OBJECTIVES: To analyze the potential causal relationship between gut microbiota and food allergy (FA) using two-sample Mendelian randomization (MR) methods. METHODS: Data from genome-wide association studies on gut microbiota and FA were utilized. MR analysis was conducted employing inverse variance weighting, MR-Egger regression, and weighted median methods to assess the causal relationship between gut microbiota and FA. Cochrane's Q test was used to evaluate heterogeneity of instrumental variables, MR-PRESSO analysis was conducted to test for outliers and pleiotropy, and MR-Egger regression was employed to assess horizontal pleiotropy. The "leave-one-out" method was used to evaluate the impact of removing individual single nucleotide polymorphisms on the causal relationship. RESULTS: Inverse variance weighting analysis revealed that the phylum Verrucomicrobia, family Verrucomicrobiaceae, order Verrucomicrobiales, genus Ruminococcaceae UCG013, and genus Akkermansia were negatively associated with FA (P<0.05). Sensitivity analyses confirmed the reliability of the findings, indicating no heterogeneity or pleiotropy present. CONCLUSIONS There is a causal relationship between gut microbiota and FA, with Verrucomicrobia, Verrucomicrobiaceae, Verrucomicrobiales, Ruminococcaceae UCG013, and Akkermansia potentially reducing the risk of developing FA. These findings provide potential targets for the treatment and prevention of FA; however, further research is needed to explore the specific mechanisms by which the microbiota influence FA.
Humans ; Mendelian Randomization Analysis ; Gastrointestinal Microbiome ; Food Hypersensitivity/microbiology* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Pancreatic cancer is a highly malignant tumor with a poor prognosis. It is very hard to treat pancreatic cancers for their high heterogeneity, complex tumor microenvironment, and drug resistance. Currently, gemcitabine plus nab-paclitaxel, capecitabine and FOLFIRINOX are standard chemotherapy for resectable or advanced metastatic pancreatic cancer. Considering the limited efficacy and toxic side effects of chemotherapy, targeted and immune drugs have gradually attracted attention and made some progress. In this article, we systematically reviewed the chemotherapeutic drugs, targets and related targeted drugs, and immunotherapy drugs for pancreatic cancer.

Objective:We investigated the incidence of surgical site infection (SSI) following emergency abdominal surgery (EAS) in China and further explored its risk factors, providing a reference for preventing and controlling SSI after EAS.Methods:This was an observational study. Data of patients who had undergone EAS and been enrolled in the Chinese SSI Surveillance Program during 2018–2021were retrospectively analyzed. All included patients had been followed up for 30 days after surgery. The analyzed data consisted of relevant patient characteristics and perioperative clinical data, including preoperative hemoglobin, albumin, and blood glucose concentrations, American Society of Anesthesiologists (ASA) score, grade of surgical incision, intestinal preparation, skin preparation, location of surgical site, approach, and duration. The primary outcome was the incidence of SSI occurring within 30 days following EAS. SSI was defined as both superficial and deep incisional infections and organ/space infections, diagnoses being supported by results of microbiological culture of secretions and pus. Secondary outcomes included 30-day postoperative mortality rates, length of stay in the intensive care unit (ICU), duration of postoperative hospitalization, and associated costs. The patients were classified into two groups, SSI and non-SSI, based on whether an infection had been diagnosed. Univariate and multivariate logistic regression analyses were performed to identify risk factors associated with SSI following EAS.Results:The study cohort comprised 5491 patients who had undergone EAS, comprising 3169 male and 2322 female patients. SSIs were diagnosed in 168 (3.1%) patients after EAS (SSI group); thus, the non-SSI group consisted of 5323 patients. The SSIs comprised superficial incision infections in 69 (41.1%), deep incision infections in 51 (30.4%), and organ or space infections in 48 (28.6%). Cultures of secretions and pus were positive in 115 (68.5%) cases. The most frequently detected organism was Escherichia coli (47/115; 40.9%). There were no significant differences in sex or body mass index between the SSI and non-SSI groups (both P>0.05). However, the proportion of individuals aged 60 years or older was significantly greater in the SSI than in the non-SSI group (49.4% [83/168] vs. 27.5% [1464/5323), χ 2=38.604, P<0.001). Compared with the non-SSI group, the SSI group had greater proportions of patients with diabetes (11.9% [20/168] vs. 4.8% [258/5323], χ 2=16.878, P<0.001), hypertension (25.6% [43/168] vs. 12.2% [649/5323], χ 2=26.562, P<0.001); hemoglobin <110 g/L (27.4% [46/168] vs. 13.1% [697/5323], χ 2=28.411, P<0.001), and albuminemia <30 g/L (24.4% [41/168] vs. 5.9% [316/5323], χ 2=91.352, P<0.001), and a reduced rate of preoperative skin preparation (66.7% [112/168] vs. 75.9% [4039/5323], χ 2=7.491, P=0.006). Furthermore, fewer patients in the SSI group had preoperative ASA scores of between one and two (56.0% [94/168] vs. 88.7% [4724/5323], χ 2=162.869, P<0.001) in the non-SSI group. The incidences of contaminated and infected incisions were greater in the SSI group (63.1% [106/168] vs. 38.6% [2056/5323], χ 2=40.854, P<0.001). There was a significant difference in surgical site distribution between the SSI and non-SSI groups (small intestine 29.8% [50/168] vs. 10.6% [565/5323], colorectal 26.2% [44/168] vs. 5.6% [298/5 323], and appendix 24.4% [41/168] vs. 65.1% [3465/5323]) χ 2=167.897, P<0.001), respectively. There was a significantly lower proportion of laparoscope or robotic surgery in the non-SSI group (24.4 % [41/168] vs. 74.2% [3949/5323], χ 2=203.199, P<0.001); the percentage of operations of duration less than 2 hours was significantly lower in the SSI than non-SSI group (35.7% [60/168] vs. 77.4% [4119/5323], χ 2=155.487, P<0.001). As to clinical outcomes, there was a higher 30-day postoperative mortality rate (3.0%[5/168] vs. 0.2%[10/5323], χ 2=36.807, P<0.001) and higher postoperative ICU occupancy rate (41.7% [70/168] vs. 19.7% [1046/5323], χ 2=48.748, P<0.001) in the SSI group. The median length of stay in the ICU (0[2] vs. 0[0] days, U=328597.000, P<0.001), median total length of stay after surgery (16[13] vs. 6[5] days, U=128146.000, P<0.001), and median hospitalization cost (ten thousand yuan, 4.7[4.4] vs. 1.7[1.8], U=175965.000, P<0.001) were all significantly greater in the SSI group. Multivariate logistic regression analysis revealed that the absence of skin preparation before surgery (OR=2.435,95%CI: 1.690–3.508, P<0.001), preoperative albuminemia <30 g/L (OR=1.680, 95%CI: 1.081–2.610, P=0.021), contaminated or infected incisions (OR=3.031, 95%CI: 2.151–4.271, P<0.001), and laparotomy (OR=3.436, 95% CI: 2.123–5.564, P<0.001) were independent risk factors of SSI. Operative duration less than 2 hours (OR=0.465, 95%CI: 0.312–0.695, P<0.001) and ASA score of 1–2 (OR=0.416, 95% CI: 0.289–0.601, P<0.001) were identified as independent protective factors for SSI. Conclusions:It is important to consider the nutritional status in the perioperative period of patients undergoing EAS. Preoperative skin preparation should be conducted and, whenever possible, laparoscope or robot-assisted surgery. Duration of surgery should be as short as possible while maintaining surgery quality and improving patient care.

Objective:We investigated the incidence of surgical site infection (SSI) following emergency abdominal surgery (EAS) in China and further explored its risk factors, providing a reference for preventing and controlling SSI after EAS.Methods:This was an observational study. Data of patients who had undergone EAS and been enrolled in the Chinese SSI Surveillance Program during 2018–2021were retrospectively analyzed. All included patients had been followed up for 30 days after surgery. The analyzed data consisted of relevant patient characteristics and perioperative clinical data, including preoperative hemoglobin, albumin, and blood glucose concentrations, American Society of Anesthesiologists (ASA) score, grade of surgical incision, intestinal preparation, skin preparation, location of surgical site, approach, and duration. The primary outcome was the incidence of SSI occurring within 30 days following EAS. SSI was defined as both superficial and deep incisional infections and organ/space infections, diagnoses being supported by results of microbiological culture of secretions and pus. Secondary outcomes included 30-day postoperative mortality rates, length of stay in the intensive care unit (ICU), duration of postoperative hospitalization, and associated costs. The patients were classified into two groups, SSI and non-SSI, based on whether an infection had been diagnosed. Univariate and multivariate logistic regression analyses were performed to identify risk factors associated with SSI following EAS.Results:The study cohort comprised 5491 patients who had undergone EAS, comprising 3169 male and 2322 female patients. SSIs were diagnosed in 168 (3.1%) patients after EAS (SSI group); thus, the non-SSI group consisted of 5323 patients. The SSIs comprised superficial incision infections in 69 (41.1%), deep incision infections in 51 (30.4%), and organ or space infections in 48 (28.6%). Cultures of secretions and pus were positive in 115 (68.5%) cases. The most frequently detected organism was Escherichia coli (47/115; 40.9%). There were no significant differences in sex or body mass index between the SSI and non-SSI groups (both P>0.05). However, the proportion of individuals aged 60 years or older was significantly greater in the SSI than in the non-SSI group (49.4% [83/168] vs. 27.5% [1464/5323), χ 2=38.604, P<0.001). Compared with the non-SSI group, the SSI group had greater proportions of patients with diabetes (11.9% [20/168] vs. 4.8% [258/5323], χ 2=16.878, P<0.001), hypertension (25.6% [43/168] vs. 12.2% [649/5323], χ 2=26.562, P<0.001); hemoglobin <110 g/L (27.4% [46/168] vs. 13.1% [697/5323], χ 2=28.411, P<0.001), and albuminemia <30 g/L (24.4% [41/168] vs. 5.9% [316/5323], χ 2=91.352, P<0.001), and a reduced rate of preoperative skin preparation (66.7% [112/168] vs. 75.9% [4039/5323], χ 2=7.491, P=0.006). Furthermore, fewer patients in the SSI group had preoperative ASA scores of between one and two (56.0% [94/168] vs. 88.7% [4724/5323], χ 2=162.869, P<0.001) in the non-SSI group. The incidences of contaminated and infected incisions were greater in the SSI group (63.1% [106/168] vs. 38.6% [2056/5323], χ 2=40.854, P<0.001). There was a significant difference in surgical site distribution between the SSI and non-SSI groups (small intestine 29.8% [50/168] vs. 10.6% [565/5323], colorectal 26.2% [44/168] vs. 5.6% [298/5 323], and appendix 24.4% [41/168] vs. 65.1% [3465/5323]) χ 2=167.897, P<0.001), respectively. There was a significantly lower proportion of laparoscope or robotic surgery in the non-SSI group (24.4 % [41/168] vs. 74.2% [3949/5323], χ 2=203.199, P<0.001); the percentage of operations of duration less than 2 hours was significantly lower in the SSI than non-SSI group (35.7% [60/168] vs. 77.4% [4119/5323], χ 2=155.487, P<0.001). As to clinical outcomes, there was a higher 30-day postoperative mortality rate (3.0%[5/168] vs. 0.2%[10/5323], χ 2=36.807, P<0.001) and higher postoperative ICU occupancy rate (41.7% [70/168] vs. 19.7% [1046/5323], χ 2=48.748, P<0.001) in the SSI group. The median length of stay in the ICU (0[2] vs. 0[0] days, U=328597.000, P<0.001), median total length of stay after surgery (16[13] vs. 6[5] days, U=128146.000, P<0.001), and median hospitalization cost (ten thousand yuan, 4.7[4.4] vs. 1.7[1.8], U=175965.000, P<0.001) were all significantly greater in the SSI group. Multivariate logistic regression analysis revealed that the absence of skin preparation before surgery (OR=2.435,95%CI: 1.690–3.508, P<0.001), preoperative albuminemia <30 g/L (OR=1.680, 95%CI: 1.081–2.610, P=0.021), contaminated or infected incisions (OR=3.031, 95%CI: 2.151–4.271, P<0.001), and laparotomy (OR=3.436, 95% CI: 2.123–5.564, P<0.001) were independent risk factors of SSI. Operative duration less than 2 hours (OR=0.465, 95%CI: 0.312–0.695, P<0.001) and ASA score of 1–2 (OR=0.416, 95% CI: 0.289–0.601, P<0.001) were identified as independent protective factors for SSI. Conclusions:It is important to consider the nutritional status in the perioperative period of patients undergoing EAS. Preoperative skin preparation should be conducted and, whenever possible, laparoscope or robot-assisted surgery. Duration of surgery should be as short as possible while maintaining surgery quality and improving patient care.

Porphyromonas gingivalis peptidylarginine deiminase (PPAD), an isoenzyme of animal endogenous peptidylarginine deaminase, is secreted by the Por system and catalyzes the citrullination of arginine. Recent studies have found that PPAD can affect the formation of Porphyromonas gingivalis biofilm and reduce the body′s immune defense function, which is related to the occurrence and development of many diseases such as periodontal diseases and rheumatoid arthritis. In this paper, we reviewed the molecular characteristics of PPAD, including the genetic and functional characteristics, as well as the mechanisms related to the inflammatory and autoimmune diseases. We also pointed some issues that should be pay attention to in the further study.

Objective: To determine the association between pulse pressure and the risk of new-onset diabetes in hypertensive patients. Methods: In this prospective cohort study, hypertensive patients from the Kailuan Study, who were diagnosed in 2006-2007 check-up, were screened for enrollment. Participants who finished the biennial follow-up until December 31, 2017 were finally included in this analysis. The primary outcome was incident diabetes development. The pulse pressure variables were divided into quartiles (Q₁-Q₄), and the Kaplan-Meier curve was used to examine and estimate the cumulative incidence of new-onset diabetes among quartiles. Cox proportional hazards regression model was performed to explore the association between pulse pressure and the risk of new-onset diabetes in hypertensive patients. Results: During an average follow-up of 8.17 years, 6 617 new-onset diabetes were identified out of the 32 917 hypertensive patients with no history or evidence of diabetes in 2006-2007 check-up. Participants were classified into quartiles according to pulse pressure levels as follows: Q₁ group(<41 mmHg (1mmHg=0.133kPa))(n=7 995); Q₂ group(41-<51 mmHg) (n=8 196); Q₃ group (51-<61 mmHg) (n= 8 270); Q₄ group (≥61 mmHg) (n=8 456). The cumulative incidences of new-onset diabetes across the quartiles were 16.94%, 19.61%, 21.07%, and 22.33%, respectively, with the incidence density was 20.27, 23.20, 24.92, and 26.10 per 1 000 person-years, respectively. The cumulative incidence of new-onset diabetes increased in proportion with increasing pulse pressure levels (P<0.01 by the Log-rank test). After multivariate adjustment, compared with the first quartile, the hazard ratios for new-onset diabetes in the third and fourth quartiles were 1.13 (95%CI 1.04-1.22, P<0.01) and 1.14 (95%CI 1.05-1.24, P<0.01), respectively. The risk of new-onset diabetes increased 5%(HR=1.05, 95%CI 1.02-1.08, P<0.01) with the fractional pulse pressure increased per 1 SD (0.13). Findings from the three sensitivity analyses were consistent with the main results in this cohort. Conclusions: Pulse pressure at baseline is positively associated with the incidence of new-onset diabetes among hypertensive individuals, and pulse pressure is an independent risk factor for the development of diabetes in hypertensive patients.

PURPOSE: Plasma cells and immunoglobulins (Igs) play a pivotal role in the induction and maintenance of chronic inflammation in nasal polyps. During secondary immune responses, plasma cell survival and Ig production are regulated by the local environment. The purpose of the present study was to investigate the presence of long-lived plasma cells (LLPCs) and specific survival niches for LLPCs in human nasal polyps.METHODS: Nasal mucosal samples were cultured with an air-liquid interface system and the Ig levels in culture supernatants were analyzed by enzyme-linked immunosorbent assay. The characteristics of LLPCs in nasal polyps were determined by immunohistochemistry and immunofluorescence. The expression of neurotrophins as well as their receptors was detected by quantitative real-time polymerase chain reaction, immunohistochemistry, immunofluorescence, and Western blotting.RESULTS: The numbers of CD138⁺ total plasma cells and BCL2⁺ plasma cells were increased in both eosinophilic and non-eosinophilic nasal polyps compared with those in normal tissues. The production of IgG, IgA, and IgE was detected in culture supernatants even after a 32-day culture of nasal polyps. Although the total numbers of plasma cells were decreased in nasal polyps after culture, the numbers of BCL2⁺ plasma cells remained stable. The expression of nerve growth factor (NGF) as well as tropomyosin receptor kinase (Trk) A, a high-affinity receptor for NGF, was upregulated in both eosinophilic and non-eosinophilic nasal polyps. In addition, BCL2⁺ plasma cell numbers were positively correlated with NGF and TrkA mRNA expression in nasal mucosal tissues. Polyp plasma cells had the expression of TrkA.CONCLUSIONS: Human nasal polyps harbor a population of LLPCs and NGF may be involved in their prolonged survival. LLPCs may be a novel therapeutic target for suppressing the local Ig production in nasal polyps.
Blotting, Western ; Enzyme-Linked Immunosorbent Assay ; Eosinophils ; Fluorescent Antibody Technique ; Humans ; Immunoglobulin A ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulins ; Immunohistochemistry ; Inflammation ; Mucous Membrane ; Nasal Polyps ; Nerve Growth Factor ; Nerve Growth Factors ; Phosphotransferases ; Plasma Cells ; Plasma ; Polyps ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Tropomyosin

BACKGROUND AND OBJECTIVE: Acute liver failure (ALF) is a type of disease with high mortality and rapid progression with no specific treatment methods currently available. Glucocorticoids exert beneficial clinical effects on therapy for ALF. However, the mechanism of this effect remains unclear and when to use glucocorticoids in patients with ALF is difficult to determine. The purpose of this study was to investigate the specific immunological mechanism of dexamethasone (Dex) on treatment of ALF induced by lipopolysaccharide (LPS)/D-galactosamine (D-GaIN) in mice. METHODS: Male C57BL/6 mice were given LPS and D-GaIN by intraperitoneal injection to establish an animal model of ALF. Dex was administrated to these mice and its therapeutic effect was observed. Hematoxylin and eosin (H&E) staining was used to determine liver pathology. Multicolor flow cytometry, cytometric bead array (CBA) method, and next-generation sequencing were performed to detect changes of messenger RNA (mRNA) in immune cells, cytokines, and Kupffer cells, respectively. RESULTS: A mouse model of ALF can be constructed successfully using LPS/D-GaIN, which causes a cytokine storm in early disease progression. Innate immune cells change markedly with progression of liver failure. Earlier use of Dex, at 0 h rather than 1 h, could significantly improve the progression of ALF induced by LPS/D-GaIN in mice. Numbers of innate immune cells, especially Kupffer cells and neutrophils, increased significantly in the Dex-treated group. In vivo experiments indicated that the therapeutic effect of Dex is exerted mainly via the glucocorticoid receptor (Gr). Sequencing of Kupffer cells revealed that Dex could increase mRNA transcription level of nuclear receptor subfamily 4 group A member 1 (Nr4a1), and that this effect disappeared after Gr inhibition. CONCLUSIONS In LPS/D-GaIN-induced ALF mice, early administration of Dex improved ALF by increasing the numbers of innate immune cells, especially Kupffer cells and neutrophils. Gr-dependent Nr4a1 upregulation in Kupffer cells may be an important ALF effect regulated by Dex in this process.
Animals ; Dexamethasone/therapeutic use* ; Disease Models, Animal ; Kupffer Cells/physiology* ; Liver Failure, Acute/pathology* ; Male ; Mice ; Mice, Inbred C57BL ; Nuclear Receptor Subfamily 4, Group A, Member 1/physiology* ; Receptors, Glucocorticoid/physiology*