Esophageal cancer is one of the malignant tumors that poses a threat to human health, with both high incidence and malignancy. Currently, surgery following neoadjuvant chemoradiotherapy is the standard treatment for locally advanced esophageal cancer; however, the long-term prognosis remains unsatisfactory. In recent years, inhibitors of programmed death protein-1 (PD-1) and its ligand (programmed death ligand-1, PD-L1) have achieved breakthrough progress in other solid tumors, and research on esophageal cancer is gradually being conducted. With the demonstration of good efficacy of PD-1/PD-L1 inhibitors in the first-line and second-line treatment of advanced unresectable esophageal cancer, their incorporation into neoadjuvant treatment regimens has become a hot topic. Therefore, this article reviews the mechanism of action of PD-1/PD-L1 inhibitors and their application in the neoadjuvant treatment of esophageal cancer.

Objective To study the protective effect of Irisin in doxorubicin(Dox)induced-Cardiomyopathy and its possible mechanism.Methods AC 16 cells were used to construct Dox injury model and divided into control group(AC 16 cells were cultured with complete medium),Irisin group(AC16 cells were treated with 10 ng·L-1 Irisin for 24 h),Dox group(AC 16 cells were treated with 4 μmol·L-1 Dox for 24 h),Dox+Irisin group(AC 16 cells were pretreated with 10 ng·L-1 Irisin for 2 h,and then treated with 4 pmol·L-1 Dox for 24 h).Cell counting kit-8(CCK-8),terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL)and lactate dehydrogenase(LDH)were used to detect the proliferation,apoptosis and mortality of AC 16 cells.Western blot was used to detect the expression levels of nuclear factor-κB(NF-κB)signaling pathway and apoptotic factors B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax)and caspase-9 protein.Mito-Tracker Red CMXRos probe was used to detect mitochondrial membrane potential.Results In the contrl group,Irisin group,Dox group,Dox+Irisin group,the rate of apoptosis were(0.97±0.09)％,0,(42.80±6.70)％,(11.74±1.79)％;the expression of Bax protein were 0.85±0.01,0.36±0.02,1.15±0.07,0.37±0.11;the expression of caspase-9 protein were 0.52±0.02,0.59±0.03,1.11±0.02,0.67±0.08;the expression of Bcl-2 protein were 1.01±0.04,1.05±0.25,0.43±0.02 and 0.99±0.30;the probability of mitochondrial damage were(0.02±0.01)％,(0.5±0.15)％,(38.6±2.39)％,(1.58±0.54)％.The difference of the above indexes between the contrl group and the Dox group were statistically significant(all P＜0.05);the difference between Dox group and Dox+Irisin group were statisically significant(all P＜0.05).Conclusion Irisin could reduce the expression level of Bax,caspase-9,p-NF-κB,and p-mTOR caused by Dox,increase the expression level of Bcl-2,ameliorate the myocardial damage caused by Dox,and reduce cardiotoxicity.

Objective:To study the feasibility and efficacy of pericranial flaps for the repairs of large anterior skull base defects.Methods:The average length of the pericranial flaps needed for skull base repair was determined with computed tomography measurements in 20 adults and anatomical dissections in 5 cadaver specimen. A series of patients who underwent endoscopic skull base surgeries and subsequent reconstructions with pericranial flaps at the Department of Otolaryngology Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People′s Hospital from 2016 to 2022 were retrospectively reviewed. There were 19 males and 6 females, aged from 11 to 59 years, including 13 cases of cerebrospinal fluid (CSF) rhinorrhea (12 traumatic) and 12 cases of sinonasal skull base tumors. Descriptive statistical methods were used.Results:The mean areas of anterior skull base, sellar, and clival defects were 16.13, 14.03 and 13.12 cm 2, respectively, and the mean pericranial flap lengths were (18.77±3.44)mm, (133.99±5.08)mm, (181.76±6.31)mm, respectively. Among sinonasal skull base neoplasms, the pathologies included olfactory neuroblastoma ( n=6), squamous cell carcinoma ( n=3), chondrosarcoma ( n=1), osteosarcoma ( n=1), and invasive schwannoma ( n=1), in whom 8 patients underwent adjuvant radiotherapy after surgery. One patient (7.7%) had acoustic neuroma-related CSF leak before radiotherapy. All 25 patients successfully underwent skull base reconstruction without complications such as CSF leak, intracranial infection, forehead wrinkles disappearance, or scalp necrosis. All flaps survived well with no CSF leaks within the follow-up period of 2-4 years. Conclusion:Pericranial flap is a safe choice for large anterior skull base defects following resection of sinonasal skull base neoplasms and complex traumatic CSF leaks when endonasal flaps are not available.

Surgery is the preferred treatment for resectable esophageal cancer, but in locally advanced esophageal cancer, the effect of surgery alone is not ideal, so surgery-based comprehensive treatment is the best option. Neoadjuvant therapy has become a standard treatment in the treatment of locally advanced resectable esophageal cancer. Neoadjuvant therapy includes neoadjuvant chemotherapy, radiochemotherapy, immunotherapy, targeted therapy, etc. With the significant efficacy and acceptable toxicity of immunotherapy in the first-line and second-line treatment of advanced esophageal cancer, neoadjuvant immunotherapy has become a research hotspot of locally advanced resectable esophageal cancer. This article reviews the latest research progress and some limitations of neoadjuvant immunotherapy in locally advanced resectable esophageal cancer.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To develop a matrix metalloproteinase(MMP)-responsive hyaluronic acid(HA)-based controlled-release material for brain-derived neurotrophic factor(BDNF)to provide a novel therapeutic strategy for intervention and repair of traumatic brain injury(TBI).Methods HA was modified with amination,followed by condensation with Suflo-SMCC carboxyl group to form amide,and then linked with glutathione(GSH)to synthesize HA-GSH.The recombinant glutathione S-transferase(GST)-tissue inhibitor of metalloproteinase(TIMP)-BDNF(GST-TIMP-BDNF)expression plasmid was constructed using molecular cloning technique with double enzyme digestion by Bam H Ⅰ and Eco R Ⅰ.The recombinant GST-TIMP-BDNF protein was expressed in the Escherichia coli prokaryotic expression system,and purified by ion exchange chromatography,confirmed by Western blotting.MMP diluents were supplemented with PBS,MMP inhibitor marimastat,and varing concentrations(0.4,0.6,0.8 mg/ml)of GST-TIMP-BDNF or GST-BDNF.MMP-2 activity was analyzed using an MMP activity detection kit to evaluate the inhibitory effect of the recombinant protein on MMP.Primary rat neurons were extracted and cultured to establish an iron death model induced by RSL3.The effect of recombinant protein GST-TIMP-BDNF on neuronal injury was detected by immunofluorescence staining.Results MRI hydrogen spectrum identification confirmed the successful synthesis of HA-GSH.Western blotting results showed the successful expression of the recombinant protein GST-TIMP-BDNF containing the GST tag using the E.coli prokaryotic expression system.MMP activity detection results indicated that the recombinant protein GST-TIMP-BDNF had a superior inhibitory effect on MMP-2 activity compared to GST-BDNF(P<0.05).Immunofluorescence staining results showed a significant increase in fluorescence intensity in rat neurons treated with GST-TIMP-BDNF after RSL3 induction(P<0.05).Conclusion A MMP-responsive HA-based BDNF controlled-release material has been successfully developed,exhibiting a protective effect on neuron damage.

Background::Risk assessment and treatment stratification for three-vessel coronary disease (TVD) remain challenging. This study aimed to investigate the prognostic value of left atrial volume index (LAVI) with the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score II, and its association with the long-term prognosis after three strategies (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], and medical therapy [MT]) in patients with TVD.Methods::This study was a post hoc analysis of a large, prospective cohort of patients with TVD in China, that aimed to determine the long-term outcomes after PCI, CABG, or optimal MT alone. A total of 8943 patients with TVD were consecutively enrolled between 2004 and 2011 at Fuwai Hospital. A total of 7818 patients with available baseline LAVI data were included in the study. Baseline, procedural, and follow-up data were collected. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was a composite of all-cause death, myocardial infarction (MI), and stroke. Secondary endpoints included all-cause death, cardiac death, MI, revascularization, and stroke. Long-term outcomes were evaluated among LAVI quartile groups. Results::During a median follow-up of 6.6 years, a higher LAVI was strongly associated with increased risk of MACCE (Q3: hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.06-1.37, P = 0.005; Q4: HR 1.85, 95%CI 1.64-2.09, P <0.001), all-cause death (Q3: HR 1.41, 95% CI 1.17-1.69, P <0.001; Q4: HR 2.54, 95%CI 2.16-3.00, P <0.001), and cardiac death (Q3: HR 1.81, 95% CI 1.39-2.37, P <0.001; Q4: HR 3.47, 95%CI 2.71-4.43, P <0.001). Moreover, LAVI significantly improved discrimination and reclassification of the SYNTAX score II. Notably, there was a significant interaction between LAVI quartiles and treatment strategies for MACCE. CABG was associated with lower risk of MACCE than MT alone, regardless of LAVI quartiles. Among patients in the fourth quartile, PCI was associated with significantly increased risk of cardiac death compared with CABG (HR: 5.25, 95% CI: 1.97-14.03, P = 0.001). Conclusions::LAVI is a potential index for risk stratification and therapeutic decision-making in patients with three-vessel coronary disease. CABG is associated with improved long-term outcomes compared with MT alone, regardless of LAVI quartiles. When LAVI is severely elevated, PCI is associated with higher risk of cardiac death than CABG.

Objective:To explore the therapeutic effect and psychological influence of biofeedback pelvic floor muscle training on fecal incontinence after anorectal surgery in children.Methods:A retrospective case-control study.A total of 37 children who were admitted to the First Affiliated Hospital of Xinxiang Medical University from July 2021 to April 2023 for fecal incontinence after anorectal surgery were collected.Biofeedback pelvic floor muscle training was performed with a Laborie biofeedback therapy device, and pelvic floor muscle contraction function exercise was performed no less than 200 times a day.The anal canal current intensity, basic motion myoelectric value, contractile myoelectric difference and continuous anal contraction time were measured at before treatment, at the end of 1 course, 1 month and 1 year after treatment.Ten healthy children of the same age were selected as the healthy control group.The Strengths and Difficulties Questionnaire was used for psychological evaluation at before treatment and 1 year after treatment.Paired sample t test and independent sample t test were used to compare and analyze the results of this study. Results:Before treatment, at the end of 1 course, 1 month and 1 year after treatment, the anal canal current intensity of children with fecal incontinence were(11.32±1.92) mA, (10.22±1.28) mA, (8.45±1.09) mA, and(7.80±1.23) mA, respectively; the anal canal basic motion myoelectric value were(235.58±55.03) μV, (185.65±34.30) μV, (124.81±36.56) μV, and(93.99±28.29) μV, respectively; the anal canal contractile myoelectric difference were(45.64±20.38) μV, (64.20±16.59) μV, (93.63±25.53) μV, and(109.83±26.95) μV, respectively; the continuous anal contraction time were(1.27±0.43) s, (1.58±0.40) s, (2.04±0.39) s, and(2.47±0.38) s, respectively.These parameters before treatment, at the end of 1 course and 1 month after treatment were significantly different from those in the healthy control group[(7.20±1.09) mA, (88.65±21.76) μV, (120.73±27.57) μV, (2.68±0.29) s](all P<0.05).These parameters at 1 year after treatment were significantly different from those before treatment and 1 month after treatment(all P<0.05).However, there were no significant differences in these parameters between the healthy control group and the treatment group at 1 year after treatment(all P>0.05).There were statistically significant differences in emotional symptoms, hyperactivity symptoms, peer interaction, prosocial behavior and difficulty scores before and after treatment[(3.46±1.88) points vs.(2.59±1.32) points, (5.78±2.12) points vs.(3.70±1.78) points, (3.05±1.72) points vs.(2.49±1.30) points, (7.30±1.54) points vs.(8.27±1.39) points, (21.57±4.57) points vs.(18.54±3.14) points](all P<0.05). Conclusions:Biofeedback pelvic floor muscle training is a reliable and non-invasive method for the treatment of postoperative fecal incontinence after anorectal surgery in children and can effectively relieve the psychological and behavioral problems caused by fecal incontinence in children.

Objective To clarify the understanding of types of laboratories and manufacturers for GB 9706.1-2020 Medical electrical equipment-Part 1:General requirements for basic safety and essential performance by laboratory proficiency testing for creepage distance and electrical clearance test.Methods An operation guide was formed according to the testing program in GB 9706.1-2020,and the homogeneity and stability of the samples were evaluated according to CNAS-GL003:2018 Guidance on Evaluating the Homogenneity and Stability of Samples Used for Proficiency Testing.Robust statistic methods were used to assess the quantitative parameters of the test results of the participating laboratories according to the requirements in GB/T 28043-2019 Statistical methods for use in proficiency testing by interlaboratory comparison;the results reported by the expert laboratories were used as the specified values of the qualitative parameters.SPSS 25.0 statistical software was used for data analysis.Results All the results of the crreepage distance and electrical clearance tests met the requirements for homogeneity and stability.Of the 46 laboratories involved in,37 ones did have comprehensive satisfactory determinations while the remained 9 ones not.Conclusion Some laboratories don't behave well in understanding the standard,which have to be reformed accordingly to enhance their proficiencies.[Chinese Medical Equipment Journal,2024,45(10):54-59]

This study was aimed at exploring the epidemiological characteristics of plague,and the evolutionary relation-ships among the isolated plague strains in the Yunnan border area,to provide clues for further studying epidemic causes and ep-idemiological patterns.Plague epidemic data in the border area during the second epidemic period(1982-2007)were collected and analyzed with descriptive epidemiological methods.Whole genome sequences of 262 strains of Yersinia pestis in the border area were obtained for phylogenetic analysis.Plague outbreaks occurred in 17 counties(cities)among 25 border counties(cit-ies);a total of 552 epidemic foci and 123 human cases were identified.The 1.ORI2,1.ORI3,1.IN3,2.ANT and 2.MED geno-types were identified among Yersinia pestis isolated from the Yunnan border area,among which the 1.ORI2 population was dominant.A total of 258 strains of Yersinia pestis from the 1.OR12 population belonged to four subclusters.The Myanmar and Vietnam clade was embedded within the Yunnan clade in the overall phylogeny.The above results indicated that during the sec-ond period of the epidemic,the intensity of plague epidemics in Yunnan's border areas was high,showing a trend of devel-opment from west to south and east.Our findings indicated a risk of cross-border transmission of plague between Yunnan and neighboring countries;therefore,the surveillance,pre-vention,and control of plague in border areas should be strengthened.