BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.

BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.

Objective: To determine the clinical efficacy and mechanism of Piwei Peiyuan Pill (PPP) combined with moxibustion for treating patients with chronic atrophic gastritis (CAG) with spleen and stomach weakness syndrome. Methods: Ninety-six CAG patients with spleen and stomach weakness syndrome who met the inclusion and exclusion criteria were enrolled at the Department of Spleen and Stomach Diseases of the Second Affiliated Hospital of Anhui University of Chinese Medicine from June 2022 to December 2023. The patients were randomly divided into a control, a Chinese medicine, and a combined group using a random number table method, with 32 cases in each group (two cases per group were excluded). The control group was treated with rabeprazole combined with folic acid tablets (both thrice daily), the Chinese medicine group was treated with PPP (8 g, thrice daily), and the combined group was treated with moxa stick moxibustion (once daily) on the basis of the Chinese medicine group for 12 consecutive weeks. Gastric mucosa atrophy in the three groups was observed before and after treatment. The gastric mucosal pathological score was evaluated. The Patient Reported Outcome (PRO) scale was used to evaluate the patients′ physical and mental health status and quality of life.An enzyme-linked immunosorbent assay was used to detect serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4, IL-10, IL-37, and transforming growth factor (TGF)-β levels in each group. Real-time fluorescence PCR was used to detect the relative expression levels of signal transducer and activator of transcription 3 (STAT3) and mammalian target of rapamycin (mTOR) mRNA in each group. Western blotting was used to detect the relative expression levels of proteins related to the STAT3/mTOR signaling pathway, and the adverse drug reactions and events were recorded and compared. Results: There was no statistical difference in age, gender, disease duration, family history of gastrointestinal tumors, alcohol consumption history, and body mass index among the three groups of patients.The total therapeutic efficacy rates of the control, Chinese medicine, and combined groups in treating gastric mucosal atrophy were 66.67% (20/30), 86.67% (26/30), and 90.00% (27/30), respectively (P<0.05). Compared to before treatment, the pathological and PRO scale scores of gastric mucosa in each group decreased after treatment, and TNF-α, IL-1β, IL-37, and TGF-β levels decreased. The relative STAT3 and mTOR mRNA expression levels, as well as the relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels decreased (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the control group, the pathological score of gastric mucosa, PRO scale score, TNF-α, IL-1β, IL-37, TGF-β content, relative STAT3 and mTOR mRNA expression levels, and relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels in the Chinese medicine and combined groups after treatment were reduced (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the Chinese medicine group, the combined group showed a decrease in relative STAT3, mTOR mRNA expression levels, and STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels (P<0.05). Conclusion The combination of PPP and moxibustion may regulate the inflammatory mechanism of the body by inhibiting the abnormal activation of the STAT3/mTOR signaling pathway, upregulating related anti-inflammatory factor levels, downregulating pro-inflammatory factor expression, and increasing related repair factor expression, thereby promoting the recovery of atrophic gastric mucosa, reducing discomfort symptoms, and improving the physical and mental state of CAG patients with spleen and stomach weakness syndrome.

Ethanol (EtOH) is a common trigger for gastric mucosal diseases, and mitigating oxidative stress is essential for attenuating gastric mucosal damage. Capsaicin (CAP) has been identified as a potential agent to counteract oxidative damage in the gastric mucosa; however, its precise mechanism remains unclear. This study demonstrates that CAP alleviates EtOH-induced gastric mucosal injuries through two primary pathways: by suppressing the chemokine receptor 4 (CCR4)/Src/p47phox axis, thereby reducing oxidative stress, and by inhibiting the phosphorylation and nuclear translocation of nuclear factor-κB p65 (NF-κB) p65, resulting in diminished inflammatory responses. These findings elucidate the mechanistic pathways of CAP and provide a theoretical foundation for its potential therapeutic application in the treatment of gastric mucosal injuries.
Ethanol/toxicity* ; Animals ; Gastric Mucosa/metabolism* ; Signal Transduction/drug effects* ; Oxidative Stress/drug effects* ; Capsaicin/pharmacology* ; Male ; NADPH Oxidases/genetics* ; Mice ; Humans ; src-Family Kinases/genetics*

OBJECTIVE To explore the clinical characteristics of patients with COVID-19-associated pulmonary as-pergillosis(CAPA)among those with acute respiratory distress syndrome(ARDS)and to analyze the risk factors for CAPA.METHODS A total of 117 patients with ARDS admitted to Peking University People's Hospital from Dec.1,2022 to Jan.31,2023 were selected.Based on the diagnostic criteria for CAPA,patients were divided into the CAPA group(n=13)and the non-CAPA group(n=104).Clinical characteristics of CAPA patients were ana-lyzed,and risk factors were summarized by multivariate logistic regression analysis.RESULTS Compared with non-CAPA patients,a high proportion of CAPA paitents had a low oxygenation index at admission(＜200 mmHg:61.54％vs.39.42％),those required more invasive respiratory support(ventilator and EC MO:38.46％vs.5.77％),and had a glucocorticoid treatment duration＞10 days(76.92％vs.16.35％).CAPA pa-tients also received more treatments such as tocilizumab(38.46％vs.11.54％)and antiviral drugs(92.31％vs.50.00％),had longer hospital stays(24.00 vs.16.00 days)and a higher in-hospital mortality rate(69.23％vs.21.15％).The use of invasive mechanical ventilation/ECMO during hospitalization(OR=11.386,P=0.013)and therapeutic doses of glucocorticoids for＞10 days(OR=15.671,P＜0.001)were risk factors for CAPA in patients with ARDS.CONCLUSIONS Among COVID-19 patients with ARDS,CAPA patients receive more thera-peutic drugs and treatments during hospitalization.CAPA is associated with the use of invasive mechanical ventila-tion or ECMO and prolonged use of therapeutic doses of glucocorticoids during hospitalization.

Objective:To investigate the clinical characteristics of non-typhoidal Salmonella（NTS）enteritis in children and the drug resistance of NTS strains.Methods:The clinical data of 138 children who were hospitalized in Children's Hospital Affiliated to Xi'an Jiaotong University from 2022 to 2023 with diarrhea as the main complaint and NTS detected in stool culture were analyzed retrospectively, and the clinical characteristics and drug resistance were summarized.Results:Among 138 children with NTS enteritis，89 were males and 49 were females，with a male-to-female sex ratio of 1.81∶1 and an average age of 1.9（1.0,3.6）years，with a high incidence rate in June,July and August.Seventeen（12.31%）cases had a history of suspected unclean diet before illness.All the children had diarrhea symptoms with changes in fecal frequency and character，including 74 cases of pus and bloody stool，119 cases of mucus stool，and 70 cases of watery stool.One hundred and twenty-five（90.57%）cases had fever.Among 138 cases of fecal culture,there were 47 (34.05%) strains of Salmonella typhimurium,36(26.09%) strains of Salmonella enteritidis,and 55(39.85%) strains of other serotypes of Salmonella .One hundred and twenty-two（88.40%）NTS strains were resistant to more than one antimicrobial agent，and 29（21.01 %）were multi-drug resistant.The resistance rates to ampicillin，ampicillin/sulbactam，ceftriaxone，trimethoprim/sulfamethazole，ceftazidime，cefepime and piperacillin/tazobactam were 73.91%，71.01%，29.71%，29.71%，23.19%，11.59%，and 3.62%，respectively.All strains were sensitive to carbapenem antibiotics（meropenem，imipenem，and ertapenem）.The drug resistance rates of Salmonella typhimurium to ceftazidime and trimethoprim/sulfamethoxazole were higher than those of Salmonella enteritidis（38.30% vs 8.33%），the difference was statistically significant ( P < 0.05). Conclusion:Infants and young children are the high-incidence group of NTS enteritis，with the peak incidence period being from June to August each year，manifested by mucus-pus-blood stools, abdominal pain, vomiting，fever and other symptoms.Reasonable selection of antibiotics in time according to the local epidemic strains,changes of antimicrobial resistance and the results of drug sensitivity test of strains can effectively resist infection and reduce the production of drug-resistant beads.

OBJECTIVE To explore the clinical characteristics of patients with COVID-19-associated pulmonary as-pergillosis(CAPA)among those with acute respiratory distress syndrome(ARDS)and to analyze the risk factors for CAPA.METHODS A total of 117 patients with ARDS admitted to Peking University People's Hospital from Dec.1,2022 to Jan.31,2023 were selected.Based on the diagnostic criteria for CAPA,patients were divided into the CAPA group(n=13)and the non-CAPA group(n=104).Clinical characteristics of CAPA patients were ana-lyzed,and risk factors were summarized by multivariate logistic regression analysis.RESULTS Compared with non-CAPA patients,a high proportion of CAPA paitents had a low oxygenation index at admission(＜200 mmHg:61.54％vs.39.42％),those required more invasive respiratory support(ventilator and EC MO:38.46％vs.5.77％),and had a glucocorticoid treatment duration＞10 days(76.92％vs.16.35％).CAPA pa-tients also received more treatments such as tocilizumab(38.46％vs.11.54％)and antiviral drugs(92.31％vs.50.00％),had longer hospital stays(24.00 vs.16.00 days)and a higher in-hospital mortality rate(69.23％vs.21.15％).The use of invasive mechanical ventilation/ECMO during hospitalization(OR=11.386,P=0.013)and therapeutic doses of glucocorticoids for＞10 days(OR=15.671,P＜0.001)were risk factors for CAPA in patients with ARDS.CONCLUSIONS Among COVID-19 patients with ARDS,CAPA patients receive more thera-peutic drugs and treatments during hospitalization.CAPA is associated with the use of invasive mechanical ventila-tion or ECMO and prolonged use of therapeutic doses of glucocorticoids during hospitalization.

Objective:To investigate the clinical characteristics of non-typhoidal Salmonella（NTS）enteritis in children and the drug resistance of NTS strains.Methods:The clinical data of 138 children who were hospitalized in Children's Hospital Affiliated to Xi'an Jiaotong University from 2022 to 2023 with diarrhea as the main complaint and NTS detected in stool culture were analyzed retrospectively, and the clinical characteristics and drug resistance were summarized.Results:Among 138 children with NTS enteritis，89 were males and 49 were females，with a male-to-female sex ratio of 1.81∶1 and an average age of 1.9（1.0,3.6）years，with a high incidence rate in June,July and August.Seventeen（12.31%）cases had a history of suspected unclean diet before illness.All the children had diarrhea symptoms with changes in fecal frequency and character，including 74 cases of pus and bloody stool，119 cases of mucus stool，and 70 cases of watery stool.One hundred and twenty-five（90.57%）cases had fever.Among 138 cases of fecal culture,there were 47 (34.05%) strains of Salmonella typhimurium,36(26.09%) strains of Salmonella enteritidis,and 55(39.85%) strains of other serotypes of Salmonella .One hundred and twenty-two（88.40%）NTS strains were resistant to more than one antimicrobial agent，and 29（21.01 %）were multi-drug resistant.The resistance rates to ampicillin，ampicillin/sulbactam，ceftriaxone，trimethoprim/sulfamethazole，ceftazidime，cefepime and piperacillin/tazobactam were 73.91%，71.01%，29.71%，29.71%，23.19%，11.59%，and 3.62%，respectively.All strains were sensitive to carbapenem antibiotics（meropenem，imipenem，and ertapenem）.The drug resistance rates of Salmonella typhimurium to ceftazidime and trimethoprim/sulfamethoxazole were higher than those of Salmonella enteritidis（38.30% vs 8.33%），the difference was statistically significant ( P < 0.05). Conclusion:Infants and young children are the high-incidence group of NTS enteritis，with the peak incidence period being from June to August each year，manifested by mucus-pus-blood stools, abdominal pain, vomiting，fever and other symptoms.Reasonable selection of antibiotics in time according to the local epidemic strains,changes of antimicrobial resistance and the results of drug sensitivity test of strains can effectively resist infection and reduce the production of drug-resistant beads.

Objective:To study the distribution of drug resistance genes and virulence genes in multidrug-resistant Salmonella typhimurium strains.Methods:A total of 96 strains of Salmonella typhimurium were collected，and drug sensitivity tests were performed to evaluate the drug resistance and multidrug-resistance of Salmonella typhimurium.Multidrug-resistant Salmonella typhimurium strains were selected to conducted whole genome sequencing，and the distribution of drug resistance genes and virulence genes in the strain were analyzed.Results:Salmonella typhimurium strains had the highest resistance rates to ampicillin and ampicillin/sulbactam，with 89.58% and 76.04%，respectively.Followed by trimethoprim/sulfamethoxazole，ceftriaxone，and aztreonam，with 47.92%，38.54% and 33.33%，respectively，and low resistance rates to ciprofloxacin and levofloxacin，with 8.33% and 4.17%，respectively.Ninety-six strains were all sensitive to carbapenem antibiotics and piperacillin/tazobactam.Fifty-seven strains（59.38%）of Salmonella typhimurium showed multidrug-resistance.Resistance genes were detected in all 57 multidrug-resistant Salmonella typhimurium strains,with higher carrier rates of 98.25%,77.19%,and 59.65% for aac(6')-Iaa,aadA22,and blaTEM-1B,respectively.The multidrug-resistant Salmonella typhimurium strains had the highest carrier rates for invA，sipA，sseL，and sopB.Conclusion:Multidrug-resistant Salmonella typhimurium strains have a high incidence and a high carrier rate for multiple drug resistance genes and virulence genes.The monitoring and prevention of Salmonella typhimurium should be strengthened in the clinic in order to reduce the spreading epidemic of multidrug-resistant strains.

Objective:To explore the protective effect of zonisamide (ZNS) on oxygen-glucose deprivation (OGD) cell model of traumatic brain injury (TBI), and its underlying mechanism.Methods:Human neuroblastoma cells (SH-SY5Y) were cultured in vitro and divided into the control group, OGD group, and drug administration group (OGD+ZNS group) according to the random number table method. The OGD method was used to establish a TBI cell model. After modeling, the cell activity, the release of lactate dehydrogenase (LDH), and β-galactosidase staining were detected to evaluate cell function and senescence. Additionally, mitochondrial morphology and potential membrane changes were observed using Mito Tracker Red and JC-1 mitochondrial membrane potential staining. ATP concentration was measured, and protein was extracted from SH-SY5Y cells and then subjected to Western blot analysis to detect endoplasmic reticulum stress-related markers, including glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), protein disulfide isomerase (PDI), and β-actin.Results:The OGD group had a significantly lower cell survival rate compared to the control group ( P<0.01), while the OGD+ZNS group had a significant higher cell survival rate than the OGD group ( P<0.01). The LDH release rate was significantly higher in the OGD group than in the control group ( P<0.01), while the OGD+ZNS group had a significant lower LDH release rate compared to the OGD group ( P<0.01). Moreover, the cell staining results indicated that compared to the control and OGD+ZNS groups, the cells in the OGD group exhibited significant damage and senescence with darker staining while the mitochondrial staining results demonstrated a significant reduction in mitochondrial linear junctions and decreased mitochondrial activity in the OGD group compared to the control and OGD+ZNS groups. Compared to the control and OGD+ZNS groups, the OGD group exhibited a significant reduction in mitochondrial staining red fluorescence, a significant increase in green fluorescence, and a significant decrease in mitochondrial membrane potential. The OGD group demonstrated a significant decrease in ATP concentration compared to the control group ( P<0.01), whereas the OGD+ZNS group exhibited a significant higher ATP concentration compared to the OGD group ( P<0.01). Western blot analysis revealed significant upregulation of GRP78, CHOP, and PDI in the OGD group compared to the control group (all P<0.05), while in the OGD+ZNS group, the expression levels of these proteins were significantly downregulated compared to the OGD group (all P<0.05). Conclusions:Zonisamide can protect OGD TBI cell model by preserving mitochondrial activity and inhibiting endoplasmic reticulum stress.