BACKGROUND: Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot. METHODS: Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness. RESULTS: In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm). CONCLUSIONS S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.
Calgranulin B/therapeutic use* ; Diabetic Foot/metabolism* ; Humans ; Datasets as Topic ; Computational Biology ; Mice, Inbred C57BL ; Animals ; Mice ; Protein Interaction Maps ; Immunohistochemistry

Sennoside A (SA), a typical prodrug, exerts its laxative effect only after its transformation into rheinanthrone catalyzed by gut microbial hydrolases and reductases. Hydrolases have been identified, but reductases remain unknown. By linking a photoreactive group to the SA scaffold, we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling (ABPP). From lysates of an active strain, Bifidobacterium pseudocatenulatum (B. pseudocatenulatum), 397 proteins were enriched and subsequently identified using mass spectrometry (MS). Among these proteins, chromate reductase/nicotinamide adenine dinucleotide (NADH) phosphate (NADPH)-dependent flavin mononucleotide (FMN) reductase/oxygen-insensitive NADPH nitroreductase (nfrA) was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource (UniProt) database screening. We also determined that recombinant nfrA could reduce SA. Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.

Sennoside A(SA),a typical prodrug,exerts its laxative effect only after its transformation into rhei-nanthrone catalyzed by gut microbial hydrolases and reductases.Hydrolases have been identified,but reductases remain unknown.By linking a photoreactive group to the SA scaffold,we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling(ABPP).From lysates of an active strain,Bifidobacterium pseudocatenulatum(B.pseu-docatenulatum),397 proteins were enriched and subsequently identified using mass spectrometry(MS).Among these proteins,chromate reductase/nicotinamide adenine dinucleotide(NADH)phosphate(NADPH)-dependent flavin mononucleotide(FMN)reductase/oxygen-insensitive NADPH nitroreductase(nfrA)was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource(UniProt)database screening.We also determined that recombinant nfrA could reduce SA.Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.

Objective To analyze the trends of suicide mortality and disease burden among the elderly aged 60 and above in Chongqing from 2012 to 2023,providing evidence for targeted interventions.Methods Death cases of elderly aged 60 and above were extracted from death registration between 2012 and 2023 according to death records(International Statistical Classification of Diseases and Related Health Problems,10th version:X60-X84,Y87).The data were analyzed to calculate indicators such as the mortality rate,standardized mortality rate,years of life lost(YLL)rate,and average years of life lost(AYLL),and the composition ratio of different causes of death with using Excel 2010 and SPSS 26.0.The comparison of mortality rates between male and female,urban and rural area was conducted using the x2 test.The trend changes of the rates were expressed by the annual percentage change(APC)and the average annual percentage change(AAPC).Results From 2012 to 2023,the suicide mortality rate and standardized mortality rate of the elderly aged 60 and above generally showed a downward trend,decreasing by 3.54%and 4.02%,respectively(P<0.05).From 2012 to 2016,the suicide mortality rate increased by an average of 4.53%per year,and from 2016 to 2021,it decreased by an average of 8.91%per year,and both trends were significant(P<0.05).Only in 2020 and 2022,the male suicide mortality rate was significantly higher than that of females(P<0.05).From 2012 to 2023,the suicide mortality rate and standardized mortality rate of males and females decreased by an average of 2.86%,3.44%,4.21%,and 4.69%per year respectively,and the trends were significant(P<0.05).The suicide mortality rate of the elderly aged 60 and above in rural areas was significantly higher than that in urban areas over the years(P<0.05).From 2012 to 2023,the suicide mortality rate and standardized mortality rate in urban areas remained relatively stable(P>0.05),while the suicide mortality rate and standardized mortality rate of the elderly aged 60 and above in rural areas decreased by an average of 3.44%and 4.02%per year respectively,and the trends were significant(P<0.05).The YLL rate and AYLL caused by suicide among the elderly aged 60 and above decreased from 3.03‰ and 18.54 years in 2012 to 2.26‰ and 17.50 years in 2023 respectively,and the AAPC were-4.02%and-0.60%respectively,and the trends were significant(P<0.05).By comparing the composition of deaths by different suicide methods over the years,it was found that the proportion of deaths due to pesticide poisoning showed a downward trend,while the proportions of deaths by hanging,jumping from a height,and drowning showed an upward trend.Conclusion The suicide mortality rate of the elderly aged 60 and above in Chongqing is relatively high.Although demonstrating an overall downward trend,enhanced efforts toward early identification and intervention for elderly suicide should be enhanced.

Objective To analyze the trends of suicide mortality and disease burden among the elderly aged 60 and above in Chongqing from 2012 to 2023,providing evidence for targeted interventions.Methods Death cases of elderly aged 60 and above were extracted from death registration between 2012 and 2023 according to death records(International Statistical Classification of Diseases and Related Health Problems,10th version:X60-X84,Y87).The data were analyzed to calculate indicators such as the mortality rate,standardized mortality rate,years of life lost(YLL)rate,and average years of life lost(AYLL),and the composition ratio of different causes of death with using Excel 2010 and SPSS 26.0.The comparison of mortality rates between male and female,urban and rural area was conducted using the x2 test.The trend changes of the rates were expressed by the annual percentage change(APC)and the average annual percentage change(AAPC).Results From 2012 to 2023,the suicide mortality rate and standardized mortality rate of the elderly aged 60 and above generally showed a downward trend,decreasing by 3.54%and 4.02%,respectively(P<0.05).From 2012 to 2016,the suicide mortality rate increased by an average of 4.53%per year,and from 2016 to 2021,it decreased by an average of 8.91%per year,and both trends were significant(P<0.05).Only in 2020 and 2022,the male suicide mortality rate was significantly higher than that of females(P<0.05).From 2012 to 2023,the suicide mortality rate and standardized mortality rate of males and females decreased by an average of 2.86%,3.44%,4.21%,and 4.69%per year respectively,and the trends were significant(P<0.05).The suicide mortality rate of the elderly aged 60 and above in rural areas was significantly higher than that in urban areas over the years(P<0.05).From 2012 to 2023,the suicide mortality rate and standardized mortality rate in urban areas remained relatively stable(P>0.05),while the suicide mortality rate and standardized mortality rate of the elderly aged 60 and above in rural areas decreased by an average of 3.44%and 4.02%per year respectively,and the trends were significant(P<0.05).The YLL rate and AYLL caused by suicide among the elderly aged 60 and above decreased from 3.03‰ and 18.54 years in 2012 to 2.26‰ and 17.50 years in 2023 respectively,and the AAPC were-4.02%and-0.60%respectively,and the trends were significant(P<0.05).By comparing the composition of deaths by different suicide methods over the years,it was found that the proportion of deaths due to pesticide poisoning showed a downward trend,while the proportions of deaths by hanging,jumping from a height,and drowning showed an upward trend.Conclusion The suicide mortality rate of the elderly aged 60 and above in Chongqing is relatively high.Although demonstrating an overall downward trend,enhanced efforts toward early identification and intervention for elderly suicide should be enhanced.

Objective:To provide references for further improving the oral health of Air Force pilots by investigating the periodontal health status and oral hygiene behavior of Air Force pilots.Methods:A total of 182 active-duty Air Force pilots who underwent physical examinations at the Air Force Medical Center were randomly selected for periodontal examination and oral hygiene behavior questionnaires survey. They were grouped by age (<35 years and ≥35 years), hometown (urban-originated and rural-originated), and aircraft type (fighter or other aircraft types like bomber, helicopter, transporter, and trainer).Results:Among the 182 Air Force pilots, the detection rate of gingival bleeding, dental calculus, periodontal pocket and loss of periodontal attachment was 86.81%, 75.27%, 6.59%, 9.89%, respectively. There was 82.42% of the pilots brushed their teeth at least twice a day, 35.16% used dental floss every day, 80.22% alternately used different toothpastes, and only 9.34% used toothpastes containing fluoride. There was 56.04% of the pilots brushed their teeth up and down, 8.24% brushed horizontally, 70.88% brushed their teeth for 2-3 min, and 53.30% smoked. In the past 6 months, 48.35% of the pilots had experienced gingival bleeding, but 67.58% had not undergone tooth cleaning treatment in the past 12 months. The detection rates of periodontal pockets, loss of periodontal attachment and the rates of flossing use in ≥35 years group were higher than those in <35 years group, with significant differences ( χ2=6.04, 4.68, 11.00, P=0.014, 0.031, 0.012), and there was also a significant difference in brushing method between the 2 groups ( χ2=17.75, P<0.001). There were significant differences in the detection rates of dental calculus, brushing frequency, brushing method, and the treatment of dental cleaning in the past 12 months between the rural-originated group and the urban-originated group ( χ2=6.25, 7.20, 13.81, 4.02, P=0.012, 0.007, 0.003, 0.045). The smoking rate in the fighter group was lower than that in the other aircraft types group, with significant difference ( χ2=10.10, P=0.018). Conclusions:The periodontal health status of Air Force pilots is still not optimistic, and the oral hygiene behavior still needs to be further improved. It is necessary to further strengthen oral hygiene education for pilots, improve their oral hygiene behavior, and enhance the support capabilities to their oral health.

Objective:To provide references for further improving the oral health of Air Force pilots by investigating the periodontal health status and oral hygiene behavior of Air Force pilots.Methods:A total of 182 active-duty Air Force pilots who underwent physical examinations at the Air Force Medical Center were randomly selected for periodontal examination and oral hygiene behavior questionnaires survey. They were grouped by age (<35 years and ≥35 years), hometown (urban-originated and rural-originated), and aircraft type (fighter or other aircraft types like bomber, helicopter, transporter, and trainer).Results:Among the 182 Air Force pilots, the detection rate of gingival bleeding, dental calculus, periodontal pocket and loss of periodontal attachment was 86.81%, 75.27%, 6.59%, 9.89%, respectively. There was 82.42% of the pilots brushed their teeth at least twice a day, 35.16% used dental floss every day, 80.22% alternately used different toothpastes, and only 9.34% used toothpastes containing fluoride. There was 56.04% of the pilots brushed their teeth up and down, 8.24% brushed horizontally, 70.88% brushed their teeth for 2-3 min, and 53.30% smoked. In the past 6 months, 48.35% of the pilots had experienced gingival bleeding, but 67.58% had not undergone tooth cleaning treatment in the past 12 months. The detection rates of periodontal pockets, loss of periodontal attachment and the rates of flossing use in ≥35 years group were higher than those in <35 years group, with significant differences ( χ2=6.04, 4.68, 11.00, P=0.014, 0.031, 0.012), and there was also a significant difference in brushing method between the 2 groups ( χ2=17.75, P<0.001). There were significant differences in the detection rates of dental calculus, brushing frequency, brushing method, and the treatment of dental cleaning in the past 12 months between the rural-originated group and the urban-originated group ( χ2=6.25, 7.20, 13.81, 4.02, P=0.012, 0.007, 0.003, 0.045). The smoking rate in the fighter group was lower than that in the other aircraft types group, with significant difference ( χ2=10.10, P=0.018). Conclusions:The periodontal health status of Air Force pilots is still not optimistic, and the oral hygiene behavior still needs to be further improved. It is necessary to further strengthen oral hygiene education for pilots, improve their oral hygiene behavior, and enhance the support capabilities to their oral health.

Purpose: We aimed to identify effectiveness-associated indicators and evaluate the optimal tumor reduction rate (TRR) after two cycles of neoadjuvant chemotherapy (NAC) in patients with invasive breast cancer. Methods: This retrospective case-control study included patients who underwent at least four cycles of NAC at the Department of Breast Surgery between February 2013 and February 2020. A regression nomogram model for predicting pathological responses was constructed based on potential indicators. Results: A total of 784 patients were included, of whom 170 (21.68%) reported pathological complete response (pCR) after NAC and 614 (78.32%) had residual invasive tumors. The clinical T stage, clinical N stage, molecular subtype, and TRR were identified as independent predictors of pCR. Patients with a TRR > 35% were more likely to achieve pCR (odds ratio, 5.396; 95% confidence interval [CI], 3.299–8.825). The receiver operating characteristic (ROC) curve was plotted using the probability value, and the area under the ROC curve was 0.892 (95% CI, 0.863–0.922). Conclusion TRR > 35% is predictive of pCR after two cycles of NAC, and an early evaluation model using a nomogram based on five indicators, age, clinical T stage, clinical N stage, molecular subtype, and TRR, is applicable in patients with invasive breast cancer.

Activated fibroblasts and M2-polarized macrophages may contribute to the progression of pulmonary fibrosis by forming a positive feedback loop. This study was aimed to investigate whether fibroblasts and macrophages form this loop by secreting SDF-1 and TGF-β and the impacts of neotuberostemonine (NTS) and tuberostemonine (TS). Mice were intratracheally injected with 3 U·kg^-1 bleomycin and orally administered with 30 mg·kg^-1 NTS or TS. Primary pulmonary fibroblasts (PFBs) and MH-S cells (alveolar macrophages) were used in vitro. The animal experiments showed that NTS and TS improved fibrosis related indicators, inhibited fibroblast activation and macrophage M2 polarization, and reduced the levels of TGF-β and SDF-1 in alveolar lavage fluid. Cell experiments showed that TGF-β1 may activated fibroblasts into myofibroblasts secreting SDF-1 by activating the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways. It was also found for the first time that SDF-1 was able to directly polarize macrophages into M2 phenotype secreting TGF-β through the same pathways as mentioned above. Moreover, the results of the cell coculture confirmed that fibroblasts and macrophages actually developed a feedback loop to promote fibrosis, and the secretion of TGF-β and SDF-1 was crucial for maintaining this loop. NTS and TS may disturb this loop through inhibiting both the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways to improve pulmonary fibrosis. NTS and TS are stereoisomeric alkaloids with pyrrole[1,2-a]azapine skeleton, and their effect on improving pulmonary fibrosis may be largely attributed to their parent nucleus. Moreover, this study found that inhibition of both the AKT and ERK pathways is essential for maximizing the improvement of pulmonary fibrosis.
Animals ; Mice ; Pulmonary Fibrosis/metabolism* ; Transforming Growth Factor beta/pharmacology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; MAP Kinase Signaling System ; Alkaloids/pharmacology* ; Fibroblasts ; Macrophages/metabolism*

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.