.001)and proximal or distal gastrectomy( HR=2.397, 95% CI: 1.237-4.574, P=0.009)were independent risk factors for surgical complications. Conclusions:The occurrence of postoperative medical complications in very elderly patients with gastric cancer undergoing radical surgery has increased, while the rate of surgical complications has not increased.Moreover, advanced age itself is not an independent risk factor for postoperative complications.More attention should be paid to medical complications, and the management of commodities and nutritional support should be strengthened during the perioperative period.

Objective:To investigate the association between the metabolic score for visceral fat(METS-VF)and sarcopenia in older adults in China.Methods:A retrospective cohort study was conducted.A total of 1 262 participants aged ≥60 years old who did not diagnose with sarcopenia in 2011 and had complete follow-up data in 2015 were selected from the China health and retirement longitudinal survey(CHARLS). Participants were divided into the low METS-VF group (n=621)and the high METS-VF group (n=641), and then the corrleation between METS-VF and sarcopenia was analyzed.Results:The inverse probability of treatment weighting(IPTW)was used to balance all covariates between the low METS-VF group and high METS-VF group.The results showed that 30 participants in the low METS-VF group and 47 participants in the high METS-VF group were diagnosed with sarcopenia, with prevalence rates of 4.83%(30/621)and 7.33%(47/641), respectively.The difference in the prevalence of sarcopenia between the two groups was statistically significant after IPTW ( χ2=3.934, P=0.048, SMD=0.150). Logistic regression analysis showed that, after adjusting for various confounders, high METS-VF was significantly associated with an increased risk of sarcopenia in older adults( OR=2.130, 95% CI: 1.294~3.572, P=0.003). Subgroup analyses further indicated that individuals without cardiovascular disease had a relatively higher risk of sarcopenia( P for interaction=0.032). Conclusions:METS-VF is associated with an increased risk of sarcopenia in older adults in China, and its predictive and diagnostic value warrants further investigation.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.