Effect of acute sleep fragmentation on cognitive function and hippocampal Homer1a expression in aged rats / 中华行为医学与脑科学杂志

Objective:To explore the effects of acute sleep fragmentation (SF) on cognitive function and the relationship between hippocampal Homer1a and synaptic plasticity in aged rats.Methods:One hundred and eight SPF grade male SD rats aged 22 to 24 months were divided into three groups according to random number table: control group (Control group), non-sleep fragmentation group (NSF group) and sleep fragmentation group (SF group), with 36 rats in each group.A sleep fragmentation model was established by sleep deprivation rod method.Morris water maze and novel object recognition tests were used to evaluate the learning and memory function of rats.Homer1a expression in hippocampus was detected by Western blot, and its distribution in CA1 area of hippocampus was observed by immunohistochemical staining.Golgi staining was used to observe the density of dendritic spines in CA1 area of hippocampus, and in vitro electrophysiological patch clamp test was used to detect the slope of field excitatory postsynaptic potential(fEPSP) from CA3 to CA1 in hippocampus.SPSS 22.0 and GraphPad Prism 9.3 softwares were used for data statistical analysis and mapping.One-way ANOVA was used for comparison among groups, and Tukey-Kramer test was used for further pairwise comparison. Results:(1)In the behavioral tests, there were statistical differences in the times of crossing the original platform, the target quadrant residence time and the new object recognition index at 1 h and 24 h among the three groups( F=13.63, 11.34, 21.26, 16.22, all P<0.01). The times of crossing the original platform in SF group((2.00±1.27) times) was lower than that of Control group ((5.67±2.16) times) and NSF group ((6.50±2.35) times) (both P<0.05). The target quadrant residence time in SF group ((9.02±4.84) s) was shorter than that in Control group ((24.73±7.37) s) and NSF group ((27.81±8.37)s) (both P<0.05). The new object recognition index at 1 h and 24 h in SF group were lower than those in Control group and NSF group (all P<0.05). (2) In Western blot assay, the expression of Homer1a protein in hippocampus of SF group(0.91±0.13) was higher than that of Control group(0.70±0.05) and NSF group(0.74±0.04)(both P<0.05). (3) In immunohistochemical staining, the optical density value of the Homer1a protein in CA1 area of hippocampus in the SF group was higher than that in the Control group and NSF group(both P<0.05). (4) In Golgi staining, the density of dendritic spines in CA1 area of hippocampus in SF group was lower than that in Control group and NSF group (both P<0.05). (5) In vitro electrophysiological test showed that the slope of fEPSP in CA3-CA1 area of hippocampus in SF group were lower than that in Control group and NSF group (both P<0.05). Conclusion:Acute SF intervention in aged rats can cause cognitive impairment, which may be associated with the inhibition of hippocampal synaptic plasticity induced by hippocampal Homer1a overexpression.

Gene mutation profiles and clinicopathological features of patients with non-small cell lung cancer harboring KRAS G12C mutation: a single-center retrospective study / 中华病理学杂志

Objective: To accurately screen non-small cell lung cancer (NSCLC) patients with KRAS G12C mutation and to evaluate their clinicopathological features, prognostic factors and current treatment status. Methods: A total of 19 410 NSCLC cases diagnosed at the Department of Pathology of Shanghai Chest Hospital, Shanghai, China from January 2018 to September 2021 were retrospectively reviewed, and the cases with KRAS gene mutation detected by next-generation sequencing were included. The clinicopathological and genetic mutation data of these cases were collected and analyzed. Results: A total of 1 633 (8.4%) NSCLC patients carried a KRAS gene mutation, among whom G12C was the most frequent (468 cases, 28.7%) mutant subtype. The mutation was more commonly found in males (414/468, 88.5%), patients with a history of smoking (308/468, 65.8%), and patients with a pathological type of invasive adenocarcinoma (231/468, 49.4%). The most common co-mutated genes in KRAS G12C mutant NSCLC were TP53 (52.4%, 245/468), STK11 (18.6%, 87/468) and ATM (13.2%, 62/468). The proportion of PD-L1 expression (≥1%) in KRAS G12C mutant NSCLC was significantly higher than that in patients without G12C mutation [64.3% (90/140) vs. 56.1% (193/344), P=0.014]. Immune checkpoint inhibitors (ICIs) treatment significantly prolonged progression-free survival (PFS) in NSCLC patients (10.0 months vs. 5.0 months, P=0.011). However, combination of chemotherapy and ICIs with anti-angiogenesis inhibitors or multi-target inhibitors did not significantly improve PFS in patients with KRAS G12C mutant NSCLC (P>0.05). Patients with KRAS G12C mutation NSCLC treated with ICIs and KRAS G12C patients with TP53 mutation had significantly longer median PFS than those with STK11 mutation (9.0 months vs. 4.3 months, P=0.012). Conclusions: Patients with KRAS G12C mutant NSCLC have relatively higher levels of PD-L1 expression and can benefit from ICIs treatment. The feasibility of chemotherapy, ICIs therapy and their combination needs further investigation.

Efficacy and safety of total neoadjuvant therapy versus neoadjuvant chemoradiotherapy in the treatment of locally advanced rectal cancer: a meta-analysis / 中华胃肠外科杂志

Objective: To systematically evaluate the efficacy and safety of total neoadjuvant therapy (TNT) in the comprehensive treatment of locally advanced rectal cancer. Methods: Literatures were screened from PubMed, Embase, Web of Science, Cochrane Library, CBM, Wanfang Data, VIP and CNKI from the inception date to May 2021 to collect the randomized controlled clinical trials (RCTs) of TNT followed by total mesorectal excision (TME) versus neoadjuvant chemotherapy (nCRT) followed by TME in the treatment of locally advanced rectal cancer. The data of overall survival, disease-free survival, R0 radical resection rate, pathological complete response (pCR) rate, T downstaging rate, the incidence of adverse events ≥ grade III, including neutropenia, nausea and vomiting, diarrhea, radiation dermatitis and nervous system toxicity, and the morbidity of complications within postoperative 30 days of the two groups were extracted from the included literatures. Review Manager 5.3 software was utilized for statistical meta-analysis. Results: Nine RCTs were finally enrolled including 2430 patients. Meta-analysis results showed that compared with nCRT group, patients in TNT group had longer overall survival (HR=0.80, 95%CI: 0.65-0.97, P=0.03) and higher pCR rate (RR=1.73, 95%CI: 1.44-2.08, P<0.01) with significant differences. Besides, there were no significant differences between two groups in disease-free survival (HR=0.86, 95%CI:0.71-1.05, P=0.14), R0 radical resection rate (RR=1.02, 95%CI: 0.99-1.06, P=0.17) and T downstaging rate (RR=1.04, 95%CI: 0.89-1.22, P=0.58) between two groups. In terms of treatment safety, the incidence of adverse events ≥ grade III (RR=1.09, 95%CI: 0.70-1.70, P=0.70) and morbidity of complications within postoperative 30 days (RR=1.07, 95%CI: 0.97-1.18, P=0.19) did not significantly differ between two groups. Conclusions: In the treatment of locally advanced rectal cancer, TNT may bring more survival benefits than nCRT and does not increase the incidence of adverse events and postoperative complications. Therefore, TNT could be used as a recommended treatment for patients with locally advanced rectal cancer.

Correlation between cervical vertigo and vestibular function evaluated by vestibular evoked myogenic potentials / 中国骨伤

OBJECTIVE@#To analyze the relationship between cervical vertigo and vestibular function evaluated by vestibular evoked myogenic potentials(VEMPs) and analyze the correlations between cervical vertigo and vestibular dysfunction, discuss the related factors of cervical vertigo and guide the clinical treatment of patients with cervical vertigo.@*METHODS@#A total of 75 patients with cervical vertigo as the main complaint in the outpatient clinic of the Second Hospital of Shanxi Medical University from August 2019 to July 2020 were set as the diseased group, and 60 patients without cervical and vestibular related diseases in the hospital were selected to set as non-diseased group. The age of diseased group was 12 to 70 years with an average of (46.40±10.91) years, including 25 males and 50 females;and the age of non-diseased group was 22 to 60 years with an average of(43.78±7.75) years, including 19 males and 51 females. VEMPs were performed in the two groups. The data of VEMPs were collected and the results were compared and analyzed. The patients with abnormal cervical myogenic vestibular evoked myogenic potential (cVEMP) were divided into light, moderate and severe groups. The correlation between VEMPs and cervical vertigo and its severity were analyzed by statistical method.@*RESULTS@#(1)The severity of cervical vertigo in diseased group:33 cases of mild, 34 cases of moderate, 8 cases of severe; cVEMP examination:62 cases were positive and 13 cases were negative, including 13 cases of mild, 33 cases of moderate, 16 cases of severe. The cVEMP of non-diseased group:4 cases were positive and 56 cases were negative.(2) The level of cVEMP in diseased group was higher than that in non-diseased group (P<0.001). It can be considered that there was a correlation between cervical vertigo and vestibular function.(3)The correlation between the level of cVEMP and the level of cervical vertigo in diseased group was analyzed. The Spearman rank sum test was used, and the correlation coefficient was 0.687, which was statistically significant (P<0.05). And it can be considered that the two indicators have a high degree of correlation.@*CONCLUSION@#It is feasible to evaluate the relationship between cervical vertigo and vestibular function by VEMPs. For patients with cervical vertigo, the higher the severity, the greater the positive rate of VEMPs, which indicates that it has a greater impact on vestibular function. The treatment of patients with cervical vertigo should be the combination of cervical rehabilitation and vestibular function.

SNHG9 promotes Hepatoblastoma Tumorigenesis via miR-23a-5p/Wnt3a Axis.

Background: Hepatoblastoma is a common hepatic tumor occurring in children between 0-5 years. Accumulating studies have shown lncRNA's potential role in distinct cancer progression and development, including hepatoblastoma. SnoRNA host gene 9 (SNHG9) is associated with the progression of distinct human cancers, but, its specific molecular mechanisms in hepatoblastoma is not unknown. Methods: In this study, we estimated SNHG9 expression in hepatoblastoma tissue and cell lines by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Next, we downregulated and upregulated SNHG9 expression in hepatoblastoma cell lines and then determined cell proliferation (CCK-8), colony formation, and cellular apoptosis activity. The dual luciferase reporter activity, RNA immunoprecipitation (RIP), biotin RNA pull down and Spemann's Pearson correlation coefficient assay were performed to establish the interaction between SNHG9, WNt3a and miR- 23a-5p. A xenograft in-vivo tumorgenicity test was performed to elucidate the role of SNHG9 hepatoblastoma in tumorigenesis. SNHG9 role in Cisplatin drug resistance in hepatoblastoma was also determined. Results: SNHG9 was significantly upregulated in hepatoblastoma tissue and cell lines. SNHG9 overexpression on HUH6 & HepG2 resulted in a significant increase in cell proliferation and clonogenic activity while SNHG9 knock down resulted in a sustained inhibition of cell proliferation and clonogenic activity. Dual luciferase activity, RNA immunoprecipitation and biotin pull down confirmed the direct interaction of miR-23a-5p with SNHG9. The xenograft tumorgenicity test showed SNHG9 downregulation significantly inhibited the tumor growth in BALB/c mice. ROC and Kaplan-Meier analysis showed potential prognostic and diagnostic importance of SNHG9 in hepatoblastoma. Conclusion: We concluded that SNHG9/miR-23a-5p/Wnt3a axis promotes the progression hepatoblastoma tumor.

Phase 1 safety and pharmacokinetics studies of BRII-196 and BRII-198, SARS-CoV-2 spike-targeting monoclonal antibodies

BackgroundBRII-196 and BRII-198 are two anti-SARS-CoV-2 monoclonal neutralizing antibodies with modified Fc region that extends half-life and are being developed as cocktail therapy for the treatment of COVID-19. Safety, tolerability, pharmacokinetics, and immunogenicity of BRII-196 and BRII-198 were investigated in healthy adults. MethodsSingle ascending doses of BRII-196 and BRII-198 were evaluated in parallel in the first-in-human, placebo-controlled phase 1 studies. A total of 32 healthy adults were randomized and received a single intravenous infusion of 750, 1500, and 3000 mg of BRII-196 (n=12), BRII-198 (n=12), or placebo (n=8) and were followed for 180 days. ResultsAll infusions were well tolerated at infusion rates between 0.5 mL/min to 4 mL/min with no dose-limiting adverse events, deaths, serious adverse events, or any systemic or local infusion reactions. Most treatment-emergent adverse events were isolated asymptomatic laboratory abnormalities of Grade 1-2 in severity. Each mAb displayed pharmacokinetics expected of Fc-engineered human IgG1 with mean terminal half-lives of approximately 46 days and 76 days, respectively, with no evidence of significant anti-drug antibody development. ConclusionsBRII-196 and BRII-198 were well-tolerated. Clinical results support further development as therapeutic or prophylactic options for SARS-CoV-2 infection.

Effect of Dihydroartemisinin on Oxidative Damage and Energy Metabolism of HepG2 Cells and Its Synergistic Effect with Sorafenib / 中国实验方剂学杂志

Objective:To explore the inhibitory effect of dihydroartemisinin （DHA） on the proliferation of HepG2 cells， elucidate the mechanism from the perspectives of oxidative damage and energy metabolism， and discuss the possibility of combined use of DHA with sorafenib （Sora）. Method:Cell counting kit-8 （CCK-8） assay was used to obtain the 50% inhibitory concentration （IC₅₀） of DHA and Sora on HepG2 and SW480 cells and Chou-Talalay method was used to obtain the combination index （CI） of DHA and Sora. HepG2 cells were classified into the control group， DHA group （10 µmol·L^-1）， Sora group （5 µmol·L^-1）， and DHA + Sora group （DHA 10 µmol·L^-1， Sora 5 µmol·L^-1） and then incubated with corresponding drugs for 8-12 h. Seahorse XF glycolytic rate assay kit and cell mito stress test kit were employed to respectively detect the glycolysis function of cells and oxidative phosphorylation function of mitochondria. DCFH-DA and lipid peroxidation MDA assay kit were separately used to analyze the intracellular levels of reactive oxygen species （ROS） and malondialdehyde （MDA）. Western blot was applied to determine the intracellular levels of heme oxygenase-1 （HO-1） and glutamate-cysteine ligase catalytic subunit （GCLC）. Result:Compared with the control group， DHA alone inhibited the ATP synthesis in mitochondrial oxidative phosphorylation and glycolysis （<italic>P</italic><0.01）， increased the levels of intracellular ROS and MDA （<italic>P<</italic>0.05）， and decreased the levels of HO-1 and GCLC （<italic>P<</italic>0.05） in HepG2 cells. DHA and Sora had synergistic inhibitory effect on proliferation of HepG2 and SW480 cells， with CI < 0.90. The DHA + Sora group showed stronger suppression of ATP synthesis in mitochondrial oxidative phosphorylation and glycolysis （<italic>P</italic><0.01）， higher levels of intracellular ROS and MDA （<italic>P<</italic>0.01）， and lower levels of intracellular antioxidation-related proteins HO-1 and GCLC in HepG2 cells （<italic>P<</italic>0.01） than the DHA group. Conclusion:DHA may increase the level of MDA by reducing HO-1 and GCLC and increasing ROS in HepG2 cells， which results in mitochondria oxidative damage， restricts cell glycolysis and mitochondrial oxidative phosphorylation， and thus finally inhibits the proliferation of HepG2 cells. DHA and Sora have synergistic inhibitory effect on the proliferation of HepG2 and SW480 cells， and the mechanism may be related to the synergistic oxidative damage that affects the mitochondrial electron transport chain and suppresses cell energy metabolism.

Effects of sevoflurane combined with propofol anesthesia on synaptic plasticity in hippocampus after operation in rats with mild cognitive impairment: relationship with KCC2/NKCC1 / 中华麻醉学杂志

Objective:To evaluate the effects of sevoflurane combined with propofol anesthesia on the synaptic plasticity in the hippocampus after operation in rats with mild cognitive impairment (MCI) and the relationship with potassium-chloride cotransporter-2 (KCC2)/sodium-potassium-chloride cotransporter 1 (NKCC1).Methods:Clean-grade healthy male Sprague-Dawley rats, aged 16-18 months, weighing 440-540 g, in which MCI was induced by severe bilateral common carotid artery stenosis (BCAS). Forty-eight rats with MCI were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (group Sham), sevoflurane anesthesia group (group S), propofol anesthesia group (group P), and sevoflurane and propofol anesthesia group (group SP). After disappearance of eyelash reflex, open reduction and internal fixation was performed after tibial fracture was induced in S, P and SP groups.Anesthesia method was as follows: 1.7% sevoflurane was inhaled and propofol 20 mg·kg -1·h -1 was intravenously infused for 3 h in group SP, 3% sevoflurane was inhaled for 3 h in group S, and propofol was intravenously infused at rate of 40 mg·kg -1·h -1 for 3 h in group P. The novel object recognition (NOR) test was performed at 14 days after operation, and the discrimination index in NOR test was calculated.The in vivo electrophysiological experiment was performed on 19 days after operation to measure long-term potentiation and amplitude of the field excitatory postsynaptic potential (fEPSP). The expression of KCC2 and NKCC1 was determined by Western blot, and the ratio of KCC2/NKCC1 was calculated.The density of dendritic spines in the hippocampal CA1 region was determined by Golgi-COX staining performed at 30 days after operation. Results:Compared with Sham group, the discrimination index in NOR test, hippocampal KCC2/NKCC1 ratio, density of dendritic spines in hippocampal CA1 region, and amplitude of fEPSP were significantly decreased in S and P groups ( P<0.05), and no significant change was found in the parameters mentioned above in group SP ( P>0.05). Compared with group S or group P, the discrimination index in NOR test, hippocampal KCC2/NKCC1 ratio, density of dendritic spines in hippocampal CA1 region, and amplitude of fEPSP were significantly increased in group SP ( P<0.05). Conclusion:Sevoflurane combined with propofol anesthesia does not aggravate postoperative cognitive dysfunction in the rats with MCI, which may be related to maintaining the balance of hippocampal KCC2/NKCC1 and protecting the synaptic plasticity in hippocampi.

A single-dose live-attenuated YF17D-vectored SARS-CoV2 vaccine candidate

The explosively expanding COVID-19 pandemic urges the development of safe, efficacious and fast-acting vaccines to quench the unrestrained spread of SARS-CoV-2. Several promising vaccine platforms, developed in recent years, are leveraged for a rapid emergency response to COVID-191. We employed the live-attenuated yellow fever 17D (YF17D) vaccine as a vector to express the prefusion form of the SARS-CoV-2 Spike antigen. In mice, the vaccine candidate, tentatively named YF-S0, induces high levels of SARS-CoV-2 neutralizing antibodies and a favorable Th1 cell-mediated immune response. In a stringent hamster SARS-CoV-2 challenge model2, vaccine candidate YF-S0 prevents infection with SARS-CoV-2. Moreover, a single dose confers protection from lung disease in most vaccinated animals even within 10 days. These results warrant further development of YF-S0 as a potent SARS-CoV-2 vaccine candidate.

STAT2 signaling as double-edged sword restricting viral dissemination but driving severe pneumonia in SARS-CoV-2 infected hamsters

Introductory paragraphSince the emergence of SARS-CoV-2 causing COVID-19, the world is being shaken to its core with numerous hospitalizations and hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that productive SARS-CoV-2 infection in the lungs of mice is limited and restricted by early type I interferon responses. In contrast, we show that Syrian hamsters are highly permissive to SARS- CoV-2 and develop bronchopneumonia and a strong inflammatory response in the lungs with neutrophil infiltration and edema. Moreover, we identify an exuberant innate immune response as a key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Finally, we assess SARS-CoV- 2-induced lung pathology in hamsters by micro-CT alike used in clinical practice. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients.

Effect of acellular repair patch of small intestinal submucosa of porcine in repairing of soft tissue defects of hand / 中华显微外科杂志

Objective:To compair the outcomes of repairing soft tissue defects of hand between a biodegrad- able repair patch—porcine small intestinal submucosa (SIS) and skin grafting.Methods:From December, 2017 to December, 2018, 36 cases of hand soft tissue defect were treated and analyzed retrospectively. According to the defect area and treatment methods, 36 cases were divided into 2 groups: SIS group (21 cases) and grafting group(15 cases). In SIS group, the area of soft tissue defects was 2.0 cm×1.5 cm-9.0 cm×3.5 cm with an average of 5.3 cm×2.1 cm, treat- ed with SIS; In grafting group, the area of soft tissue defects was 9.0 cm×4.0 cm-16.0 cm×9.0 cm with an average of 12.0 cm×8.5 cm, treated with autologous skin grafting after wet dressing. Wound healing was evaluated at 14, 21 and 28 days, and 3 months after the surgery according to the appearance of colour, elasticity, sensory recovery and prog- noses of partial tendon exposure.Results:All patients were followed-up for 3 to 10 months, with an average of 5 months. All wounds in both groups were completely healed; the appearance was normal, and the skin elasticity and sensation had recovered. Sensation recovery in SIS group: 14 cases were good (66.6%), 5 cases were fine (23.8%), and 2 cases were bad (9.6%); in grafting group: 9 cases were good (60.0%), 4 cases were fine (26.0%), and 2 cases were bad (14.0% ). Wound healing effect in SIS group: 14 cases were good, 5 cases were fine, and 2 cases were bad; in grafting group: 9 cases were good, 4 cases were fine, and 2 cases were bad.Conclusion:The SIS patch can be used in the reconstruction of soft tissue defects in hand. There was no significant difference in colour compared to the sur- rounding skin and left no scar. The patch is an ideal repair material for superficial skin defects.

Effects of antimalarial drugs on mitochondrial respiration in erythrocytic stages of Plasmodium falciparum 3D7 / 中国临床药理学与治疗学

AIM: The Seahorse XFe96 analyzer was used to evaluate the effects of thirteen types of international first-line antimalarial drugs in six categories on the mitochondrial electron transport chain (ETC) of Plasmodium falciparum 3D7 (P. falciparum 3D7). METHODS: The antimalarial activity of in vitro drugs acting on P. falciparum 3D7 was evaluated using the three-day inhibition method and SYBR Green I fluorescence analysis method. MACS technology was used to separate and purify P. falciparum 3D7. The mitochondrial oxygen consumption rate (OCR) of Seahorse XF analysis system was used to characterize the bioenergy of P. falciparum 3D7 mitochondria at different times to investigate the effects of antimalarial drugs on mitochondrial aerobic respiration of Plasmodium falciparum. RESULTS: The results of flow cytometry showed that the Plasmodium of trophozoite stages was enriched successfully. The results of in vitro antimalarial activity evaluation showed that, except for the antimalarial drug proguanil (Pro), the other twelve antimalarial drugs were all of the nmol/L level against P. falciparum 3D7. The results of the mitochondrial aerobic respiration showed that the five concentrations of dihydroartemisinin (DHA) and chloroquine (CQ) (0.4, 1, 5, 10, 50×IC

Association between depression behavior and expression of calreticulin precursor, tropomyosin 1, milogen activated prolein kinase 1 and dual specificity mitogen-activated protein kinase 1 in spontaneous diabetes mellitus rats / 实用医学杂志

Objective To investigate the association between depression behavior and the expression of calreticulin precursor, tropomyosin I, milogen activated prolein kinase 1 and dual specificity mitogen-activated protein kinase 1 in spontaneous diabetes mellitus rats. Methods Twenty adult male healthy rats (control group) and 40 spontaneous diabetic rats were studied. Forty spontaneous diabetic rats were further divided into diabetes group and diabetic depression group, and the latter was to construct depression model. The depressive behavior of the 3 groups was measured by sucrose water consumption test and wilderness test. The expression level of calreticulin precursor, tropomyosin 1, milogen activated prolein kinase 1, and dual specificity mitogen-activated protein kinase 1 in the hippocampus of the 3 groups was measured by western blot. Results In the 15 th day and 22 nd days of stress, the amount of sucrose water drinking of the rats in diabetic depression group was significantly lower than that of the control group and the diabetes group (P < 0.05) , and there was no significant difference between the control group and the diabetic group (P> 0.05). The score of field test and vertical score in the diabetic depression group were significantly lower than those of the control group and the diabetes group (P < 0.05) , but there was no significant difference between the control group and the diabetic group (P> 0.05). The expression of calreticulin precursor, tropomyosin 1, milogen activated prolein kinase 1, and dual specificity mitogen-activated protein kinase 1 in the hippocampus of diabetic depression group was significantly lower than that in the control group and the diabetic group (P < 0.05) , and there was no significant difference between the control group and the diabetic group (P> 0.05).Conclusions The depressive behavior of spontaneously diabetic rats is associated with the decrease of the expression level of calreticulin precursor, tropomyosin 1, milogen activated prolein kinase 1, and dual specificity mitogenactivated protein kinase 1 in the hippocampus of rats.

Efficacy and safety of Yangzheng Xiaoji capsule combined with radiotherapy and chemotherapy in the treat－ment of gastric cancer and its influence on immune function / 中国基层医药

Objective To explore the efficacy and safety of Yangzheng Xiaoji capsule combined with radiotherapy and chemotherapy in the treatment of gastric cancer and its influence on immune function .Methods From October 2016 to October 2018,80 patients with gastric cancer in the First Peopleˊs Hospital of Yongkang were divided into two groups according to the random number table ,with 40 cases in each group.The control group received conventional radiotherapy plus chemotherapy ,namely oxaliplatin,5 －fluorouracil combined with calcium leucovorin conventional chemotherapy.The observation group received Yangzheng Xiaoji capsule on the basis of the control group.The clinical symptoms ,objective tumor efficacy,TCM symptoms and signs score ,safety,immune function of the two group were observed.Results The total effective rate of the observation group was 87.5%,which was significantly higher than 72.5%of the control group(χ2 ＝3.52,P＜0.05).The RR,DCR of the observation group were 62.5%, 87.5%,respectively,which were significantly higher than 30.0%,72.5% of the control group ( χ2 ＝4.31, P ＜0.05).The TCM symptoms and signs scores of the two groups after treatment were significantly improved compared with those before treatment(all P＜0.05),which of the observation group after treatment was significantly lower than that of the control group (t＝5.13,P＜0.05).There were no statistically significant differences in WBC ,Hb and PLT of the observation group before and after treatment ( t＝1.24,1.62,1.37,all P＞0.05),and there were statistically significant differences in WBC ,Hb and PLT of the control group before and after treatment (t＝4.85,3.64,3.85,all P＜0.05),and the WBC,Hb and PLT of the observation group were significantly higher than those of the control group after treatment(t＝6.37,4.15,5.27,all P＜0.05).In the observation group,leukopenia decreased in 4 cases, hemoglobin decreased in 6 cases and transaminase increased in 6 cases,which were significantly lower than 8 cases, 10 cases and 10 cases in the control group (χ2 ＝4.26,P＜0.05).Before treatment,there were no statistically signifi－cant differences in the levels of CD +3 ,CD+4 ,CD+8 ,CD+4 ／CD+8 between the two groups (all P＞0.05).There were no statistically significant differences in the levels of CD +3 ,CD+4 ,CD+8 ,CD+4 ／CD+8 of the observation group before and after treatment(t＝2.14,2.08,1.69,2.47,all P＞0.05),and compared with before treatment ,the levels of CD +3 , CD+4 ,CD+4 ／CD+8 of the control group were significantly decreased ( t＝5.12,4.26,5.38,all P＜0.05),while the level of CD+8 was significantly increased (t＝3.86,P＜0.05).After treatment,the levels of CD +3 ,CD+4 ,CD+8 ,CD+4 ／CD+8 of the observation group were significantly better than those of the control group (t＝4.79,3.52,4.28,3.61,all P＜0.05).Conclusion Yangzheng Xiaoji capsule combined with radiotherapy and chemotherapy can improve the curative effect of patients with gastric cancer ,and it has high safety,less toxic and side effects,and can improve the immune function of patients with gastric cancer.It is worthy of promoting.

Effect of dexmedetomidine on pulmonary function in elderly patients with mild obstructive ventilatory dysfunction under protective ventilation during laparoseopic gallbladder surgery / 国际生物医学工程杂志

Objective To evaluate the effect of dexmedetomidine on pulmonary function in elderly patients with mild obstructive ventilatory dysfunction under protective ventilation during laparoseopic gallbladder surgery. Methods Sixty patients were included who underwent laparoseopic gallbladder surgery with general anesthesia. For the all subjects, the age ranged from 65 to 75 years old, the body mass index range was 18.5～23.9 kg/m2, and the ASA grade wasⅡorⅢ. In the subject selection, the gender was not limited, and the included subjects were diagnosed with mild obstructive ventilation dysfunction by preoperative pulmonary function tests. All the subjects were randomly divided into 2 groups (n=30), including dexmedetomidine group (group D) and control group (group C). In the group D, dexmedetomidine was intravenously infused at a dose of 1 μg/kg 10 min before and after the general anesthesia induction, and at a rate of 0.4μg/(kg·h) after tracheal intubation until the end of operation. Group C was given an equal volume of normal saline. Airway peak pressure (Ppeak), mean airway pressure (Pmean), airway plateau pressure (Pplat), and positive end-expiratory pressure (PEEP) were measured at 5 min after intubation (before pneumoperitoneum) (T1), end of pneumoperjtoneum (T2), and 10 min after the end of pneumoperitoneum (T3). The driving pressure (DP) was calculated. The blood samples of the radial artery were collected for blood gas analysis, and PaO2 and PaCO2 were recorded. The oxygenation index (PaO2/FiO2), respiratory index (RI), dead space ventilation rate (VD/VT), and alveolar-arterial oxygen partial pressure difference (A-aDO2) were calculated. The time of removal of the tracheal tube and the occurrences of complications such as hypercapnia and hypoxemia within 48 hours after extubation were recorded. Results Compared with group C, Ppeak, Pmean, DP, RI, VD/VT and A-aDO2 at T1, T2, T3 were decreased in group D, PaO2/FiO2 was increased, postoperative extubation time was shortened, and the incidence of hypoxemia was reduced within 48 h after operation (P<0.05). Compared with T1, Ppeak, Pmean, DP, RI, VD/VT and A-aDO2 at T2 were increased, and PaO2/FiO2 was decreased(P<0.05). Conclusions Dexmedetomidine can improve the pulmonary function in elderly patients with mild obstructive ventilatory dysfunction under protective ventilation during laparoseopic gallbladder surgery.

Isolation and identification of Oct4 RNA-binding proteins / 上海交通大学学报（医学版）

Objective: To identify the RNA binding proteins of Oct4, a key factor of embryonic stem cells. Methods: Total RNA was extracted from mouse embryonic stem cells (R1), which was reverse-transcribed into cDNA. Then PCR product of Oct4 mRNA were transcribed into Oct4 mRNA. Finally the candidate RNA-binding proteins were eluted applying the streptomycin affinity chromatography, and submitted for high-performance liquid chromatography combined with the mass spectrometry. The identified RNA binding proteins were further confirmed by RNA immunoprecipitation (RIP). Results: 121 RNA binding proteins of Oct4 3' untranslated region (UTR) and Oct4 5' UTR were identified with liquid chromatography / mass spectrometry. There were 11 proteins with the number of peptide spectrum matches more or equal to 2, and 7 of them were selected for additional confirmation using RIP method. RIP results showed that Oct4 interacted with DSP, SOD1, LMNA, NPM1, PSIP1, NCL and HDGF. Among them, HDGF had the strongest binding ability to Oct4 mRNA. Conclusion: Identification of Oct4 RNA binding proteins will provide a theoretical basis for the regulation mechanism of Oct4, and will be a basis for the further study of its function.

Efficacy and safety of Yangzheng Xiaoji capsule combined with radiotherapy and chemotherapy in the treatment of gastric cancer and its influence on immune function / 中国基层医药

Objective@#To explore the efficacy and safety of Yangzheng Xiaoji capsule combined with radiotherapy and chemotherapy in the treatment of gastric cancer and its influence on immune function.@*Methods@#From October 2016 to October 2018, 80 patients with gastric cancer in the First People's Hospital of Yongkang were divided into two groups according to the random number table, with 40 cases in each group.The control group received conventional radiotherapy plus chemotherapy, namely oxaliplatin, 5-fluorouracil combined with calcium leucovorin conventional chemotherapy.The observation group received Yangzheng Xiaoji capsule on the basis of the control group.The clinical symptoms, objective tumor efficacy, TCM symptoms and signs score, safety, immune function of the two group were observed.@*Results@#The total effective rate of the observation group was 87.5%, which was significantly higher than 72.5% of the control group(χ2=3.52, P<0.05). The RR, DCR of the observation group were 62.5%, 87.5%, respectively, which were significantly higher than 30.0%, 72.5% of the control group(χ2=4.31, P<0.05). The TCM symptoms and signs scores of the two groups after treatment were significantly improved compared with those before treatment(all P<0.05), which of the observation group after treatment was significantly lower than that of the control group(t=5.13, P<0.05). There were no statistically significant differences in WBC, Hb and PLT of the observation group before and after treatment(t=1.24, 1.62, 1.37, all P>0.05), and there were statistically significant differences in WBC, Hb and PLT of the control group before and after treatment(t=4.85, 3.64, 3.85, all P<0.05), and the WBC, Hb and PLT of the observation group were significantly higher than those of the control group after treatment(t=6.37, 4.15, 5.27, all P<0.05). In the observation group, leukopenia decreased in 4 cases, hemoglobin decreased in 6 cases and transaminase increased in 6 cases, which were significantly lower than 8 cases, 10 cases and 10 cases in the control group (χ2=4.26, P<0.05). Before treatment, there were no statistically significant differences in the levels of CD3＋, CD4＋, CD8＋, CD4＋/CD8＋ between the two groups(all P>0.05). There were no statistically significant differences in the levels of CD3＋, CD4＋, CD8＋, CD4＋/CD8＋ of the observation group before and after treatment(t=2.14, 2.08, 1.69, 2.47, all P>0.05), and compared with before treatment, the levels of CD3＋, CD4＋, CD4＋/CD8＋ of the control group were significantly decreased(t=5.12, 4.26, 5.38, all P<0.05), while the level of CD8＋ was significantly increased(t=3.86, P<0.05). After treatment, the levels of CD4＋, CD4＋, CD8＋, CD4＋/CD8＋ of the observation group were significantly better than those of the control group (t=4.79, 3.52, 4.28, 3.61, all P<0.05).@*Conclusion@#Yangzheng Xiaoji capsule combined with radiotherapy and chemotherapy can improve the curative effect of patients with gastric cancer, and it has high safety, less toxic and side effects, and can improve the immune function of patients with gastric cancer.It is worthy of promoting.

Clinical application of the lateral branch of lateral circumflex femoral artery in the anterolateral thigh perforator flap / 中华显微外科杂志

Objective To investigate the feasibility and technique of using the anterolateral thigh perforator flap pedicled with the lateral branch of the lateral circumflex femoral artery (LBLCFA) to repair soft tissue defect of extremities.Methods Eighty-six cases of anterolateral thigh perforator flap transplantation were performed from May,2014 to May,2018.A total of 37 cases of soft tissue defect of extremities were treated by anterolateral thigh perforator flap used the LBLCFA as vascular pedicle,of which there were 19 cases of upper limbs and 18 of lower limbs.There were 27 cases of defects caused by trauma,and 10 by soft tissue tumor resection.The flaps were designed centering around the point proximal to the midpoint of the iliac-patellar line.The dimensions of soft tissue defect were from 9.0 cm×6.0 cm to 26.0 cm×10.0 cm,and the flap were from 10.0 cm×7.0 cm to 27.0 cm×11.0 cm.The length of vascular pedicle ranged of 7.0-13.0 cm,with an average of 11.5 cm.The donor sites were directly sutured.All of the patients were followed-up regularly in the outpatient department.Results All the flaps survived and the donor sites were primarily healed.Of these 37 cases,2 trauma patients and 2 patients treated with local radiotherapy had poor wound healing,but still healed after multiple dressing changes.All the patients were followed-up for 3-26 months,with an average of 13 months.The texture,color and elasticity of the flap were similar to the surrounding tissue of the recipient sites,while only a linear scar remained at the donor sites.Ten tumor patients were treated with routine radiotherapy and chemotherapy after the repairation;there was no tumor recurrence during the follow-up period.Conclusion The LBLCFA gives off a relatively large and thick perforator proximal 5.0-7.0 cm of the iliacpatellar line,which locates in the upper lateral side,travels parallel to the vastus lateralis,and give off the skin and muscular perforators.The lateral branch can be used as pedicle to make into perforator flap or chimeric flap,which provides a novel selection of vascular pedicel for anterolateral thigh perforator flap.When the descending branch does not provide a thick and large perforator,the LBLCFA has important practical value and is worth utilizing in the clinic.

Research on knee posteromedial complex / 中华创伤骨科杂志

Injury to the knee posteromedial complex can cause serious joint dysfunction,leading to rotational instability and degeneration of cartilage.Lack of overall understanding of the knee posteromedial complex can often result in ineffective clinical treatment of the injury.On the basis of extensive review of domestic and international literature about the injury to the knee posteromedial complex in recent years,this article summarized the anatomy,biomechanics and function of the structure,and analyzed the classification and treatment of the iniurv.

Association study between a genetic polymorphism in cytochrome P450 19 gene rs10046 and colon and rectal cancer / 中国医师杂志

Objective To investigate the relationship between the polymorphism of cytochrome P450 19 (CYP19) gene rs10046 and the risk of colon and rectal cancer.Methods Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to analyze gene polymorphism in CYP 19 gene rs10046 in 198 cases of colon and rectal cancer patients (case group) and 309 cases of healthy controls (control group).The genotype frequency and relative risk of CYP19 gene rs10046 between the two groups were compared and the relationship with the clinicopathological features of colorectal cancer was analyzed.Results In case group,the prevalence rates of CYP19 rs10046 genotypes C/C,C/T and T/T were 28.3％,44.4％ and 27.3％,respectively,and 17.2％,51.8％ and 31.1％ in the control group,respectively,with statistical significant difference (P ＜ 0.05).Compared with wild-type C/C,the susceptibility of colorectal cancer with the genotypes of C/T and T/T was decreased by 0.521 (95％ CI:0.330-0.822)and 0.532 (95 ％ CI:0.322-0.880) respectively.Moveover,in the non-smoking group,the risk of colorectal cancer with genotype T/T or C/T was decreased by 0.409 (95％ CI:0.210-0.798) compared with genotype C/C.The interaction was not exist in smoking group.Conclusions The polymorphism of CYP19 gene rs10046 is related to the susceptibility of colon and rectal cancer.The T/T,C/T genotype of CYP19 rs10046 decrease the risk of colon and rectal cancer,and which might be the protective factor of colon and rectal cancer.