Objective To study the expression of hypoxia inducible factor-1 (HIF-1 ) and Notch signaling pathway downstream gene HES 1 in the hippocampus of pubertal rats with status epilepsy (SE), and to explore the regulation site of HIF-1αin Notch signaling pathway. Methods One hundred and seventy-six 21-day-old SD rats were randomly divided into control group (NS group), pentetrazole (PTZ)-induced SE group (PTZ group), and Notch signaling pathway speciifc inhibitor (DAPT) intervention group (DAPT group). In PTZ group PTZ was intraperitoneally injected to build SE model and in NS group normal saline was injected as control. The intraperitoneal injection of diazepam was used to terminate SE seizures. After successful modeling, the bilateral hippocampuses were isolated after the rats were sacriifced at 0.5, 1, 2, 4 and 8 h, respectively, and RT-PCR was performed to detect the mRNA expression of HES 1 and HIF-1α. The Western Blot was performed to detect protein expression in hippocampuses which were collected at 2 , 4 , 8 , 12 , and 24 h after successful modeling. DAPT group received intraperitoneal injection of DAPT 30 min before the start of molding, then the hippocampuses were isolated at 2 and 8 h after successful modeling. RT-PCR was performed to detect the mRNA expression of HES 1 and HIF-1αat 2 h, and Western blot was performed to detect protein expression at 8 h. Results At each time point after SE, the expression of mRNA of HES 1 and HIF-1αand the expression of protein were higher than the same time point of NS group (P

Objective To investigate the function and mechanism of miR-149 in nasopharyngeal carcinoma (NPC).Methods The expression of miR-149 was examined by real-time PCR and calculated by 2-△△Ct method. The cell proliferation was analyzed by MTT assay. The cell migration and invasion were shown by the wound healing assay and transwell migration assay, and the expression of E-cadherin was detected by Western blot. Results The expression of miR-149 was higher in NPC cell lines 5-8F and 6-10B than that in normal immortalized nasopharyngeal epithelial NP69. MTT assay showed that miR-149 promoted the proliferation of NPC cell lines. The wound healing assay showed miR-149 promoted the mobility and invasion of NPC cell lines. Inhibition of miR-149 reduced the ability of NPC cell lines to proliferate and invade. miR-149 downregulated the expression of E-cadherin, whereas antagomir which mediated knockdown of miR-149 significantly upregulated the expression of E-cadherin. Conclusion miR-149 might be involved in the invasion and metastasis of NPC through regulation of epithelial-mesenchymal transition (EMT).

ObjectiveTo evaluate the adverse events occurred during tumour necrosis factor (TNF)-αblocker treatment in Chinese Han population patients with ankylosing spondylitis (AS).MethodsThis study had enrolled 369 Chinese Han population patients with ankylosing spondylitis.They all received TNF-αblocker treatment in the hospital.All 1011 administration were recorded in total.All of them were evaluated for adverse events 2 hours after injection,126 of them had received long-term TNF-α blocker injection,and they were followed-up at week 8,12,52,104.Mild immediate adverse events and long-term adverse events were all counted.SPSS 10.0 software package was used for Fisher's exact test.ResultsThree hundred and sixty-nine patients had 1011 administrations in total,652 had received rhTNFR:Fc,316 had infliximab,21had etanercept,22 had adalimumab injections.Adverse events 2 hours after injection were:17 (2.6％) for rhTNFR:Fc,12 (3.8％) for infliximab,0 for etanercept,1 (4.5％) for adalimumab.Twenty adverse events were mild(12 for rhTNFR:Fc,9 for infliximab),5 events were moderate(3 for rhTNFR:Fc,1 for infliximab,1 for adalimumab),4 events were severe(2 for rhTNFR:Fc,2 for infliximab).The frequency of adverse events were comparable between rhTNFR:Fc and Infliximab injection in immediate adverse reactions (P=0.31).One hundred and twenty-six (69 rhTNFR:Fc,57 infliximab) patients had long-term usage,and were followed-up at week 8,12,52,104,39 patients had adverse reactions:20 (51.3％) for rhTNFR:Fc,19(48.7％) for infliximab.Thirty-seven patients had infectious events(94.9％ ),1 neurological event(2.6％),and 1 patient had tuberculosis relapse (2.6％).Outcomes were comparable with rhTNFR:Fc and infliximab in long-term usage(P=0.69).ConclusionAttention should be paid to the above events in Chinese Han patients with ankylosing spondylitis who were treated with TNF-α blocker treatment.Special attention should be paid to those patients who are in their third or fourth injection.The occurrence of immediate reaction or long-term adverse events between rhTNFR:Fc and infliximab are comparable.

OBJECTIVETo explore the therapeutic alternatives and evaluate the related clinical results of patients with primary central nervous system lymphoma (PCNSL) treated with gamma knife radiosurgery (GKS).

METHODSFrom January 1995 to December 2001, 44 patients suffering from PCNSL, who had undergone stereotactic biopsy or craniotomy, and who had received a confirmed diagnosis through pathological examination, were treated with GKS. All cases were followed up for 1 - 46 months with an average postoperative period of 27 months. The clinical materials, image features, treatment methods and results of follow-up, were retrospectively reviewed.

RESULTSThe symptoms and signs of the patients were markedly improved within 1 - 3 weeks after GKS. The Kanofsky performance status was also improved from a preoperative average of 40% to a postoperative one of 90%. Thirty-eight patients (86.36%) were in complete remission (CR), the other six (13.63%) were in partial remission (PR). The local control rate reached 100%, and the median survival time was 26.5 months. The main side effect was brain edema, which can be treated with dexamethasone and mannitol.

CONCLUSIONGKS is a safe and effective method in multimodality treatment of PCNSL. A stereotactic biopsy coupled with GKS is the first choice for diagnosis and treatment. Adjuvant chemotherapy or radiotherapy should then be given according to the patient's condition.

Adult ; Aged ; Aged, 80 and over ; Brain Neoplasms ; surgery ; Combined Modality Therapy ; Female ; Humans ; Lymphoma ; surgery ; Male ; Middle Aged ; Radiosurgery ; Retrospective Studies ; Treatment Outcome

Objective To investigate the therapeutic effect of three-line anchors combined with modified Mason-Allen technique in repair of moderate to massive rotator cuff tear under arthroscopy.Methods The clinical data of 48 patients(repair of moderate to massive rotator cuff tear using modi-fied Mason-Allen technique)were analyzed retrospectively.According to the anchors used,patients were divided into control group(double-wire anchors,n=23)and observation group(three-wire an-chors,n=25).Age,gender,operation time,the number of anchors used during operation and postop-erative complications were recorded in the two groups.American shoulder and elbow surgeon(ASES)scores,Constant-Murley shoulder function scores and Visual Analogue Scale(VAS)scores were com-pared between the two groups before and after surgery(last follow-up).During follow-up,magnetic resonance imaging(MRI)was used to evaluate rotator cuff retear.Results At the last follow-up,VAS score of the shoulder in the two groups was significantly lower than before surgery,constant-Mur-ley shoulder function score and ASES score were significantly higher than before surgery(P＜0.05).The number of anchors used in the control group was significantly higher than that in the observation group(P＜0.05).Conclusion The clinical effect of three-line anchor combined with the modified Mason-Allen technique in repair of moderate to massive rotator cuff tear is better,which is consistent with the traditional two-wire anchors,but the amount of anchors is less.

Objective To investigate the therapeutic effect of three-line anchors combined with modified Mason-Allen technique in repair of moderate to massive rotator cuff tear under arthroscopy.Methods The clinical data of 48 patients(repair of moderate to massive rotator cuff tear using modi-fied Mason-Allen technique)were analyzed retrospectively.According to the anchors used,patients were divided into control group(double-wire anchors,n=23)and observation group(three-wire an-chors,n=25).Age,gender,operation time,the number of anchors used during operation and postop-erative complications were recorded in the two groups.American shoulder and elbow surgeon(ASES)scores,Constant-Murley shoulder function scores and Visual Analogue Scale(VAS)scores were com-pared between the two groups before and after surgery(last follow-up).During follow-up,magnetic resonance imaging(MRI)was used to evaluate rotator cuff retear.Results At the last follow-up,VAS score of the shoulder in the two groups was significantly lower than before surgery,constant-Mur-ley shoulder function score and ASES score were significantly higher than before surgery(P＜0.05).The number of anchors used in the control group was significantly higher than that in the observation group(P＜0.05).Conclusion The clinical effect of three-line anchor combined with the modified Mason-Allen technique in repair of moderate to massive rotator cuff tear is better,which is consistent with the traditional two-wire anchors,but the amount of anchors is less.

Objective:To explore the effect of long-term exposure to ambient particulate matter (PM 10) on the prevalence of diabetes and fasting plasma glucose (FPG). Methods:The subjects of the study were from the baseline population of "Jinchang Cohort", and 24 285 subjects were finally included after excluding incomplete home address information and diabetic diagnosis information. The demographic characteristics, lifestyle and health status of the survey subjects were collected through questionnaire, physical examination and laboratory tests. ArcGIS software was used to match the nearest environmental monitoring stations for each subject according to residential address. Two-year average concentrations of PM 10 were calculated to estimate exposure level. The logistic regression and the multiple linear regression were conducted to assess the effects of ambient PM 10 on the prevalence of diabetes and FPG. The restricted cubic spline was used to quantify the dose-response relationship. Stratified analysis and effect modification analysis were also performed. Results:The age of 24 285 participants was (49.32±8.60) years, and the BMI was (24.22±6.09) kg/m 2. There were 13 950 (57.44%) males and 2 066 (8.51%) diabetic patients. After adjusting for confounders, for every 10 μg/m 3 increase in the average PM 10 concentration in the first two years of the survey, the prevalence of diabetes increased [ OR (95% CI) =1.05 (1.01-1.09)]and the FPG level elevated [β (95% CI) = 0.061 (0.047-0.076) mmol/L]. The results of the restricted cubic spline analysis showed a nonlinear relationship between PM 10 concentration and FPG level ( P<0.001). Further subgroup analysis showed that female [ OR (95% CI) =1.10 (1.03-1.18)], people over 50 years old [ OR (95% CI) =1.06 (1.02-1.11) ], subjects with family history of diabetes [ OR (95% CI) = 1.13 (1.04-1.23) ], and with hypertension [ OR (95% CI) = 1.07 (1.02-1.12) ] had a stronger association between the prevalence of diabetes and PM 10 exposure (all P interaction values were<0.05). The effects of PM 10 on FPG were more significant in people older than 50 years[β (95% CI) = 0.080 (0.050-0.109) mmol/L], with family history of diabetes [β (95% CI) = 0.087 (0.036-0.137) mmol/L], and hypertension [β (95% CI) = 0.077 (0.046-0.108) mmol/L] (all P interaction values were<0.05). Conclusions:Long-term exposure to ambient PM 10 increases the diabetes prevalence and FPG. People older than 50 years old, with family history of diabetes and hypertension could be more sensitive to the effects of PM 10 exposure.

Objective:To explore the effect of long-term exposure to ambient particulate matter (PM 10) on the prevalence of diabetes and fasting plasma glucose (FPG). Methods:The subjects of the study were from the baseline population of "Jinchang Cohort", and 24 285 subjects were finally included after excluding incomplete home address information and diabetic diagnosis information. The demographic characteristics, lifestyle and health status of the survey subjects were collected through questionnaire, physical examination and laboratory tests. ArcGIS software was used to match the nearest environmental monitoring stations for each subject according to residential address. Two-year average concentrations of PM 10 were calculated to estimate exposure level. The logistic regression and the multiple linear regression were conducted to assess the effects of ambient PM 10 on the prevalence of diabetes and FPG. The restricted cubic spline was used to quantify the dose-response relationship. Stratified analysis and effect modification analysis were also performed. Results:The age of 24 285 participants was (49.32±8.60) years, and the BMI was (24.22±6.09) kg/m 2. There were 13 950 (57.44%) males and 2 066 (8.51%) diabetic patients. After adjusting for confounders, for every 10 μg/m 3 increase in the average PM 10 concentration in the first two years of the survey, the prevalence of diabetes increased [ OR (95% CI) =1.05 (1.01-1.09)]and the FPG level elevated [β (95% CI) = 0.061 (0.047-0.076) mmol/L]. The results of the restricted cubic spline analysis showed a nonlinear relationship between PM 10 concentration and FPG level ( P<0.001). Further subgroup analysis showed that female [ OR (95% CI) =1.10 (1.03-1.18)], people over 50 years old [ OR (95% CI) =1.06 (1.02-1.11) ], subjects with family history of diabetes [ OR (95% CI) = 1.13 (1.04-1.23) ], and with hypertension [ OR (95% CI) = 1.07 (1.02-1.12) ] had a stronger association between the prevalence of diabetes and PM 10 exposure (all P interaction values were<0.05). The effects of PM 10 on FPG were more significant in people older than 50 years[β (95% CI) = 0.080 (0.050-0.109) mmol/L], with family history of diabetes [β (95% CI) = 0.087 (0.036-0.137) mmol/L], and hypertension [β (95% CI) = 0.077 (0.046-0.108) mmol/L] (all P interaction values were<0.05). Conclusions:Long-term exposure to ambient PM 10 increases the diabetes prevalence and FPG. People older than 50 years old, with family history of diabetes and hypertension could be more sensitive to the effects of PM 10 exposure.

OBJECTIVE To mine and analyze adverse drug event （ADE） signals after the marketing of pazopanib and provide references for clinically safe medication. METHODS OpenVigil 2.1 data platform was used to mine ADE signals from the US FDA adverse event reporting system （FAERS） database. ADE reports of pazopanib from October 2009 to June 2022 were collected， and ADE signals were analyzed using proportional reporting ratio （PRR） method and reporting odds ratio （ROR） method in the proportional imbalance method. RESULTS A total of 16 655 ADE reports were identified with pazopanib as the primary suspect drug. Through ROR and PRR analysis， 220 ADE signals involving 19 system organ classes were identified. The top 10 ADE signals by frequency were recorded in the drug instruction. Additionally， 88 new ADE signals were discovered， mainly related to the gastrointestinal system， various investigations， and the renal and urinary system. Decreased basophil count， nail bed hemorrhage， tumor rupture， and vaginal fistula were both new ADE signals and the top 10 ADE signals by strength. CONCLUSIONS The occurrence of common ADEs （diarrhea， hair color changes， hypertension， etc.） during the use of pazopanib after marketing is generally consistent with its drug instruction； the number of reported cases for new suspected risk signals （decreased basophil count， nail bed hemorrhage， tumor rupture， and vaginal fistula， etc.） is limited， and continuous monitoring is required.