AIM:To study the effect of neuregulin-1 ( NRG-1β) or captopril alone and their combination on myocardial cell apoptosis and related gene expression in rats with chronic heart failure .METHODS:Young male Sprague-Dawley rats were randomly divided into sham-operated group, heart failure group, NRG-1βgroup, captopril group and combined treatment group .The volume overloaded heart failure model in the rats was established by aortocaval fistula .The cardiac function was evaluated by determining the changes of hemodynamics and plasma BNP level .The apoptotic index ( AI) of myocardial cells was assayed by TUNEL .The protein levels of p-Akt, Bax and Bcl-2 in left ventricular tissue were detected by Western blot .RESULTS: The LVEDP, AI and the expression of Bax were significantly lower in NRG-1βgroup, captopril group and combined treatment group than those in heart failure group ( P<0.05 ) , while the values of ±dp/dtmax and the protein levels of p-Akt and Bcl-2 were significantly higher in NRG-1βgroup, captopril group and com-bined treatment group than those in heart failure group (P<0.05).The effect of combined treatment group was more signifi-cant ( P<0.05) than that in NRG-1βgroup and captopril group .CONCLUSION: Neuregulin-1βor captopril alone and the combination of them effectively improve the cardiac function and inhibit myocardial cell apoptosis in chronic heart failure rats.The therapeutic effect of combination of NRG-1βand captopril is better than that of NRG-1βor captopril alone .

Objective To investigate the relationship between occult pancreaticobiliary reflux (OPR) and biliary diseases.Methods Forty-four patients with primary biliary diseases was enrolled,and serum amylase level was determined,and the bile in common bile duct (CBD) was collected to measure the amylase level,then the △ amylase was calculated,which equals bile amylase level minus serum amylase level.OPR was confirmed if bile amylase level was higher than serum amylase level,otherwise it would be defined as the control group.Results Among the 44 patients with primary biliary diseases,the incidence of OPR was 72.7％ (n =32).The bile and serum amylase activity of patients with OPR were (1 513 ± 2 725),(44 ± 21)U/L;and they were (18 ± 14) and (38 ± 17) U/L in the control group.The bile amylase level in OPR group was significantly higher than that in the control group,and the difference was statistically significant (P ＜ 0.05),while there was no significant difference in serum amylase activity between the two groups.The incidence of OPR in patients with CBD stones was 100％,and the bile amylase activity was (1 048 ± 1 317) IU/L,and the △ bile amylase activity was (996 ± 1 322) U/L;the incidence of OPR in patients with choledocholithiasis and cholecystolithiasis was 75％,and the bile amylase activity was (2 457 ± 3 312),the △ amylase activity was (2 412 ± 3 320)IU/L;and the corresponding values in patients with gallbladder stones were 80％,(95 ± 82),(57 ± 76)IU/L;and the corresponding values in patients with bile duct cancer were 50％,(73 ± 51),(40 ± 37)U/L.Conclusions The occurrence of OPR is closely related to CBD stones only,CBD stones and gallbladder stones,and it may be one of the main pathogenic factors of bile duct stones.

Objective To investigate the influence of combined thrombolysis therapy on clinical effects for short -and long -term of patients with acute cerebral infarction caused by sudden occlusion of anterior and posterior circulation.Methods 75 patients with cerebral infarction caused by sudden occlusion of anterior and posterior circulation were chosen and divided into A group (46 patients)with sudden occlusion of anterior circulation and B group (29 patients)with sudden occlusion of posterior circulation by comprehensive therapy for intra -arterial thrombolysis combined with mechanical crushing and dilation.The recanalization rate,the excellent and good rate of ADL -Barthel score,NIHSS score and GCS score before and after treatment,intracranial hemorrhage rate and mortality rate of two groups were compared.Results The recanalization rates of A group and B group were 50.00%(23 /46), 89.66%(26 /29).After treatment,the excellent and good rates of ADL -Barthel score of A group and B group were 58.70%(27 /46),62.07%(18 /29).The recanalization rate of B group was significantly higher than A group(χ2 =7.44,P <0.05).There was no significant difference in the excellent and good rate of ADL -Barthel score after treatment between the two groups(χ2 =1.21,P >0.05).After treatment,the NIHSS scores of A group and B group were (8.66 ±2.48)points,(8.72 ±2.51 )points,the GCS scores of A group and B group were (12.89 ± 3.61)points,(13.10 ±3.72)points.There were no significant differences in NIHSS score and GCS score after treatment between the two groups(t =1.47,1.52,all P >0.05).After treatment,the intracranial hemorrhage rate of B group was significantly lower than A group (χ2 =8.16,P <0.05 ).There was no significant difference in the mortality rate between the two groups(χ2 =0.98,P >0.05).Conclusion Compared with acute cerebral infarction caused by sudden occlusion of anterior circulation,combined thrombolysis therapy in treatment of patients with sudden occlusion of posterior circulation has advantages including higher recanalization rate and lower risk of intracranial hemorrhage.

Objective To construct an eukaryotic expression vector of human telomerase reverso transcriptase (hTERT) gene specific shRNA, and investigate the effect of pshRNA-hTERT combined with γ-irradiation on telomerase activity and DNA damage. Methods The recombinant expression plasmid pshRNA-hTERT was constructed and transfected into Hep-2 cells. The telomerase activity was examined by the PCR-hased telomeric repeat amplification protocol (TRAP). DNA single-stranded break (SSB) and the DNA double-stranded break (DSB) were detected by Comet assay. The xenograft model of human laryngeal carcinoma with the same genetic background and different radiosensitivity (Hep-2 and Hep-2R) was established in nude mice. The mixture of pshRNA-hTERT and liposome was injected to the transplanted tumor to observe the inhibition of the tumor growth. The cell apoptosis was detected by TUNEL. The hTERT protein expression was determined by streptavidin-peroxidase conjugated method (AP). Results Recombinant expression plasmid pshRNA-hTERT was successfully constructed and transfected into Hep-2 cells. The hTERT expression inhibition rate reached 60.78 %. pshRNA-hTERT not only inhibited telomerase activity of Hep-2 inehiding the increase of telomerase activity induced by γ-irradiation, but also inhibited the repair of the SSB and DSB induced by irradiation in the human laryngeal carcinoma xenograft in nude mice with the same genetic background and different radiosensitivity. The pshRNA-hTERT combined with γ-irradiation could inhibit the growth of transplanted tumor (Hep-2: EPO = 1.79; Hep-2R: EPO = 2.01) with reduced telomerase activity and hTERT protein expression. Conclusions The eukaryotic expression vector pshRNA-hTERT could enhance the radiosensitivity of Hep-2 cells in vitro and the human laryngeal carcinoma xenograft in nude mice which had the same genetic background with different radiosensitivity.

Objective:To investigate the modulatory function of interleukin-7 (IL-7)/CD 127 signaling pathway on CD 8+T cells in patients with myasthenia gravis (MG). Methods:Fifty-seven treatment-naive MG patients who were hospitalized in Department of Neurology, Nanyang Central Hospital between 2017 and 2020 as well as 35 healthy controls were enrolled. Peripheral blood was collected, while plasma and peripheral blood mononuclear cells were isolated. Plasma IL-7 and soluble CD 127 (sCD 127) were measured by enzyme linked immunosorbent assay (ELISA). Membrane-bound CD 127 (mCD 127) percentage in CD 8+T cells was measured by flow cytometry. The differences of above indices between different gender, onset age, afflicting with thymoma, or different Osserman type and their correlation with Quantitative Myasthenia Gravis (QMG) score were analyzed. Purified CD 8+T cells from MG patients were stimulated with recombinant human IL-7 (5 μg/L). Changes of sCD 127 and mCD 127 level were analyzed. Levels of perforin, granzyme B, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) in the cultured supernatants were measured by ELISA. Immune checkpoint molecules mRNA in CD 8+T cells was semi-quantified by real-time fluorescence quantitative polymerase chain reaction. Results:Plasma IL-7 level was up-regulated in MG patients compared with controls [(293.4±74.7) pg/ml vs (233.8±70.8) pg/ml, t=3.78, P<0.001], while sCD 127 level was down-regulated in MG patients compared with controls [(102.7±13.7) pg/ml vs (131.2±20.9) pg/ml, t=7.91, P<0.001]. Peripheral CD 8+T cells percentage was up-regulated in MG patients compared with controls (35.4%±7.1% vs 30.2%±7.5%, t=3.31, P=0.001), and mCD 127+CD 8+T cell percentage was also elevated (45.5%±7.7% vs 34.7%±11.5%, t=5.44, P<0.001). There were no significant differences of above indices between different gender, onset age, afflicting with thymoma, or different Osserman type. There was no significant correlation between above indices and QMG score. There were no significant differences of sCD 127 in cultured supernatants, mCD 127+CD 8+T cell percentage, or immune checkpoint molecules mRNA expression between CD 8+T cells from MG patients with and without IL-7 stimulation. IL-7 stimulation promoted the secretion of perforin [(208.1±67.2) pg/ml vs (168.8±46.2) pg/ml, t=2.16, P=0.038], granzyme B [(941.8±273.9) pg/ml vs (782.4±137.2) pg/ml, t=2.33, P=0.025], and IFN-γ [(19.1±5.2) pg/ml vs (15.3±4.5) pg/ml, t=2.47, P=0.018] by CD 8+T cells. However, there was no remarkable difference of TNF-α production between CD 8+T cells with and without IL-7 stimulation. Conclusion:Elevated IL-7-mediated signaling pathway enhanced the secretion of cytotoxic molecules and cytokines by CD 8+T cells, leading to increased activity of CD 8+T cells in MG patients.

Objective: To evaluate the safety and therapeutic efficacy of clinical pathways(CP)for cerebral infarction in patients aged 75 years and above. Methods: A cohort of 363 cerebral infarction patients aged 75 years and above after excluding clinical variants were recruited from January 2016 to June 2018 at the neurology department of Nanyang City Center Hospital.Patients were randomly divided into the CP group(n=184)and the control group(n=179). The day-90 modified Rankin scale score(mRS), mortality, incidences of complications, length of hospital stay, total hospital costs and drug costs were compared between the two groups. Results: The proportion of patients with mRS 0-1 was higher in the CP group than in the control group(77.2% or 142/184 vs.55.3% or 99/179, χ²=19.443, P=0.000). The incidences of pulmonary infection(23.9%, 44/184)and deep venous thrombosis(14.7%, 27/184)were lower in the CP group than in the control group(42.5%, 76/179 & 29.1%, 52/179; χ²=14.101, 11.014, P=0.000, 0.001). There was a significant difference in mortality between the two groups[4.9%(9/184)vs.11.2%(20/179), χ²=4.871, P=0.027]. There was no significant difference in the other incidences of complications between the groups(P>0.05). Hospital stay length(18.3±2.9) d, total cost(2.72±0.42)×10⁴ yuan, and drug cost(0.87±0.29)×10⁴ yuan in the clinical pathway group were lower than those in the control group[(22.8±4.4)d, (3.55±0.81)×10⁴ yuan, (1.42±0.29)×10⁴ yuan](t=11.546, 12.168 and 18.335, all P=0.000). Conclusions The adoption of clinical pathways can improve medical quality, shorten hospitalization days and reduce hospitalization costs and medical costs in elderly patients with cerebral infarction.

Objective:To analyze and summarize the clinical and genetic features of Noonan syndrome (NS) caused by mutations in the leucine zipper-like transcription regulator 1 ( LZTR1) gene. Methods:The retrospective study analyzed a patient who was examined at the Center of Prenatal and Hereditary Disease Diagnosis, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University in January 2021 because of fetal nuchal translucency thickening and a previous history of problematic pregnancies. Subsequently, the patient was diagnosed with Noonan syndrome (NS) through whole exome sequencing. Using keywords such as "Noonan syndrome," "Leucine zipper-like transcription regulator 1", and " LZTR1", clinical and genetic characteristics of NS derived from LZTR1 mutations were summarized by extracting relevant literature from China National Knowledge Infrastructure, Wanfang Database, Yiigle, PubMed and Web of Science, covering from January 2013 to October 2022. Descriptive analysis was applied to the data. Results:(1) Case report: WES and Sanger sequencing showed the existence of the biallelic variants of LZTR1 gene c.842C>T and c.2248G>A in the fetus (Ⅱ-3) and the proband (Ⅱ-2) that inherited from the father and the mother, respectively. Based on the typical special facial appearance and short stature in the proband indicative of NS, the fetus and the proband were diagnosed with autosomal recessive inheritance (AR) NS. The pregnant woman terminated her pregnancy at 22 weeks due to severe edema of the fetus. At the age of three, the proband exhibited typical craniofacial features and short stature characteristics of NS when presented to our hospital. The proband received regular follow-ups in the pediatrics department of other hospitals, where recombinant human growth hormone was used to improve his height. He attended kindergarten at age four and can communicate and play with other children normally. (2) Literature review: 95 cases of NS associated with LZTR1 mutations have been retrieved and included. When including the fetus and the proband of this case, the total reached 97 cases, involving 79 different mutation sites. Forty-three cases (44.3%) were AR, and 54 (55.7%) were autosomal dominant inheritance (AD). Missense mutation was the most prevalent type of mutation, whereas nonsense mutation and frameshift mutation were more common in biallelic variants. Across all cases, the clinical manifestations encompassed multiple systems, primarily characterized by craniofacial dysmorphia, skeletal deformities, heart defects, and short stature. Developmental delay, learning disabilities, and mental retardation of varying degrees may accompany these symptoms. Eighteen cases described antenatal phenotypes, with 16 of them reporting biallelic AR variants. Ultrasound findings of 18 prenatal cases revealed 11 cases of fetal NT thickening, seven cases of cystic hygroma, four cases of fetal pericardium or pleural effusion, two cases of severe fetal edema, and 11 cases of cardiovascular defects. Conclusions:NS induced by LZTR1 mutations is an autosomal dominant or recessive inherited genetic syndrome with a broad spectrum of clinical phenotypes. The severity of the disease varies among children with the same genotype. NS should be considered when prenatal ultrasound indicates nonspecific manifestations, such as fetal NT thickening, cervical lymphatic hydrops, polyhydramnios, fetal edema, and congenital heart defects. Prenatal identification is crucial for evaluating the prognosis of children and assisting families in making clinical decisions.

Objective To compare the efficacy of mediastinoscope-assisted transhiatal esophagectomy (MATHE) and functional minimally invasive esophagectomy (FMIE) for esophageal cancer. Methods Patients who underwent minimally invasive esophagectomy at Jining No.1 Hospital from March 2018 to September 2022 were retrospectively included. The patients were divided into a MATHE group and a FMIE group according to the procedures. The patients were matched via propensity score matching (PSM) with a ratio of 1 : 1 and a caliper value of 0.2. The clinical data of the patients were compared after the matching. Results A total of 73 patients were include in the study, including 54 males and 19 females, with an average age of (65.12±7.87) years. There were 37 patients in the MATHE group and 36 patients in the FMIE group. Thirty pairs were successfully matched. Compared with the FMIE group, MATHE group had shorter operation time (P=0.022), lower postoperative 24 h pain score (P=0.031), and less drainage on postoperative 1-3 days (P<0.001). FMIE group had more lymph node dissection (P<0.001), lower incidence of postoperative hoarseness (P=0.038), lower white blood cell and neutrophil counts on postoperative 1 day (P<0.001). There was no statistically significant difference in the bleeding volume, R0 resection, hospital mortality, postoperative hospital stay, anastomotic leak, chylothorax, or pulmonary infection between the two groups (P>0.05). Conclusion Compared with the FMIE, MATHE has shorter operation time, less postoperative pain and drainage, but removes less lymph nodes, which is deficient in oncology. For some special patients such as those with early cancer or extensive pleural adhesions, MATHE may be a suitable surgical method.