Background and purpose:Pain is one of the most common symptoms in advanced cancer patients, and morphine is a representative drug in controlling moderate to severe cancer-induced pain, but some unacceptable adverse effects limited its use in part of patients.We evaluated the effect and safety of morphine sulfate controlled-release tablet (MS-CRT) combined with celecoxib for the treatment of moderate to severe cancer pain, and assessed the life quality of patients. Methods:Retrospective analysis of 125 cancer patients with moderate to severe cancer pain who were divided into two groups, one(including 67 patients) was treated by single drug of MSCRT whose initial dosage was 20 mg/12 hrs, then evaluated by verbal rating scale within 24 to 48 hrs, dosage was adjusted personally according to the state of pain (increasing rate was 50% and declining rate was 25%) until the maintenance dosage was reached; the other(including 58 patients) was treated by MS-CRT with the same initial dosage and combined with celecoxib whose dosage was 200 mg/12 hrs at first, and increased to 400 mg/12 hrs if the pain was not relieved well, then gradually increased the dosage of MS-CRT to the maintenance dosage, and analyzed the effect, dose adjustment,side effect of drug combination and improvement of quality of life for the patients. Results:The mean of maintenance dosage for MS-CRT alone was 67.3 mg/day, and for the combination of MS-CRT and celecoxib was 51.3 mg/day, the reduction rate of MS-CRT in the drug combination group compared with MS-CRT alone was 23.77% with the same analgesia effect, and the incidence of side effects such as constipation and nausea/vomiting was statistically reduced compared with the single drug group. The quality of life in both groups was improved aftertreatment. Conclusion:The combination of MS-CRT and celecoxib can effectively control moderate to severe cancer pain, , improve the quality of life in advanced cancer patients, and reduce the consumption of MS-CRT with similar side effects as morphine alone.

Objective To explore the mechanism and inhibition of botulinum toxin type A (BTXA) on hypertrohic scar fibroblasts.Methods The cells were treated by 0 (control),0.2,0.4,0.8 U/ml BTXA for 48 h.Cell viability was detected by MTT assay.Cell apoptosis was detected by Hoechst staining.Cell cycle was detected by flow cytometry.The level of cell cycle related protein D1 (Cyclin D1),proliferation nuclear antigen (PCNA) and activation of phosphatidylinositol 3 kinase (PI3K) / protein kinase B (AKT) signaling pathway were assayed by western blot.Results Compared with control group(0.75±0.07),0.2,0.4,0.8 U/mL BTXA(0.59 ± 0.06,0.43 ± 0.04,0.34± 0.03) inhibited hypertrohic scar fibroblasts cell viability,increased cell apoptotic rate[control group(2.38±0.24)％;BTXA(15.79±1.54)％,(27.32±2.69)％,(38.46±3.90)％],down-regulated the expression of Cyclin D1(control group 1.57±0.18;BTXA 0.93±0.07,0.42±0.04,0.35±0.03) and PCNA(control group 1.46±0.16;BTXA 0.50±0.05,0.59±0.05,0.37±0.03),inhibited the expression of PI3K(control group 0.98±0.06;BTXA 0.49±0.04,0.50±0.04,0.39±0.03) and the phosphorylation of AKT(control group 1.38±0.08;BTXA 0.97±0.06,0.60±0.04,0.29± 0.02),made cell cycle arrested in G1 phase,The difference was statistically significant (P＜0.05).Conclusion These results suggested BTXA inhibit proliferation via blocking the activation of PI3K/AKT signal pathway and down-stream related cell cycle related protein.

Objective To analyze mRNA expression of silent information regulator 6 (SIRT6) gene in the blood of population with family history of longevity in Bama county of Guangxi and to explore its association with SIRT6 gene polymorphism and its protein Methods One hundred and thirty-seven people (aged 30 ~ 106, 70 males, 67 females, 6.57% Han nationality, 93.43% Zhuang and Yao nationalities) with family history of longevity (long-lived family history group), and 91 people (aged 22~89, 51 males, 40 females, all Zhuang and Yao nationalities) without family history of longevity were recruited in the study (non-long-lived family history group). Real-time fluorescence quantitative RT-PCR was used to detect mRNA expression of SIRT6 gene in two groups. Results SIRT6 mRNA expression of total and femals in long-lived family history group were higher than those in non-long-lived family history group (P<0.05). mRNA expression of GG and CG genotype of SIRT6 (rs350846) and G allele carriers in long-lived family history group were all higher than those in non-long-lived family history group and the difference was statistically significant (P<0.05). SIRT6 mRNA expression was not associated with serum SIRT6 protein in long-lived family history group (P>0.05). Conclusion The expression of mRNA in SIRT6 gene may be associated with familial aggregation of longevity in Bama County of Guangxi and high expression of mRNA of SIRT6 in G allele carriers contributes to longevity.

OBJECTIVETo investigate the morphology and proliferation effects of adenovirus containing bone morphogenetic protein-2(BMP-2) on tongue cancer Tca8113 cells.

METHODSTca8113 cells were transfected with the Ad-BMP-2 of 0, 50, 100 multiplicity of infection (MOI) respectively. Inverted fluorescence microscope was used to evaluate the morphological changes of these cells. Western blot analysis was performed to determine the expression levels of BMP-2 in the transfected cells. Methyl thiazolyl tetrazolium (MTT) assay was performed to monitor the proliferative activity of the infected Tca8113 cells and then the growth curve was made.

RESULTSThe transfection efficiency reached the highest when the MOI was 100. Moreover, the expression of BMP-2 was detected in Tca8113 cells by Western blot. There were no obvious morphological changes of the Tca8113 cells before and after transfection. And the proliferation of transfected Tca8113 cells decreased compared with control.

CONCLUSIONAd-BMP-2 gene can inhibit the proliferation of Tca8113 cells in vitro.

Objective To evaluate non-enhancement magnetic resonance venography (MRV) of iliac vein in diagnosing Cockett syndrome.Methods Magnetic resonance iliac venography was performed with Ingenia 3.0 T superconducting type MRI system.Abdominal surface coil was employed.The scanning sequences included M2DIPEAR (TR/TE=45/5.8 ms,flip angle=60°),THRIVE (TR/TE=6.8/3.5 ms,flip angle=10°),BTFESPAIR (TR/TE=3.4/1.7 ms,flip angle=80°) and FLAIR (TR/TE=9 000/120 ms,flip angle 90°).The layer thickness of 3 mm was used in all scanning,and the average number of acquisition was 3 times.Results On MRV imaging,Cockett syndrome was characterized by narrowed anteroposterior diameter and broadened transverse diameter of the compressed iliac vein,and curved impression could be seen on its anterior border,and collateral vessel formation could be observed.The mean diameters of the left iliac veins in the light,mnedium and severe patients with Cockett syndrome were 7.52,4.83 and 2.76 mm respectively,with the average compression ratios being 37％,69％ and 83％ respectively.Conclusion Non-enhanced MRV is a feasible method for the diagnosis of iliac vein stenosis,this examination is especially suitable for the checking needs of specific population.

Objective:To evaluate the efficacy of esketamine-based anesthesia in lumbar spine surgery.Methods:Ninety-four patients of both sexes, aged 18-64 yr, with body mass index of 18.5-29.9 kg/m 2, of American Society of Anesthesiologists Physical Status classification ⅠorⅡ, scheduled for elective lumbar posterior decompression bone grafting fusion internal fixation under general anesthesia from June 2022 to December 2022, were divided into control group(group C) and esketamine group(group K) using a random number table method, with 47 cases in each group. Midazolamm, sufentanil, etomidate and cisatracurium were intravenously injected for anesthesia induction in both groups, and esketamine 0.5 mg/kg was intravenously injected on this basis in group K. Propofol and remifentanil were intravenously infused to maintain anesthesia, and cisatracurium besylate was intermittently injected to maintain muscle relaxation in both groups, and esketamine 0.25 mg·kg -1·h -1 was intravenously infused on this basis in group K. The patients were connected to an analgesic pump for patient-controlled intravenous analgesia at 10 min before the end of surgery, and flurbiprofen axetil 50 mg was intravenously injected for rescue analgesia when the numeric rating scale score >4. The time of first pressing the analgesia pump, effective pressing times of the analgesia pump within 48 h after operation and requirement for rescue analgesia were recorded. The initial dose of remifentanil, cumulative amount of remifentanil used during operation, time of tracheal extubation, and adverse reactions within 48 h after surgery were recorded. Results:Compared with group C, the cumulative use of remifentanil during operation was significantly reduced, the time of first pressing the self-control button of the analgesia pump after surgery was prolonged, the pressing times of the analgesia pumps were decreased( P<0.05), and no significant change was found in terms of the initial dose of intraoperative remifentanil, rate of postoperative rescue analgesia, time of extubation, and incidence of adverse reactions after surgery in group K( P>0.05). Conclusions:Esketamine-based anesthesia can reduce the amount of intraoperative opioids, delay the time of postoperative pain and reduce the early postoperative pain when used for lumbar spine surgery.

Objective From the perspective of health economics, to evaluate 23 pneumococcal polysaccharide vaccination programme among chronic obstructive pulmonary disease (COPD) patient. Methods In the pilot counties of the project of integrated care pathway for COPD patient (Hanbin district of Hanzhong city in Shanxi Province, Qianjian district of Qingqing city, Huandao district of Qindao city in Shangdong Province, Wen county of Jiaozuo city in Henan Province), information of insurance participants of New Rural Cooperative Medical System (NRCS) was collected by local NRCM information system, which included general information as well as records of medical care and medical fee. Nonprobability sampling method was applied to select a total of 860 objects, who were over 60 years old with local household registration, hospitalized within one recent year due to COPD acute exacerbation, and without vaccination of 23 voluntary pneumococcal polysaccharide vaccine within 3 years. A quasi-experimental design without control group was adopted. Objects were vaccinated with 23-valent pneumococcal polysaccharide vaccine from January to December in 2013, then were followed up from January in 2014 for one year. Data of effectiveness and medical cost was collected by self-designed questionnaire and (Chinese version). Paired rank sum test applied to test the difference of quality of life, number and direct medical cost of treatment (including outpatient treatment and hospitalization) due to COPD acute exacerbation, one year before and after intervention. The incremental cost-effectiveness ratio (ICER) and cost-benefit ratio (CBR) of the programme were calculated. Results By January 2014, eight hundred sixty objects were vaccinated. By January 2015, seven hundred eighty eight objects were followed up, with 72 cases withdrawed (8.4%). On average, COPD patients reduced 1.12±2.51 treatments due to acute exacerbation, including 0.28±2.09 outpatient treatments and 0.85±1.15 hospitalizations. Total medical cost was saved by 3 610.21 per capita yuan, including outpatient cost of 241.41 yuan and hospitalization cost of 269.82 yuan; Quality of life was gained by 0.03 QALY gain per capita. The ICER was dominant and CBR was 12.00. Conclusion COPD patients vaccinated with 23-valent pneumococcal polysaccharide vaccine within one year reduced treatments due to acute exacerbation. The vaccination was cost effective and cost saving , and we suggest the vaccine should be covered in the public health program or health insurance scheme in conditional region.

Objective:To explore the changes in serum metabolic profile in patients with oral squamous cell carcinoma (OSCC) and to identify the diagnostic biomarkers in order to provide new ideas for the early diagnosis of OSCC.Methods:In total, 76 OSCC patients who were diagnosed at the Department of Oral and Maxillofacial Surgery and 70 healthy individuals who at the Department of Medical Center of The First Affiliated Hospital of Zhengzhou University from August 2019 to January 2020 were recruited in The study. According to the random number table method, all subjects were divided into a test group ( n=96) and a verification group ( n=50). Subjects in the test group consisted of 51 OSCC patients and 45 healthy subjects and subjects in the verification group included 25 OSCC patients and 25 healthy individuals. Serum samples and clinical data of each of the subjects were collected. The serum samples were analyzed by ultra-high-performance liquid chromatography quadrupole-Orbitrap high resolution accurate mass spectrometry. Principal component analysis, orthogonal partial least square discrimination analysis and t-test were used to profile the differential metabolites in the test group. Pathway analysis of differential metabolites was performed. In addition, binary logistic regression analysis and receiver operating characteristic analysis were used in order to establish the potential diagnostic panel. Results:Twenty-one endogenous differential metabolites were identified showing significant association with OSCC. Results of pathway analysis suggested that OSCC associated with lipid metabolism and amino acid metabolism ( P<0.05). A novel diagnostic panel consisting of lysophosphatidylcholine (LysoPC) (16∶0/0∶0), LysoPC[18∶1(9z)/0∶0], taurine and D-glutamic acid was defined. The panel performed a high area under the receiver operating characteristic curve (0.998, 95% CI: 0.994-0.999, P<0.05). Conclusions:There were obvious lipid and amino acid metabolism disorders in OSCC patients. It was an effective method to establish a diagnostic model by metabolomics.

Objective From the perspective of health economics, to evaluate 23 pneumococcal polysaccharide vaccination programme among chronic obstructive pulmonary disease (COPD) patient. Methods In the pilot counties of the project of integrated care pathway for COPD patient (Hanbin district of Hanzhong city in Shanxi Province, Qianjian district of Qingqing city, Huandao district of Qindao city in Shangdong Province, Wen county of Jiaozuo city in Henan Province), information of insurance participants of New Rural Cooperative Medical System (NRCS) was collected by local NRCM information system, which included general information as well as records of medical care and medical fee. Nonprobability sampling method was applied to select a total of 860 objects, who were over 60 years old with local household registration, hospitalized within one recent year due to COPD acute exacerbation, and without vaccination of 23 voluntary pneumococcal polysaccharide vaccine within 3 years. A quasi-experimental design without control group was adopted. Objects were vaccinated with 23-valent pneumococcal polysaccharide vaccine from January to December in 2013, then were followed up from January in 2014 for one year. Data of effectiveness and medical cost was collected by self-designed questionnaire and (Chinese version). Paired rank sum test applied to test the difference of quality of life, number and direct medical cost of treatment (including outpatient treatment and hospitalization) due to COPD acute exacerbation, one year before and after intervention. The incremental cost-effectiveness ratio (ICER) and cost-benefit ratio (CBR) of the programme were calculated. Results By January 2014, eight hundred sixty objects were vaccinated. By January 2015, seven hundred eighty eight objects were followed up, with 72 cases withdrawed (8.4%). On average, COPD patients reduced 1.12±2.51 treatments due to acute exacerbation, including 0.28±2.09 outpatient treatments and 0.85±1.15 hospitalizations. Total medical cost was saved by 3 610.21 per capita yuan, including outpatient cost of 241.41 yuan and hospitalization cost of 269.82 yuan; Quality of life was gained by 0.03 QALY gain per capita. The ICER was dominant and CBR was 12.00. Conclusion COPD patients vaccinated with 23-valent pneumococcal polysaccharide vaccine within one year reduced treatments due to acute exacerbation. The vaccination was cost effective and cost saving , and we suggest the vaccine should be covered in the public health program or health insurance scheme in conditional region.

Objective:Explore the expression pattern of transcription factor activator protein 2C (TFAP2C) and identify the roles of Tfap2c during tooth development.Methods:Real-time fluorescence quantitative PCR (RT-qPCR) was used to analyze the relative expression level of Tfap2c in various organs of embryonic day(E)14.5 mouse embryos and mouse molar germs at E12.5-E18.5 and postnatal day (P)0-P7. The expression position of Tfap2c in mouse molar germs was demonstrated by frozen section immunofluorescence staining. Cultured mandibular molar germs were transfected with control small interfering RNA (siRNA) or Tfap2c siRNA to evaluate the effect of Tfap2c on tooth molar germs development, and RT-qPCR was used to detect the relative expression level of genes related to odontoblast expression. Dental mesenchymal cells were isolated from E14.5 molar germs and transfected with control siRNA or Tfap2c siRNA, cell counting kit 8 (CCK-8) and scratch healing test were applied to detect dental mesenchymal cell viability and migration.Results:Tfap2c was highly expressed in the early development period of mouse molar germs. Tfap2c was expressed in the epithelial and mesenchymal tissues of E13.5 mouse molar germs and there was no significant difference of relative expression of Tfap2c between them ( t=1.06, P=0.472). Tfap2c was expressed in mesenchymal tissues of E14.5 mouse molar germs and the relative expression of Tfap2c in mesenchymal tissues was significantly higher than epithelial tissues ( t=37.29, P<0.0001). For molar germs transfected with Tfap2c siRNA, the relative height of cusps (0.708±0.171) and the ratio of cusp height and crown height (0.321±0.068) was significantly lower than control group (1.000±0.287 and 0.483±0.166) ( t=2.79, P=0.012; t=2.85, P=0.015). But there was no significant difference in relative height (1.078±0.206, 0.993±0.254, t=0.83, P=0.419)and relative width (1.000±0.116, 0.999±0.122, t=0.01, P=0.992) of crowns between two groups. The relative expression level of genes related to odontoblast expression was decreased (Dspp: t=15.33, P<0.001; Dmp1: t=13.81, P<0.001). Tfap2c siRNA hinders cell migration in dental mesenchymal cells ( t=29.86, P=0.001), but there was no significant difference in CCK-8 absorbance value between two groups. The relative expression level of genes related to odontoblast expression was also decreased in dental mesenchymal cells transfected with Tfap2c siRNA (Dspp: t=3.86, P=0.031; Dmp1; t=4.36, P=0.022). Conclusions:Tfap2c highly expressed in the early morphogenesis period of mouse molar germs, mainly in mesenchymal tissues. Tfap2c affected the cusps formation of mouse molar germs and migration of dental mesenchymal cells.