Acute pancreatitis (AP) is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available. One of the pharmacological targets that merits further research is the neurokinin 1 receptor (NK1R), which is found on pancreatic acinar cells and responds to the neuropeptide substance P (SP) that participates in AP. Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development, the regulatory mechanism remains unclear. In this study, we found that following activation of NK1R by SP, β-arrestin1, a scaffold protein of NK1R, down-regulated transcription of Adss, Adsl, and Ampd in the purine nucleotide cycle, thereby inhibiting mitochondrial function through fumarate depletion. Interestingly, we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure. It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels. Our study not only provides new therapeutic strategies, leading compounds, and drug translation possibilities for AP, but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective:To observe the effect of local excision under ultrasonography with immediate mammoplasty in granulomatous lobular mastitis.Methods:Fifty-three patients with granulomatous lobular mastitis admitted from Jan 2017 to Jul 2020 were retrospectively analyzed. Combined with sonographic findings and clinical manifestations, patients were divided into four types: type Ⅰ, single mass; Type Ⅱ, single mass located in one quadrant with one or no skin lesion; Type Ⅲ, multi-quadrant involved with one or no skin lesion; Type Ⅳ, multiple abscesses with multiple lesions in the skin. Twenty-five patients underwent wide local excision (control group); Twenty-eight patients underwent local excision under ultrasonography with immediate mammoplasty (experiment group). Patients with erythema nodosum or in type Ⅳ were given antibiotics and corticosteroid therapy preoperatively for 1 week and postoperatively for 5 days. The others went straight to surgery.Results:All patients were followed up for 1 year. In the experiment group, 28 patients had primary wound healing, and 3 patients had poor wound healing after operation (all were of type Ⅳ). The control group had 6 cases of recurrence(were of type Ⅲ and type Ⅳ). There was significant difference of the recurrence rate between the two groups (0 vs. 24%, χ 2=6.033, P=0.014), and the aesthetic effect of local excision under ultrasonography with immediate mammoplasty was better than that of wide local excision(93% vs. 68%, χ 2=5.330, P=0.020). Conclusion:The recurrence rate of local excision under ultrasonography with immediate mammoplasty is low, and with a satisfactory cosmetic effect.

Objective:To examine the effect of“lesion removal plus whole breast exploration and washing plus micro-plastic surgery”in granulomatous lobular mastitis.Methods:A single-center prospective randomized controlled study method was used to enroll patients diagnosed with granulomatous lobular mastitis for whom surgical procedures were projected from March 2017 to September 2019 at Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University. The sample size is determined by the superiority test. Based on the literatures and the previous work, the two groups require 97 cases. Fifty-two patients underwent“lesion removal+whole breast exploration and washing plus micro-plastic surgery”(observation group). Forty-five cases underwent“empirical breast lesion resection plus fascia tissue flap plasty plus nipple and areola correction”(control group). The primary study endpoint is the recurrence rate, and the secondary study endpoints include surgical complications, incision healing time, and postoperative patient satisfaction. Independent sample t test, Wilcoxon rank-sum test, χ2 test and Fisher exact test were used for comparison between groups. Results:All procedures were completed successful, with no severe complications. All patients were followed up for (15.2±1.9) months (range: 12 to 24 months). There were no significant differences in incidence of postoperative complications (7.7% (4/52) vs. 6.7%(3/45), P=1), drainage time ((8.6±0.6) days vs. (8.4±0.8) days, t=1.921, P=0.053) and hospital stay ((7.7±0.6) days vs. (7.6±0.5) days, t=1.633, P=0.102) between the two groups. The recurrence rate of the observation group was lower significantly than that of the control group (3.8% (2/52) vs. 24.4%(11/45), χ2=8.819, P=0.003). The observation group had better cosmetic effects ( Z=-2.657, P=0.008) and patient satisfaction than control group ( Z=-5.730, P=0.000). Conclusion:The “lesion removal plus whole breast exploration and flushing plus micro-plastic surgery” has a good therapeutic effect and cosmetic value for patients with refractory granulomatous lobular mastitis.

Objective:To examine the effect of“lesion removal plus whole breast exploration and washing plus micro-plastic surgery”in granulomatous lobular mastitis.Methods:A single-center prospective randomized controlled study method was used to enroll patients diagnosed with granulomatous lobular mastitis for whom surgical procedures were projected from March 2017 to September 2019 at Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University. The sample size is determined by the superiority test. Based on the literatures and the previous work, the two groups require 97 cases. Fifty-two patients underwent“lesion removal+whole breast exploration and washing plus micro-plastic surgery”(observation group). Forty-five cases underwent“empirical breast lesion resection plus fascia tissue flap plasty plus nipple and areola correction”(control group). The primary study endpoint is the recurrence rate, and the secondary study endpoints include surgical complications, incision healing time, and postoperative patient satisfaction. Independent sample t test, Wilcoxon rank-sum test, χ2 test and Fisher exact test were used for comparison between groups. Results:All procedures were completed successful, with no severe complications. All patients were followed up for (15.2±1.9) months (range: 12 to 24 months). There were no significant differences in incidence of postoperative complications (7.7% (4/52) vs. 6.7%(3/45), P=1), drainage time ((8.6±0.6) days vs. (8.4±0.8) days, t=1.921, P=0.053) and hospital stay ((7.7±0.6) days vs. (7.6±0.5) days, t=1.633, P=0.102) between the two groups. The recurrence rate of the observation group was lower significantly than that of the control group (3.8% (2/52) vs. 24.4%(11/45), χ2=8.819, P=0.003). The observation group had better cosmetic effects ( Z=-2.657, P=0.008) and patient satisfaction than control group ( Z=-5.730, P=0.000). Conclusion:The “lesion removal plus whole breast exploration and flushing plus micro-plastic surgery” has a good therapeutic effect and cosmetic value for patients with refractory granulomatous lobular mastitis.

Objective To Screen serum protein markers related to CRF and establish a diagnosis model,exploring and discussing its significance in serodiagnosis by comparing differences of serum protein spectrum expression between patients with chronic renal failure (CRF) and control group.Methods The trial included 62 CRF patients and 28 control ones.Serum samples were tested by surface enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS).The data were analyzed to screen serum proteomic biomarkers.By bioinformatics analysis,decision classification tree models were to be established and tested.Results A total of 19 effective protein peaks were significantly different between CRF and normal control (P＜0.001) at m/z range of 1 500 to 30 000,among which 18 showed low expression and 1 showed high expression in CRF.CRF and normal control were obviously different in the clustering;By bioinformatics analysis,a CRF-normal controls of the diagnostic decision tree model was developed,which was 87.8% in with prediction accuracy rate of 87.8% sensitivity of 87.1% and a specificity of 89.3%.Condusion Diagnostic decision tree model provides a more accurate prediction and solid experimental evidence for early clinical diagnosis.