ObjectiveTo evaluate the effectiveness of PBL teaching model for medical students in surgery bed side teaching.MethodsThe method of meta-analysis.ResultsFinally,twenty-six documents met the requirement.The resuhs of Meta-analysis showed that,in the aspect of theory improvement for medical students,WMD=6.46,95 ％ CI 为 2.56 ～ 10.36,P＜0.01 ; in the aspect of skill ability improvement,WMD=5.32,95 ％ CI 为 2.47 ～ 8.16,P ＜0.01.ConclusionThe model of PBL teaching could significantly improve the effectiveness in theoretical knowledge and skill ability.

Objective To study the role of transcranial Doppler (TCD) in early diagnosis of posttraumatic vasospasm in traumatic brain injury patients and in treatment effect monitoring of hyperxia liquid for this condition. Methods Seventy-four patients with posttraumatic vasospasm were divided into two groups. The control group (n=42) received the general treatment, while the treatment group (n=32) received the treatment of hyperxia liquid in addition to the general treatment. Their cerebral blood flow velocities of bilateral MCA and extra-cranial portion of ICA were monitored regularly by TCD, starting from the first day after head injury until 14th day. The changes of physiological and neurofunctional parameters in both groups were compared, including cerebral vasospasm(CVS),arterial blood oxygen pressure (PaO 2),arterial blood oxygen saturation (SaO 2), the Glasgow coma scale (GCS)and the ultimate effects of treatment as indicated by Glasgow outcome scale(GOS). Results Cerebral vasospasm occurred in 1 to 3 days and peaked to the 3 to 7 days after injury, then markedly relieved at 14 days after injury. After infusion of hyperxia liquid, the PaO 2 and SaO 2 in the treatment group were significantly higher than those of the control group. The degree of vasospasm was significantly higher in the control group than that in the treatment group. GCS and GOS of the treatment group were significantly higher than those of the control group. Poor outcome was common in patients with severe cerebral vasospasm. Conclusion Early posttraumatic vasospasm can be detected by TCD. High-oxygen liquid is effective for treating posttraumatic vasospasm.

Objective The incidence of complications after esophageal cancer surgery is relatively high.The purpose of this paper was to explore the feasibility of combined thoraco-laparoscopy surgical treatment for senile esophageal cancer(over 70 years old).Methods A total of 526 esophageal cancer cases were retrospectively analyzed in this study.The operative procedures was esophageal carcinoma resection surgery and thoracic and abdominal lymphadenectomy which were operated through video-assisted by thoracoscope and laparoscopic From January 2010 to June 2014 in the Union Hospital of Fujian Medical University,divided into aged groups(≥70 years old,n =132) and non-aged group(＜ 70 years old,n =394).Statistical analysis was carried on the rate of two groups of preoperative risk factors(hypertension,diabetes,cardiac insufficiency,pulmonary insufficiency,cerebral infarction),surgical trauma and the number of lymph node dissection (laryngeal recurrent nerve injury,operation time,intraoperative blood loss),postoperative complications(cardiac complications,chylothorax,pulmonary complications,anastomotic fistula,poor healing of the incision,intrathoracic stomach atony),postoperative recovery and early postoperative mortality.Results Preoperative risk factors:the prevalence of the aged group with hypertension,cerebral infarction,cardiac insufficiency,and pulmonary insufficiency was significantly higher than the non-aged group (P ＜ 0.05) but diabetes (P ＞ 0.05).Surgical trauma and the number of lymph node dissection:no significant difference (P ＞ 0.05).Postoperative complications:the aged group was higher in the incidence of pulmonary complications and cardiac complications than the other (P ＜ 0.05) ; but the chylothorax,anastomotic fistula and poor healing of incision,intrathoracic stomach atony in the two groups seemed no significant difference(P ＞ 0.05).Furthermore,pulmonary complications were highest in the all complications,significantly higher than the others in both groups.Postoperative recovery:significant difference existed in postoperative hospitalization days,the aged group was obviously longer than the non-age groups.Early postoperative mortality rates in the two groups had no significant difference.Conclusion The aged patiences had a higher prevalence in the preoperative risk factors and so was the cardiac complications as well as pulmonary complications among the postoperative complications.However the combined thoraco-laparoscopy in the surgical treatment of elderly patients with esophageal cancer is safe and feasible.

Objective To investigate the expression of pattern recognition receptor (PRR)of immune cells from the patients with enterovirus 71 ( EV 71 ) infection and the changes of cytokines. Methods Seventy-one patients and 20 age-matched healthy children were enrolled in the study. The patients were divided into three groups according to the critical degree: 20 mild patients, 25 severe patients and 26 critical patients. Real-time PCR were used to evaluate the levels of retinoic acidinducible gene Ⅰ ( RIG- Ⅰ ), melanoma differentitation-associated gene 5 ( MDA5 ) and cytokines IL-12, IFN-α mRNA expression in peripheral blood mononuclear cells (PBMC). The proportions of Toll like receptors(TLRs) on monocytes/macrophages (MC) , myloiddentritic cells (mDC) and plasmacytoiddentritic cells (pDC) were analyzed by flow cytometry. The concentrations of plasma cytokines( IL-12, IFN-α) were measured by ELISA. Results ( 1 ) The proportion of TLR7 is the unique TLR which is increased in mild patients and it was significantly elevated in MC, mDC and pDC in severe group (P＜0.05), TLR2, TLR3 and TLR4 also had an enhanced expression in MC and mDC. The enhanced expression of TLRs mentioned above had a decreased trend in critical patients. (2)Transcription levels of RIG- Ⅰ and MDA5 was significantly elevated in EV71 infected children.(3)The expression levels of DC-associated cytokines gene( IL-12 and IFN-α) have an increased trend in mild cases and these cytokines were remarkably increased in severe patients (P＜0.05), whereas decreased in critical cases (P＜0.05). ConclusionTLR7 might be the main PRR recognizing EV71 in immune cells and RIG-Ⅰ/MDA5 might also take part in the recognition of EV71. The exogenous or endogenous ligands released from bacterial infection and cell destruction could result in the activation of TLR2 or TLR4, inducing the inflammatory response.

Objective To investigate the regulation of miR-939-5p on USP22 gene expression and its effect on liver cancer migration and proliferation.Methods The expression of miR-939-5p in hepatoma cell lines (HepG2,MHCC-97H,SMMC-7721,BEL-7404 and Huh7) and normal liver cell line LO2 was detected by realtime PCR (qPCR).The liver cancer cells with the lowest expression were used as experimental subjects,and transfected with miR-939-5p (Experimental group) or miR-NC (Control group).qPCR was used to detect the transfection efficiency of miR-939-5p.Transwell migration assay and MTT proliferation assay were used to detect the migration and proliferation of hepatoma cells after transfected miR-939-5p.Bioinformatics software predicted target genes for miR-939-5p.The dual luciferase reporter gene verified the interaction of miR-939-5p with the target gene.qPCR and Western blotting were used to detect the expression of target genes at mRNA and protein levels after over-expression of miR-939-5p.Measurement data were expressed as (Mean ± SD),and t test was used for comparison between groups.Results The expression of miR-939-5p was significantly lower in hepatoma cell lines than in normal hepatocytes (P ＜0.01),and the expression of miR-939-5p was the lowest in SMMC-7721 cells (P＜0.01).miR-939-5p was efficiently transfected into SMMC-7721 cells [(1.01 ±0.07) vs (20.12 ± 1.27),P ＜0.01].High expression of miR-939-5p inhibited the migration ability (P ＜ 0.01) and proliferative capacity of liver cancer SMMC-7721 cells (P ＜0.05).The USP22 gene may be a target gene of miR-939-5p.The luciferase reporter gene confirmed that miR-939-5p specifically binds to the 3'-UTR of USP22 mRNA (P ＜ 0.01).USP22 expression was decreased at mRNA and protein levels after high expression of miR-939-5p (P ＜ 0.01).Conclusions The expression of miR-939-5p was down-regulated in hepatocellular carcinoma cell lines,and miR-939-5p inhibited the migration and proliferation of liver cancer SMMC-7721 cells.The molecular mechanism was to interfere with the expression of USP22 gene.

Objective:To investigate the changes of CD8 + CD28 - regulatory T cells (Treg) and its role in the pathogenesis of Kawasaki disease (KD). Methods:A total of 48 children with KD were enrolled in the present study from June 2019 to December 2021. Blood samples were collected from them during acute phage of KD and after intravenous immunoglobulin (IVIG) treatment. Another 32 age-matched healthy children were recruited as control group. The proportions of CD8 + CD28 -Treg cells and the expression of programmed cell death protein 1 (PD-1), factor associated suicide ligand (FasL), inducible T-cell co-stimulator ligand (ICOSL), CD80 and CD86 protein were evaluated by flow cytometry. The expression of Helios, perforin, granzyme B, immunoglobulin-like transcript 3 (ILT3) and ILT4 at the transcription level was measured by real-time PCR. Concentrations of IL-10 and TGF-β in the culture supernatants of CD8 + CD28 -Treg cells stimulated with activated CD4 + T cells were measured by ELISA. Results:⑴ The proportions of CD8 + CD28 -Treg cells and the expression of Helios in patients with acute KD were higher than those in the control group ( P<0.05), and reduced remarkably after IVIG therapy ( P<0.05). The two afore-mentioned indexes were lower in patients combined with coronary artery lesion (CAL) than in those without coronary artery lesion (NCAL) ( P<0.05). ⑵ Compared with the control group, the patients with acute KD showed increased expression of FasL, PD-1, ICOSL and perforin in CD8 + CD28 -Treg cells ( P<0.05). The concentrations of IL-10 and TGF-β1 in the culture supernatants of CD8 + CD28 -Treg cells from patients with acute KD were lower than those in the control group after stimulation with activated CD4 + T cells ( P<0.05), which restored to some extent after IVIG treatment ( P<0.05). All of the six above-mentioned indexes in the CAL group were found to be lower than those in the NCAL group ( P<0.05). There were slight differences in granzyme B expression between different groups ( P>0.05). (3) In comparison with the healthy controls, the patients with acute KD showed overexpressed co-stimulatory molecules such as CD80 and CD86 on CD14 + cells ( P<0.05) and up-regulated expression of inhibitory molecules ILT3 and ILT4 ( P<0.05), which were restored remarkably after IVIG treatment ( P<0.05). Furthermore, the expression of CD80 and CD86 at protein level increased in the CAL group than in the NCAL group ( P<0.05), while the expression of ILT3 and ILT4 at transcriptional level decreased in the CAL group ( P<0.05). Conclusions:Relative insufficiency and impaired function of CD8 + CD28 -Treg cells might be one of the important factors resulting in immune dysfunction and vascular damage in KD patients.

Objective:To explore the effect of Notch1 signaling on regulatory T cells and its roles in vascular damage in patients with Kawasaki disease (KD).Methods:A total of 42 children with KD were enrolled in the present study from March 2019 to June 2020, as 32 age-matched healthy children were recruited as control. The proportions of CD4 +CD25 hiFoxp 3+ regulatory T cells (Treg) and expressions of transcription factor forkhead box protein 3 (Foxp3), cytotoxic T lymphocyte associated antigen-4 (CTLA4), glucocorticoid-induced tumor necrosis factor receptor (GITR), and Notch1 protein were evaluated by flow cytometry. Chromatin immunoprecipitation was conducted to detect acetylation level of histone H4 (H4Ac) associated with the promoter of Foxp3 gene and its binding abilities of Notch1 intracellular domain 1 (NICD1), recombination signal binding protein for immunoglobulin kappa J region (RBP-J) and p300 in CD4 + T cells. Transcription levels of Foxp3, presenilin 1 (PSEN1), mastermind like transcriptional coactivator 1 (MAML1), and RBP-J in CD4 + T cells were determined by real-time polymerase chain reaction (PCR). Concentrations of interleukin (IL)-10 and transforming growth factor-β (TGF-β) in plasma and culture supernatant stimulated with Jagged1 were measured by enzyme linked immunosorbent assay. Independent-sample t-test, Pearson correlation analysis was used as the statistical method in this study. Results:① The frequencies of Treg in acute KD patients decreased significantly [(4.3±1.5)% vs (7.9±2.9)%; t=6.41, P<0.001], as protein levels of Foxp3, CTLA4 and GITR and concentrations of IL-10 and TGF-β in plasma reduced remarkably in acute KD patients ( t=6.87, P<0.001; t=4.26, P<0.001; t=7.88, P<0.001; t=8.42, P<0.001; t=13.01, P<0.001). All parameters afore-mentioned in patients combined with coronary artery lesions (CAL) were lower than those of patients without coronary artery lesions (NCAL) ( t=5.83, P<0.001; t=3.83, P<0.001; t=3.28, P=0.002; t=5.05, P<0.001; t=5.96, P<0.001; t=5.17, P<0.001), and increased after therapy ( t=7.13, P<0.001; t=6.10, P<0.001; t=4.31, P<0.001; t=6.55, P<0.001; t=7.40, P<0.001; t=7.84, P<0.001). ② H4Ac associated with promoter of Foxp3 gene and the binding abilities of NICD1 and p300 in acute KD patients were lower than those of the controls ( t=10.25, P<0.001; t=6.93, P<0.001; t=6.75, P<0.001), and increased remarkably after therapy ( t=7.72, P<0.001; t=4.16, P<0.001; t=5.76, P<0.001). Meanwhile, the three items in CAL group were found to be less than those of NCAL group ( t=6.08, P<0.001; t=2.66, P=0.011; t=6.02, P<0.001). Pearson correlation analysis showed a positive correlation between H4Ac associated with Foxp3 promoter and its mRNA level in acute KD patients ( r=0.47, P<0.001). No statistical significant difference about the binding ability of RBP-J with Foxp3 promoter were found among the groups ( t=0.57, P>0.05; t=0.61, P>0.05; t=1.20, P>0.05). ③ Protein level of Notch1 and the expressions of PSEN1, MAML1 and RBP-J mRNA in CD4 + T cells from acute KD patients were down-regulated remarkably ( t=5.28, P<0.001; t=6.31, P<0.001; t=11.78, P<0.001; t=8.06, P<0.001), and restored after therapy ( t=4.77, P<0.001; t=6.43, P<0.001; t=11.95, P<0.001; t=7.79, P<0.001). In parallel, the four indexes aforementioned of CAL group were lower than those of NCAL group ( t=3.16, P=0.003; t=4.13, P<0.001; t=5.42, P<0.001; t=4.05, P<0.001). Upon rhJagged1 stimulation for 48 hours, H4Ac level of Foxp3 promoter and its binding abilities with NICD1 and p300 in CD4 + T cells in KD patients and control group was significantly higher than those of untreated group [(KD: t=15.36, P<0.001; t=7.25, P<0.001; t=14.29, P<0.001), (Ctrl: t=7.87, P<0.001; t=5.71, P<0.001; t=8.74, P<0.001)], as the binding ability of RBP-J with Foxp3 promoter increased slightly without statistically significant difference (KD: t=1.11, P>0.05; Ctrl: t=1.37, P>0.05). Simultaneously, H4Ac level of Foxp3 promoter and its binding abilities with NICD1 and p300 in KD group were still lower than those of the control group after stimulation ( t=3.86, P<0.001; t=3.42, P=0.001; t=2.85, P=0.006). ④ After incubation of PBMC from heathy children with KD serum, the proportion of Treg cells, protein level of Foxp3 and expressions of Notch1 and RBP-J in CD4 + T cells in the group treated with IVIG increased significantly compared with the untreated group ( t=7.10, P<0.001; t=10.16, P<0.001; t=8.06, P<0.001; t=9.77, P<0.001), as well as H4Ac level of Foxp3 promoter and its binding abilities with NICD1 in the group treat with IVIG were also higher than the latter ( t=7.24, P<0.001; t=8.24, P<0.001). Conclusion:Insufficiency and impaired function of Treg caused by aberrant Notch1 signaling may be the important factor contributing to immune dysfunction and vascular damage in KD.

Objective:To analyze the effect and mechanism of gadolinium chloride on hepatic ischemia-reperfusion injury (HIRI) in Sprague Dawley (SD) rats.Methods:Thirty six eight weeks special pathogen free SD rats, were included in the project. The body weight ranged from 200 to 250 g. Thirty six rats were randomly divided into sham operation group, model group and gadolinium chloride group with 12 rats/group. Model of ischemia-reperfusion injury was generated in the rats of model group; In the gadolinium chloride group, preoperative intraperitoneal injection of gadolinium chloride was performed before the model of HIRI was established; In the sham operation group, only the abdomen was opened and closed and the hilum was dissected. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected in the three groups. The relative expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1 β (IL-1β) mRNA were detected by Q-PCR. Western blot was used to detect the expression of markers involved in the Toll like receptor 2/myeloid differentiation factor 88 (MyD88) signaling pathway. Immunohistochemistry staining was used to detect the expression of Fas and Fas ligands in hilar bile duct epithelial cells.Results:ALT and AST were (55±8) U/L, (92±22) U/L in sham operation group, lower than those in model group (1 247±62) U/L, (1 117±60) U/L, respectively, and ALT and AST in gadolinium chloride group were (622±50) U/L and (552±41) U/L, lower than those in model group (all P<0.05). Compared with the sham operation group, the relative expression of TNF-α, IL-1 β, IL-6 mRNA in the model group was significantly higher (all P<0.05), but the expression of those markers were higher than gadolinium chloride group (all P<0.05). Gadolinium chloride down-regulated the expression of Toll like receptor 2/MyD88 signaling pathway in rat with liver ischemia-reperfusion. The percentage of Fas protein positive cells in model group was (40.2±3.8)%, and the percentage of Fas ligand positive cells was (36.9±2.9)%, which was higher than those in gadolinium chloride group (29.7±2.3)% and (23.6±2.1)% with statistically significant differences (all P<0.05). Conclusion:Gadolinium chloride can reduce the injury of liver function and inhibit the expression of inflammatory factors in liver tissue of SD rats with hepatic ischemia-reperfusion, which may play a protective role by down regulating the expression of relative protein in Toll like receptor 2/MyD88 signaling pathway.

¹⁷⁷Lu- prostate specific membrane antigen (PSMA) radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China. Based on domestic clinical practice and experimental data and referred to international experience and viewpoints, the expert group forms a consensus on the clinical application of ¹⁷⁷Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.