Objective To investigate the effects of remazolam on melatonin secretion,sleep rhythm and postoperative delirium(POD)in elderly patients undergoing spinal surgery.Methods A total of 160 elderly patients,76 males and 84 females,aged 65-80 years,BMI 18.5-24.0 kg/m2,ASA physical status Ⅱ or Ⅲ,from November 2023 to January 2024 undergoing spinal surgery(lumbar interbody fusion,posterior approach)under general anesthesia were selected.The patients were divided into two groups by random number table method:the remazolam group(group R)and the propofol group(group P),80 pa-tients in each group.Group R was given remazolam 0.3 mg/kg for anesthesia induction,and then continued to pump remazolam 0.3-0.8 mg·kg-1·h-1 for anesthesia maintenance.Group P was given propofol 2.0 mg/kg for anesthesia induction,and then continued to pump propofol 4-6 mg·kg-1·h-1 for anesthesia maintenance.The levels of melatonin and cortisol were recorded at 04:00 a.m.on the day of surgery,1 day,2 and 3 days after surgery.Pittsburgh sleep quality index(PSQI)and VAS pain scores at rest were recorded 1 day before surgery,1 day and 2 days after surgery and before discharge.The occurrence of POD and post-operative sleep disorder(POSD)were recorded.The duration of extubation,PACU stay time,total analgesia pump compressions,effective analgesia pump compressions,number of remedial analgesia cases,intraoperative hypotension,postoperative nausea and vomiting,dizziness,respiratory depression and other adverse events were recorded.Results Compared with group P,the extubation time and PACU residence time in group R were significantly shortened(P＜0.05),the level of melatonin was significantly increased while the level of cortisol was significantly decreased at 4:00 a.m.,and the PSQI was significantly decreased 1 day after surgery(P＜0.05),the incidence of POD,POSD,and intraoperative hypotension were signifi-cantly decreased(P＜0.05).There were no significant differences in extubation time,total and effective times of analgesic pump,rate of remedial analgesia,intraoperative hypotension,postoperative nausea,vom-iting,dizziness and respiratory depression between the two groups.Conclusion Remazolam has little effect on the secretion rhythm of melatonin and cortisol and the sleep rhythm after spinal surgery in elderly pa-tients,and the recovery is faster,which can reduce the incidence of POD and alleviate the sleep disorder af-ter spinal surgery.

Male infertility is a multifactorial disease, of which the cause of male infertility cannot be determined, which is called idiopathic male infertility, and the incidence rate is gradually rising. Because its cause is unknown, it has become a major problem in the department of reproductive endocrinology. With the in-depth study of epigenetics, the diagnosis and treatment of idiopathic male infertility also has a new direction, especially the important role of DNA methylation in spermatogenesis and embryonic development. More and more gene fragments and loci have been found by scholars, which makes it possible to achieve accurate identification and targeted treatment. This article reviews and summarizes the research progress of DNA methylation related to idiopathic male infertility in recent years, aiming to further elaborate the pathogenesis of idiopathic male infertility and provide new ideas for clinical diagnosis and treatment.

Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genome ; Humans ; Liver Neoplasms/metabolism* ; Metformin/therapeutic use* ; Mice ; Phosphorylation ; Synthetic Lethal Mutations ; Transcription Factors/metabolism* ; rac GTP-Binding Proteins/metabolism*

Objective To explore the features of resting state functional magnetic resonance imaging (rs-fMRI) in the patients with mild cognitive impairment (MCI) after during the process of converting to Alzheimer's disease (AD) dementia. To study the correlation of the brain function imaging and neuropsychological scores in converted MCI subjects with the purpose of finding the potential functional biomarkers which may predict the conversion of MCI to AD dementia in short term using resting state functional MRI. Methods Twenty-seven patients with MCI and 31 age, gender and years of education matched normal controls (NC) were enrolled in this study and neuropsychological assessment and rs-fMRI data were acquired respectively at the baseline and follow-up. Functional connectivity strength (FCS) analyses were used to assess the functional differences among the groups of MCI-converters (MCI-c) , MCI-non converters (MCI-nc) and NC. Variance analyses were used to compare the group differences in age, years of education and each neuropsychological assessment. In addition, Chi-squared test was used to compare group differences in gender. Then, Kruskal-Wallis test was used to compare group differences in the interval time of twice data collection. Group differences in FCS values were analyzed by general linear model. Finally, correlation analyses were used to evaluate the relationships between the FCS values of the brain regions with group differences and neuropsychological assessment scores in MCI patients. Results (1) Significant group differences of FCS among the MCI-c, MCI-nc and NC groups were observed in bilateral angular gyri, bilateral orbitofrontal cortex, right precentral gyrus, left paracentral lobule, left precuneus, right fusiform, right middle occipital gyrus, right superior occipital gyrus, left cerebellum. (2) The MCI-c showed decreased FCS in bilateral angular gyri, right middle occipital gyrus, right superior occipital gyrus, right inferior occipital gyrus, right fusiform, left precuneus, and left paracentral lobule, as compared to MCI-nc, the cluster was 149, 114, 186, 56, 48, 33, 38 and 102 voxels, respectively;P<0.05, respectively. The correlation analysis showed that the FCS values of the right angular gyrus were negative correlated with the MMSE scores (r=-0.561, P=0.017) . Conclusions This study revealed that the comparison of rs-fMRI imaging data between MCI-c and MCI-nc at baseline is of great benefits in analysing the imaging characteristics of patients during converting from MCI to AD. The feature of FCS in rs-fMRI in right angular gyrus might serve as early indicators for the dysfunction and progression from MCI to AD.

Objective To explore the features of resting state functional magnetic resonance imaging (rs-fMRI) in the patients with mild cognitive impairment (MCI) after during the process of converting to Alzheimer's disease (AD) dementia. To study the correlation of the brain function imaging and neuropsychological scores in converted MCI subjects with the purpose of finding the potential functional biomarkers which may predict the conversion of MCI to AD dementia in short term using resting state functional MRI. Methods Twenty-seven patients with MCI and 31 age, gender and years of education matched normal controls (NC) were enrolled in this study and neuropsychological assessment and rs-fMRI data were acquired respectively at the baseline and follow-up. Functional connectivity strength (FCS) analyses were used to assess the functional differences among the groups of MCI-converters (MCI-c) , MCI-non converters (MCI-nc) and NC. Variance analyses were used to compare the group differences in age, years of education and each neuropsychological assessment. In addition, Chi-squared test was used to compare group differences in gender. Then, Kruskal-Wallis test was used to compare group differences in the interval time of twice data collection. Group differences in FCS values were analyzed by general linear model. Finally, correlation analyses were used to evaluate the relationships between the FCS values of the brain regions with group differences and neuropsychological assessment scores in MCI patients. Results (1) Significant group differences of FCS among the MCI-c, MCI-nc and NC groups were observed in bilateral angular gyri, bilateral orbitofrontal cortex, right precentral gyrus, left paracentral lobule, left precuneus, right fusiform, right middle occipital gyrus, right superior occipital gyrus, left cerebellum. (2) The MCI-c showed decreased FCS in bilateral angular gyri, right middle occipital gyrus, right superior occipital gyrus, right inferior occipital gyrus, right fusiform, left precuneus, and left paracentral lobule, as compared to MCI-nc, the cluster was 149, 114, 186, 56, 48, 33, 38 and 102 voxels, respectively;P<0.05, respectively. The correlation analysis showed that the FCS values of the right angular gyrus were negative correlated with the MMSE scores (r=-0.561, P=0.017) . Conclusions This study revealed that the comparison of rs-fMRI imaging data between MCI-c and MCI-nc at baseline is of great benefits in analysing the imaging characteristics of patients during converting from MCI to AD. The feature of FCS in rs-fMRI in right angular gyrus might serve as early indicators for the dysfunction and progression from MCI to AD.

Objective To investigate the expression of elongation of very long-chain fatty acids family member 6 (ELOVL6) in high-grade serous ovarian carcinoma (HSOC), and explore the correlation between its expression and clinical prognosis in these patients. Methods The expression of ELOVL6 at mRNA and protein levels were respectively detected by reverse transcription (RT)-PCR and immune histochemistry method in 12 cases with normal ovarian tissues and 172 cases with HSOC from primary tumor site, forty of which had paired peritoneal metastatic tissues. Results (1) The results tested by RT-PCR showed that ELOVL6 expression in normal ovarian tissue was 4.8±1.1, while 1.2±0.7 in primary tumors and 1.8 ± 0.9 peritoneal metastatic sites in HSOC. Compared with normal ovarian tissue, the level of ELOVL6 mRNA was significantly lower in HSOC (P<0.05). There was no significant difference between primary and peritoneal metastatic sites in HSOC (P=0.610). It was shown that ELOVL6 protein localized in cytoplasm of ovarian cancer cell by immunostaining assay. (2) ELOVL6 expression was observed in all normal ovarian tissue, 70.2%of G1-G2 and 48.8%of G3 HSOC (P<0.05). ELOVL6 expression in drug-resistant group were significantly lower than that in non-resistant group (39.1% vs 65.0%, P<0.01). The median disease-free survival was 41 months in the ELOVL6-positive group and 39 months in ELOVL6-negative group (P>0.05). The total median survival was 52 months in ELOVL6-positive group and 44 months in ELOVL6-negative group (P>0.05). Conclusion Low expression of ELOVL6 may correlate with the poor differentiation and drug resistance in HSOC.

Objective To investigate the effect of depression on the incidence of osteoporosis in patients with maintenance peritoneal dialysis (MPD).Methods We enrolled 80 MPD patients,who underwent peritoneal dialysis in our dialysis center.The clinical data and biochemical parameters of all patients were collected,bone mineral density was detected and the Self-rating depression scale was used to evaluate depression state.Results Among the 80 enrolled MPD patients,34 patients had osteoporosis (42.5％),48 patients had the presence of depression (60％).Logistic regression analysis showed that age,dialysis age,gender,diabetes history and depression state were the risk factors for osteoporosis in MPD patients,the depression state was negatively correlated with BMD of lumbar and femoral neck (r=-0.347,r=0.426,P＜0.05).Conclusion Depression state may be a risk factor for osteoporosis in clinic,it is of great significance to focus on the psychological state of MPD patients in the prevention and treatment of osteoporosis.

OBJECTIVETo study polymorphisms of catechol-O-methyltransferase (COMT) and monoamine oxidase B (MAO-B) genes among Chinese patients with Parkinson's disease.

METHODSGenotypes of the COMT and MAO-B genes of 1408 patients with Parkinson's disease was sequenced using Sanger method. And these patients were recruited by Chinese Parkinson Study Group from 29 research centers throughout the country.

RESULTSThe genotypic frequencies of COMT rs4680 AA, AG, GG were 8.9%, 42.0% and 49.1%. Those of rs4818 CC, CG, GG were 42.5%, 45.6% and 11.9%, respectively. The genotype frequencies of MAO-B rs1799836 A/AA, AG, G/GG were 74.4%, 14.1% and 11.5%, respectively. The haplotype formed by COMT rs4680 (GG) and MAO-B rs1799836 (A/AA) genotype has a frequency of 36.86%.

CONCLUSIONPolymorphisms of COMT and MAO-B genes has a unique characteristics among Chinese patients with Parkinson's disease. They may be related with differences in drug response in such patients.

Asian Continental Ancestry Group ; genetics ; Catechol O-Methyltransferase ; genetics ; Female ; Genotype ; Humans ; Male ; Monoamine Oxidase ; genetics ; Parkinson Disease ; genetics ; Polymorphism, Genetic

This paper analyzed the system,methods,content,scope and standards of last two competition in order to further improve the clinical skills competition for national medical students in China.According to the characteristics of medical education,the paper proposed several opinions and suggestions as follows:repechage should be cancelled in competition system and objective structured clinical examination should be used in competition; the content,scope and criteria of the competition should take the actual ability of the medical students at graduation into consideration.

Objective To investigate the preventative effect of perioperative intervention to lower extremity deep venous thrombosis (DVT) after gynecologic surgery. Methods The 1062 patients, who received gynecologic surgery during 2007 June to 2008 June, were derided into intervention and nonintervention groups randomizely. According to the risk factors of DVT, the patients in intervention group were divided into 4 subgroups: low, mid, high and extremely high rise Each group had its own preventive measures. If patients had spontaneous pain, tenderness and swelling, positivity of Neuhof or Homan syndrome, and extension of one low extremity superficial vein, the low extremity color Doppler ultrasound would be carried out immediately. The ultrasound would also be routinely carried out in the high and extremely high risk groups in intervention group after 2 and 7 days after surgery. A prospective study was carried out investigating incidence of DVT and coagulation function perioperation. The vein blood samples were taken at in a week before surgery and 48 hours post-operation. Results The incidence of DVT of intervention group was 1.10% (6/546), and in nonintervention group, the incidence was 3.29% (17/ 516). There was significant difference between two groups (P<0.05). The incidence of DVT in extremely high risk subgroup was 21.05% (4/19), which was significantly higher than that of low(0), mid(0) and high risk groups[2.13% (2/94), P<0.05]. D-dimer, antithrombin-Ⅲ(AT-Ⅲ) post-operation were all higher than that pre-operation in the two groups, but there was no significant difference (P>0.05). The indexes of coagulation system, such as blood platelet count, prothrombin time (PT), active partial throraboplastin time (APTT), fibrinogen (Fbg), thrombin time (TT), tissue-plasminogen activator (t-PA), plasminogen activator inhibitor(PAI), were not significantly changed perioperation (P>0.05 in all pre-or post-operation indexes). Conclusions Perioperative intervention measurement according to different risk of DVT could cut down the incidence of DVT. DVT preventive intervention is suggested to high and extremely high risk people.