Objective:To investigate the expressions of serum cytokines in patients with autoimmune retinopathy (AIR), and their association with disease diagnosis as well as clinical features.Methods:A prospective case-control study was conducted.A total of 90 eyes of 45 AIR patients were consecutively collected in Beijing Tongren Hospital from September 2018 to December 2023.Additionally, age-matched 43 controls (86 eyes) were enrolled, consisting of 21 patients (42 eyes) with retinitis pigmentosa as a disease control group and 22 healthy subjects (44 eyes) as a normal control group.The main clinical outcome measures included best-corrected visual acuity (BCVA), mean deviation (MD) of visual field, central retinal thickness and the maximal response amplitude and implicit time of full-field electroretinography (ff-ERG). A total of 21 serum cytokines were detected by Luminex multiple cytokines assay or ELISA.Differences in serum cytokine concentrations of among groups, the correlation between cytokine levels and clinical outcomes, and the contribution of cytokines to the diagnosis of AIR were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital (No.TRECKY2018-048). Written informed consent was obtained from each subject.Results:In AIR patients, the expression levels of Th1-type cytokines or receptors (including interferon-γ[IFN-γ], interleukin [IL]-8, C-X-C motif chemokine ligand [CXCL]9, and CXCL10) and Th17-type cytokines (including IL-17 and IL-6) were elevated.There were statistically significant overall differences in pro-inflammatory cytokines/chemokines (IL-6, IL-8, CXCL10, IL-10, IFN-γ, IL-17, C-X3-C motif chemokine ligand 1 [CX3CL]1, CXCL9) among the three groups ( H=10.823, 10.816, 9.633, 10.103, 23.670, 16.493, 9.050, 9.253; all P<0.05). Compared with the disease control group and the healthy control group, the IFN-γ level was significantly increased in the AIR group (both P=0.001). Compared with the healthy control group, the serum levels of IL-6, IL-8, CXCL10, IL-10, IL-17, and CXCL9 in the AIR group were significantly elevated (all P<0.05). The serum level of CX3CL1 was significantly higher in the AIR group than in the disease control group ( P=0.039). The serum level of IFN-γ was significantly higher in the AIR group than in the healthy control and disease control groups, but no association with AIR diagnosis was found ( OR=1.402, 95% CI: 0.710-2.870, P=0.245). Multilevel mixed-effects regression modeling analysis showed that the serum levels of IL-8 and CXCL9 in AIR patients were positively correlated with LogMAR BCVA ( β=0.028, P=0.033; β=0.023, P=0.003). The C-C motif chemokine ligand 11 level was positively correlated with implicit time of ERG a-wave ( β=13.950, P<0.001). The tumor necrosis factor-α level was positively correlated with MD value of visual field ( β=6.310, P=0.002). Granulocyte-macrophage colony-stimulating factor was negatively correlated with the amplitude of ERG a-wave and granulocyte colony-stimulating factor was negatively correlated with ERG b-wave amplitude ( β=-152.700, P<0.001; β=-14.790, P=0.003). Conclusions:Serum Th1 and Th17-type cytokines/chemokines may be involved in the pathogenesis of AIR and are related to disease severity.

Objective To investigate the causes for the continuous detection of Pseudomonas fluorescens(P.fluo-rescens)from bronchoalveolar lavage fluid(BALF)in pediatric department of a hospital,formulate intervention measures and evaluate its effectiveness,and provide basis for improving the whole process infection control of fiber bronchoscopy.Methods Epidemiological investigation was conducted on three children from whose BALF P.fluorescens were detected in May 3-6,2024.The comprehensive methods were adopted,including case revie-wing,on-site process tracking,environmental hygiene monitoring,laboratory testing on disinfectant sterilization effect,fiber bronchoscope structure maintenance and checking,etc.Risks were identified and targeted interventions were implemented.Results Among the 5 pediatric patients who underwent fiber bronchoscopy within 4 days,P.fluorescens was detected from BALF of 3 cases,with a detection rate of 60.0％.The children were 5-8 years old and were admitted to the hospital due to lobar pneumonia.They underwent fiber bronchoscopy from the day of admission to the second day,and bacterial strains were clinically determined to be contaminated strains.Environ-mental sampling showed that the detection rate of P.fluorescens at sampling points such as fiber bronchoscope and enzyme solution storage tank was 15.7％(8/51).After implementing intervention,no target bacteria were detected again,and the difference was statistically significant(P＜0.05).From January 1 to May 2,2024,71 BALF from pediatric department were not detected P.fluorescens;From May 3 to 6,among 5 detected BALF,3 were detected P.fluorescens;After intervention(May 16 to December 31),no specimen was detected P.fluorescens.Conclusion This event is a pseudo-outbreak caused by fiber bronchoscope damage as well as improper cleaning and disinfection procedures.Through collaborative investigation and timely intervention by multiple departments,the event was ef-fectively controlled.

Objective To investigate the effect and mechanism of zanthoxylum bungeanum seed oil on autophagy and apoptosis of laryngeal cancer cells.Methods Human bronchial epithelial cells BEAS-2B and human laryngeal cancer cells Hep-2 were treated with different volume fractions(v/v)of Zanthoxylum bungeanum seed oil(0,0.02%,0.04%,0.06%,0.08%,0.10%),respectively,cell viability was detected by cell counting kit-8 method(CCK-8).Hep-2 cells in logarithmic growth phase were randomly divided into control group,Zanthoxylum bungeanum seed oil low,medium and high dose groups and Zanthoxylum bungeanum seed oil high dose+insulin-like growth factor 1(IGF-1)(PI3K agonist)group,cell apoptosis and cell cycle progression were detected by flow cytometry(FCM)assay,the formation of autophagic vesicles was detected by monodansyl cadaverine(MDC)staining,the expression of apoptosis,autophagy and phosphatidylinositide 3-kinases(PI3K)/protein kinase B(AKT)/mechanistic target of rapamycin(mTOR)pathway-related proteins were detected by Western blotting(WB).Results Compared with the control group Hep-2(99.03%±0.82%),treatment with zanthoxylum bungeanum seed oil(0.02%,0.04%,0.06%,0.08%,0.10%)(v/v)could reduce cell survival rate(84.63%±0.73%,57.34%±0.84%,19.76%±0.62%,17.22%±0.72%,12.19%±0.81%),and the differences were statistically significant(t=22.718～133.559,all P<0.001),while it has no inhibitory effect on BEAS-2B activity(t=0.283～1.980,all P>0.05).Compared with the control group,the Hep-2 apoptosis rate,G1/G0 phase cell proportion,autophagic vesicle integrated optical density(IOD)value,Cleaved-caspase-3,Bcl-2 associated X protein(Bax),microtubule-associated protein 1A/1B 1ight chain 3I/Ⅱ(LC 3I/Ⅱ)and Beclin-1 expression were all increased in the low,medium,and high-close groups of zantheoxylum bungeanum seed oil(t=4.270～58.425);the proportion of G2/M phase cells,ubiquitin-binding protein P62,Bcl-2 expression and p-PI3K/PI3K,p-AKT/AKT and p-mTOR/mTOR expression were all decreased(t=3.041～58.765),and the differences were statistically significant(all P<0.05).Compared with the high-dose zanthoxylum bungeanum seed oil group,the apoptosis rate of Hep-2,the proportion of G1/G0 phase cells,the expression of Cleaved-caspase-3,Bax,LC3Ⅱ/I and Beclin-1,the IOD value of autophagic vesicles(t=4.931～39.507),the expression of Bcl-2 and ubiquitin-binding protein P62,the proportion of G2/M phase cells,the ratio of p-PI3K/PI3K,p-AKT/AKT and p-mTOR/mTOR in the high-dose zanthoxylum bungeanum seed oil+IGF-1 group were decreased(t=3.402～14.207),and the differences were statistically significant(all P<0.05).Conclusion Zanthoxylum bungeanum seed oil can promote autophagy and apoptosis of Hep-2 cells,and its mechanism may be related to the inhibition of PI3K/AKT/mTOR pathway activation.

[Purpose]To analyze the trends in incidence,mortality and potential life loss of esophageal cancer in Linzhou City of Henan Province from 2010 to 2019.[Methods]The data of esophageal cancer incidence and mortality from 2010 to 2019 were collected from Linzhou cancer registries.The crude incidence and mortality rates,age-standardized rates(ASR)by sex and age group,the potential years of life lost(PYLL),average potential years of life lost(APYLL),and potential years of life lost rate(PYLLR)were calculated.The average annual percentage change(AAPC)from 2010 to 2019 were analyzed with Joinpoint software.[Results]From 2010 to 2019,there were a total of 8 447 newly diagnosed cases and 6 475 deaths of esophageal cancer in Linzhou.The ASR incidence and ASR mortality of esophageal cancer in the total population,males,females all showed significant downward trends,with AAPCs of-3.97％,-4.35％,-3.29％and-3.78％,-2.68％,-4.95％,respectively(all P＜0.05).The crude incidence and mortality rates in all age groups also showed significant downward trends.The AAPCs of incidence rate for the age groups of 0～49,50～59,60～69,and ≥70 years old were-9.92％,-8.27％,-1.41％,and-3.86％,respectively(all P＜0.05),and the AAPCs of mortality rate were-950％,-12.36％,-2.61％,and-2.98％,respectively(all P＜0.05).From 2010 to 2019,the total PYLL caused by esophageal cancer was 60 880 person years,APYLL was 13.73 person years,and PYLLR was 5.77‰.The PYLL,APYLL,and the PYLLR of the total population and those stratified by sex all showed a decreasing trend(all P＜0.05).[Con-clusion]From 2010 to 2019,the incidence,mortality and potential life loss of esophageal cancer in Linzhou City all decreased,and the long-term effect and screening programs is significant.How-ever,the risk of esophageal cancer among men and the elderly is still relatively high,indicating that more targeted prevention and control strategies should be developed.

[Purpose]To analyze the trends of incidence and mortality of malignant tumors in Linzhou City of Henan Province from 2010 to 2019.[Methods]The incidence and mortality data of malignant tumors of Linzhou cancer registration areas from 2010 to 2019 were collected and evaluated for data quality.The crude incidence/mortality rates and age-standardized incidence/mortality rates by Chinese standard population(ASIRC/ASMRC)were calculated by sex,age and can-cer type.Joinpoint software was used to calculate the average annual percentage change(AAPC)to analyze the trends from 2010 to 2019.[Results]From 2010 to 2019,the crude incidence of malig-nant tumors in Linzhou City showed an upward trend,with an AAPC of 2.09％(95％CI:0.58％～3.63％),while the ASIRC tended to be stable.The incidence of malignant tumors showed a signifi-cant upward trend in the 15～29 and 60～69 age groups,and a significant downward trend in the 70～79 age group.From 2010 to 2019,the ASIRC of esophageal cancer and stomach cancer in both men and women showed a significant downward trend,while that of lung cancer and prostate cancer increased in men,and the incidences of thyroid cancer,uterus cancer,cervical cancer,lung cancer and breast cancer increased significantly in women.From 2010 to 2019,the crude mortality of malignant tumors in Linzhou showed a significant upward trend,with an AAPC of 1.18％(95％CI:0.88％～1.48％),while ASMRC showed a significant downward trend,with an AAPC of-1.63％(95％CI:-1.86％～-1.40％).The mortality increased in the group aged 80 and above,while the other age groups remained in a downward or stable state.From 2010 to 2019,the ASMRC of stomach cancer and esophageal cancer in both men and women showed a down-ward trend,while those of prostate cancer,and malignant tumors of the lip,oral cavity and pha-ryngeal in men increased,and that of ovarian cancer in women increased significantly.[Conclu-sion]The disease burden of malignant tumors in Linzhou City is still heavy.The incidence of common cancer types such as thyroid cancer,prostate cancer and lung cancer shows a significant-ly increasing trends from 2010 to 2019.

AIM:To research the regulatory effects of Butein on lipid deposition and inflammation in non-alcoholic steatohepatitis(NASH).METHODS:HepG2 cells were divided into solvent control group(1‰ dimethyl sulfoxide)and different concentration of Butein groups(1,3,6,12,25,50 μmol/L).The sur-vival rate of HepG2 cells were detected,the low and high concentration groups of butein were deter-mined.HepG2 cells were divided into solvent con-trol group(1‰ DMSO),model group(induction with 1 mmol/L free fatty acids in vitro),low and high concentration of Butein groups.After 24 hours'cell culture in each group,expression of triglyceride(TG),lipid synthesis-related factors SREBP-1c,FAS,SCD-1,lipid oxidation-related factors PPARα,CPT1A,MLYCD,and inflammatory factors TNF-α and MCP-1 in each group were detected.The model of NASH was constructed on C57BL/6J mouse by methionine choline deficiency diet(MCD).Normal diet group(ND group),model group(MCD group),low dose(100 mg·kg-1·d-1)and high dose(200 mg·kg-1·d-1)of Butein groups were established.After 4 weeks of feeding,pathological changes of liver tissues in each group were observed,contents of liver and serum TG and TC in each group were detected,and protein expression levels of lipid synthesis-related factors SREBP-1c,FAS,SCD-1 and lipid oxidation-related fac-tors PPARα,CPT1A,ACOX1 and MLYCD,inflammato-ry factors TNF-α and MCP-1in liver tissues were de-tected.RESULTS:Compared with solvent control group,Butein inhibited HepG2 cell growth when the concentration was ≥12 μmol/L(P＜0.05).Make 5 and 10 μmol/L as low and high concentration groups,re-spectively.Compared with the solvent control group,the intracellular TG content of HepG2 cells in butein group was significantly lower(P＜0.05).Com-pared with the model group,mRNA expressions of SREBP-1c,FAS,and SCD-1 was significantly lower(P＜0.05),while mRNA expression of PPARα,CPT1A,and MLYCD was significantly higher(P＜0.05),mRNA ex-pression of TNF-α,MCP-1 was significantly de-creased(P＜0.05)in high-concentration butein group.Compared with the model group,the expres-sion of SREBP-1c,FAS,SCD-1,MCP-1,TNF-α protein decreased and the expression of PPARα,CPT1A,MLYCD protein increased in the high concentration group.Compared with ND group,liver histological sections of MCD group showed obvious fat accumu-lation and inflammatory cell infiltration.Compared with the MCD group,the pathological manifesta-tions of fat accumulation and inflammatory cell infil-tration in the liver tissue of the butein groups were significantly improved,and the contents of TG and TC in the liver tissue of the butein groups were sig-nificantly decreased(P＜0.05),while the protein ex-pressions of PPARα,CPT1A,ACOX1,MLYCD were in-creased,and the protein expressions of SREBP-1c,FAS,SCD-1,TNF-α and MCP-1 were decreased in bu-tein groups.CONCLUSION:Butein can improve lipid deposition and inflammation in NASH livers.Its mechanism may be to reduce the expression of lipid synthesis-related factors,enhance the expression of lipid oxidation-related factors,and reduce the ex-pression level of inflammatory factors.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

In January 2021, a young male patient was admitted to the Department of Hand Surgery, Suzhou Ruihua Orthopeadic Hospital for a soft tissue degloving defect of distal segment of right thumb caused by machine compression. The thumb defect was reconstructed using a tiled flap with a right hallux nail flap and a lateral flap of left second toe. Donor site of the hallux nail flap was reconstructed by a lateral flap of right second toe, while the donor site of lateral flap of left second toe was covered by a skin graft of abdomen. At 1-year follow-up, the reconstructed nail was found excellent according to the established criteria. Two-point discrimination (TPD) was measured at 5 mm, and the affected thumb exhibited satisfactory flexion and extension and functions of thumb-to-palm and thumb-to-fingers oppositions. Donor sites in both feet achieved favorable appearance and function, with a Maryland foot score of 96. Only a linear scar was in abdominal donor site.

Objective:To compare postoperative inflammatory markers and surgical outcomes between open reduction and internal fixation versus double reverse traction closed reduction and percutaneous internal fixation for tibial plateau fractures.Methods:A retrospective analysis was conducted of the data of 229 patients with tibial plateau fracture who had been admitted to Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University from January 2023 to December 2023. There were 155 males and 74 females with an age of (48.7±10.9) years. According to the surgical methods, the patients were divided into 2 groups. A conventional group of 87 cases were treated by open reduction and internal fixation while a minimally invasive group of 142 cases treated with double reverse traction closed reduction and percutaneous internal fixation. The 2 groups were compared in terms of hematological indexes [white blood cell count (WBC), neutrophil count (NEUT), lymphocyte count (LYM), monocyte count (Mono), platelet count (PLT), and albumin (ALB)] and composite inflammatory indexes [neutrophil to lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), systemic inflammatory response index (SIRI)] before operation and on the first day after operation, intraoperative blood loss, operation time, fracture healing time, Hospital for Special Surgery (HSS) knee score and incidence of thrombosis.Results:There were no significant differences in baseline characteristics or treatment variables between the 2 groups, indicating comparability ( P > 0.05). All the 229 patients were followed up for (16.5±2.8) months. In each group, comparisons between preoperation and postoperation showed that LYM and ALB significantly decreased while WBC, NEUT, Mono, PLT, NLR, PLR, SII and SIRI significantly increased on the first day after operation ( P < 0.05). Preoperatively, there were no significant differences between the 2 groups in terms of hematological or composite inflammatory indexes ( P > 0.05). On the first day after operation, there was no significant difference in WBC, NEUT, LYM, ALB or NLR between the 2 groups ( P > 0.05), but Mono, PLT, PLR, SII and SIRI in the minimally invasive group were significantly lower than those in the conventional group ( P < 0.05). The intraoperative blood loss, operation time, fracture healing time, HSS knee score and incidence of thrombosis in the minimally invasive group were significantly better than those in the conventional group ( P < 0.05). Conclusion:In the treatment of tibial plateau fractures, compared with conventional open reduction and internal fixation, double reverse traction closed reduction and percutaneous internal fixation shows obvious advantages in reducing inflammatory indicators and leads to better surgical outcomes.

Hilar cholangiocarcinoma is insidious in onset and often causes obstructive jaundice due to bile stasis,leading to impaired liver function.For tumors with malignant obstructive jaundice,biliary drainage is often performed before surgery in clinical practice.Currently,the commonly used drainage methods are percutaneous transhepatic biliary drainage(PTBD)and endoscopic retrograde biliary drain-age(ERBD),but there are controversies over the advantages and disadvantages of the two drainage methods.PTBD drainage can often lead to tumor implantation metastasis,but the underlying mechanism remains unclear.We detected tumor cells in PTBD and ERBD bile samples from hilar cholangiocarcino-ma patients,subsequently explored their tumorigenicity and mechanisms through tumorsphere assay in vitro and xenograft tumor models in vivo.The experiments included benign gallstones group(30 cases)as a negative control,PTBD group(14 cases)and ERBD group(13 cases).Tumorsphere formation was i-dentified in 3 cases(23％)among the 13 cases of ERBD group,in 6 cases(42％)among the 14 cases of PTBD group,but there were no tumor cells or formed tumorspheres in the 30 cases of benign gallstone group.The tumor sphere formation ability of cells in the PTBD group was significantly higher than that in ERBD group.Subcutaneous xenograft tumor assays showed that tumor growth in the PTBD group was sig-nificantly higher than that in the ERBD group.Tumor cells in PTBD bile possessed stronger tumorigenici-ty compared with the ERBD group.Mechanically,stem cell transcription factor Nanog mRNA levels were significantly higher in the PTBD group compared to the ERBD group.Both tumorsphere formation and xenograft tumor growth were reduced by Nanog knockdown in three cases of the PTBD group,indicating the important roles of Nanog in tumorigenicity of PTBD group tumor cells.The half-life of Nanog mRNA was longer in PTBD group cells than in ERBD group cells,suggesting potential post-transcriptional regu-lation on Nanog mRNA.The Nanog m6A level was higher in PTBD group tumor cells compared to the ERBD group.Analysis of methyltransferases and demethylases,ALKBH5(α-ketoglutarate dependent dioxygenase alkb family homolog 5)mRNA levels were lower in the PTBD group than in the ERBD group and significantly correlated with the m6A level of Nanog.ALKBH5 knockdown led to an increase in the m6A level of Nanog,while ALKBH5 overexpression decreased the m6A level of Nanog.Dual-luciferase activity assays demonstrated that ALKBH5 knockdown significantly enhanced luciferase activity,whereas ALKBH5 overexpression reduced it.Further studies confirmed that ALKBH5 knockdown upregulated both the mRNA and protein levels of Nanog,whereas overexpressing ALKBH5 downregulated them.ALKBH5 mediated the demethylation modification of Nanog mRNA,and the lower levels of ALKBH5 expression in the PTBD group promoted Nanog's m6A modification.Overexpressing ALKBH5 decreased tumorsphere growth,while ALKBH5 knockdown increased it,which was subsequently reduced by the simultaneous Nanog knockdown again.In sum,tumor cells in PTBD and ERBD drainage bile from hilar cholangiocar-cinoma patients exhibited tumorigenicity.Compared to the ERBD group,tumor cells in PTBD bile with lower ALKBH5 expression levels enhanced Nanog's m6A modification to upregulate Nanog expression levels,resulting in stronger tumorigenicity.These findings are significant for elucidating propensity to tumor implantation metastasis from PTBD drainage.