The aim of this study is to evaluate the in vitro and in vivo antibacterial potential of Ly-sZHSHW,a phage lysin against Acinetobacter baumannii infections,and to study its characteris-tics.The pET28a-Lys recombinant plasmid containing LysZHSHW coding gene was constructed by PCR,enzyme digestion and ligation using the expression plasmid pET28a as the backbone and ex-pressed in E.coli BL21(DE3).After confirming the expression of the LysZHSHW through West-ern blot analysis,its characterization and potential applications were assessed both in vitro and in vivo.The results showed that the pET28a-Lys recombinant plasmid was successfully constructed and the LysZHSHW protein was expressed correctly.The mass concentration of the purified en-zyme was 4 086 mg/L,which could be used for subsequent experiments.The enzymatic activity of LysZHSHW was determined to be 630 U/μg,with maximum activity observed at 25 ℃ and pH9.0.In vitro experiments demonstrated that 1 000 or 750 mg/L of LysZHSHW,in the presence of EDTA,resulted in a four-log reduction in bacterial counts without any cytotoxicity.In vivo,2.5 μg of LysZHSHW combined with EDTA could increase the survival rate of Galleria mellonel-la larvae infection model to 92.86％after 24 hours,and 0.15 mg of LysZHSHW reduced the bacte-rial load in the thighs of mice by 2.8 logs and alleviated the inflammatory response in muscle fi-bers.In conclusion,LysZHSHW derived from Acinetobacter baumannii bacteriophage exhibited characteristics such as stability at room temperature,alkaline pH,and safety,making it a promis-ing candidate as a novel antimicrobial agent.

Objective:To observe the effects of histone deacetylase 3(HDAC3)-nuclear factor-erythroid 2-related factor 2(Nrf2)signaling pathway on the adipogenesis of condylar chondrocytes in rats with temporomandibular joint(TMJ)osteoarthritis(OA).Meth-ods:60 6-week-old female SD rats were randomly divided into 10 groups(n=6):control,unilateral anterior crossbite(UAC)stimula-tion,UAC with HDAC3 inhibitor RGFP966 injection(UAC+RGFP966)and UAC with Nrf2 agonist Bardoxolone injection(UAC+Bard-oxolone)groups.The animals were sacrificed at 4,8 and 12 weeks after set up of the experiment,and TMJ condylar cartilage was taken for immunohistochemical(IHC)staining of HDAC3,Nrf2 and Adiponection.Results:Compared with the control group,the de-generation of TMJ condylar cartilage in the UAC group was obvious,the positive cell rates of HDAC3 and Adiponectin were increased(P＜0.05),while the positive cell rate of Nrf2 decreased(P＜0.05).Compared with UAC group,after injection of RGFP966 and Bardox-olone,the positive cell rates of HDAC3 and Adiponectin in TMJ condylar cartilage of rats were decreased(P＜0.05),the positive cell rate of Nrf2 increased(P＜0.05),and the degree of cartilage degeneration was reduced.Conclusion:UAC promotes the adipogenesis of TMJ OA condylar chondrocytes through HDAC3-Nrf2 signaling pathway.Local drug injection intervention of HDAC3-Nrf2 signaling can inhibit the adipogenesis and cartilage degeneration of TMJ OA condylar chondrocytes.

Objective:To investigate the clinicopathological and molecular genetic characteristics of Crohn′s disease (CD).Methods:A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes.Results:Among the 52 patients, 34 were males and 18 were females, male-to-female ratio was 1.9∶1.0, with a median age of 45 years at surgery and 35 years at diagnosis. According to the Montreal classification, A3 (51.9%,27/52), B2 (61.5%, 32/52), and L3 (50.0%,26/52) subtypes were the most predominant. Abdominal pain and diarrhea were the common symptoms. Histopathological features seen in all 52 patients included transmural inflammation, disruption of cryptal architecture, lymphoplasmacytic infiltration, varying degrees of submucosal fibrosis and thickening, increased enteric nerve fibers and neuronal proliferation. Mucosal defects, fissure ulcers, abscesses, pseudopolyps, and adenomatous proliferation were also observed in 51 (98.1%), 38 (73.1%), 28 (53.8%), 45 (86.5%), and 28 (53.8%) cases, respectively. Thirty-one (59.6%) cases had non-caseating granulomas, and 3 (5.8%) cases had intestinal mucosal glandular epithelial dysplasia. Molecular analysis showed that 12/17 CD patients exhibited mutations in at least one mucin family gene (MUC2, MUC3A, MUC4, MUC6, MUC12, MUC17), and MUC4 was the most frequently mutated in 7/17 of cases. Immunohistochemical stains showed reduced MUC4 expression in epithelial cells, with increased MUC4 expression in the epithelial surface, particularly around areas of inflammatory cell aggregation; and minimal expression in the lower half of the epithelium.Conclusions:CD exhibits diverse clinical and pathological features, necessitating a comprehensive multidimensional analysis for diagnosis. Mutations and expression alterations in mucin family genes, particularly MUC4, may play crucial roles in the pathogenesis of CD.

Light adaptation enables the vertebrate visual system to operate over a wide range of ambient illumination. Regulation of phototransduction in photoreceptors is considered a major mechanism underlying light adaptation. However, various types of neurons and glial cells exist in the retina, and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic investigation. Therefore, we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in mice. The results demonstrated that, in addition to photoreceptors, other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark adaptation. Importantly, Müller glial cells (MGs) were identified as hub cells for intercellular interactions, displaying complex cell‒cell communication with other retinal cells. Furthermore, light increased the transcription of the deiodinase Dio2 in MGs, which converted thyroxine (T4) to active triiodothyronine (T3). Subsequently, light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light conditions. As cones specifically express the thyroid hormone receptor Thrb, they responded to the increase in T3 by adjusting light responsiveness. Loss of the expression of Dio2 specifically in MGs decreased the light responsive ability of cones. These results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling.
Animals ; Mice ; Dark Adaptation ; Light ; Retina ; Retinal Cone Photoreceptor Cells/metabolism* ; Adaptation, Ocular ; Neuroglia/physiology* ; Cell Communication ; Thyroid Hormones

Objective To study the effects of pressure controlled ventilation(PCV)and volume controlled ventilation(VCV)on diaphragm function and the incidence of postoperative pulmonary complica-tions(PPCs)in patients undergoing laparoscopic surgery.Methods Sixty-six patients underwent laparo-scopic gynecological surgery under general anesthesia,aged 18-64 years,BMI 18-30 kg/m2,ASA physical status Ⅰ or Ⅱ were recruited.The patients were randomly divided into two groups:PCV group(group P)and VCV group(group V),33 cases in each group.All the patients were ventilated in VCV mode after induction.Group P was switched to PCV after pneumoperitoneum and group V maintained VCV until the end of operation after pneumoperitoneum.The diaphragm ultrasonic evaluation indexes including di-aphragmatic excursion(DE),diaphragm contraction velocity(DCV),and diaphragmatic rapid shallow breathing index(D-RSBI)were recorded before anesthesia induction,immediately after extubation,and 30 minutes after extubation.The mechanical ventilation time,artificial pneumoperitoneum time,the time from the end of artificial pneumoperitoneum to extubation,the cumulative dosage of cisatracuriumbesylate,and the patient's observer's assessment alert/sedation(OAA/S)immediately after extubation,the incidence of diaphragm dysfunction immediately after extubation and 30 minutes after extubation,and the cumulative in-cidence of PPCs in 1-3 days after operation.Results Compared with group V,DE in group P was in-creased significantly immediately after extubation(P＜0.05),but there was no significant difference in DE of 30 minutes between the two groups after extubation.Compared with group V,DCV in group P was in-creased significantly immediately after extubation and 30 minutes after extubation(P＜0.05),the inci-dence of PPCs in group P was significantly lower on the 1st day after operation(P＜0.05).There were no significant differences in D-RSBI,time of mechanical ventilation,time of artificial pneumoperitoneum,time from the end of pneumoperitoneum to extubation,cumulative dosage of atracurium besylate,OAA/S score immediately after extubation,and the incidence of diaphragm dysfunction immediately after extubation and 30 minutes after extubation,and the cumulative incidence of PPCs on the 2nd and 3rd day after operation.Conclusion In lower abdominal endoscopic gynecological surgery,compared with volume-controlled venti-lation mode,pressure-controlled ventilation mode dose not reduce the incidence of postoperative diaphragm dysfunction,but dose alleviate the weakening of diaphragm inspiratory force and reduce the incidence of pul-monary complications on the first day after operation.

The number of investigator initiated research (IIR) is increasing. But the recognition and management of IIR in China is still in its infancy, and there is a lack of specific and operable guidance for the implementation process. Based on our practical experiences, previous literature reports, and current policy regulations, the authors took prospective IIR as an example to summarize the implementation process of IIR into 14 steps, which are as the following: study initiation, ethical review, study registration, study filing, case report form design, database establishment, standard operating procedure making, investigator training, informed consent, data collection, data entry, data verification, data locking and data archiving.

Objective:To investigate mentor-mentee dual evaluation of the current status of mentor competency of clinical and translational research mentors, and provide the basis for mentor training focused on the mentor competences.Methods:A total of 121 clinical and translational research mentors and 170 mentees from Peking Union Medical College Hospital were enrolled. The Chinese version of the Mentor Competency Assessment (MCA) questionnaire was used to evaluate the mentor competency, including maintaining effective communication, aligning expectations, assessing understanding, fostering independence, addressing diversity, promoting professional development total 6 parts with 26 sub-items. The Likert scale was used to quantitatively evaluate the clinical and translational research mentor competency by mentor-mentee dual evaluations. And the composition and training needs of clinical and translational research mentors were investigated. SPSS 25.0 was used for t-test. Results:Seventy percent (119/170) of mentees considered the mentor guidance was very helpful, and 78.5% (95/121) of the mentors considered it necessary to carry out the mentor training. The mentee evaluation of mentor competency was significantly higher than that of mentor self-evaluation [total score (162.35±23.59) vs. (154.80±19.81), P < 0.01]. And the excellent rate of 26 sub-items by mentees and mentors were 100.0%(170/170) and 46.3%(56/121) respectively. The mentors and mentees shared the agreement of the strengths on trust-based relationship and encouraging mentees, and weaknesses on taking into account the possible prejudices in mentor-mentee relationship. Conclusion:The clinical and translational research mentors have already had good competences, but mentor training is still highly warranted. It's expected that to carry out targeted mentor training and assessment according to the mentor's competences will help to improve the construction of the medical talents training system.

Objective:To explore the value of 5G robotic remote ultrasound in the diagnosis of plateau pulmonary edema(HAPE).Methods:A total of 27 patients who quickly entered Nagqu, Tibet at an altitude of 4 600 m-5 600 m from March to December 2021 and developed one of the clinical symptoms of HAPE were collected. All patients were examined by 5G remote robotic ultrasound and lung CT respectively. Kappa test was used to analyze the consistency of the two diagnostic results, and McNemar test was used to compare the difference in diagnostic results. The ROC curve was used to analyze the sensitivity and specificity of remote lung ultrasound scores in the diagnosis of HAPE.Results:Among the 27 patients, 16 showed thickening of pleural line, increasing of B line, lung consolidation, pleural effusion, etc. Meanwhile, 11 showed no abnormality. Additionally, 8 cases had diffuse pulmonary fluid in both lungs, and 8 cases had localized pulmonary fluid. ROC curve showed that the area under the curve of lung ultrasound score for the diagnosis of HAPE was 0.947 (95% CI=0.78-0.99, P<0.001). The sensitivity and specificity were 0.933 and 0.917, respectively. Lung CT diagnosis was positive in 15 cases. Lung CT showed thickening of lung texture, ground glass, small nodular shadow, fine reticulate shadow, etc. The diagnostic results of the two techniques were in good agreement (Kappa=0.924, P<0.001), and there was no significant difference between the two methods ( P>0.05). Conclusions:5G remote robotic ultrasound has high consistency with CT in the diagnosis of HAPE and is an alternative early diagnosis method for HAPE. It may have clinical application value in scattered medical resources and remote plateau areas.

The interleukin (IL) -23/IL-17 axis is the main pathway in the pathogenesis of plaque-type psoriasis vulgaris, and IL-17A plays a key role in the relevant immune pathways. IL-17A mediates overlapping inflammatory pathways in atherosclerosis and psoriasis, promotes inflammation, coagulation and thrombosis, and plays an important role in the occurrence and development of cardiovascular comorbidities in patients with psoriasis. Inhibiting the inflammatory effect of IL-17A can reduce the incidence and mortality of cardiovascular comorbidities in patients with severe psoriasis. This review summarizes recent research progress in IL-17A-mediated systemic inflammation and cardiovascular comorbidities in patients with psoriasis, and provides a reference for prevention and reduction of cardiovascular comorbidities in patients with psoriasis in clinical practice.

Objective:To analyze clinical characteristics of neurosyphilis patients with abnormal mental behaviors as the initial symptom, and to provide a reference for clinical classification of, as well as outcome prediction and efficacy monitoring in neurosyphilis.Methods:Clinical data were collected from 67 HIV-negative neurosyphilis patients with abnormal mental behaviors as the initial symptom in the Second Affiliated Hospital of Soochow University from November 2012 to November 2019, and retrospectively analyzed. Statistical analysis was carried out by using t test. Results:Among the 67 patients, 52 (77.6%) were males, and 15 (22.4%) were females; there were 63 (94.0%) middle-aged and elderly patients and 4 (6.0%) adolescent patients; 38 (56.7%) patients were diagnosed with progressive general paresis, 21 (31.3%) with meningovascular neurosyphilis, 1 (1.5%) with meningeal neurosyphilis, 3 (4.5%) with tabes dorsalis, and 4 (6.0%) with mixed-type neurosyphilis. As laboratory examination showed, 67 patients all presented with positive serum rapid plasma reagin (RPR) test, serum Treponema pallidum particle agglutination (TPPA) test, and cerebrospinal fluid TPPA test, 55 (82.1%) had positive cerebrospinal fluid RPR test, 47 (70.1%) had elevated cerebrospinal fluid protein levels of > 0.45 g/L, 50 (74.6%) had increased white blood cell counts of > 8 ×10 6/L in cerebrospinal fluids, and 28 (41.8%) had elevated IgG levels in cerebrospinal fluids. Magnetic resonance imaging of the brain revealed multiple ischemic foci in 21 (31.3%) cases, multiple leukodystrophy in 17 (25.4%) , cerebral atrophy in 15 (22.4%) , infarction in 8 (11.9%) , and encephalitis-like changes in 2 (3.0%) . Of the 67 patients, 48 were treated with penicillin in aqueous solutions, 15 with ceftriaxone, and 4 with doxycycline. Six months later, the follow-up showed that 46 (68.7%) patients responded to the treatment, and the early course of disease was significantly shorter in the highly responsive group than in the poorly responsive group ( P < 0.05) . Conclusion:The middle-aged and elderly males were predominant in the neurosyphilis patients with abnormal mental behaviors as the initial symptom, magnetic resonance imaging is helpful for clinical classification and prognosis prediction of neurosyphilis, and early and standardized antisyphilitic treatment can markedly improve the prognosis of patients.