Objective To evaluate the economic value of using glucagon-like peptide-1 receptor agonist(GLP-1RA)in combination with metformin for the treatment of type 2 diabetes mellitus(T2DM).Methods Based on 7 randomized controlled clinical trials(RCTs),Markov model was built to simulate the dynamic changes of metformin alone or combined with GLP-1RA in the treatment of T2DM patients without or with complications and death from the perspective of China's health system.Quality-adjusted life years(QALYs)was used as a health output indicator and 3 times China's per capita gross domestic product(GDP)in 2023 was set as the willingness-to-pay(WTP)threshold.The cycle was at the rate of 1 year and a total of 20 years cohort simulation in Markov model was applied to obtain long-term cost and effect of each treatment strategy.The incremental cost-utility ratio(ICUR)was analyzed as the primary evaluation indicator and the sensitivity of cost,utility and discount was performed to test the stability of the results.Results Compared with metformin alone,the ICUR of GLP-1RA including liraglutide,dulaglutide,exenatide,loxenatide,semaglutide combined with metformin were all below the WTP threshold,and the increased cost was acceptable.Extending the simulation time to 30 years or 50 years had no effect on results.The results of probability sensitivity analysis showed that the cost effect of semaglutide 0.5 mg combined with metformin had the highest probability of a cost-utility advantage of 99.7％among all the treatment strategies when WTP threshold was 3 times China's per capita GDP in 2023(268 074 yuan).Conclusion GLP-1RA,including liraglutide,dulaglutide,exenatide,lixisenatide,and semaglutide,at the regular recommended dose combined with metformin,would present higher cost-utility compared to metformin monotherapy.

Objective To evaluate the efficacy and safety of glucagon-like peptide 1 receptor agonists(GLP-1RA)in type 2 diabetes mellitus(T2DM)patients with overweight or obese.Methods PubMed,Embase,Cochrane Library,Ovid,ClinicalTrial.gov,SinoMed,CNKI,WanFang Data and VIP databases were electronically searched to collect randomized controlled trials(RCTs)on the efficacy of GLP-1RA in the treatment of T2DM patients with overweight or obese from January 1,2005 to November 1,2023.Two researchers independently screened the literature,extracted data and evaluated the risk of bias of the included studies.R software was then used for meta-analysis.The level of evidence was assessed by using the GRADE system.Results A total of 71 RCTs were included,including 29 476 patients.The results of Meta-analysis showed that compared with other hypoglycemic drugs,GLP-1RA showed superior effects in improving HbAlc status(WMD=-0.55,95％CI-0.65 to-0.45,P＜0.001)and weight loss(WMD=-2.61,95％CI-3.25 to-1.97,P＜0.001),while the effect on fasting plasm glucose was time-dependent(within 16 weeks:WMD=0.25,95％CI-0.17 to 0.66,P=0.250;16 to 52 weeks:WMD=-0.06,95％CI-0.32 to 0.20,P=0.650;over 52 to 104 weeks:WMD=-1.67,95％CI-1.91 to-1.43,P＜0.001).In terms of safety,the incidence of GLP-1RA's adverse reactions was higher than other hypoglycemic drugs(RR=1.11,95％CI 1.07 to 1.15,P＜0.001);the incidence of hypoglycemia was lower with GLP-1RA than with insulin(RR=0.58,95％CI 0.48 to 0.71,P＜0.001)and similar to oral hypoglycemic drugs(RR=0.83,95％CI 0.58 to 1.19,P=0.310).According to the GRADE assessment,only the certainty of the evidence for the results of the incidence of hypoglycemia was moderate,and the certainty of the evidence for the other results was low.Conclusion Current evidence shows that for T2DM patients with overweight or obese,GLP-1RA especially semaglutide,was more effective in lowering blood glucose,controlling body weight and reducing the occurrence of hypoglycemia than placebo,insulin and oral hypoglycemic drugs.

Objective:To explore the relationship between heart rate variability, severity, and prognosis in patients with acute cerebral infarction (ACI).Methods:A prospective study was conducted on 80 patients with acute cerebral infarction (ACI) admitted to Qinhuangdao Workers′ Hospital from February 2021 to March 2023. The severity of ACI patients was evaluated based on their National Institutes of Health Stroke Scale (NIHSS) scores, and they were divided into mild group (26 cases, NIHSS scores 0-15), moderate group (32 cases, NIHSS scores 16-30), and severe group (22 cases, NIHSS scores 31-45); And 30 healthy individuals who underwent physical examinations during the same period were selected as the control group. The improved Rankin Scale (MRS) was used to evaluate the prognosis of patients, who were divided into a good prognosis group (59 cases) and a poor prognosis group (21 cases) based on the scoring results. All patients underwent dynamic electrocardiogram examination, and the heart rate variability parameters of each group were compared [standard deviation of R-R interval for all sinus beats at 24 hours (SDNN), mean standard deviation of R-R interval for 5 consecutive minutes at 24 hours (SDNN Index), standard deviation of R-R interval mean every 5 minutes (SDANN), root mean square of all adjacent R-R interval differences (rMSSD), and the proportion of adjacent NN interval differences greater than 50 ms (PNN50%)]. The predictive value of heart rate variability parameters on the severity and prognosis of ACI patients was analyzed using receiver operating characteristic (ROC) curves. Logistic regression analysis was used to identify the risk factors for the severity and prognosis of ACI patients.Results:The SDNN, SDANN, SDNN Index, rMSSD, and PNN50% of the mild, moderate, and severe groups were significantly lower than those of the control group ( F=59.382, 11.859, 12.376, 11.699, 47.703, all P<0.01), and the severe group was less than the moderate group and less than the mild group (all P<0.05). The SDNN, SDANN, SDNN Index, rMSSD, and PNN50% in the poor prognosis group were lower than those in the good prognosis group ( t=4.536, 4.181, 5.091, 4.384, 2.851, all P<0.01). The results of logistic regression analysis showed that heart rate variability parameter was an independent influencing factor for the severity and poor prognosis of ACI patients (all P<0.01). The area under the curve for the combined diagnosis of the severity of ACI patients using SDNN, SDANN, SDNN Index, rMSSD, and PNN50% was 0.950, and the area under the curve for the combined prediction of ACI patients′ prognosis was 0.970. Conclusions:The heart rate variability parameter is an independent influencing factor on the severity and prognosis of ACI patients, and its predictive power for the severity and prognosis of ACI patients is high. It can be used as an effective indicator for evaluating the severity and prognosis of ACI patients.

Objective:To evaluate the pancreatic subclinical dysfunction after intensity-modulated radiation therapy (IMRT) for gastric cancer by analyzing biochemical indexes and pancreatic volume changes, and to reduce the dose of pancreas by dosimetric prediction and dose limitation.Methods:30 patients with gastric cancer who received 45 Gy postoperative adjuvant radiotherapy were retrospectively selected. The pancreas was delineated and its dose and anatomical relationship with planning target volume (PTV) were evaluated. Fasting blood glucose, serum lipase and amylase, and pancreatic volume changes before and after radiotherapy were analyzed. The correlation between the changes of biochemical indexes and volume and pancreatic dose was evaluated by Pearson analysis. The threshold of the dosimetric prediction was obtained by receiver operating characteristic (ROC) curve. Finally, the feasibility of dosimetric limitation in IMRT was assessed.Results:The pancreatic volume of 30 patients was 37.6 cm 3, and 89.0% of them were involved in PTV. D mean of the pancreas was 45.92 Gy, and 46.45 Gy, 46.46 Gy and 45.80 Gy for the pancreatic head, body and tail, respectively. The fasting blood glucose level did not significantly change. The serum lipase levels were significantly decreased by 66% and 77%(both P<0.001), and the serum amylase levels were significantly declined by 24% and 38%(both P<0.001) at 6 and 12 months after radiotherapy. Pancreatic volumes of 22 patients was decreased by 47% within 18 months after radiotherapy. ROC curve analysis showed that pancreatic V 45Gy had the optimal predictive value for the decrease by 1/3 of serum lipase and amylase levels at 6 months and serum amylase level at 12 months after radiotherapy, and the cut-off value was V 45Gy<85%. Pancreatic D mean yielded the optimal predictive value for the decrease by 2/3 of serum lipase level at 12 months after radiotherapy, and the cut-off value was D mean<45.01 Gy. After" whole pancreas" and" outside PTV pancreas" dose limit, V 45Gy of the pancreas was decreased by 11% and 7%, D mean of the pancreas was declined by 2% and 2%, and D mean of the pancreatic tail was decreased by 3%, respectively. Conclusions:Serum lipase and amylase levels significantly decline at 6 and 12 months after adjuvant radiotherapy for gastric cancer, and pancreatic volume is decreased significantly within 18 months after radiotherapy. Pancreatic V 45Gy<85% and D mean<45.01 Gy are the dose prediction values for the decrease of serum lipase and amylase levels. The dose can be reduced to certain extent by dosimetric restriction.

Objective To preliminarily explore the effects of human dermis derived mesenchymal stem cells (hDMSCs) on expressions of α-smooth muscle actin (α-SMA) and decorin (DCN) in hypertrophic scars fibroblasts (HSFB) at different periods,and to explore the feasibility of MSCs in prevention and treatment of HSFBs.Methods hDMSCs were cultured with mechanical method combined with enzyme digestion.The cells of the third generation which were well grown were taken,and flow cytometry (FCM) was used to detect CD molecules in hDMSCs.Immunocytochemistry was used to detect cytokeratin 19 (CK19) and vimentin and identify the separated cells.The cells were differentiated into lipoblasts,chondroblasts and osteoblasts.According to the formation course of hypertrophic scar,the scar specimens were divided into 6-month,l-year,and 2-year group with three cases in each group.HSFBs from different groups were co-cultured with well-adherent hDMSCs of the third generation in non-contact transwell co-culture system for 21 days.And HSFBs from the corresponding groups were cultured in normal six-well plate as the controls.Real-time fluorescent-polymerase chain reaction (RT-PCR) and Western Blot were used to detect the expressions of mRNA and proteins of α-SMA and DCN in HSFBs from different groups.Results hDMSCs highly expressed the surface markers including CD73,CD105,CD44 and CD90,etc.,but did not express hematopoietic stem cell surface markers including CD 14,CD34 and CD45.They positively expressed vimentin but not CK19.The cells can be differentiated into lipoblasts,chondroblasts and osteoblasts,which was in line with the minimum identification standards of mesenchymal stem cells.For HSFB cultured in normal six-well plates,α-SMA mRNA and protein expressions of HSFB in the 6-month,1-year and 2-year groups were 198.20 ± 15.46/0.29 ± 0.070,175.24 ± 17.04/0.38 ± 0.110,and 125.73 ± 6.99/0.33 ±0.085,respectively;while DCN mRNA and protein expressions of HSFB in the corresponding groups were 61.30 ± 9.79/0.015 ± 0.003,70.89 ± 11.29/0.020 ± 0.007,and 77.31 ± 4.80/0.023 ± 0.003,respectively.For HSFB co-cultured with 5 × 104 hDMSCs,oα-SMA mRNA and protein expressions of HSFB in the 6-month,1-year and 2-year groups were 48.40 ± 6.42/ 0.100 ± 0.020,192.16 ± 11.37/0.110 ± 0.014,and 73.33 ± 6.29/0.110 ± 0.016,respectively;while DCN mRNA and protein expressions of HSFB in the corresponding groups were 156.92 ± 14.91/0.049 ±0.015,154.42 ± 18.17/0.033 ± 0.008,and 140.82 ± 7.32/0.030 ± 0.004,respectively.Compared with the control group(Cultured in normal six-well plates),mRNA and protein expressions of α-SMA in HSFBs were decreased after co-culture with 5 × 104 hDMSCs,mRNA and protein expressions of DCN were increased.Furthermore,it suggested that hypertrophic scar changed significantly in the early formation stage namely in the 6-month group.Conclusions hDMSCs can down-regulate α-SMA mRNA and protein expressions of HSFBs and up-regulate mRNA and protein expressions of DCN in the in-vitro culture system.Those effects were particularly obvious on fibroblasts at the early formation of hyperplastic scar.Anti fibrosis role of hDMSCs is expected to be used in increasing the healing quality of the wound and in the prevention and treatment of pathological scars.

Objective To preliminarily explore the effects of human dermis derived mesenchymal stem cells (hDMSCs) on expressions of α-smooth muscle actin (α-SMA) and decorin (DCN) in hypertrophic scars fibroblasts (HSFB) at different periods,and to explore the feasibility of MSCs in prevention and treatment of HSFBs.Methods hDMSCs were cultured with mechanical method combined with enzyme digestion.The cells of the third generation which were well grown were taken,and flow cytometry (FCM) was used to detect CD molecules in hDMSCs.Immunocytochemistry was used to detect cytokeratin 19 (CK19) and vimentin and identify the separated cells.The cells were differentiated into lipoblasts,chondroblasts and osteoblasts.According to the formation course of hypertrophic scar,the scar specimens were divided into 6-month,l-year,and 2-year group with three cases in each group.HSFBs from different groups were co-cultured with well-adherent hDMSCs of the third generation in non-contact transwell co-culture system for 21 days.And HSFBs from the corresponding groups were cultured in normal six-well plate as the controls.Real-time fluorescent-polymerase chain reaction (RT-PCR) and Western Blot were used to detect the expressions of mRNA and proteins of α-SMA and DCN in HSFBs from different groups.Results hDMSCs highly expressed the surface markers including CD73,CD105,CD44 and CD90,etc.,but did not express hematopoietic stem cell surface markers including CD 14,CD34 and CD45.They positively expressed vimentin but not CK19.The cells can be differentiated into lipoblasts,chondroblasts and osteoblasts,which was in line with the minimum identification standards of mesenchymal stem cells.For HSFB cultured in normal six-well plates,α-SMA mRNA and protein expressions of HSFB in the 6-month,1-year and 2-year groups were 198.20 ± 15.46/0.29 ± 0.070,175.24 ± 17.04/0.38 ± 0.110,and 125.73 ± 6.99/0.33 ±0.085,respectively;while DCN mRNA and protein expressions of HSFB in the corresponding groups were 61.30 ± 9.79/0.015 ± 0.003,70.89 ± 11.29/0.020 ± 0.007,and 77.31 ± 4.80/0.023 ± 0.003,respectively.For HSFB co-cultured with 5 × 104 hDMSCs,oα-SMA mRNA and protein expressions of HSFB in the 6-month,1-year and 2-year groups were 48.40 ± 6.42/ 0.100 ± 0.020,192.16 ± 11.37/0.110 ± 0.014,and 73.33 ± 6.29/0.110 ± 0.016,respectively;while DCN mRNA and protein expressions of HSFB in the corresponding groups were 156.92 ± 14.91/0.049 ±0.015,154.42 ± 18.17/0.033 ± 0.008,and 140.82 ± 7.32/0.030 ± 0.004,respectively.Compared with the control group(Cultured in normal six-well plates),mRNA and protein expressions of α-SMA in HSFBs were decreased after co-culture with 5 × 104 hDMSCs,mRNA and protein expressions of DCN were increased.Furthermore,it suggested that hypertrophic scar changed significantly in the early formation stage namely in the 6-month group.Conclusions hDMSCs can down-regulate α-SMA mRNA and protein expressions of HSFBs and up-regulate mRNA and protein expressions of DCN in the in-vitro culture system.Those effects were particularly obvious on fibroblasts at the early formation of hyperplastic scar.Anti fibrosis role of hDMSCs is expected to be used in increasing the healing quality of the wound and in the prevention and treatment of pathological scars.

Objective To study the morphological characteristics of eyes of female Uygur youth for providing the relevant data for eye aesthetic plastic surgery.Methods Compared with 150 cases of Han youth in the same school,the somatological survey was carried out in 150 female Uighur college students with the morphological characteristics of the eyes and good facial harmony.SPSS 17.0 was used for statistical analysis of the measured data in groups divided according to different race.Results 59.3％ (89/150) of the Uighur young women had prominent brow ridges tall nose and superior orbit cave,18.7％ (28/150) of them were similar to the Han type of eye,and 22.0％ (33/150) in between.The rate of epicanthus in Uighur women was 28.0％ (42/150),which was significantly lower than the Han nationality women 62.7％ (94/150).Double eyelid incidence was 96.7％ (145/150),which was significantly higher than that of Chinese Han women 67.3％ (101/150).There was a no statistically significant difference between them in palpebral fissure length inner canthic diameter and outer canthic diameter (P＞0.05),but a statistically significant difference was found in the height of palpebral fissure,the width of double eyelid and the distance between the eyebrow eyelid (P＜0.05).Conclusions The Uighur women's eye morphology has dual characteristics of Caucasoid and Mongoloid.The data have great significance and value in guiding the eye's cosmetic plastic surgery.

Objective To observe the relationship of IL-10 gene single nucleotide polymorphism and the susceptibility to ALL. Methods The bone marrow and peripheral blood samples from 115 ALL patients and 323 healthy controls were collected in Peking University First Hospital and Beijing Dao-pei Hospital from January 2007 to December 2009. The DNA were extracted from all samples. The primers of -819C/T and -592A/C in the promoter region of IL-10 gene were designed for the PCR. The restrictive fragment length polymorphism of IL-10 gene was analyzed by using restrictive enzyme Msl Ⅰ and HpyCH4 Ⅲ.Sequencing was done in part of these samples to confirm the results of PCR. The differences of genotypes and allele ratio of -819 and -592 sites were analyzed between the ALL patients and healthy controls. Real-time quantitative PCR was performed to detect the EB virus (EBV) infection and the expression of BCR/ABL fusion gene. The differences of genotypes and allele ratio of -819 and -592 sites were analyzed between the positive and negative group. Results The genotype ratios of -819CC, -819TT, - 819CT, -592AA,- 592CC and - 592AC were 14. 8% ( 17/115 ), 45.2% ( 52/115 ), 40. 0% ( 46/115 ), 43.5% ( 50/115 ),16. 5% ( 19/115 ), 40. 0% ( 46/115 ) in ALL patients, and were 9. 9% ( 32/323 ), 16. 4% ( 53/323 ),73.7% ( 238/323 ), 11.8% ( 38/323 ), 15.5% ( 50/323 ), 72. 8% ( 235/323 ) in the healthy controls,respectively. The genotypes of -819 and -592 sites had statistically significant differences between the two groups(x2 values were 46.000 and 54.550, all P ＜ 0. 05 ). The allele ratio of -819T and -592A were (65.2%, 150/230) and (63.5%, 146/230) in ALL patients, while they were 53.5% (344/646) and 48. 1% (311/646)in the healthy controls. There were statistically significant differences between the two groups (x2 values were 9. 877 and 15.986, all P ＜ 0. 05 ). The EBV DNA were detected in 42 ALL patients,among which 22 were positive and 20 were negative. The genotype ratios of -819CC, -819TT, -819CT,-592AA, - 592CC, - 592AC in EBV positive group were 9. 1% ( 2/22 ), 40. 9% ( 9/22 ), 50. 0%(11/22) ,31.8% ( 7/22 ), 13.6% ( 3/22 ), 54. 5% ( 12/22 ), while they were 35.0% ( 7/20 ), 45.0%(9/20) ,20. 0% (4/20) ,35.0% (7/20) ,45.0% (9/20) ,20. 0% (4/20) in the EBV negative group. The genotypes of -819 and -592 sites showed no statistical differences between the two groups( all P ＞ 0. 05 ).The BCR/ABL fusion gene were detected in 36 ALL patients, among which 20 were positive and 16 were negative. The genotype ratios of - 819CC, - 819TT, - 819CT, - 592AA, - 592CC, - 592AC in BCR/ABL positive group were 0% (0/20) ,45.0% (9/20) ,55.0% ( 11/20), 45. 0% (9/20) ,5.0% (1/20) ,50. 0%( 10/20), while they were 18. 8% ( 3/16 ), 50. 0% ( 8/16), 31.3% ( 5/16 ), 50. 0% ( 8/16 ), 18. 8%(3/16), 31.3 % (5/16)in the BCR/ABL negative group. The genotypes of -819 and -592 sites showed no statistical differences between the two groups ( all P ＞ 0. 05 ). Conclusion The population with - 819TT and - 592AA genotype of IL-10 gene shows susceptibility to ALL.

European countries have long history of medical education.Medical colleges have their independence in comprehensive universities and have high degree of standardization ad systematization in management.Besides,long schooling and high cost,small-size class teaching,good matrabulate quality and the combination of professional and part-time clinic teachers are the characteristics in their talent cultivation,which guarantee the medical education quality and can be used by us for reference.

0.05). The observation about reliability markers indicated:there were no toxic and side effects. Conclusion There was no obvious difference in the effectiveness on treating cough in children for attacking on the lung by wind and heat (acute bronchitis) between the treated group and the control group. During the reliability observation, Kechuanling Effervescent Troche indicated good clinical reliability.