Objective To compare the application effect of platelet rich fibrin(PRF)prepared at different centrifugal speeds in tooth extraction wounds using network meta-analysis statistical method.Methods PubMed,Co-chrane Library,Embase,Web of Science,CNKI,Wanfang,VIP and China Biology Medicine disc(CBM)databases were searched to collect the randomized controlled trials on the effect of PRF in tooth extraction from January 1,2024.Note-Express software was used to select literatures,RevMan5.3 was used to evaluate the quality of the included literatures,and Stata14.0 software was used to perform mesh meta-analysis on outcome indicators such as bone mineral density,bone height loss,visual analog scale of pain(VAS),dry groove,and bleeding after tooth extraction.Results A total of 31 randomized controlled trials were included,including 2 824 extraction sites,involving 7 rotational speeds for PRF preparation(3 000,2 800,2 700,2 300,1 500,1 400,1 300 r/min).The results of cu-mulative sequencing showed that PRF prepared by 2 700 r/min centrifugation had the best effect in improving bone mineral density.In terms of improving the buccal bone height,the PRF prepared by 2 700 r/min centrifu-gation had the best effect.In terms of pain improvement,PRF prepared by 1 500 r/min centrifugation had the best effect;PRF prepared by 2 500 r/min centrifugation had the best effect in reducing the incidence of dry trough.PRF prepared by 2 500 r/min centrifugation was the most effective in reducing bleeding.Conclusion Based on the available evidence,PRF prepared with 2 700 r/min has the best effect on improving bone density and bone height after tooth extraction.In terms of pain improvement,1 500 r/min was the most effective;2 500 r/min was the most effective in improving the incidence of dry trough and bleeding.

Objective To investigate the effects and mechanisms of Huatan Quyu Decoction on learning and memory abilities in rats with vascular dementia(VD).Methods Totally 112 male SD rats were randomly selected with 16 rats as the sham-operation group,the remaining rats were used to prepare VD models by segmental ligation of the common carotid artery.The successfully modeled rats were randomly divided into model group,Huatan Quyu Decoction low-,medium-and high-dosage groups(6.1,12.1,24.2 g/kg),donepezil hydrochloride group(0.5 mg/kg)and combination group(Huatan Quyu Decoction 12.1 g/kg+donepezil hydrochloride 0.5 mg/kg),with 16 rats in each group.Each group was given the corresponding treatment measures for 4 weeks.The Morris water maze test was used to assess learning and memory abilities,neurological function was evaluated using Garcia score,HE staining was used to observe the morphology of the hippocampal tissue,ELISA was employed to detect the serum content of Aβ,immunohistochemistry was utilized to observe the β-catenin,LRP6 and GSK-3β protein expression in brain tissue.Results Compared with the sham-operation group,the escape latency of the model group rats was prolonged(P<0.01),the number of crossing platforms was reduced(P<0.01),and the neurological deficit score was decreased(P<0.01),the arrangement of hippocampal tissue cells was disorderly,and the tissue was severely damaged,the serum Aβ content increased(P<0.01),the expressions of β-catenin and LRP6 protein in brain tissue decreased,and the expression of GSK-3β protein increased(P<0.01).Compared with the model group,the escape latency of rats in each administration group was shortened,the number of crossing platforms increased,the neurological deficit score increased,the number of hippocampal cells was relatively more,the arrangement was more orderly,and the structure was relatively complete,the serum Aβ content decreased,the expressions of β-catenin and LRP6 proteins increased,and the expression of GSK-3β protein decreased.Among them,Huatan Quyu Decoction high-dosage group had a significantly better effect than Huatan Quyu Decoction low-and medium-dosage groups(P<0.01),and there was no statistical significance in various indicators compared with the donepezil hydrochloride group(P>0.05).Compared with the donepezil hydrochloride group,the combination group showed significant improvements in learning and memory abilities(P<0.01),the neurological deficit score significantly increased(P<0.01),the number of hippocampal cells significantly increased,arranged neatly,and structurally intact,the serum Aβ content significantly decreased(P<0.01),the expression of β-catenin and LRP6 proteins significantly increased,and the expression of GSK-3β protein significantly decreased(P<0.01).Conclusion Huatan Quyu Decoction can repair cognitive function in VD rats,improve learning and memory abilities,and alleviate VD symptoms by activating the Wnt/β-catenin signaling pathway to reduce serum Aβ content,decrease the apoptosis of nerve cells and alleviate the degree of pathological damage in hippocampal tissue.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Objective To investigate the effects and mechanisms of Huatan Quyu Decoction on learning and memory abilities in rats with vascular dementia(VD).Methods Totally 112 male SD rats were randomly selected with 16 rats as the sham-operation group,the remaining rats were used to prepare VD models by segmental ligation of the common carotid artery.The successfully modeled rats were randomly divided into model group,Huatan Quyu Decoction low-,medium-and high-dosage groups(6.1,12.1,24.2 g/kg),donepezil hydrochloride group(0.5 mg/kg)and combination group(Huatan Quyu Decoction 12.1 g/kg+donepezil hydrochloride 0.5 mg/kg),with 16 rats in each group.Each group was given the corresponding treatment measures for 4 weeks.The Morris water maze test was used to assess learning and memory abilities,neurological function was evaluated using Garcia score,HE staining was used to observe the morphology of the hippocampal tissue,ELISA was employed to detect the serum content of Aβ,immunohistochemistry was utilized to observe the β-catenin,LRP6 and GSK-3β protein expression in brain tissue.Results Compared with the sham-operation group,the escape latency of the model group rats was prolonged(P<0.01),the number of crossing platforms was reduced(P<0.01),and the neurological deficit score was decreased(P<0.01),the arrangement of hippocampal tissue cells was disorderly,and the tissue was severely damaged,the serum Aβ content increased(P<0.01),the expressions of β-catenin and LRP6 protein in brain tissue decreased,and the expression of GSK-3β protein increased(P<0.01).Compared with the model group,the escape latency of rats in each administration group was shortened,the number of crossing platforms increased,the neurological deficit score increased,the number of hippocampal cells was relatively more,the arrangement was more orderly,and the structure was relatively complete,the serum Aβ content decreased,the expressions of β-catenin and LRP6 proteins increased,and the expression of GSK-3β protein decreased.Among them,Huatan Quyu Decoction high-dosage group had a significantly better effect than Huatan Quyu Decoction low-and medium-dosage groups(P<0.01),and there was no statistical significance in various indicators compared with the donepezil hydrochloride group(P>0.05).Compared with the donepezil hydrochloride group,the combination group showed significant improvements in learning and memory abilities(P<0.01),the neurological deficit score significantly increased(P<0.01),the number of hippocampal cells significantly increased,arranged neatly,and structurally intact,the serum Aβ content significantly decreased(P<0.01),the expression of β-catenin and LRP6 proteins significantly increased,and the expression of GSK-3β protein significantly decreased(P<0.01).Conclusion Huatan Quyu Decoction can repair cognitive function in VD rats,improve learning and memory abilities,and alleviate VD symptoms by activating the Wnt/β-catenin signaling pathway to reduce serum Aβ content,decrease the apoptosis of nerve cells and alleviate the degree of pathological damage in hippocampal tissue.

Objective:To investigate the risk factors of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) complicated with pancreatogenic portal hypertension (PPH) and to establish a prediction model.Methods:From January 1, 2016 to December 31, 2022, a total of 1 095 patients diagnosed with MSAP or SAP at the First Affiliated Hospital of Kunming Medical University were enrolled and divided into PPH group (145 cases) and non-PPH group (950 cases) according to the presence or absence of concomitant PPH. The general data (gender, etiology of acute pancreatitis, days of hospitalization, etc.), complications (portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, etc.), laboratory indicators (albumin, D-dimer, etc.), and scores of modified computed tomography severity index (MCTSI) were collected in the two groups. The least absolute shrinkage and selection operator(LASSO) and multivariate logistic regression analysis were performed to analyze the independent risk factors of MSAP and SAP complicated with PPH, and the nomogram prediction model was established. The area under the curve of the receiver operating characteristic curve was calculated to evaluate the discrimination of the calibration curve and Hosmer-Lemeshow goodness of fit test were used to assess the predictive accuracy of the model, and clinical decision curve analysis (DCA) was used to evaluate the clinical practicability of the model.Results:The results of LASSO and multivariate logistic regression analysis showed that portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, days of hospitalization, MCTSI and decreased albumin were independent risk factors of MSAP and SAP complicated with PPH ( OR=7.013, 2.085, 1.846, 1.030, 1.235 and 0.955; 95% confidence interval 4.061 to 12.112, 1.255 to 3.463, 1.066 to 3.199, 1.013 to 1.047, 1.123 to 1.357 and 0.927 to 0.983; all P<0.05). The area under the curve of the model was 0.820 (95% confidence interval 0.780 to 0.859), the calibration curve was close to the reference curve, and the Hosmer-Lemeshow goodness-fit test showed that the model had a good fit ( χ2=9.82, P=0.278). The result of DCA indicated that the model had a high net benefit in a wide range of risk threshold (threshold probability 0.1 to 0.9), and had certain clinical practicability. Conclusions:Portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, days of hospitalization, MCTSI and decreased albumin are the independent risk factors of MSAP and SAP complicated with PPH. The established nomogram model has good differentiation, calibration and clinical practicability.

Objective:To investigate the risk factors of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) complicated with pancreatogenic portal hypertension (PPH) and to establish a prediction model.Methods:From January 1, 2016 to December 31, 2022, a total of 1 095 patients diagnosed with MSAP or SAP at the First Affiliated Hospital of Kunming Medical University were enrolled and divided into PPH group (145 cases) and non-PPH group (950 cases) according to the presence or absence of concomitant PPH. The general data (gender, etiology of acute pancreatitis, days of hospitalization, etc.), complications (portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, etc.), laboratory indicators (albumin, D-dimer, etc.), and scores of modified computed tomography severity index (MCTSI) were collected in the two groups. The least absolute shrinkage and selection operator(LASSO) and multivariate logistic regression analysis were performed to analyze the independent risk factors of MSAP and SAP complicated with PPH, and the nomogram prediction model was established. The area under the curve of the receiver operating characteristic curve was calculated to evaluate the discrimination of the calibration curve and Hosmer-Lemeshow goodness of fit test were used to assess the predictive accuracy of the model, and clinical decision curve analysis (DCA) was used to evaluate the clinical practicability of the model.Results:The results of LASSO and multivariate logistic regression analysis showed that portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, days of hospitalization, MCTSI and decreased albumin were independent risk factors of MSAP and SAP complicated with PPH ( OR=7.013, 2.085, 1.846, 1.030, 1.235 and 0.955; 95% confidence interval 4.061 to 12.112, 1.255 to 3.463, 1.066 to 3.199, 1.013 to 1.047, 1.123 to 1.357 and 0.927 to 0.983; all P<0.05). The area under the curve of the model was 0.820 (95% confidence interval 0.780 to 0.859), the calibration curve was close to the reference curve, and the Hosmer-Lemeshow goodness-fit test showed that the model had a good fit ( χ2=9.82, P=0.278). The result of DCA indicated that the model had a high net benefit in a wide range of risk threshold (threshold probability 0.1 to 0.9), and had certain clinical practicability. Conclusions:Portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, days of hospitalization, MCTSI and decreased albumin are the independent risk factors of MSAP and SAP complicated with PPH. The established nomogram model has good differentiation, calibration and clinical practicability.

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300-β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.

Objective:To explore the clinical application value of fetal heart quantification (fetal HQ) in the analysis of 24-segment spherical index (SI) of fetal heart in normal second and third trimestries.Methods:In July 2019, sixty-five normal singletons with gestational age (GA) of 28(24, 31) weeks were examined by echocardiography in Sir Run Run Shaw Hospital. The global spherical index (GSI) of the heart was measured and the dynamic images of the standard four chamber view were collected. Twenty-four-segment SI of the left and right ventricles were measured by using the fetal HQ analysis system and the correlation between SI and gestational age was analyzed.Results:There were no significant correlations between GSI, SI of left and right ventricles and gestational age ( r s=-0.22-0.14, all P>0.05). The SI of the first segment of left ventricle was lower than those of the other 23 segments (all P<0.05). There were no significant differences of SI among the second to the eleventh segments of the left ventricle (all P>0.05). In the 13th to the 24th segments of the left ventricle, the closer to the apex of the heart, the greater the SI of the segment were noted (all P<0.05). For the right ventricle, the closer to the apex of the heart, the greater the SI of the 4th to the 24th segments were found (all P<0.05), and there were no significant differences in SI among the first to third segment( P>0.05). The success rate of fetal HQ software was 95.4%. Conclusions:The 24-segment SI of RV and LV provides a feasible and reliable quantitative method which allows for the assessment of fetal heart function from the four-chamber view.

Objective To understand the rationality and safety of oral antihypertensive drugs on chronic renal disease(CKD)combined with hypertension hospitalized patients. Methods It was a multi-center and retrospective investigation. The electronic medical records of CKD with hypertension patients who were hospitalized in 6 comprehensive hospitals in Beijing and used oral antihypertensive drugs on October 1st,2013 to March 31st,2015 were collected. The pharmacists who participated in the project from the 6 research centers filled out the investigation form. According to the drug instruction,the rationality of antihypertensive medication was evaluated by daily dose,frequency of drug delivery,the dosage for renal insufficiency,contraindications and adverse interactions. Results There were 2 833 valid cases in this study,1 730 males and 1 103 females. The ratio of male to female was 1:0.64. The range of age was 18~101 years. The average age was(61 ± 18)years. There were 1 630(57.54%)cases whose age was≥60;314(11.1%)cases were CKD level 1,526(18.6%)cases were CKD level 2,1 117(39.4%)cases were CKD level 3,423(14.9%)cases were CKD level 4,453(16.0%)cases were CKD level 5. 144 (5.1%)cases were hypertension level 1,592(20.9%)cases were hypertension level 2,1 398 cases (49.3%)were hypertension level 3,and 699(24.7%)cases were not graded. The oral hypotensive drugs applied during the hospitalization of 2 833 patients included calcium channel blockers(CCB),beta blockers,diuretics,angiotensin Ⅱ receptor blocker(ARB),angiotensin converting enzyme inhibitors (ACEI),alpha/beta blockers and alpha blockers. 1 022(36.1%)cases used 1 kind of antihypertensive drugs,1 032(36.4%)cases used 2 kinds of antihypertensive drugs,591(20.9%)cases used 3 kinds of antihyper-tensive drugs,157(5.5%)cases used 4 kinds of antihypertensive drugs and 31(1.1%)cases used 5 kinds of antihypertensive drugs. A total of 6038 cases of antihypertensive drugs were administered. The top priority was CCB(35.11%,2 120),the second was beta blockers(17.26%,1 042)and the third was diuretics(16.23%,980). The choice of a single drug for antihypertensive drugs was reasonable. The 2,3,4,5 combined drug users who were not recommended by the guidelines were 4.8%(50/1 032), 21.2%(125/591),28.0%(44/157)and 64.5%(20/31)respectively. The situation of blood pressure control was evaluated with blood pressure target values achieved rate. With blood pressure below 130/80 mmHg as the standard,the admission and discharge blood pressure target achieved rate was 31.2%(884/2 833)and 29.5%(799/2 705)respectively. With blood pressure below 140/90 mmHg as the standard, the admission and discharge blood pressure target achievement rate was 53.6%(1 519/2 833)and 64.4%(1 743/2 705)respectively. Among the 2 833 cases,903(31.9%)cases had 1 204 times of unreasonable use of the drug. The top three were excessive daily frequency of medication(1 029,85.5%),total daily dosage(114,9.5%),and use of drugs that were contraindicated(51,4.2%). Two cases had adverse drug reactions related to antihypertensive drugs. Conclusion The use of antihypertensive drugs in patients with CKD in the six hospitals involved in the investigation was reasonable,but there was still some problems in the combination of drugs. Some doctors are not familiar with the drug instructions,and there are some problems such as increasing the frequency of drug use,overdose medication,and use of drugs that are contraindicated. Clinical pharmacists should be more involved in clinical work in these areas.

Objective To understand the rationality and safety of oral antihypertensive drugs on chronic renal disease(CKD)combined with hypertension hospitalized patients. Methods It was a multi-center and retrospective investigation. The electronic medical records of CKD with hypertension patients who were hospitalized in 6 comprehensive hospitals in Beijing and used oral antihypertensive drugs on October 1st,2013 to March 31st,2015 were collected. The pharmacists who participated in the project from the 6 research centers filled out the investigation form. According to the drug instruction,the rationality of antihypertensive medication was evaluated by daily dose,frequency of drug delivery,the dosage for renal insufficiency,contraindications and adverse interactions. Results There were 2 833 valid cases in this study,1 730 males and 1 103 females. The ratio of male to female was 1:0.64. The range of age was 18~101 years. The average age was(61 ± 18)years. There were 1 630(57.54%)cases whose age was≥60;314(11.1%)cases were CKD level 1,526(18.6%)cases were CKD level 2,1 117(39.4%)cases were CKD level 3,423(14.9%)cases were CKD level 4,453(16.0%)cases were CKD level 5. 144 (5.1%)cases were hypertension level 1,592(20.9%)cases were hypertension level 2,1 398 cases (49.3%)were hypertension level 3,and 699(24.7%)cases were not graded. The oral hypotensive drugs applied during the hospitalization of 2 833 patients included calcium channel blockers(CCB),beta blockers,diuretics,angiotensin Ⅱ receptor blocker(ARB),angiotensin converting enzyme inhibitors (ACEI),alpha/beta blockers and alpha blockers. 1 022(36.1%)cases used 1 kind of antihypertensive drugs,1 032(36.4%)cases used 2 kinds of antihypertensive drugs,591(20.9%)cases used 3 kinds of antihyper-tensive drugs,157(5.5%)cases used 4 kinds of antihypertensive drugs and 31(1.1%)cases used 5 kinds of antihypertensive drugs. A total of 6038 cases of antihypertensive drugs were administered. The top priority was CCB(35.11%,2 120),the second was beta blockers(17.26%,1 042)and the third was diuretics(16.23%,980). The choice of a single drug for antihypertensive drugs was reasonable. The 2,3,4,5 combined drug users who were not recommended by the guidelines were 4.8%(50/1 032), 21.2%(125/591),28.0%(44/157)and 64.5%(20/31)respectively. The situation of blood pressure control was evaluated with blood pressure target values achieved rate. With blood pressure below 130/80 mmHg as the standard,the admission and discharge blood pressure target achieved rate was 31.2%(884/2 833)and 29.5%(799/2 705)respectively. With blood pressure below 140/90 mmHg as the standard, the admission and discharge blood pressure target achievement rate was 53.6%(1 519/2 833)and 64.4%(1 743/2 705)respectively. Among the 2 833 cases,903(31.9%)cases had 1 204 times of unreasonable use of the drug. The top three were excessive daily frequency of medication(1 029,85.5%),total daily dosage(114,9.5%),and use of drugs that were contraindicated(51,4.2%). Two cases had adverse drug reactions related to antihypertensive drugs. Conclusion The use of antihypertensive drugs in patients with CKD in the six hospitals involved in the investigation was reasonable,but there was still some problems in the combination of drugs. Some doctors are not familiar with the drug instructions,and there are some problems such as increasing the frequency of drug use,overdose medication,and use of drugs that are contraindicated. Clinical pharmacists should be more involved in clinical work in these areas.