Objective To investigate the impact of dexmedetomidine on epidural fibrosis after spinal surgery in rats through the transforming growth factor-β1(TGF-β1)signaling pathway.Meth-ods A total of 40 rats were selected,with 10 rats assigned to control group.The remaining 30 rats underwent spinal surgery modeling and were randomly divided into model group,dexmedetomidine group,and dexmedetomidine+TGF-β1 agonist group,with 10 rats in each.Rats with unsuccessful modeling were excluded,resulting in 9 rats in each group for subsequent analysis.Pathological char-acteristics of epidural scar tissue,fibroblast count,PCNA-positive cell expression rate,levels of in-flammatory markers[interleukin(IL)-6,IL-1β,IL-8],stress response indicators[malondialdehyde(MDA),superoxide dismutase(SOD)],and expression levels of mRNAs and proteins related to the TGF-β1 signaling pathway were observed and compared among the groups.Results Compared with the control group,the other three groups showed increased fibroblast count,elevated PCNA-positive cell expression rate,higher levels of IL-6,IL-1β,IL-8,and MDA,lower SOD levels,and increased expression levels of TGF-β1 mRNA,Smad3 mRNA,and TGF-β1 and Smad3 proteins,with statistically significant differences(P＜0.05).Compared with the model group,both the dexmedetomidine group and the dexmedetomidine+TGF-β1 agonist group exhibited decreased fibroblast count,re-duced PCNA-positive cell expression rate,lower levels of IL-6,IL-1 β,IL-8 and MDA,higher SOD levels,and decreased expression levels of TGF-β1 mRNA,Smad3 mRNA,and TGF-β1 and Smad3 proteins,with statistically significant differences(P＜0.05).Compared with the dexmedetomidine group,the dexmedetomidine+TGF-β1 agonist group showed increased fibroblast count,elevated PCNA-positive cell expression rate,higher levels of IL-6,IL-1 β,IL-8 and MDA,lower SOD lev-els,and increased expression levels of TGF-β1 mRNA,Smad3 mRNA,and TGF-β1 and Smad3 proteins,with statistically significant differences(P＜0.05).Conclusion Dexmedetomidine can significantly alleviate the inflammatory response and stress response after spinal surgery in rats and reduce postoperative epidural fibrosis by inhibiting the TGF-β1 signaling pathway.

OBJECTIVE To study the way in which hypidone hydrochloride(code:YL-0919)improves motor function after ischemic stroke(IS)and explore the related mechanism.METHODS Adult male SD rats were used to establish a middle cerebral artery occlusion(MCAO)model that simulated acute IS.All animals were randomly divided into four groups:sham group,MCAO group,MCAO+YL-0919 group,and MCAO+YL-0919+erastin(Era,ferroptosis inducer)group.The drug administration groups received the first ip injection 6 h after operation,followed by continuous ip injection once per day.After 7-10 d of drug administration,the effect of YL-0919 on motor function after IS were evaluated via neu-rological function test,adhesive-removal test,rotarod test,balance beam test and open field test.After 7 d of drug administration,TTC staining was used to detect the cerebral infarction area while the colo-rimetry method was used to measure the contents of glutathione(GSH),malondialdehyde(MDA),and ferrous ions(Fe2+)in the penumbra of the cerebral cortex.Western blotting was used to detect the expression levels of glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(xCT),acyl-CoA synthetase long-chain family member 4(ACSL4),and transferrin receptor 1(TFR1)in the cortical penumbra.RESULTS Compared with the sham group,the MCAO group showed higher neurological function scores(P<0.01),with notably prolonged time for tape removal and first contact with the right forepaw(P<0.01),spent significantly more time crossing the balance beam(P<0.01)but endured a notably shorter duration on the rotarod(P<0.01),reduced the movement distance in the open field(P<0.01),had a remarkably increased infarct area(P<0.01)but significantly level of GSH in the cortical penumbra region decreased(P<0.01),while MDA and Fe2+levels were markedly increased(P<0.01).Protein expression levels of GPX4 and xCT were reduced(P<0.05),while those of ACSL4 and TFR1 were elevated(P<0.05).Compared with the MCAO group,these changes were significantly reversed after YL-0919 administration.However,when Era and YL-0919 were administered simultaneously,the reversal effect of YL-0919 was significantly weakened.CONCLUSION YL-0919 can improve motor function impairment and reduce cerebral infarction areas in rats after IS,and the mechanism may be related to the inhibition of ferroptosis.

The overuse of antibiotics has led to the severe contamination of water bodies,posing a considerable hazard to human health.Therefore,the development of an accurate and rapid point-of-care testing(POCT)platform for the quantitative detection of antibiotics is necessary.In this study,Cerium oxide(CeO2)and Ferrosoferric oxide(Fe3O4)nanoparticles were simultaneously encapsulated into N-doped nanofibrous carbon microspheres to form of a novel nanozyme(CeFe-NCMzyme)with a porous struc-ture,high surface area,and N-doped carbon material properties,leading to a considerable enhancement of the peroxidase(POD)-like activity compared with that of the CeO2 or Fe3O4 nanoparticles alone.The POD-like activity of CeFe-NCMzyme can be quenched using L-Cysteine(Cys)and subsequently restored by the addition of a quinolone antibiotic(norfloxacin,NOR).Therefore,CeFe-NCMzyme was used as a colorimetric sensor to detect NOR via an"On-Off"model of POD-like activity.The sensor possessed a wide linear range of 0.05-20.0 μM(R2=0.9910)with a detection limit of 35.70 nM.Furthermore,a smartphone-assisted POCT platform with CeFe-NCMzyme was fabricated for quantitative detection of NOR based on RGB analysis.With the use of the POCT platform,a linear range of 0.1-20.0 μM and a detection limit of 54.10 nM were obtained.The spiked recoveries in the water samples were ranged from 97.73％to 102.01％,and the sensor exhibited good accuracy and acceptable reliability.This study provides a portable POCT platform for the on-site and quantitative monitoring of quinolone antibiotics in real samples,particularly in resource-constrained settings.

Objective:To observe the interobserver agreement of classification of macular degeneration in severe pathological myopia (PM) by ophthalmologists with different clinical experience.Methods:A retrospective study. From January 2019 to December 2021, 171 eyes of 102 patients with severe PM macular degeneration who were examined at Eye Center of Beijing Tongren Hospital of Capital Medical University were included in the study. The clinical data such as age, gender, axial length, spherical equivalent power, fundus color photography, and optical coherence tomography (OCT) were collected in detail. Six independent ophthalmologists (A, B, C, D, E, F) classified each fundus photography based on META-PM and ATN classification of atrophy (A) system and interobserver agreement was assessed by Kappa statistics. According to the classification standard of traction (T) in the ATN classification, the OCT images were interpreted and classified, in which T0 was subdivided into retinal pigment epithelium (RPE) and choroidal thinning, choroidal neovascularization (CNV) with partial RPE and choroidal atrophy, RPE, and choroidal atrophy. Lamellar macular hole can't be classified by ATN system, which was defined as TX. Kappa ( κ) test was used to analyze the consistency of classification results between physicians A, B, C, D, E and F. κ value ≤0.4 indicates low consistency, 0.4 < κ value ≤ 0.6 indicates moderate consistency, and κ value >0.6 indicates strong consistency. Results:Among the 171 eyes of 102 cases, there were 20 males with 37 eyes (19.6%, 20/102), and 82 females with 134 eyes (80.4%, 82/102); age was 61.97±8.78 years; axial length was (30.87±1.93) mm; equivalent spherical power was (-16.56±7.00) D. Atrophy (A) classification results in META-PM classification and ATN classification, the consistency of physician A, B, C, D, E and physician F were 73.01%, 77.19%, 81.28%, 81.28%, 88.89%; κ value were 0.472, 0.538, 0.608, 0.610, 0.753, respectively. In the ATN classification, the T0, T1, T2, T3, T4, and T5 were in 109, 18, 11, 12, 9, and 8 eyes, respectively; TX was in 4 eyes.Conclusions:There are differences in the consistency of classification of severe PM macular lesions among physicians with different clinical experience, and the consistency will gradually improve with the accumulation of clinical experience.

[摘 要] 目的：分析甲状旁腺激素样激素（PTHLH）基因与肺鳞状细胞癌（LSCC）患者预后及其与肿瘤微环境（TME）免疫细胞浸润的相关性。方法：通过UALCAN、TIMER、cBioPortal数据库在泛癌水平分析PTHLH在泛癌中的表达情况，运用Kaplan-Meier Plotter数据库分析PTHLH在LSCC中的表达及其与患者的预后关联。选用2017年1月至2020年12月在甘肃省肿瘤医院手术切除的24例LSCC患者的癌及癌旁组织标本，用qPCR和WB法分别检测LSCC组织中PTHLH mRNA和蛋白的表达，用qPCR法检测各种趋化因子和MHC分子的表达水平。采用TIMER数据库联合CIBERSORT反卷积法分析PTHLH基因表达和LSCC的TME中免疫细胞浸润的关系。结果：LSCC组织中PTHLH mRNA和蛋白的表达水平均显著高于癌旁组织（均P<0.05），且PTHLH高表达LSCC患者的OS明显缩短（P<0.01）。PTHLH的表达与LSCC患者TME密切相关（P<0.01）。PTHLH的表达与B细胞、CD8+ T细胞、CD4+ T细胞、中性粒细胞和DC等免疫浸润呈显著负相关（r=-0.142、-0.123、-0.224、-0.166、-0.213，均P<0.01）。PTHLH高表达抑制趋化因子、MHC分子的表达，从而抑制炎症反应、免疫浸润、抗肿瘤免疫反应等。PTHLH的表达与免疫检查点分子CTLA-4、PDCD1、TIGIT呈负相关（r=-0.340、-0.441、-0.38，均P<0.01）。结论：PTHLH与肿瘤免疫抑制相关，有望成为预测LSCC患者预后和免疫治疗效果的潜在生物标志物。

Objective To investigate the application prospect of the most extensive genome engineering pig internationally in preclinical xenotransplantation. Methods Porcine endogenous retrovirus (PERV) knockout combined with 3 major heterologous antigen gene knockouts and 9 humanized genes for inhibition of complement activation, regulation of coagulation disorders, anti-inflammatory and anti-phagocytosis were transferred into a pig (PERV-KO/3-KO/9-TG) as a donor, and the heart, liver and kidney were obtained and transplanted to 3 Rhesus macaque recipients respectively to establish a preclinical research model of pig-to-Rhesus macaque xenotransplantation. The functional status of xenografts after blood flow reconstruction was observed and the survival of recipients was summarized. The hemodynamics of xenografts were monitored. The change of hematological indexes of each recipient was compared. The histopathological manifestation of xenografts was observed. Results After the blood flow was reconstructed, all xenografts showed ruddy color, soft texture and good perfusion. The transplant heart, liver and kidney showed full arterial and venous blood flow and good perfusion at 1 d after operation. The postoperative survival time of heart, liver, and kidney transplant recipients was 7, 26, and 1 d, respectively. The levels of creatine kinase, creatine kinase isoenzyme, and lactate dehydrogenase increased in heart transplant recipient at 1 d after operation, and gradually recovered to near normal levels at 6 d after operation. All indexes increased sharply at 7 d after operation. The level of aspartate aminotransferase increased in liver transplant recipients at 2 d after operation, and the alanine aminotransferase basically returned to normal at 10 d after operation, but the total bilirubin continued to increase. Both aspartate aminotransferase and alanine aminotransferase increased at 12 d after operation, and reached a peak at 15 d after operation. The kidney transplant recipient developed mild proteinuria at 1 d after operation, and died of sudden severe arrhythmia. Histopathology showed that the tissue structure of cardiac and renal xenografts was close to normal, and liver xenografts presented with patchy necrosis, the liver tissue structure was disordered, accompanied by inflammatory damage, interstitial hemorrhage and thrombotic microangiopathy. Conclusions PERV-KO/3-KO/9-TG pig shows advantages in overcoming hyperacute rejection, mitigating humoral rejection and coagulation dysregulation. However, whether it can be used as potential donor for clinical xenotransplantation needs further evaluation.

Objective: To compare the curative effect of three different surgical methods: peritoneal varicocele ligation, peritoneal single-port laparoscopy and microscopy on varicocele. Methods: Retrospective analysis of the case data of 150 patients with varicocele treated in the Affiliated Hospital of Xuzhou Medical University from September 2016 to September 2018. The average age was 24.5 years, and the age range was 22-30 years. The patients were divided into three groups according to different surgical methods: open group, laparoscopy group and microscope group, with 50 cases in each group. Patients in the open group were treated with retroperitoneal spermatic cord ligation. Patients in the laparoscopic group were treated with single-hole laparoscopic laparoscopic surgery. Patients in the microscope group were treated with microscope surgery. Operation time, postoperative hospitalization time, hospitalization cost reserved arteries, surgical complications (such as testicular hydrocele, scrotal edema, epididymitis, testicular atrophy), recurrence, and semen quality improvement were compared between three groups. Measurement data were expressed as mean ± standard deviation(Mean±SD), the two comparisons used the t test, the comparison between the three groups used the analysis of variance, and the comparison between the count data groups using the Chi-square test. Results: The operation time of the patients in the microscope group [(52.52 ± 4.29) min] was longer than that of the open group [(36.60±3.69) min] and the laparoscopic group [(39.54±2.87) min]. The difference between the two groups was statistically significant (P<0.05); but the postoperative hospitalization time and hospitalization cost of patients in the microscope group [(2.16±0.95) d, (5 251 ± 300) yuan] were higher than those in the open group [(3.80±0.78) d, (64 75±415) yuan)]and the laparoscopic group [(3.28±1.01)d, (7 379±273) yuan] . The results of pairwise comparison showed that the difference between the microscope group, the open group and the laparoscopic group was statistically significant (P<0.05). Arterial preservation in the microscope group [47(94.0%)] were compared with the open group [35 (70.0%)], and laparoscopic group [30(60.0%)] had obvious advantages. Pairwise comparison results showed that the comparison between the microscope group and the open group and the laparoscopic group was statistically significant (P<0.05). After follow-up for six months, 2 cases were lost to follow-up in the microscope group, 1 cases were lost to the open group, and 5 case was lost to the unilateral laparoscopic group. 2(4.2%) patients had complications in the microscope group, and 14 (28.6%) patients had complications in the open group; 9 (20.0%) patients had complications in the laparoscopic group, and the total incidence of complications showed a pairwise comparison, the difference between the microscope group, the open group and the laparoscopic group was significant (P<0.05). The recurrence rate in the microscope group was 2.1% (1/48), the recurrence rate in the open group was 18.4% (9/49), and the recurrence rate in the laparoscopic group was 13.3% (6/45); the recurrence rate was compared in pairs, the difference between the microscope group, the open group and the laparoscopic group was significant (P<0.05) . The improvement rate of semen quality in the microscope group was 68.8% (33/48), the open group was 42.9%(21/49), the laparoscopic group was 55.6%(25/45), pairwise comparison results showed that the microscope group compared with the open group and laparoscopy group, the difference were statistically significant (P<0.05). Conclusions Microscopic surgery has less trauma, faster postoperative recovery, shorter operation cost and hospitalization time. Postoperative complications and recurrence, and improved semen quality are all superior to open spermatic vein ligation and single-hole umbilical laparoscopic surgery, it is a safe and effective way to treat varicocele.

Objective:To study the effect of left atrioventricular interphase (LAVI) via esophageal electrocardiogram on cardiac function after dual-chamber pacemaker implantation in patients with high-degree atrioventricular block.Methods:Using a prospective approach, 40 patients with high-degree atrioventricular block who would undergo dual-chamber pacemaker implantation from January 2017 to March 2018 in Department of Cardiovascular Medicine, Dalian Municipal Central Hospital Affiliated of Dalian Medical University were enrolled. All patients accepted esophageal electrocardiogram tests at 3 months after the implantation, to exam the interatrial conduction time (IACT) of sinus rhythm and pacing rhythm, and interventricular conduction time (IVCT). Then based on the outcome of the echocardiography test, the optimal atrioventricular delay (AVD) of the pacemaker of each patient was determined while the LAVI differed from 100 ms to 150 ms. The left ventricular ejection fraction (LVEF), peak speed of blood flow velocity in early mitral orifice diastole (E), E peak deceleration time (EDT), peak speed of early mitral annular diastolic movement (e′), isovolumic relaxation time (IVRT) and left atrial volume (LAV) were tested by echocardiogram before implantation, before AVD adjustment at 3 months after implantation, after AVD adjustment at 3 months after implantation, and 6, 12, and 18 months after implantation. Then, the left atrial volume index (LAV/body surface area) and E/e′ were calculated.Results:Among the 40 patients, the IACT of sinus rhythm was (55.55 ± 10.33) ms, the IACT of pacing rhythm was (93.95 ± 12.77) ms, and the mean IVCT was (63.20 ± 17.84) ms; the optimal LAVI was 110 to 150 (132.00 ± 10.43) ms, and notably, the optimal LAVI between 120 and 140 ms was 82.5% (33/40). The LVEF, EDT, IVRT, left atrial volume index and E/e′ from before AVD adjustment of 3 months after implantation to follow-up endpoint (18 months after implantation) were significantly improved compared with those before implantation, and there were statistical differences ( P<0.01); the EDT and IVRT after AVD adjustment at 3 months after implantation were significantly improved than those before AVD adjustment at 3 months after implantation: (142.15 ± 35.58) ms vs. (125.94 ± 31.13) ms and (119.52 ± 22.15) ms vs. (133.92 ± 23.87) ms, and there were statistical differences ( P<0.05); the IVRT and left atrial volume index 18 months after implantation were significantly improved compared with those before AVD adjustment at 3 months after implantation: (122.07 ± 16.99) ms vs. (133.92 ± 23.87) and 32.94 ± 3.22 vs. 35.43 ± 5.76, and there were statistical differences ( P<0.05). Conclusions:Optimizing the LAVI after dual-chamber pacemaker implantation via esophageal electrocardiogram can improve the long-term prognosis of patients with high-degree atrioventricular block.

Objective To investigate the effects of Lactobacillus rhamnosus GG (LGG) colonization in early life on intestinal barrier and intestinal development in offspring mice and its possible mechanism.Methods Six C57BL/6 pregnant mice with the same conception time of 6 weeks were selected and randomly divided into experiment group given 108 cfu/ml LGG live bacteria and control group given LGG inactivated bacteria by gavage from the 18th day of pregnancy until natural birth.The progeny mice in the two groups were continued to be gavaged with 107 cfu/ml of LGG live bacteria or LGG inactivated bacteria on days 1-5 of birth.The body weight changes of 3 week'progeny mice were recorded.The colonization of LGG bacteria in offspring mice was detected at 2nd and 3rd weeks.The mRNA of intestinal proinflammatory cytokines and tight junction molecules were evaluated by real-time PCR method.HE,immunohistochemistry,immunofluorescence staining and enzyme-linked immunosorbent assay were used to evaluate the intestinal barrier of 3-week old off spring mice.Results Compared with the control group,the progeny mice of the experiment group showed no significant difference in body weight at the first week,and the body weight increased at the second week and the third week [2ndweek:(3.790±0.240) g vs.(4.326±0.140) g,t=3.707,P=0.006;3rd week:(7.295±0.326) g vs.(8.040±0.370) g,t=3.130,P=0.011].LGG colonization can be detected only in the feces of progeny mice in the experiment group.Intestinal colonization can promote the growth of small intestine villi and colon crypt depth [jejunum:(320.000±22.514) μm vs.(265.100±15.611) μm,t=8.258,P＜0.001;ileum:(150.500±13.099) μm vs.(111.000±11.308) μm,t=9.958,P＜0.001;colon:(295.000±15.209) μm vs.(233.100±6.678) μm,t=9.129,P＜0.001].Compared with the control group,the number of goblet cells in the colonic crypt of the experiment group increased (11.62 ± 0.780 vs.35.24 ±1.370,t=15.000,P＜0.001),and the relative mRNA expression levels of pro-inflammatory factors as IFN-γ (1.280±0.232 vs.0.512±0.206,t=4.970,P=0.001),IL-6 (1.364±0.271 vs.0.941±0.215,t=2.452,P=0.040),IL-10 (1.341±0.320vs.0.744±0.294,t=2.762,P=0.025)andTNF-α (3.702±0.150 vs.2.581±0.500,t=2.553,P=0.034) in the experiment group decreased;the expression levels of the intimate tight junction molecules (Claudin3) (1.283±0.152 vs.1.881±0.172,t=4.932,P=0.001) and the atresia protein molecule (Occludin) (1.164±0.342 vs.0.812±0.224,t=3.67,P=0.016) significantly increased.Conclusion Early life LGG colonization protects the intestinal barrier by inhibiting lowgrade intestinal inflammation.This study will lay the experimental foundation for the supplementation of probiotics in early life so as to prevent intestinal diseases.

BACKGROUND:How to control the orderly formation of colage in skin repair and scarring process is worthy of attention. OBJECTIVE: To investigate the effect of basic fibroblast growth factor (bFGF) combined with insulin-like growth factor 1 (IGF-1) on the proliferation and colagen synthesis of rat bone marrow mesenchymal stem celsin vitro. METHODS:Rat bone marrow mesenchymal stem cels were isolated and cultured to induce adipogenic differentiation assessed by oil red O staining and osteogenic differentiation identified by alizarin red stainingin vitro. Passage 3 cels were cultured in the medium containing bFGF, IGF-1, combination of them or the control fluid, respectively. MTT assay was used to detect cel proliferation at 12, 24, 48, 72 and 96 hours of culture. The expression of type I colagen and type III colagen were detected by RT-PCR and western blot after 10 days of incubation. RESULTS AND CONCLUSION:Compared with the control group, bFGF or IGF-1 alone significantly promoted the proliferation of bone marrow mesenchymal stem cels, and inhibited the expression of type I colagen and type III colagen. After combined use of bFGF and IGF-1, the proliferation of bone marrow mesenchymal stem cels was improved more significantly, and the expression of type I colagen and type III colagen returned to normal levels. These findings indicate that the combination of IGF-1 and bFGF can promote proliferation of bone marrow mesenchymal stem cels and restrain the expression of type I colagen and type III colagen, which may be helpful for control and repair of scar formation during wound healing.