AIM: To compare the efficacy and safety of posterior scleral, peripupillary, and intravitreal injections of triamcinolone acetonide(TA)in treating retinal vein occlusion-macular edema(RVO-ME).METHODS: From June 2021 to September 2024, patients with RVO-ME admitted to our hospital were assigned to three groups: group A(posterior scleral injection), group B(peripupillary injection), and group C(intravitreal injection). At 3 mo after treatment, the efficacy, best corrected visual acuity(BCVA LogMAR), central macular thickness(CMT), central retinal artery blood flow parameters, and incidence of complications were compared among the three groups of patients.RESULTS: A total of 93 cases(93 eyes)of RVO-ME were included, with 31 cases(31 eyes)in each group. The mean age in the group A was 50.37±5.71 years old, with 15 males and 16 females, the group B was 48.92±5.36 years old, with 14 males and 17 females, and the group C was 49.66±5.54 years old, with 18 males and 13 females. The overall efficacy rate in the group A(94%)was higher than that in the groups B and C(68% and 74%), and the complication rate(6%)was lower than in the groups B and C(29% and 32%; P<0.05). At 1 and 3 mo after treatment, the BCVA of group A was 0.46±0.06, 0.36±0.04, the end diastolic velocity(EDV)was 11.45±1.79, 13.97±2.28 cm/s, and the peak systolic velocity(PSV)was 2.16±0.31, 2.83±0.42 cm/s; the BCVA of group B was 0.55±0.07, 0.46±0.05, EDV was 9.57±1.38, 12.03±2.14 cm/s, and PSV was 1.93±0.26, 2.41±0.39 cm/s. The BCVA of group C was 0.57±0.09, 0.48±0.06, EDV was 9.39±1.25, 11.91±2.06 cm/s, PSV was 1.87±0.24, 2.35±0.36 cm/s. The BCVA in the group A was better than that of the groups B and C, and EDV and PSV in the group A were greater than those of the groups B and C(all P<0.05); at 1 and 3 mo after treatment, the CMT of patients in the group A was 249.62±29.33 and 141.13±21.59 μm, and resistance index(RI)was 0.71±0.08 and 0.70±0.08, patients in the group B had CMT of 307.13±34.86 and 227.99±28.43 μm, and RI of 0.77±0.09 and 0.76±0.09, while patients in the group C had CMT of 311.42±40.66 and 232.56±31.44 μm, and RI of 0.79±0.11 and 0.78±0.10, with CMT and RI significantly lower in the group A than those in the groups B and C(all P<0.05).CONCLUSION: All three methods improved visual acuity, reduced macular edema, and optimized retinal blood flow parameters. However, posterior scleral injection demonstrated the most significant improvement across all efficacy metrics. In contrast, although peripupillary injection and intravitreal injection demonstrated therapeutic effects, their improvements were relatively limited, and both had a higher incidence of complications. Therefore, posterior scleral injection may represent a superior treatment for RVO-ME.

Patients with inflammatory bowel disease (IBD) require long-term pharmacotherapy. Due to the wide variety of clinically available drugs, medication safety has become increasingly concerning. As an indispensable component of pharmaceutical formulations, drug excipients may induce various adverse reactions, including rash, allergic responses, and gastrointestinal discomfort, and may even lead to severe organic injury. However, they are often overlooked in clinical practice. Therefore, identifying and managing excipient-related adverse reactions is crucial for ensuring medication safety. To address this issue, this article systematically reviews common excipients in IBD therapeutics, the underlying mechanisms of excipient-induced adverse reactions, and corresponding management strategies, aiming to enhance clinicians' awareness of excipient-related issues, improve their ability to recognize and manage such reactions, and ultimately ensure patient safety.

Objective: To perform transient transfection of recombinant human Factor X(rhFX) into HEK293 cells,to optimize transfection parameters,to develop a high-yield in vitro expression system for rhFX production,and to assess the biological activity of expressed rhFX. Methods: The eukaryotic expression vector pcDNA3. 1-EGFP-FX was constructed by inserting the F10 gene into pcDNA3. 1-EGFP and subsequently transfected into HEK293cells to validate the transfection system efficiency. The recombinant expression vector pcDNA3. 1-FX was generated through ligation of the F10 gene fragment with pcDNA3. 1, followed by liposome-mediated transfection into HEK293 cells. The expression of rhFX in the cell supernatant was analyzed by Western blot and sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE). Transfection conditions were systematically optimized,and rhFX concentration was quantified by enzyme-linked immunosorbent assay(ELISA). The coagulation bioactivity of rhFX was evaluated through prothrombin time(PT) assay and chromogenic substrate method. Results: rhFX was successfully expressed in the supernatant of HEK293 cells. rhFX was successfully expressed in the supernatant of HEK293 cells. The highest expression level of rhFX was achieved on the third day after transfection when the cell density was 80% and the ratio of plasmid DNA to polyethyleneimine(PEI) transfection reagent was 1 ∶ 2.Triplicate ELISA measurements demonstrated a maximum rhFX concentration of 5. 20 ng/mL in the supernatant.The prothrombin time(PT) of rhFX-containing supernatant was significantly shorter(P 50) of etoxaban was determined to be 1. 449 nmol/L using the chromogenic substrate method based on rhFX,which was in the same order of magnitude as the reported 0. 78 nmol/L in the literature. Conclusion HEK293cells successfully express biologically active recombinant human Factor X(rhFX) protein,laying a foundation for advancing the development of rhFX-based therapeutics.

Objective:To determine the epidemic characteristics of polymyxin resistance ( mcr) genes of Enterobacteriales colonized in patients admitted to hospitals in Zhejiang, Henan, Gansu and Shandong provinces in China in 2023. Methods:A comprehensive collection of 667 fecal specimens from patients admitted to five medical facilities across the provinces of Zhejiang, Henan, Gansu, and Shandong in 2023 was collected. Epidemiological characteristics of Enterobacteriales bacteria positive for the mcr gene were examined, employing techniques such as microbial culturing, using agarose gel electrophoresis, PCR, whole-genome sequencing, bioinformatics analysis, and the induction of antimicrobial resistance. Statistical analysis was subsequently applied to the gathered data. Results:Among 667 fecal samples from admitted patients, five samples were positive for mcr gene, with a carrier rate of 0.75%(5/667), and from two of the samples, two different strains carrying the mcr gene were isolated, respectively. A total of seven strains of Enterobacteriales carrying the mcr gene were detected, of which four strains carried mcr-1 gene and three strains carried mcr-9 gene. The positive isolates included three strains of Escherichia coli, one strain of Citrobacter braakii, Citrobacter freundii, one strain of Klebsiella pneumoniae, and one strain of Enterobacter hormaechei. The seven mcr positive strains were isolated from two distinct geographical locations within China, with four from Zhejiang Province and three from Henan Province. After whole-genome sequencing, it was found that the 16S rRNA sequences of the three strains of mcr-1 positive Escherichia coli had high homology. The three isolates of mcr-9 positive strains preserved a significant degree of homology within the mcr-9 and wbuC regions. Following polymyxin exposure, there was a marked difference in the growth kinetics of the ZJ-307, HN-11-1, and HN-135 strains post-induction compared to their pre-induction growth rates, and their motility capacity was reduced. Conclusions:The prevalence of Enterobacteriales harboring the mcr gene is minimal among hospitalized patients. However, it is noteworthy that these genes are prone to horizontal transfer. They can move into drug-resistant strains, which may have elevate minimum inhibitory concentration(MIC). Resistance to polymyxin can alter the bacterial growth rate and motility, potentially impacting the MIC of other antibiotics, thereby complicating clinical management. Consequently, it is imperative to focus on the proactive screening of susceptible populations to prevent the further dissemination of plasmid-mediated polymyxin resistance among clinically significant gram-negative bacterial pathogens.

The contents of Zhang Zhongjing's works Treatise on Exogenous Febrile Disease,the Jade Case Classic of the Golden Cabinet,and Essentials from the Golden Cabinet(collectively known as the three classical medical books of Zhang Zhongjing),as well as Important Formulas Worth A Thousand Gold Pieces and Supplement to"Important Formulas Worth a Thousand Gold Pieces",which were cited in the Arcane Essentials from the Imperial Library(Wai Tai Mi Yao Fang)during comparative proofreading were analyzed.Wai Tai Mi Yao Fang is a book edited and public by the Bureau of Revising Medical Books in Northern Song Dynasty.The contents in the collation records for Wai Tai Mi Yao Fang were compared to the original text of the above five classical medical books proofread in Song Dynasty.The results showed that:(1)the ministers of Song Dynasty which were in charge of the proofreading mainly took the previously-proofread books as references,and widely referenced to the other editions of Wai Tai Mi Yao Fang,which reflected the proofreading principles of the Bureau of Revising Medical Books in Northern Song Dynasty,i.e.,collecting various editions widely and then identifying similarities and differences;(2)the analysis of the collation record in Zhongjing's Treatise on Exogenous Febrile Disease by using comparative proofreading method plus reasoning proofreading method showed that,the medical knowledge of the ministers of Song Dynasty had some limitations;(3)some of the medical terminology used by the ministers of Song Dynasty in their collation record influenced the naming convention of later generations of medical science,for example,making the Piyue Pills be the synonym of the Maziren Wan(Maren Wan).The results indicated that the complexity and uncertainty of the textual content of the popular edition of Wai Tai Mi Yao Fang should deserve the attention,and their influences on the development of later generations'scholarship need further in-depth study.

Sepsis is a systemic inflammatory response syndrome triggered by infection,and the abnormal inflammatory response leads to the damage of intestinal mucosal barrier.The intestinal mucosal barrier consists of four parts,namely biological barrier,chemical barrier,mechanical barrier,and immune barrier.The injured intestinal mucosal barrier is considered as the"initiating organ"of multiple organ dysfunctions in sepsis,with the immune barrier being particularly critical to the progression of sepsis.Berberine(also known as berberine hydrochloride)is an active alkaloid extracted from Berberaceae plants such as Coptidis Rhizoma,and possesses multiple pharmacological actions including antibacterial and anti-inflammatory effects.It has been widely used in the treatment of various diseases,including diarrhea and arrhythmias.This article reviewed the progress in recent research on the protective effects and mechanism of Berberine against sepsis-induced intestinal mucosal immune barrier damage.The recent studies have shown that berberine can modulate intestinal mucosal immune function in sepsis via regulating the TLRs signaling pathway,Notch signaling pathway,and dendritic cell(DC)function,by inducing ferroptosis of macrophages in intestinal mucosa,and by regulating the imbalance of gut microbiota in sepsis patients.The unique advantages of berberine and its promising application prospects in the treatment of sepsis have been demonstrated by its effects on protecting and repairing the intestinal mucosal barrier and on improving the sepsis-induced intestinal mucosal barrier damage.The in-depth research into its therapeutic mechanisms and the exploration of optimized strategies for using berberine to prevent and treat sepsis-induced intestinal mucosal barrier damage are of great significance for enhancing clinical outcomes in sepsis treatment,and will provide new insights and directions for the prevention and treatment of sepsis.

Objective:To investigate the clinical distribution and diagnostic value of anti-total phospholipid-antibodies(aTPL) patients with in antiphospholipid syndrome(APS).Methods:We collected the clinical data and laboratory test results of patients diagnosed with APS, systemic lupus erythematosus, Sj?gren′s syndrome, osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, mixed connective tissue disease, and adult Still′s disease in Peking University People′s Hospital from February 2009 to October 2017. A total of 335 cases were studied, of which 163 were APS patients, 122 were disease control(DC) and 50 were health control(HC). Enzyme-linked immunosorbent assay(ELISA) was used to measure aTPL, anti-cardiolipin antibody (aCL), and anti-beta-2-glycoprotein Ⅰ antibody (aβ 2GPⅠ). The Chi-square test was used to compare the differences between groups. Results:The prevalence of aTPL in APS, DC and HC were 39.9%, 3.3%and 2.0% respectively. The sensitivity and specificity were 39.9%, 97.1%. The proportion of thrombosis[75.4%(49/65) vs. 51.0%(50/98), χ2=9.73, P=0.002] and arterial thrombosis[49.2%(32/65) vs. 25.5%(25/98), χ2=9.67, P=0.002] was significantly higher in the aTPL positive group than that of the negative group. In aTPL positive group, the positive rate of aCL[84.6%(55/65) vs.29.6%(29/98), χ2=47.37, P<0.001], aβ 2GPⅠ[83.1%(54/65) vs.37.8%(37/98), χ2=32.55, P<0.001] and LA[61.5%(40/65) vs. 42.9%(42/98), χ2=5.46, P=0.020] was significantly higher than that of negative group.The area under ROC curve (95% CI) of aTPL [0.694(0.636, 0.751)] was slightly higher than that of aCL [0.668(0.610, 0.726)], but lower than that of aβ 2GPⅠ [0.746(0.694, 0.799)]. Conclusion:aTPL exhibits a strong correlation with thrombosis in patients with APS, particularly arterial thrombosis, and demonstrates high specificity, which can assist in the diagnosis of seronegative APS.

Objective To elucidate the role of gut microbiota in cognitive impairment induced by adolescent social isolation(ASI)and identify key pathogenic microbial communities.Methods Sixteen male C57BL/6 mice(postnatal days 21～23)were randomly assigned to a control group(group-housed,4/cage,n=8)or an ASI group(single-housed,1/cage,n=8).After 5 weeks of ASI(5-ASI),fecal samples underwent 16S rRNA sequencing for microbiota analysis.Cognitive behavior was assessed using open field,Y-maze,novel object recognition tests.Correlation analysis integrated microbial abundance with behavioral parameters to screen cognition-associated taxa.Results(1)Behavior:5-ASI mice showed unchanged locomotion(open field)but significantly reduced spontaneous alternation(Y-maze,P<0.01)and lower cognitive index(novel object recognition,P<0.001),confirming spatial and recognition memory deficits.(2)Microbiota:5-ASI mice exhibited decreased α-diversity(P<0.05)and altered β-diversity(P<0.001).LEfSe analysis revealed depleted taxa(e.g.,Prevotellaceae_NK3B31_group,Tyzzerella,Allobaculum,Ruminococcus)and enriched taxa(e.g.,Butyricicoccus,Lachnoclostridium).(3)Correlations:Positive associations with cognitive performance were observed for Prevotellaceae_NK3B31_group,Allobaculum,and Ruminococcus(P<0.05),while Butyricicoccus and Lachnoclostridium showed negative correlations(P<0.05).Conclusion Adolescent social isolation induces spatial/recognition memory impairment and gut microbiota dysbio-sis.Specific microbial alterations(Prevotellaceae_NK3B31_group,Butyricicoccus)correlate with cognitive deficits,providing novel insights into microbiota-mediated mechanisms and potential therapeutic targets.

Objective:To explore the effect of necroptosis inhibitor necrosulfonamide (NSA) on traumatic brain injury (TBI) mouse model and BV2 cell pyroptosis model and their mechanisms.Methods:(1) In vivo experiments: 50 mice were randomly divided into sham-operated group, TBI group, TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group, and TBI+10 mg/kg NSA group, with 10 mice in each group. TBI model was established using a modified Feeney's weight-drop method; 4 h after modeling, 90% corn oil, 1 mg/kg NSA, 5 mg/kg NSA, or 10 mg/kg NSA was administered into the mice, respectively. Mice in the sham-operated group only had circular bone window opened without being subjected to impact. At 48 hours after modeling, neurological function was evaluated by modified neurological function score (mNSS), serum lactate dehydrogenase (LDH) content was detected by LDH detection kit, contents of interleukin (IL)-18, IL-1β and tumor necrosis factor-α (TNF-α) in the brain tissues were detected by enzyme-linked immunosorbent assay (ELISA), and expressions and localizations of ionized calcium binding adaptor molecule 1 (IBA-1), cysteinyl aspartate specific proteinase-1 (Caspase-1) p20 and gasdermin D (GSDMD) in the injured parietal cortex were detected by double immunofluorescent staining. (2) In vitro experiments: BV2 cells were divided into control group, lipopolysaccharide (LPS)+adenosine triphosphate (ATP)+dimethyl sulfoxide (DMSO) group, LPS+ATP+5 μmol/L NSA group, LPS+ATP+10 μmol/L NSA group, and LPS+ATP+15 μmol/L NSA group. Cells in the latter 4 groups were induced by LPS+ATP to establish BV2 cell pyroptosis model, and incubated with 2 μL DMSO, 5 μmol/L NSA, 10 μmol/L NSA, and 15 μmol/L NSA for 1 hour, respectively; cells in the control group were cultured conventionally. Contents of LDH, IL-1β, IL-18, and TNF-α in the cell culture supernatant were detected by ELISA; pyroptosis was detected by calcein acetoxymethyl ester (CAM)/propidium iodide (PI) double staining; protein expressions of nucleotide binding domain-like receptor protein 3 (NLRP3), Caspase-1 p20, GSDMD, and N-terminal fragment of GSDMD (GSDMD-N) were detected by Western blotting. Results:(1) Compared with the TBI group, the TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group and TBI+10 mg/kg NSA group had decreased mNSS score and serum LDH content, decreased IL-1β and IL-18 contents in the brain tissues and number of Caspase-1 p20 + cells in the injured parietal cortex, successively, with significant differences ( P<0.05). Compared with the TBI group ([287.80±12.26] cells/mm 2), the TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group, and TBI+10 mg/kg NSA group had decreased number of Iba-1 +GSDMD + cells in the injured parietal cortex ([213.70±11.87] cells/mm 2, [205.30±9.15] cells/mm 2, [131.70±13.69] cells/mm 2),successively, with significant differences ( P<0.05). Compared with the TBI group, the TBI+5 mg/kg NSA group and TBI+10 mg/kg NSA group had significantly decreased number of Iba-1 + cells in the injured parietal cortex, and the TBI+10 mg/kg NSA group had significantly decreased TNF-α content in the brain tissues and number of GSDMD + cells in the injured parietal cortex ( P<0.05). Compared with the TBI group ([247.20±9.88] cells/mm 2), the TBI+10 mg/kg NSA group had significantly decreased number of Iba-1 +Caspase-1 p20 + cells in the injured parietal cortex ([181.70±9.37] cells/mm 2, P<0.05). (2) Compared with the LPS+ATP+DMSO group, the LPS+ATP+5 μmol/L NSA group, LPS+ATP+10 μmol/L NSA group, and LPS+ATP+15 μmol/L NSA group had decreased IL-18 content in the supernatant, successively, with significant differences ( P<0.05); and compared with the LPS+ATP+DMSO group, the LPS+ATP+10 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased contents of LDH, IL-1β, and TNF-α in the supernatant and ratio of PI +/CAM + cell counts ( P<0.05). Compared with the LPS+ATP+DMSO group (2.62±0.50), the LPS+ATP+10 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased Caspase-1 p20 protein expression (1.36±0.14, 1.32±0.07, P<0.05). Compared with the LPS+ATP+DMSO group (5.00±1.67), the LPS+ATP+5 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased GSDMD protein expression (1.42±0.26, 1.68±0.32, P<0.05). Compared with the LPS+ATP+DMSO group (2.28±0.24), the LPS+ATP+15 μmol/L NSA group had significantly decreased GSDMD-N protein expression (1.23±0.08, P<0.05). Conclusion:NSA can inhibit microglial pyroptosis after TBI by inhibiting the Caspase-1 p20/GSDMD pathway, thereby playing a neuroprotective role.

Objective To evaluate the safety and efficacy of ciprofol in the anesthesia of elderly patients undergoing bronchoscopy.Methods A total of 96 elderly patients(≥65 years old)undergoing fiberoptic bronchos-copy under sedation and anesthesia were randomly assigned to either the ciprofol group(Group C,n=48)or the propofol group(Group P,n=48).In Group C,anesthesia was induced with an intravenous injection of sufentanil at 0.1 μg/kg and ciprofol at 0.3 mg/kg.In Group P,anesthesia was induced with an intravenous injection of sufent-anil at 0.1 μg/kg and propofol medium/long-chain fat emulsion at 1.5 mg/kg.Hemodynamic parameters,including heart rate(HR),mean arterial pressure(MAP),and peripheral oxygen saturation(SpO2),were recorded at five time points:before anesthesia induction(T1),immediately after the bronchoscope passed through the glottis(T2),immediately after it reached the carina(T3),immediately after the bronchoscope was withdrawn from the nostril post-procedure(T4),and upon full consciousness after leaving the recovery room(T5).Additionally,the success rate of sedation and anesthesia,cough severity scores,induction time(t1),bronchoscopy duration(t2),recovery time(t3),and orientation recovery time(t4)were documented for both groups.Intraoperative complications,such as hypotension,hypoxemia(SpO2<90%),injection pain during induction,airway interventions(e.g.,jaw support,mask ventilation),and the number of additional sedative doses administered,were also recorded.Results Compared with T1,MAP in both groups decreased at T2 and T3(P<0.05).Compared with group P,group C exhibited a higher MAP at T2 and T3(P<0.05).between the two groups in terms of sedation success rate,induction time,cough score,examination time,recovery time,and orientation recovery time(P>0.05).Compared with group P,group C demonstrated lower incidences of hypotension,hypoxemia,injection pain,and fewer airway intervention events(P<0.05).Conclusions Compared with propofol,ciprofol in combination with sufentanil demonstrates superior circulatory stability,a lower incidence of respiratory system-related adverse reactions,and reduced injection pain.Therefore,it can be safely and effectively utilized for painless bronchoscopic diagnosis and treatment in elderly patients.