Poly-(adenosine diphosphate-ribose)-polymerase(PARP)inhibitors are a novel group of small molecule targeted therapeutic drugs.It has become an effective treatment for ovarian cancer,prostate cancer and breast cancer carrying BRCA1/2 mutations.Studies have demonstrated that PARP inhibitors(PARPi)can improve treatment outcomes by targeting genetic defects in tumors with syner-gistic effects with standard therapies for glioma treatment,such as increasing radiation sensitivity and overcoming temozolomide resistance.Howev-er,the limited blood-brain barrier permeability,the adverse reactions of drug combination and the oc-currence of drug resistance are the key factors af-fecting the therapeutic effect.This article reviews the mechanism of action and research progress of PARP inhibitors involved in the treatment of brain glioma,and analyzes the challenges to be faced in clinical practice,in order to provide references for future research in this field.

Objective:To analyze the effect of joint management of type 2 diabetes mellitus (T2DM) between specialty and community under the model of National Diabetes Prevention and Control Center (DPCC).Methods:A total of 2 527 T2DM patients managed by DPCC Pingshan Center of Shenzhen from January 1, 2022 to December 31, 2024 were retrospectively included. After management, the rate of downturn, reexamination rate, blood pressure compliance rate, metabolic indicators (waist circumference, body mass index, fasting blood glucose, glycosylated hemoglobin, blood lipids) and screening rate of chronic complications of diabetes (atherosclerotic cardiovascular disease, microvascular disease, diabetic peripheral neuropathy) were analyzed. Those included 2022 ( n=564), 2023 ( n=1 477), and 2024 ( n=2 527). Results:The downturn rate in 2022, 2023 and 2024 increased year by year (22.8% vs 67.2% vs 89.9%, P<0.01), and the review rate (41.1% vs 62.2% vs 52.7%, P<0.01), complication screening rate (51.6% vs 85.3% vs 62.2%, P<0.01), blood pressure compliance rate (53.1% vs 78.0% vs 67.2%, P<0.01), body mass index compliance rate (13.2% vs 17.3% vs 28.6%, P<0.01), fasting blood glucose meeting rate (46.4% vs 60.2% vs 68.5%, P<0.01), glycated hemoglobin meeting rate (58.4% vs 63.2% vs 45.6%, P<0.01) were relatively improved. Waist circumference compliance rate (30.6% vs 27.7% vs 21.6%) and blood lipid compliance rate (33.6% vs 35.5% vs 31.9%) were not significantly improved, and the review rate, blood pressure compliance rate and complication screening rate in 2024 were lower than those in 2023 and higher than those in 2022. Conclusions:The combined management of type 2 diabetes under the DPCC model has significant effects on improving the down-conversion rate, rediagnosis rate, blood pressure compliance rate, metabolic index compliance rate and the screening rate of diabetes-related chronic complications in patients with diabetes. At the same time, it was also found that with the progress of hierarchical diagnosis and treatment, the review rate, complication screening rate, blood pressure, waist circumference, blood lipid and glycosylated hemoglobin reached the standard of patients decreased compared with the previous situation, which needs to be further analyzed and improved.

Objective To investigate the effects of m6A methylation modification and changes in oxidative stress levels on the progression of colorectal cancer(CRC)in Apemin/+mice with normal and high-fat diets.Methods C57BL/6J mice and Apcmin/+mice were fed with a normal or high-fat diet(60％fat)for 2(S group),6(M group),or 12 weeks(L group),respectively.Food intake,body mass,and the size,number,and volume of small intestinal polyps and colon tumors were then measured.Protein expression levels of the cancer markers Ki-67 and proliferating cell nuclear antigen in colon tissues were detected by immunohistochemical staining and the serum levels or activities of the antioxidant enzymes catalase,reduced glutathione,and lipid peroxide malondialdehyde were detected using appropriate kits.mRNA expression levels of m6A methylation-related enzymes in colon tissues were detected by RT-qPCR and total levels of m6A methylation modification in colon tissues were detected.Results(1)Apcmin/+mice showed rapid tumor growth from the early to middle stages of cancer.Tumor proliferation from the middle to late stages of cancer was slowed in mice fed a normal diet,while a high-fat diet promoted the further development of cancer.(2)Decreased m6A methylation levels and enhanced antioxidant capacity may have delayed advanced tumor development in Apcmin/+mice fed a normal diet.(3)In contrast,a high-fat diet may have promoted the sustainable development of CRC by increasing the total level of m6A methylation,while the enhanced antioxidant capacity may have been insufficient to resist the promoting effect of m6A methylation on CRC.Conclusions A high-fat diet may promote the advancement of CRC compared with a normal diet by affecting m6A methylation modification.Both normal and high-fat diets enhanced the antioxidant capacity,suggesting that antioxidant effects may initiate self-protection mechanisms during cancer progression.

Investigated the mechanisms by which baicalein regulates nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)to ameliorate lipopolysaccharide(LPS)-induced sepsis-asso-ciated acute kidney injury(AKI)in mice.Sixty male C57BL/6 mice were randomly divided into six groups:control,model,low-dose baicalein(50 mg/kg),medium-dose baicalein(100 mg/kg),high-dose baicalein(200 mg/kg),and high-dose baicalein+brusatol(4 mg/kg).Baicalein was adminis-tered orally for 7 days as a preventative measure.Sepsis was induced via intraperitoneal injection of LPS.Murine sepsis score(MSS)was assessed within 12 hours post-induction.Serum creatinine(Scr),blood urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)were measured using an automatic biochemical analyzer and enzyme-linked immunosorbent assays(ELISA),respectively.Histopathological changes in kidney tissues were ob-served via hematoxylin-eosin(HE)staining.Western blot analysis was employed to determine the protein expression levels of Nrf2,HO-1,caspase-8,TNF-α,IL-1β,and IL-6 in kidney tissues.Additionally,total superoxide dismutase(SOD)activity in kidney tissues was assessed using com-mercially available kits.Compared to the model group,baicalein treatment significantly improved renal histopathological changes,alleviated cellular damage,and reduced the levels of inflammatory cytokines(TNF-α,IL-1βand IL-6)(P＜0.01)and kidney injury markers(Scr and BUN)(P＜0.01).Moreover,baicalein treatment significantly increased the protein expression levels of Nrf2 and HO-1(P＜0.01)and enhanced antioxidant enzyme activity.In conclusion,baicalein may pro-tect against LPS-induced sepsis-associated AK1 in mice by modulating the Nrf2/HO-1 signaling pathway,thereby attenuating oxidative stress,reducing inflammation,and disrupting the vicious cycle between inflammation and oxidative stress.

Objective To explore the influencing factors of adhesive ileus after laparoscopic appendectomy(LA)in patients with acute appendicitis,then establish and verify its prediction model.Methods 100 cases of acute appendicitis treated by LA from January 2021 to January 2024 were retrospectively analyzed.According to the ratio of 7:3,the patients were randomly divided into the training group(70 cases)and the verification group(30 cases),and then the patients in the training group were divided into the occurrence group(12 cases)and the non-occurrence group(58 cases)according to whether adhesive ileus occurred during the follow-up for 6 months after LA.The difference of clinical data between the two groups was compared,and multivariate Logistic regression method was used to analyze the independent risk factors of adhesive ileus after LA.The nomogram prediction model was constructed,and the performance of the prediction model was evaluated by Bootstrap method,calibration curve,receiver operator characteristic curve(ROC curve)and decision curve.Results The results of multivariate Logistic regression model showed that the risk factors of postoperative adhesive ileus in patients with acute appendicitis after LA were the course of disease>24 h,preoperative albumin≤34 g/L,the number of LA operating tables for LA operators<60,the operation time>1 h,and the time of getting out of bed for the first time after operation>24 h were independent risk factors for adhesive ileus after LA operation(P<0.05).In the training set and verification set,the results of Bootstrap method and ROC curve showed that the prediction model had good discrimination,and the C indexes were 0.723(95%CI:0.642～0.875)and 0.706(95%CI:0.628～0.768)respectively.AUCs were 0.874(95%CI:0.625～0.924)and 0.867(95%CI:0.612～0.895)respectively.Goodness-of-fit test showed that the prediction model had good fitting effect(P>0.05).The calibration curves of training set and verification set were close to the ideal curve,and the prediction model had good accuracy.The decision curves of training set and verification set showed that the nomogram model could produce better clinical benefits when the threshold probability of high risk was 0.10～0.80 and 0.25～0.48 respectively,and the net benefit rate was greater than 0.Conclusion The occurrence of adhesive ileus after LA in patients with acute appendicitis is related to the course of disease,albumin level,operator experience,operation time and the first time to get out of bed after surgery.The nomogram model has good predictive performance.

Objective:To investigate the effect of dulagopeptide on physical examination indexes,plasma glucose metabolism and islet function in type 2 diabetes mellitus(T2DM)patients with poorly controlled plasma glucose.Methods:135 T2DM patients with poorly controlled plasma glucose who were admitted in our hospital from January 2023 to July 2024 were selected.A prospective randomized controlled design was adopted,they were divided into control group 1(received treatment with sitagliptin,n=45),control group 2(received treatment with insulin glargine,n=45),and observation group(received treatment with dulaglutide,n=45)according to the random number table method.Physical examination indexes,plasma glucose indicators,islet function,and incidence of adverse reactions were compared among the three groups.Results:12 weeks after treatment,body mass index(BMI),waist circumference,fasting plasma glucose(FPG),glycated hemoglobin(HbA1c),and postprandial 2-hour plasma glucose(2hPG)in the observation group were lower than those in control group 1 and control group 2(P＜0.05).12 weeks after treatment,the observation group had the highest HbA1c compliance rate,reaching 71.1％(P＜0.05).12 weeks after treatment,the fasting C-peptide(FC-P)and HOMA-islet(CP-DM)levels in the observation group were higher than those in control group 1 and control group 2(P＜0.05).Conclusion:Dulagopeptide can effectively improve physical examination indexes,plasma glucose indicators,and islet function in T2DM patients with poorly controlled plasma glucose.

Objective:To explore the influencing factors of swallowing function after stroke based on the semi-quantita-tive assessment of the videofluoroscopic dysphagia scale(VDS),to provide a basis for clinical screening and treatment.Method:A retrospective survey method was conducted on 120 stroke patients who met the inclusion criteria.Clinical characteristics were collected,including gender,age,type of stroke,lesion location,disease duration,food consistency,nasogastric tube placement,tracheostomy,and comorbidities.All patients underwent a video-fluoroscopic swallowing study(VFSS),and swallowing function was assessed using the videofluoroscopic dys-phagia scale(VDS).Univariate and multivariate linear regression analyses were conducted to examine the ef-fects of clinical characteristics on oral phase,pharyngeal phase,and global swallowing function.Result:Univariate analysis revealed that subcortical lesions in the middle cerebral artery(MCA)region(ex-cluding the basal ganglia)(P＜0.001),basal ganglia lesions(P=0.040),and medullary lesions(P＜0.001)were significantly associated with global swallowing function after stroke.Multivariate linear regression analysis indi-cated that medullary lesions(P＜0.001),subcortical lesions in the MCA region(excluding the basal ganglia)(P＜0.001),and MCA(including basal ganglia)lesions(P=0.019)were risk factors for global swallowing function after stroke.Regarding food consistency,consumption of thickened liquids(P=0.018)and pureed foods(P=0.006)were protective factors for global swallowing function.Subgroup analysis of global swallow-ing function revealed that MCA(including basal ganglia)lesions(P=0.003),female gender(P＜0.001)and tra-cheotomy(P＜0.001)were risk factors for oral phase swallowing function after stroke.Compared with patients without a gastrostomy tube,those with a gastrostomy tubes(P=0.034)had less effect on swallowing function in the oral phase.Compared with hemorrhagic stroke,ischemic stroke(P＜0.001)had a less impact on the oral phase swallowing function.Medullary lesions(P＜0.001)and subcortical lesions in the MCA region(ex-cluding the basal ganglia)(P＜0.001)were risk factors for pharyngeal phase swallowing function.For food con-sistency,the consumption of thickened liquids(P=0.005)and pureed foods(P=0.002)were protective factors for pharyngeal phase swallowing function after stroke.Conclusion:Identifying clinical characteristics in the assessment of swallowing function in stroke patients helps to determine the type of dysphagia and the key points of treatment.This approach may facilitate the de-velopment and implementation of more targeted rehabilitation treatment plans,and accelerate the recovery of swallowing function and feeding ability in stroke patients.

Investigated the mechanisms by which baicalein regulates nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)to ameliorate lipopolysaccharide(LPS)-induced sepsis-asso-ciated acute kidney injury(AKI)in mice.Sixty male C57BL/6 mice were randomly divided into six groups:control,model,low-dose baicalein(50 mg/kg),medium-dose baicalein(100 mg/kg),high-dose baicalein(200 mg/kg),and high-dose baicalein+brusatol(4 mg/kg).Baicalein was adminis-tered orally for 7 days as a preventative measure.Sepsis was induced via intraperitoneal injection of LPS.Murine sepsis score(MSS)was assessed within 12 hours post-induction.Serum creatinine(Scr),blood urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)were measured using an automatic biochemical analyzer and enzyme-linked immunosorbent assays(ELISA),respectively.Histopathological changes in kidney tissues were ob-served via hematoxylin-eosin(HE)staining.Western blot analysis was employed to determine the protein expression levels of Nrf2,HO-1,caspase-8,TNF-α,IL-1β,and IL-6 in kidney tissues.Additionally,total superoxide dismutase(SOD)activity in kidney tissues was assessed using com-mercially available kits.Compared to the model group,baicalein treatment significantly improved renal histopathological changes,alleviated cellular damage,and reduced the levels of inflammatory cytokines(TNF-α,IL-1βand IL-6)(P＜0.01)and kidney injury markers(Scr and BUN)(P＜0.01).Moreover,baicalein treatment significantly increased the protein expression levels of Nrf2 and HO-1(P＜0.01)and enhanced antioxidant enzyme activity.In conclusion,baicalein may pro-tect against LPS-induced sepsis-associated AK1 in mice by modulating the Nrf2/HO-1 signaling pathway,thereby attenuating oxidative stress,reducing inflammation,and disrupting the vicious cycle between inflammation and oxidative stress.

Objective:To explore the influencing factors of swallowing function after stroke based on the semi-quantita-tive assessment of the videofluoroscopic dysphagia scale(VDS),to provide a basis for clinical screening and treatment.Method:A retrospective survey method was conducted on 120 stroke patients who met the inclusion criteria.Clinical characteristics were collected,including gender,age,type of stroke,lesion location,disease duration,food consistency,nasogastric tube placement,tracheostomy,and comorbidities.All patients underwent a video-fluoroscopic swallowing study(VFSS),and swallowing function was assessed using the videofluoroscopic dys-phagia scale(VDS).Univariate and multivariate linear regression analyses were conducted to examine the ef-fects of clinical characteristics on oral phase,pharyngeal phase,and global swallowing function.Result:Univariate analysis revealed that subcortical lesions in the middle cerebral artery(MCA)region(ex-cluding the basal ganglia)(P＜0.001),basal ganglia lesions(P=0.040),and medullary lesions(P＜0.001)were significantly associated with global swallowing function after stroke.Multivariate linear regression analysis indi-cated that medullary lesions(P＜0.001),subcortical lesions in the MCA region(excluding the basal ganglia)(P＜0.001),and MCA(including basal ganglia)lesions(P=0.019)were risk factors for global swallowing function after stroke.Regarding food consistency,consumption of thickened liquids(P=0.018)and pureed foods(P=0.006)were protective factors for global swallowing function.Subgroup analysis of global swallow-ing function revealed that MCA(including basal ganglia)lesions(P=0.003),female gender(P＜0.001)and tra-cheotomy(P＜0.001)were risk factors for oral phase swallowing function after stroke.Compared with patients without a gastrostomy tube,those with a gastrostomy tubes(P=0.034)had less effect on swallowing function in the oral phase.Compared with hemorrhagic stroke,ischemic stroke(P＜0.001)had a less impact on the oral phase swallowing function.Medullary lesions(P＜0.001)and subcortical lesions in the MCA region(ex-cluding the basal ganglia)(P＜0.001)were risk factors for pharyngeal phase swallowing function.For food con-sistency,the consumption of thickened liquids(P=0.005)and pureed foods(P=0.002)were protective factors for pharyngeal phase swallowing function after stroke.Conclusion:Identifying clinical characteristics in the assessment of swallowing function in stroke patients helps to determine the type of dysphagia and the key points of treatment.This approach may facilitate the de-velopment and implementation of more targeted rehabilitation treatment plans,and accelerate the recovery of swallowing function and feeding ability in stroke patients.

Objective:To investigate the effect of dulagopeptide on physical examination indexes,plasma glucose metabolism and islet function in type 2 diabetes mellitus(T2DM)patients with poorly controlled plasma glucose.Methods:135 T2DM patients with poorly controlled plasma glucose who were admitted in our hospital from January 2023 to July 2024 were selected.A prospective randomized controlled design was adopted,they were divided into control group 1(received treatment with sitagliptin,n=45),control group 2(received treatment with insulin glargine,n=45),and observation group(received treatment with dulaglutide,n=45)according to the random number table method.Physical examination indexes,plasma glucose indicators,islet function,and incidence of adverse reactions were compared among the three groups.Results:12 weeks after treatment,body mass index(BMI),waist circumference,fasting plasma glucose(FPG),glycated hemoglobin(HbA1c),and postprandial 2-hour plasma glucose(2hPG)in the observation group were lower than those in control group 1 and control group 2(P＜0.05).12 weeks after treatment,the observation group had the highest HbA1c compliance rate,reaching 71.1％(P＜0.05).12 weeks after treatment,the fasting C-peptide(FC-P)and HOMA-islet(CP-DM)levels in the observation group were higher than those in control group 1 and control group 2(P＜0.05).Conclusion:Dulagopeptide can effectively improve physical examination indexes,plasma glucose indicators,and islet function in T2DM patients with poorly controlled plasma glucose.