OBJECTIVE To analyze the safety and efficacy of vonoprazan （VPZ） in the treatment of peptic ulcer （PU） and post-endoscopic submucosal dissection （ESD） ulcers， providing evidence-based pharmaceutical evidence for clinical practice and medical decision-making. METHODS Retrieved from CNKI， Wanfang， VIP， CBM， PubMed， Embase， Web of Science， and the Cochrane Library， meta-analyses/systematic reviews related to VPZ in the treatment of PU and post-ESD ulcers were collected. Two researchers independently performed literature screening， data extraction， quality assessment of included studies， and evaluation of literature overlap. By employing the umbrella review analysis， a fresh meta-analysis was conducted on all relevant raw research data when a high degree of overlap was identified among the included studies. RESULTS A total of 17 meta-analyses were included， with quality ranging from high to very low； all outcome measures involved showed a very high level of overlap in the included meta-analyses （corrected covered area： 22.22%-100%）. In the treatment of post-ESD ulcers， compared to proton pump inhibitor （PPI）， VPZ significantly improved the ulcer healing rate at 4 weeks post-ESD [RR＝1.27， 95%CI （1.03， 1.56）， Z＝2.21， P＝ 0.027] and the ulcer contraction rate post-ESD [MD＝0.08， 95%CI （0.00， 0.16）， Z＝2.09， P＝0.037]， while significantly reducing the ulcer recurrence rate in patients with a history of PU [RR＝0.49， 95%CI （0.32， 0.73）， Z＝3.49， P＝0.001]； the delayed bleeding rate in the VPZ group was significantly lower than that in the lansoprazole subgroup [RR＝0.47， 95%CI （0.25， 0.90）， Z＝2.28， P＝0.02]. In the treatment of PU， the incidence of adverse events with VPZ was significantly higher than that with PPI in the duodenal ulcer subgroup [RR＝1.13， 95%CI （1.02， 1.26）， Z＝2.38， P＝0.017]. CONCLUSIONS For post-ESD ulcers， VPZ demonstrates superior therapeutic efficacy compared to PPI and can reduce ulcer recurrence rates in patients with a history of PU. However， it does not offer advantages in terms of safety for duodenal ulcer treatment.

OBJECTIVE To investigate the efficacy and safety of omadacycline in the treatment of macrolide-unresponsive Mycoplasma pneumoniae pneumonia （MUMPP） in children. METHODS A retrospective study was conducted on children aged 1-18 years old with MUMPP who were hospitalized in the Department of Pediatrics， the First Affiliated Hospital of Xinjiang Medical University from January 2022 to June 2025. According to the selection of secondary antibiotics after 72 h of initial treatment with macrolides， they were divided into the omadacycline group and the doxycycline group. Based on conventional treatment， children in the omadacycline group were given intravenous infusion of 2.4 mg/kg （once daily） of omadacycline tosylate， while children in the doxycycline group were given oral doxycycline hydrochloride tablets at 2 mg/kg （twice daily）. The efficacy and safety were compared between the two groups of pediatric patients. Univariate analysis and multivariate Logistic regression analysis were performed on clinical efficacy， and subgroup analysis along with multiple sensitivity analyses were conducted to verify the robustness of the conclusions. RESULTS A total of 284 children with MUMPP were included in this study， with 142 in the omadacycline group and 142 in the doxycycline group. In terms of efficacy， although the hospitalization time of children in the omadacycline group was longer than that in the doxycycline group （ P ＜0.05）， the lung lesion absorption rate and clinical efficacy were significantly higher or better than those in the doxycycline group （ P ＜0.05）. The results of multivariate Logistic regression analysis showed that medication （OR＝5.300， 95%CI： 2.526-11.123）， length of hospital stay （OR＝1.348， 95%CI： 1.167-1.556）， and medication duration （OR＝1.422， 95%CI： 1.169-1.729） were influencing factors of clinical efficacy （ P ＜0.05）. The subgroup analysis results showed that the clinical efficacy of omadacycline was significantly better than that of doxycycline in all subgroups （ P ＜0.05）. The results of multiple sensitivity analysis showed that the regression coefficients B of the four models （gradually adjust variables） before and after inverse probability of treatment weighting were significantly greater than 1 （ P ＜0.05）. In terms of safety， there was no statistically significant difference in the inci dence of adverse drug reactions between the two groups of patients （ χ 2 ＝0.447， P ＝0.504）. CONCLUSIONS In the case of hospitalization and prolonged medication， the efficacy of omadacycline in treating childhood MUMPP is superior to that of doxycycline， and its safety is good.

Objective: To investigate the mechanism by which serum amyloid P component (SAP) alleviates periodontitis in mice, providing an experimental basis to establish SAP as a novel therapeutic agent for periodontitis. Methods: Ethical approval was obtained from the Institutional Animal Ethics Committee. Periodontitis models were established in wild-type (WT) mice and SAP-transgenic (SAP-Tg) mice, divided into four groups: WT control (WT group), WT periodontitis (WT+P group), SAP-Tg control (Tg group), and SAP-Tg periodontitis (Tg+P group). On day 7, the mice were euthanized, and periodontal tissues, teeth, and alveolar bone were collected. SAP protein expression was detected by enzyme-linked immunosorbent assay (ELISA). Micro-CT and HE staining were used to measure alveolar bone resorption (distance from the cementoenamel junction to the alveolar bone crest). Tartrate-resistant acid phosphatase (TRAP) staining was performed to assess osteoclast number, and immunohistochemistry (IHC) was employed to evaluate macrophage infiltration. The expression levels of inflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured by qRT-PCR. Oral microorganism composition was analyzed using 16S ribosomal RNA (16S rRNA) gene sequencing. Additionally, macrophages from WT and SAP-Tg mice were isolated to establish an in vitro inflammation model, divided into WT+LPS and Tg+LPS groups. The expression of macrophage polarization-related genes including inducible nitric oxide synthase (iNOS), CD86, CD163, and CD206) were assessed by qRT-PCR. After the induction of osteoclast differentiation, TRAP staining was performed. Results: ELISA results demonstrated that periodontal tissues from Tg+P group mice exhibited higher levels of SAP expression compared to the WT+P group. Micro-CT and HE staining analyses revealed that the Tg+P group showed reduced alveolar bone resorption, indicated by a shorter distance between the cementoenamel junction and alveolar bone crest, compared to the WT+P group. Furthermore, TRAP staining results indicated a decrease in osteoclast numbers in the Tg+P group compared to the WT+P group. IHC and qRT-PCR results indicated reduced macrophage infiltration and decreased expression of IL-1β, IL-6, and TNF-α in the Tg+P group. Oral microorganism sequencing showed no significant difference in periodontitis-associated pathogenic bacteria between WT+P and Tg+P groups. In vitro experiments demonstrated that compared to the WT+LPS group, the Tg+LPS group exhibited downregulated M1 macrophage markers (iNOS and CD86) and upregulated M2 macrophage markers (CD163 and CD206). TRAP staining confirmed fewer osteoclasts in the Tg+LPS group. Conclusion SAP overexpression effectively alleviates periodontitis severity in mice by inhibiting M1 macrophage polarization, reducing pro-inflammatory cytokine expression, and suppressing osteoclast differentiation, thereby attenuating alveolar bone resorption.

Objective:To investigate the induction effect of different concentrations of glucose on the polarization of Raw264.7 macrophages in vitro.Methods:The Raw264.7 cells cultured in DMEM medium were divided into control group(5.5 mmol·L-1 glucose),different high-glucose groups(15.0,25.0,35.0,and 45.0 mmol·L-1 glucose),and positive control group[lipopolysaccharide(LPS)].The cells were cultured for 3,6,and 9 h,respectively.Cell morphology was observed in various groups.Cell counting kit-8(CCK-8)method was used to assess the survival rates of cells in various groups.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and interleukin-10(IL-10)mRNA in cells in various groups.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of IL-6,TNF-α,and IL-10 in the cell supernatants in various groups.Flow cytometry was used to determine the percentages of M1 and M2 macrophage markers,CD86+and CD163+cells,in various groups.Results:In control group,theRaw264.7 cells adhered to the culture dish,with a predominantly round morphology.The cells in 35.0 mmol·L-1 high-glucose group and positive control group showed elongated shapes and pseudopodium formation,indicating inflammatory changes.Compared with control group,the survival rates in different high-glucose groups at 6,12,24,and 48 h after treatment were increased(P＜0.05).Compared with control group,after 3 h of treatment,the expression levels of IL-6 and IL-10 mRNA in the cells in 35.0 mmol·L-1 high-glucose group were increased(P＜0.05 or P＜0.01),while no significant changes were observed in IL-6,TNF-α,and IL-10 levels in the cell supernatants(P＞0.05);after 6 h of treatment,the expression level of TNF-α mRNA in the cells in 35.0 mmol·L-1 high-glucose group was increased(P＜0.001),and the levels of IL-6,TNF-α,and IL-10 in the cell supernatants were significantly increased(P＜0.05 or P＜0.001);after 3 h of treatment,the percentages of macrophage markers CD86+cells and CD163+cells in 35.0 mmolL-1 high-glucose group were significantly increased(P＜0.01 or P＜0.001).Conclusion:A certain high concentration of glucose may induce the polarization of Raw264.7 macrophages towards the M1 subtype in vitro.

Objective To explore the role of dapansutrile(OLT1177)in radiation-induced intestinal injury and the mechanism.Methods C57BL/6J mice were locally irradiated in the abdomen with 60Co to induce a model of radiation-induced intestinal injury.OLT1177 was intraperitoneally injected at a dose of 100 mg/kg 2 hours before irradiation and 6 hours after irradiation before the drug was administered once a day.At 12 hours after irradiation,intestinal tissues were taken for terminal deoxynucleotidyl transferase mediated nick end labeling(TUNEL)staining to detect apoptosis in intestinal tissues.At 4 days after irradiation,mouse serum was collected to detect the levels of inflammatory factors in the serum.Hematoxylin-eosin(HE)stainingwas used for the evaluation of the damage to the intestinal villus structure.Immunohistochemical staining was adopted to detect the changes in crypt proliferation in intestinal tissues.Finally,proteins were isolated from intestinal tissues,and Western blotting was employed to evaluate the activation of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome.Results After irradiation,the intestinal villi in mice were shortened.Meanwhile,there was a notable declinein the number of cells that were proliferating in the crypts,a surge in the number of apoptotic cells,and a significant spike in the overall inflammatory level.However,administration of OLT1177 inhibited the activation of the NLRP3 inflammasome,reduced apoptosis and pyroptosis,decreased the inflammatory level,and thus improved radiation-induced intestinal injury.Conclusion Administration of OLT1177 can significantly mitigate radiation-induced intestinal injury.

Objective:To evaluate the safety of early enteral nutrition (EEN) support in patients with severe intra-abdominal infection and intestinal fistulas.Methods:This was a retrospective cohort study. We collected relevant clinical data of 204 patients with severe intra-abdominal infection and intestinal fistulas who had been managed in the No. 1 Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University between 1 January 2017 and 1 January 2020. The patients were allocated to EEN or delayed enteral nutrition (DEN) groups depending on whether enteral nutrition had been instituted within 48 hours of admission to the intensive care unit. The primary outcome was 180-day mortality. Other outcomes included rates of intraperitoneal hemorrhage, septic shock, open abdominal cavity, bloodstream infection, mechanical ventilation, and continuous renal replacement therapy. Risk factors for mortality were analyzed by logistic regression.Results:There were no significant differences in hematological data or other baseline characteristics between the two groups at the time of admission to the intensive care unit (all P>0.05). However, septic shock (31.2% [15/48] vs. 15.4% [24/156], χ 2=4.99, P=0.025), continuous renal replacement therapy (27.1% [13/48] versus 9.0% [14/156], χ 2=8.96, P=0.003), and 180-day mortality (31.2% [15/48] vs. 7.7% [12/156], χ 2=15.75, P<0.001) were significantly more frequent in the EEN than the DEN group (all P<0.05). Multivariate regression analysis showed that older age (OR=1.082, 95%CI:1.027-1.139, P=0.003), worse Acute Physiology and Chronic Health Evaluation (APACHE) II scores (OR=1.189, 95%CI: 1.037-1.363, P=0.013), higher C-reactive protein (OR=1.013, 95%CI:1.004-1.023, P=0.007) and EEN (OR=8.844, 95%CI:1.809- 43.240, P=0.007) were independent risk factors for death in patients with severe intra-abdominal infection and intestinal fistulas. Conclusion:EEN may lead to adverse events and increase mortality in patients with both enterocutaneous fistulas and severe abdominal infection. EEN should be implemented with caution in such patients.

Objective:To evaluate the safety of early enteral nutrition (EEN) support in patients with severe intra-abdominal infection and intestinal fistulas.Methods:This was a retrospective cohort study. We collected relevant clinical data of 204 patients with severe intra-abdominal infection and intestinal fistulas who had been managed in the No. 1 Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University between 1 January 2017 and 1 January 2020. The patients were allocated to EEN or delayed enteral nutrition (DEN) groups depending on whether enteral nutrition had been instituted within 48 hours of admission to the intensive care unit. The primary outcome was 180-day mortality. Other outcomes included rates of intraperitoneal hemorrhage, septic shock, open abdominal cavity, bloodstream infection, mechanical ventilation, and continuous renal replacement therapy. Risk factors for mortality were analyzed by logistic regression.Results:There were no significant differences in hematological data or other baseline characteristics between the two groups at the time of admission to the intensive care unit (all P>0.05). However, septic shock (31.2% [15/48] vs. 15.4% [24/156], χ 2=4.99, P=0.025), continuous renal replacement therapy (27.1% [13/48] versus 9.0% [14/156], χ 2=8.96, P=0.003), and 180-day mortality (31.2% [15/48] vs. 7.7% [12/156], χ 2=15.75, P<0.001) were significantly more frequent in the EEN than the DEN group (all P<0.05). Multivariate regression analysis showed that older age (OR=1.082, 95%CI:1.027-1.139, P=0.003), worse Acute Physiology and Chronic Health Evaluation (APACHE) II scores (OR=1.189, 95%CI: 1.037-1.363, P=0.013), higher C-reactive protein (OR=1.013, 95%CI:1.004-1.023, P=0.007) and EEN (OR=8.844, 95%CI:1.809- 43.240, P=0.007) were independent risk factors for death in patients with severe intra-abdominal infection and intestinal fistulas. Conclusion:EEN may lead to adverse events and increase mortality in patients with both enterocutaneous fistulas and severe abdominal infection. EEN should be implemented with caution in such patients.

Objective:To explore the effect of free transplantation of composite tissue flap from the anterior lateral aspect of the femur in repairing head skin defects with artificial dural exposure infection.Methods:A retrospective study was conducted on 13 patients admitted to the First Affiliated Hospital of Air Force Military Medical University from April 2018 to August 2020 with craniotomy complications, including craniotomy skin and soft tissue defects combined with artificial dural exposure and infection. After preoperative anti infection treatment, the neurosurgery department participated in debridement and removed the artificial dura mater as much as possible during the operation. A composite tissue flap carrying the fascia lata was designed for the anterior lateral aspect of the thigh, and the flap artery and vein were anastomosed with the superficial temporal artery and superficial temporal vein/middle temporal vein respectively. The defect of the dura mater was repaired with the fascia lata with blood supply. The flap was used to seal the wound, and the donor site was directly sutured or transplanted with autologous medium thick skin graft. The postoperative blood supply and survival of the flap, the presence of cerebrospinal fluid leakage, and the healing of the donor site were observed; The observation of dural integrity and postoperative effects of skull reconstruction using cranial magnetic resonance imaging was followed up.Results:Among the 13 patients in this group, 11 patients had their artificial dura mater completely removed, while 2 patients were not completely removed due to severe adhesion. Among them, 1 patient had a residual area of 0.8 cm×1 cm, and the other had 3 residual areas, with a maximum area of 0.5 cm×0.7 cm; All transplanted skin flaps survived, with 12 cases achieving primary healing and 1 case of partial wound rupture after suture removal, which healed after conservative dressing change; All patients had no cerebrospinal fluid leakage; There was one case of partial necrosis of the graft in the donor site, which healed after supplementing the graft; Thirteen patients underwent cranial magnetic resonance imaging at 3-6 months postoperatively, all of which showed intact dura mater; Among them, 8 patients have completed skull reconstruction surgery, and all of them have healed well after reconstruction, with a good appearance of the surgical area.Conclusions:For wounds with head skin defects and exposed artificial dura mater infection, free transplantation of the anterior lateral composite tissue flap carrying the fascia lata can effectively cover the wound and repair the dura mater defect, achieve good function and appearance, and create favorable conditions for later skull reconstruction.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Objective:To investigate the relationship between body mass index(BMI) and osteoporosis using Mendelian randomization analysis.Methods:The genetic variation strongly related to BMI was selected as the instrumental variables in the collection data set of the genome-wide association study(GWAS). The MR-Egger regression, weighted median estimator(WME), inverse variance weighted(IVW), simple mode and weighted mode were used for Mendelian randomization(MR) analysis. The causal association between BMI and osteoporosis was evaluated by odds ratio and 95% confidence interval. The MR-APSS method was applied to make the causal inference results based on MR more reliable. The Linkage disequilibrium score regression was applied to evaluate the genetic correlation, and the horizontal pleiotropy test, heterogeneity test, and leave-one-out method were used to evaluate whether the results were reliable, The influence of heterogeneity and horizontal pleiotropy were reduced by the MR-PRESSO outlier test.Results:A total of 421 SNPs were included, with inverse variance-weighted method as the main analysis approach. The calculated OR value and 95% CI were 0.994(95% CI 0.992-0.997), indicating a protective effect of BMI on osteoporosis. The MR-APSS method showed that the effect of BMI on osteoporosis was statistically significant. Linkage disequilibrium score regression demonstrated a genetic correlation between BMI and osteoporosis. MR-Egger regression intercept showed no horizontal pleiotropy of instrumental variables, and the funnel plot showed no bias in instrumental variables. Leave-one-out analysis confirmed robust results. Conclusion:There may be a negative causal relationship between BMI and osteoporosis and BMI is a protective factor for osteoporosis.