In recent years， the potential anti-tumor effects of metformin have attracted widespread attention in the field of cancer treatment. This article summarizes the research progress of metformin in the treatment of malignant tumors，finding its potential application in the treatment of malignant tumors in the digestive system （biliary tract cancer，gastric cancer，esophagus cancer，colorectal cancer，pancreatic cancer，liver cancer） and reproductive system （prostate cancer，ovarian cancer，breast cancer， cervical cancer），non-small cell lung cancer，renal cell carcinoma，and melanoma. Metformin can inhibit the proliferation of tumor cells and extend the overall survival of patients. Its mechanisms of action include，but are not limited to，inhibiting the activity of mitochondrial complex Ⅰ，activating adenosine monophosphate-activated protein kinase/p53 signaling pathway，and blocking the cell cycle. Additionally，the combined use of metformin with chemotherapy drugs has shown potential for reducing toxicity and enhancing efficacy. It can enhance the sensitivity of biliary tract cancer，ovarian cancer，and melanoma cells to chemotherapy drugs， improve the drug resistance of gastric and colorectal cancer cells to chemotherapy，and reduce the toxic reactions of breast cancer patients during chemotherapy. Metformin is also used as an immunomodulator，applied in the immunotherapy of patients with esophagus cancer，colorectal cancer，cervical cancer，non-small cell lung cancer，and melanoma.

Objective:To investigate the effect of sleep on physical performance and the correlation between sleep quality and physical performance in the elderly.Methods:In this prospective multicenter case-control study, 472 elderly people aged 60-80 years were recruited from three regions in China, Beijing, Tianjin, and Hainan Province.Basic information of study participants was collected through face-to-face interviews, and physical performance of study participants was assessed by the time up and go(TUG)test on site, with 106 cases(22.5%)in the normal physical performance group and 366 cases(77.5%)in the abnormal group.The Pittsburgh Sleep Quality Index(PSQI)and the Epworth Sleepiness Scale(ESS)were applied to assess sleep quality of study subjects.Correlation analysis was performed to examine factors affecting subjects' physical performance.Results:Age, history of alcohol consumption, BMI, past medical history, the ESS score, daytime sleepiness, and some components of PSQI, such as sleep quality, sleep efficiency, sleep disturbances, use of sleeping drugs and daytime dysfunction, were influencing factors of the TUG score.Two components of PSQI, sleep duration and habitual sleep efficiency, and the ESS score were positively correlated with physical performance.Logistic regression analysis showed that risk factors for decreased physical performance in the elderly included increased age( OR=1.125, 95% CI: 1.083-1.168, P<0.01), history of alcohol consumption( OR=0.482, 95% CI: 0.384-0.605, P<0.001), abnormally high body mass index( OR=1.663, 95% CI: 1.340-2.063, P<0.01), hyperlipemia( OR=0.156, 95% CI: 0.077-0.318, P<0.01), digestive system diseases( OR=0.154, 95% CI: 0.044-0.532, P<0.01), use of sleeping drugs( OR=0.415, 95% CI: 0.202-0.854, P<0.05), daytime sleepiness( OR=4.234, 95% CI: 2.800-6.403, P<0.01), a high habitual sleep efficiency score of PSQI( OR=1.425, 95% CI: 1.214-1.672, P<0.01)and a high sleep disturbances score in PSQI( OR=3.356, 95% CI: 2.337-4.819, P<0.01). Conclusions:The incidence of physical performance decline is high in the elderly.There is a correlation between physical performance and sleep quality.

Objective:To investigate the resistance of Culex pipiens pallens to pyrethroid insecticides in Hangzhou City, and explore the mutation of knock down resistance (kdr) gene of Culex pipiens pallens, providing scientific basis for control of Culex pipiens pallens in the region. Methods:In September 2022, larvae and pupae of Culex pipiens pallens were collected from various locations at national monitoring sites in Shangcheng District and Gongshu District of Hangzhou City. They were bred in the laboratory and their resistance to three commonly used pyrethroid insecticides (permethrin, deltamethrin and beta-cypermethrin) was determined using the adult mosquito contact tube method and larval immersion method recommended by the World Health Organization. The genomic DNA was extracted from individual adult mosquito, and kdr gene mutation was detected via PCR amplification and Sanger sequencing. Results:The 24-hour mortality rates of adult mosquitoes of Culex pipiens pallens exposed to 0.25% permethrin, 0.025% deltamethrin, and 0.025% beta-cypermethrin were 20.00% (15/75), 17.33% (13/75), and 18.67% (14/75), respectively, indicating resistance. The resistance ratios of Culex pipiens pallens larvae to permethrin, deltamethrin, and beta-cypermethrin were 27.08, 341.00, and 15.88, respectively. Among 183 adult mosquitoes that survived under the diagnostic doses of pyrethroid insecticides, 180 mosquitoes (98.36%) had mutation at the L1014 site of the kdr gene. Among 42 adult mosquitoes that died under the diagnostic doses of pyrethroid insecticides, 5 mosquitoes (11.90%) had L1014 mutation in the kdr gene. Conclusions:Culex pipiens pallens in Hangzhou City has developed varying degrees of resistance to permethrin, deltamethrin and beta-cypermethrin, with a high frequency of kdr gene mutation in resistant mosquitoes. We should strengthen the monitoring of the resistance of Culex pipiens pallens in Hangzhou City and use chemical insecticides reasonably.

Objective:To investigate the distribution and seasonal fluctuations of flies in Hangzhou, study the resistance of Musca domestica ( M. domestica) to five commonly used sanitary insecticides and changing patterns in Hangzhou and provide a basis for scientific control of flies. Methods:From April to November 2023, the cage trap method was used for ecological monitoring of flies. From May to June 2023, the swing net method was used to collect M. domestica from various districts (counties and cities) in Hangzhou. After indoor breeding, the resistance of F1 generation female adult flies to five commonly used sanitary insecticides was determined using the micro-drop method. Probit regression model was used to calculate the median lethal dose (LD 50), 95% confidence interval ( CI) and virulence regression equation. Results:In 2023, the fly density in Hangzhou was 5.99 flies/cage, with a higher density of flies belonging to the Sarcophagus family (2.39 flies/cage), making it the dominant fly species in Hangzhou. Among different monitoring points, the fly density in Linping District was relatively high (20.97 flies/cage). In different habitats, the fly density in agricultural markets was relatively high (fly density from April to November: 2.86, 5.39, 8.86, 16.86, 31.32, 6.39, 3.75 and 1.89 flies/cage). The seasonal fluctuation of fly density showed a unimodal pattern, with the higher density in August (13.45 flies/cage). The M. domestica population in Hangzhou was sensitive to dichlorvos [resistance ratio ( RR): 3.08 times]. Different degrees of resistance were developed to propoxur, deltamethrin, beta-cypermethrin, and beta-cyhalothrin. The degree of resistance from high to low was propoxur (> 336.36 times), beta-cypermethrin (906.61 times), beta-cyhalothrin (432.29 times), and deltamethrin (72.56 times). Based on the monitoring results from 2003 to 2023, the RR of dichlorvos reached the higher level in 2008 (33.47 times) and gradually decreased to a sensitive level. The resistance level of propoxur had been at an extremely high level over the years. Three types of pyrethroid insecticides all had high resistance. Conclusions:The species of flies in the Sarcophagus family are the dominant population in Hangzhou, and M. domestica has developed high resistance to four commonly used insecticides except for dichlorvos. The use of physical control techniques is advocated to reduce the use of chemical pesticides, and prevent the continuous increase of resistance in M. domestica.

Objective To explore the clinical features,diagnoses,differential diagnoses and treatments of superior cerebellar artery aneurysms.Methods The clinical data of 16 patients with superior cerebellar artery aneurysms,admitted to our hospital from January 2013 to March 2018,were retrospectively collected.Their clinical manifestations,imaging features,surgical effects and related problems in the process of diagnoses and treatments were analyzed.Results Among the 16 patients,11 were caused by aneurysm rupture;8 had subarachnoid hemorrhage alone,and three had subarachnoid hemorrhage accompanied by ventricular hemorrhage;CT and CTA confirmed that 8 were superior cerebellar artery aneurysms,two were posterior cerebral artery aneurysms,and one was with unclear diagnosis.In the other 5 patients,three had eyelid ptosis and two had abducent nerve palsy;CT,CTA or MR imaging showed that two were considered as ventral brainstem occupying lesions,and three did not have clear diagnosis.Finally,all patients were diagnosed as having superior cerebellar artery aneurysms by three-dimensional DSA.Five patients were treated with interventional embolization first,and one was treated with surgical clipping because of vertebral artery stenosis and difficulty of catheter access;two patients were transferred to our department for surgical clipping due to aneurysm rupture after embolization treatment in other hospitals;and 9 patients were treated by surgical clipping directly.After treatments,one patient was in bed for a long time due to cerebellar infarction and systemic complications,and the other 15 patients recovered well;two of them underwent ventricular peritoneal shunt due to hydrocephalus.Conclusions Superior cerebellar artery aneurysm has onset of subarachnoid hemorrhage mostly,and oculomotor and abductor nerve paralysis,and space occupying manifestation around the brainstem sometimes.For patients with suspicious posterior circulation aneurysms whose diagnosis or location are unclear,three-dimensional DSA examination should be performed early to confirm the diagnosis.Treatment should be taken as soon as possible once the superior cerebellar artery aneurysm is defined.Interventional embolization may be the first choice,but it is necessary to master the methods of surgical clipping in order to treat the disease timely.

Stroke at the acute stage is a major cause of disability in adults, and is associated with dysfunction of brain networks. However, the mechanisms underlying changes in brain connectivity in stroke are far from fully elucidated. In the present study, we investigated brain metabolism and metabolic connectivity in a rat ischemic stroke model of middle cerebral artery occlusion (MCAO) at the acute stage using F-fluorodeoxyglucose positron emission tomography. Voxel-wise analysis showed decreased metabolism mainly in the ipsilesional hemisphere, and increased metabolism mainly in the contralesional cerebellum. We used further metabolic connectivity analysis to explore the brain metabolic network in MCAO. Compared to sham controls, rats with MCAO showed most significantly reduced nodal and local efficiency in the ipsilesional striatum. In addition, the MCAO group showed decreased metabolic central connection of the ipsilesional striatum with the ipsilesional cerebellum, ipsilesional hippocampus, and bilateral hypothalamus. Taken together, the present study demonstrated abnormal metabolic connectivity in rats at the acute stage of ischemic stroke, which might provide insight into clinical research.
Acute Disease ; Animals ; Brain ; diagnostic imaging ; metabolism ; Brain Mapping ; Disease Models, Animal ; Fluorodeoxyglucose F18 ; Glucose ; metabolism ; Infarction, Middle Cerebral Artery ; diagnostic imaging ; metabolism ; Male ; Neural Pathways ; diagnostic imaging ; metabolism ; Positron-Emission Tomography ; Radiopharmaceuticals ; Random Allocation ; Rats, Sprague-Dawley

Positron emission tomography (PET) imaging of functional metabolism has been widely used to investigate functional recovery and to evaluate therapeutic efficacy after stroke. The voxel intensity of a PET image is the most important indicator of cellular activity, but is affected by other factors such as the basal metabolic ratio of each subject. In order to locate dysfunctional regions accurately, intensity normalization by a scale factor is a prerequisite in the data analysis, for which the global mean value is most widely used. However, this is unsuitable for stroke studies. Alternatively, a specified scale factor calculated from a reference region is also used, comprising neither hyper- nor hypo-metabolic voxels. But there is no such recognized reference region for stroke studies. Therefore, we proposed a totally data-driven automatic method for unbiased scale factor generation. This factor was generated iteratively until the residual deviation of two adjacent scale factors was reduced by < 5%. Moreover, both simulated and real stroke data were used for evaluation, and these suggested that our proposed unbiased scale factor has better sensitivity and accuracy for stroke studies.
Animals ; Computer Simulation ; Disease Models, Animal ; Female ; Fluorodeoxyglucose F18 ; Image Processing, Computer-Assisted ; methods ; Infarction, Middle Cerebral Artery ; diagnostic imaging ; Male ; Positron-Emission Tomography ; methods ; Rats ; Rats, Sprague-Dawley ; Stroke ; diagnostic imaging

Objective To investigate the specific immune therapeutic effect of the T cell fusion peptide vaccine from group II allergens from Dermatophagoides pteronyssinus(Der p2). Methods Thirty mice were randomly divided into three groups, namely a negative control group(a PBS group),positive control group(an asthma group)and protein Der p2 T cell fusion epit?ope for specific immunotherapy(SIT)group(a Der p2 T group). The extract of house dust mites(HDM)was used to establish the asthmatic models in BALB/c mice,and the PBS group was always used with PBS buffer. Thirty minutes before spray inhala?tion from 25 to 27 days,the mice of the Der p2 T group were respectively injected subcutaneously with the therapeutic proteins for SIT,then the serum and bronchoalveolar lavage fluid(BALF)were collected. ELISA was used to assay the levels of IFN?γ, IL?4,and IL?13 in BALF,as well as serum levels of specific IgE and IgG2a. The lung tissue sections were stained with haematox?ylin and eosin(H&E)for pathological examinations. Results The ELISA detection revealed that the number of eosinophil in BALF of the asthmatic mice was(5.57 ± 0.64)× 105/ml,which was significantly higher than that in the PBS group[(0.50 ± 0.30)× 105/ml,P < 0.01],the number of eosinophil in the Der p2 T immunotherapy group decreased significantly[(3.45 ± 0.36)×105/ml,P<0.01]. The content of IFN?γin the PBS group,asthma group and Der p2 T group were(267.00 ± 21.98), (155.80 ± 20.53)pg/ml and(234.40 ± 24.46)pg/ml respectively. Compared with the asthma group,the mice with Der p2 T vac?cine specific immune treatment produced a high level of IFN?γ(P<0.01). The content of IL?4 in the PBS group,asthma group and Der p2 T group were(23.40 ± 5.96),(53.28 ± 8.26)pg/ml and(30.00 ± 5.50)pg/ml respectively. Compared with the asth?ma group,the content of IL?4 in the mice of the Der p2 T treatment group was significantly lower(P<0.01). Compared with the asthma group[(308.10 ± 28.32)pg/ml],the content of IL?13 in BALF of the mice in the Der p2 T treatment group was signifi?cantly decreased,which was[(174.50 ± 25.99)pg/ml,P<0.01]. The content of IL?13 in the PBS group was(95.99 ± 31.14) pg/ml. The lung tissue sections showed that the lung inflammation in the p2 T Der group was significantly less than that in the asthma group,and the inflammatory cell infiltration was significantly decreased,and airway epithelial construction remodeled. Conclusion The Der p2 T cell fusion epitope,which is as vaccines for specific immunotherapy with asthma models,can allevi?ate effectively allergic inflammation of airway and lung in the mice,and it may be used as a candidate vaccine for asthma.

Objective To observe the Tyrophagus palmarum and its hypopus in feed of Tenebrio molitor. Methods Feed samples were collected from T. molitor farms,and T. palmarum and its hypopus were separated from the samples by the vibra?tion sieve method and floating method. The glass specimens were prepared and T. palmarum and its hypopus were observed un?der an optical microscope. Results Under the light microscope,the skin of T. palmarum was smooth and bright,the color of legs and chelicerae was relatively dark,the length of dorsal seta d2 was 3?4 times longer than d1 and la;Theω1 in tarsus of legⅠ,Ⅱwas short rod,and its top was not tapered;the sucker plate in tarsus of legⅣlocated in the middle of the section. The hypopus was oblate,and there were two pairs of legs in front which extended to body. The rear end of hypopus became pointless and round,wrapping around a transparent and ossification skin. Conclusion Light microscopy shows the morphological charac?teristics of T. palmarum and its dormant body,providing the basis for identifying the hypopus.

Objective To investigate the effects of pramipexole on serum cystatin C, antioxidant indexes and brain derived neurotrophic factor ( BDNF) in the treatment of patients with Parkinson’s disease.Methods Retrospective a total of 96 patients with Parkinson’s disease were collected and randomly divided into experimental group and control group with 48 cases in each group.Patients in the control group were treated by levodopa,patients in the experimental group were treated on the basis of the control group with pramipexole, movement and non-movement symptoms were assessed by unified Parkinson’ s disease rating scale ( UPDRS), the serum cystatin C, antioxidant indexes and brain derived neurotrophic factor levels were measured, and the clinical efficacy and adverse reactions were compared.Results The effective rate of the control group (68.75%) was lower than the experimental group (87.50%), with statistical significance (P<0.05); compared with the control group, the movement and non-movement symptoms of the experimental group reduced after treatment, after treatment the serum CRP, serum cystatin C decreased, serum BDNF increased, after treatment the glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidate (GPX) levels increased, with statistical significance (P<0.05).Conclusion Pramipexole in the treatment of patients with Parkinson’s disease could reduce serum cystatin C, improve the levels of BDNF and antioxidant capacity, the effect is remarkable.