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.

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.

Objective To evaluate the predictive value of dual-modality ultrasound,incorporating conventional ultrasound and ultrasound elastography,in combination with S-Detect for cervical lymph node metastasis(CLNM)in patients with papillary thyroid carcinoma(PTC).Methods A retrospective analysis was conducted on the clinical data of 135 patients diagnosed with PTC who received treatment at the First Affiliated Hospital of Shihezi University between November 2023 and August 2024.For all patients,clinical baseline characteristics,conventional ultrasound findings,ultrasound elastography results,and S-Detect analysis data were collected.Independent predictors of CLNM in PTC were identified,and predictive models were developed.Receiver operating characteristic(ROC)curves were generated to compare the area under the curve(AUC)of the models.The most effective predictive model was selected to construct a risk probability nomogram,and the predictive performance and clinical applicability of this nomogram were subsequently evaluated.Results Age,maximum nodule diameter,boundary characteristics,capsular invasion,transverse-sectional morphological findings assessed by S-Detect,and ECI-based elasticity grading were identified as independent predictors of CLNM in PTC(all P<0.05).The AUC of the predictive model constructed using these six variables was 0.890(95%CI:0.835～0.945).The calibration curve demonstrated strong agreement between predicted and observed outcomes,and decision curve analysis indicated that the nomogram provided a favorable net clinical benefit within a threshold probability range of 2%to 91.5%.Conclusions Age,maximum nodule diameter,boundary characteristics,capsular invasion,sonographic features assessed by S-Detect in the transverse plane,and ECI-based elasticity grading are independent predictors of CLNM in PTC.A nomogram model incorporating these parameters demonstrates effective performance in predicting the likelihood of CLNM.

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 investigate the utility of combining breast mass growth orientation quantification with the S-Detect technique for predicting axillary lymph node(ALN)metastasis in breast cancer.Methods Data was collected from 163 breast cancer patients admitted to our hospital between March 2023 and October 2024,who were categorized into metastatic(n=62)and non-metastatic(n=101)groups based on ALN pathology results.All patients underwent routine preoperative ultrasound and S-Detect examination.Univariate and multivariate regression analyses were performed to assess the correlation between each observational index and ALN metastasis.Significant indexes were identified through screening,leading to the establishment of a logistic regression prediction model.The predictive value of the model was evaluated using receiver operating characteristic(ROC)curve analysis.Results The univariate analysis revealed statistically significant differences(P<0.05)in the maximum diameter of the mass,border characteristics,margin features,calcification patterns,orientation angle,and blood flow between the two groups.Multifactorial analysis demonstrated that calcification,border characteristics,orientation angle,margin features,and maximum diameter independently influenced the prediction of axillary lymph node(ALN)status in breast cancer patients(P<0.05).Consequently,a logistic regression prediction model was constructed as follows:Y=-7.995+2.299×maximal diameter+1.171×border+2.137×margin+1.397×calcication+0.034×orientation angle.The area under curve(AUC)for this combined prediction model was 0.869 which significantly outperformed each independent influencing factor alone(P<0.05),indicating good agreement between this joint prediction model and pathological results(Kappa=0.701,P<0.05).Conclusions Quantification of the orientation angle of a breast mass aids in predicting axillary lymph node(ALN)metastasis and enhances the interpretation and application of non-parallel orientations.The combination of quantifying growth orientation based on breast mass with artificial intelligence S-Detect technique demonstrates promising predictive value for ALN metastasis in breast cancer,providing a reference basis for personalized treatment.

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.

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 explore the correlation between the ratio of free triiodothyronine/free thyroxine(FT3/FT4)and the early-phase insulin secretion index(ΔI30/ΔG30)in type 2 diabetes mellitus(T2DM)patients with normal thyroid function.Methods 200 patients with T2DM with normal thyroid function in Hebei General Hospital from September 2019 to June 2021 were selected and divided into the Q1 group with FT3/FT4≤0.26(n=67),the Q2 group with 0.27≤FT3/FT4≤0.29(n=67),and the Q3 group with FT3/FT4≥0.30(n=66)according to the tertiles of the FT3/FT4.The general data,biochemical indicators and islet functions of the three groups were compared,and the relationship between the FT3/FT4 ratio and the ΔI30/ΔG30 as well as the islet β cell function was analyzed.Results The fasting insulin(FIns),2 h postprandial insulin(2 hIns),homeostatic model assessment of islet β cell(HOMA-β)and area under the curve of insulin(AUCI)in Q3 group were higher than those in Q1 and Q2 groups(P<0.05),2 h postprandial blood glucose(2 hPG)in Q3 group was lower than those in Q1 and Q2 groups(P<0.05).Systolic blood pressure in Q2 group was higher than those in Q1 group(P<0.05).Compared with Q1 group,diastolic blood pressure,body mass index(BMI),alanine aminotransferase(ALT),fasting C-peptide(FC-P),area under curve of C-P(AUCC),2 h postprandial C-peptide(2 hC-P)and ΔI30/ΔG30 in Q3 group were significantly higher(P<0.05),and HbA1c was significantly lower(P<0.05).Spearman correlation analysis showed that Δ I30/Δ G30,HOMA-β,AUCI,AUCC and HOMA-IR were positively correlated with BMI,ALT,FC-P,2 hC-P,FIns,2 hIns and FT3/FT4(P<0.05),it was negatively correlated with HbA1c and 2 hPG(P<0.05).Linear regression analysis showed that ΔI30/ΔG30,HOMA-β,AUCI and AUCC were the influencing factors of FT3/FT4 after adjusting for confounding factors.Conclusions ΔI30/ΔG30,HOMA-β,AUCI and AUCC are the influencing factors of FT3/FT4 in T2DM patients with normal thyroid function,suggesting that FT3/FT4 is higher in patients with better islet β cell secretion function.

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.