Application of bioactive ceramics iRoot BP Plus? in pulpotomy for complicated crown fracture of immature permanent anterior teeth in children / 北京大学学报(医学版)

Objective:To analyze the clinical and radiographic effectiveness of a calcium silicate-based bioactive ceramic iRoot BP Plus? pulpotomy of immature permanent teeth with complicated crown fracture and to evaluate the factors influencing its long-term success rate.Methods:The digital medical records of patients under 13 years old who had undergone iRoot BP Plus? pulpotomy in the Department of Oral Emergency or the First Clinical Division,Peking University School and Hospital of Stomatology from March 2017 to September 2022 due to complicated crown fracture of anterior teeth,and had taken at least one post-operation apical radiograph were reviewed.The clinical and radiographic information at the initial examination and follow-up period were obtained,including crown color,mobility,percussion,cold test(partial pulpotomy teeth),dental restoration,fistula,swelling or inflammation of the gingival tissue,the formation of apical foramen,pathologic radiolucency and calcification of pulp chamber or root canal obliteration.Data were tested by Fisher exact test and a multiple comparison.Results:In the study,64 patients including 37 males(57.8％)and 27 females(42.2％)with a mean age of 9.1 years were finally enrolled.The total number of permanent teeth that received pulpotomy was 75,and the average follow-up time was 19.3 months.The success rate was 93.1％with the time interval between dental injury and treatment in 24 h,while the success rate dropped to 88.2％with the time intervals beyond 24 h.The time intervals did not significantly affect the pulp survival rate(P=0.61)after pulpotomy(partial or co-ronal).The success rate 6 months after pulpotomy was 96.0％,and one-year success rate was 94.7％.A total of 23 cases were reviewed for more than 2 years after pulpotomy,and 6 cases failed.The mobility had no significant effect on the success rate(P=0.28).Pulp chamber calcification and pulp canal obli-teration were not observed in all the post-operative radiographs.Conclusion:The one year clinical and radiographic success rates obtained in this study indicate that iRoot BP Plus? is an appropriate pulp cap-ping material option for pulpotomy treatment of complicated crown fracture in immature permanent teeth without displacement injuries.This technique has broad promotional value.

Risk factors for acute pancreatitis in long-term drinking participants: a longitudinal UK Biobank-based study / 西安交通大学学报(医学版)

【Objective】 To examine risk factors for acute pancreatitis (AP) in individuals with chronic alcohol consumption habits. 【Methods】 The study incorporated participants from the initial survey (2006-2010) and subsequent follow-ups (2014+) taken from the UK Biobank database, with the observation period ending on November 30, 2022. During this period, 176 individuals were newly diagnosed with AP, while 59,512 remained unaffected. Vital characteristics of the target population, such as their medical histories, surgical experiences and dietary patterns, were collected during the enrolment phase (2006-2010). The Cox proportional hazard model was employed to ascertain whether these characteristics were potent risk factors for AP. Concurrently, a subgroup from the target population with documented drinking behavior was selected. The multivariate Cox proportional hazard model was utilized to analyze the relationship of the established factors, variances in alcohol consumption, and increased alcohol intake (Δ) with the onset of AP, and whether the additional alcohol intake served as a risk factor. 【Results】 Multivariate analysis revealed that consumption quantity of cooked vegetables inversely correlated with AP risk (HR=0.44, 0.39, 0.42 and 0.41 for one, two, three and four+ tablespoons per day, respectively, as compared to non-consumers). Coffee consumption (2-3 cups per day) also reduced AP risk (HR=0.45 for 2 cups/day; HR=0.39 for 3 cups/day as compared to non-coffee drinkers). However, those with biliary disease without cholecystectomy exhibited a marked increase in AP risk (HR=7.82), which reduced albeit remained elevated for those with biliary disease post-cholecystectomy (HR=2.15). Subgroup analysis showed minimal impact of alcohol intake levels on AP incidence. Yet, increased alcohol consumption (Δ of 1 bottle/week) was linked to a heightened AP risk (HR=1.05, 95% CI:1.02-1.09, P<0.05). 【Conclusion】 Among longstanding alcohol consumers, a diet rich in cooked vegetables and moderate coffee consumption offers protective effects against AP. Conversely, biliary disease (particularly without cholecystectomy) and elevated alcohol intake present considerable risk factors for the development of this condition.

NE activates Nrf2/HO⁃1 signaling pathway to regulate oxidative stress in human endometrial epithelial cells / 安徽医科大学学报

Objective @#To investigate whether norepinephrine (NE) regulates the oxidative stress in human endometrial epithelial cells (hEECs) by activating nuclear factor E2⁃related factor 2(Nrf2)/ heme oxygenase ⁃1(HO⁃1) signal pathway.@*Methods @#C ultured hEECs were used. The expression of α and β adrenergic receptors was detected by reverse transcription⁃polymerase chain reaction (RT⁃PCR) . Cell counting kit ⁃8(CCK⁃8) assay was applied to test the effect of NE on cell viability , then the cells were divided into C ontrol group and NE treatment group , and the appropriate concentrations were chosen. The expression of tight j unction proteins Occludin and zona occludens-1 (ZO⁃1) , apoptosis⁃related proteins apoptosis⁃related protein B ⁃cell lymphoma⁃2 protein(Bcl ⁃2) and Bcl ⁃2 associated X protein(Bax) , antioxidant proteins Nrf2 and HO⁃1 were examined by Western blot. The apoptosis was detected by flow cytometry. The malonaldehyde (MDA) and superoxide dismutase(SOD) in the cell culture medium were detected by enzyme⁃linked immunosorbent assays kit ( ELISA) .@*Results @#The mRNA expression of α1 a ,α1 b , α2 a , α2 b , α2 c , β1 , β3 was detected in the hEECs. After the NE treatment , no significant change in cell viability was ob served in low concentration (5 μmol/L and 10 μmol/L) groups , while 15 μmol/L and 20 μmol/L NE treatments for 6 h or 24 h promoted the cell viability significantly. The expression of ZO⁃1 and Occludin increased significantly in 15 μmol/L group after 24 h treatment , the expression of ZO⁃1 decreased in 6 h treatment group , significant down regulation was ob served after 15 μmol/L NE application , the expression of Occludin increased in 6 h group. The cell apoptosis increased compared with the control group after NE stimulation , espeserved after 24 h treatment. The ration of Bcl ⁃2/Bax > 1 . The expression of Nrf2 and HO⁃1 was elevated by NE. There was no obvious change in MDA level while significant elevation in SOD was detected in cell culture medium.@*Conclusion@#Nrf2/H0-1 signal is activated after application of NE to the hEECs, which may responsible for the upregulation of SOD, antioxidant and anti-apoptotic effect in the hEECs.

Mechanism studies underlying the alleviatory effects of isoliquiritigenin on abnormal glucolipid metabolism triggered by type 2 diabetes / 药学学报

Isoliquiritigenin (ISL) is an active chalcone compound isolated from licorice. It possesses anti-inflammatory and anti-oxidative activities. In our previous study, we uncovered a great potential of ISL in treatment of type 2 diabetes mellitus (T2DM). Therefore, this study aims to reveal the mechanism underlying the alleviatory effects of ISL on T2DM-induced glycolipid metabolism disorder. High-fat-high-sugar diet (HFD) combined with intraperitoneal injection of streptozotocin (STZ) were used to establish T2DM mice model. All animal experiments were carried out with approval of the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments, and sodium palmitate (SP) was applied to establish insulin resistance (IR) model cells. The effects of ISL on body weight, fasting blood glucose levels, and pathological changes in the livers of mice were examined. Enzyme-linked immune sorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) were applied to detect the regulatory effects of ISL on key targets involved in glucolipid metabolism. Additionally, molecular docking and analytical dynamics simulation methods were used to analyze the interaction between ISL and key target protein. The results indicate that ISL significantly downregulates the transcriptional levels and inhibits the activities of key enzymes involved in gluconeogenesis, including pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), and fructose-1, 6-bisphosphatase (FBP). It also downregulates the transcriptional and protein levels of hepatocyte nuclear factor 4α (HNF4α) and cAMP response element binding protein (CREB), the two transcriptional factors involved in gluconeogenesis. Thus, ISL inhibits hepatic gluconeogenesis in T2DM mice. In addition, ISL reduces total cholesterol (TC) and triglyceride (TG) levels in the livers of T2DM mice. Moreover, ISL downregulates the mRNA levels of lipogenesis genes and upregulates those of genes involved in fatty acid oxidation, lipid uptake, and lipid export. In conclusion, ISL suppresses hepatic gluconeogenesis, promotes lipolysis, and restrains lipogenesis in T2DM mice, thereby improving the abnormal glycolipid metabolism caused by T2DM.

Mechanism of action of traditional Chinese medicine in treatment of nonalcoholic fatty liver disease based on intestinal microecology / 临床肝胆病杂志

Nonalcoholic fatty liver disease （NAFLD） is a multisystem disease associated with obesity， insulin resistance， and dyslipidemia and has a complex pathogenesis. Studies have shown that gut microbiota dysbiosis is closely associated with the onset of NAFLD， and traditional Chinese medicine treatment can improve the laboratory markers and clinical symptoms of NAFLD patients by regulating intestinal microbiota and its metabolites. This article elaborates on the association between NAFLD and gut microbiota， the involvement of gut microbiota dysbiosis in the pathogenesis of NAFLD， and the possible mechanism of traditional Chinese medicine treatment in improving NAFLD from the perspective of gut microbiota， in order to provide new ideas for the treatment of NAFLD.

Myricetin attenuates renal fibrosis by activating Nrf2/HO-1 pathway to inhibit oxidative stress / 药学学报

This paper investigates the effect of myricetin (MYR) on renal fibrosis induced by unilateral ureteral obstruction (UUO) and common bile duct ligation (CBDL) in mice and its mechanism. The animal experiment has been approved by the Ethics Committee of China Pharmaceutical University (NO: 2022-10-020). Thirty-five ICR mice were divided into control, UUO, UUO+MYR, CBDL and CBDL+MYR groups. H&E and Masson staining were used to detect pathological changes in kidney tissues. Western blot (WB) was used to detect the expression of fibrosis-related proteins in renal tissue, and total superoxide dismutase (SOD) activity detection kit (WST-8) was used to detect the changes of total SOD in renal tissue of CBDL mice. In vitro, HK-2 cells and transforming growth factor beta 1 (TGF-β1, 10 ng·mL-1) were used to induce fibrotic model, and high glucose (30 mmol·L-1) was used to induce oxidative stress model, and then treated with different concentrations of MYR, WB was used to detect the expression of fibrosis and oxidative stress-related proteins, while NIH/3T3 cells were treated with different concentrations of MYR, and their effects on cell proliferation were detected by 5-bromo-2′-deoxyuridine (Brdu). The results showed that the renal lesions in UUO group and CBDL group were severe, collagen deposition was obvious, the expression of collagen-Ⅰ (COL-Ⅰ), α-smooth muscle actin (α-SMA), fibronectin (FN), vimentin and plasminogen activator inhibitor-1 (PAI-1) protein was up-regulated, and the activity of SOD enzyme in CBDL group was significantly decreased. MYR partly reversed the above changes after treatment. MYR inhibited the proliferation of NIH/3T3 cells but had no effect on the proliferation of HK-2 cells, and decreased the upregulation of PAI-1, FN and vimentin in HK-2 cells stimulated by TGF-β1. MYR can also up-regulate the down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in HK-2 cells stimulated by high glucose. To sum up, MYR can improve renal fibrosis in vivo and in vitro, probably by inhibiting the proliferation of fibroblasts and activating Nrf2/HO-1 signal pathway to inhibit oxidative stress.

Study on effect of Wumei Pill on apoptosis of colon cells in rats with ulcerative colitis and its mechanism by regulating miR-146a / 中国免疫学杂志

Objective:To investigate effect of Wumei Pill on colon cell apoptosis in ulcerative colitis(UC)rats by regulating miR-146a and its mechanism.Methods:A total of 50 SD rats were selected,with 10 rats in each group,and divided into control group,model group,Wumei Pill low,medium and high doses groups.Transfected with anti-miR-NC,anti-miR-146a,miR-NC,miR-146a as anti-miR-NC group,anti-miR-146a group,Wumei Pill+miR-NC group,Wumei Pill+miR-146a group.CCK-8 was used to de-tect cell proliferation;flow cytometry was used to detect cell apoptosis;RT-qPCR was used to detect cell miR-146a expression;ELI-SA was used to detect cell IL-1β and IL-13 contents;Western blot was used to detect expressions of B-cell lymphoma 2(Bcl-2)and Bax proteins.Results:Compared with control group,cell survival rate,Bcl-2 protein expression in model group were decreased,while apoptosis rate,Bax protein expression,IL-1β,IL-13 contents and miR-146a expression were increased(P<0.05).Compared with model group,Wumei Pill significantly increased cell survival rate and Bcl-2 protein expression,decreased cell apoptosis rate,Bax protein expression,IL-1β,IL-13 contents and miR-146a expression(P<0.05).Inhibition of miR-146a increased cell survival rate,Bcl-2 protein expression,decreased cell apoptosis rate,IL-1β,IL-13 contents and Bax protein expression(P<0.05).Overexpression of miR-146a reversed effects of Wumei Pills on proliferation and apoptosis of colon cells in UC rats.Conclusion:Wumei Pill can reduce apoptosis of colon cells in UC rats by up-regulating expression of miR-146a.

Predictive value of triglyceride-glucose index on the outcome in patients with acute ischemic stroke undergoing intravenous alteplase thrombolysis / 中国医科大学学报

Objective To explore the predictive role of the triglyceride-glucose(TyG)index in patients with acute ischemic stroke(AIS)treated with alteplase thrombolysis and create a comprehensive predictive model integrating multiple factors for assessing patient out-comes.Methods The clinical data of 302 patients with AIS undergoing alteplase intravenous thrombolysis at the Neurology Department of Fushun Central Hospital from January 2019 to October 2022 were retrospectively analyzed.The patients were categorized into a good prognosis group(n= 193)and a poor prognosis group(n= 109)based on their mRS scores at 90 days post-thrombolysis.Univariate and multivariate logistic regression analyses were employed to identify risk factors influencing adverse outcomes and to establish a predictive model.The predictive performance of the model was assessed using receiver operating characteristic(ROC)curve analysis.Results The results of the multivariate logistic regression analysis revealed that pre-thrombolysis high NIHSS score and TyG index≥9.37 were inde-pendent risk factors for unfavorable prognosis in AIS patients.A predictive model for AIS patient prognosis was successfully established:Logit(Y)=-17.167 + 1.681×TyG index+0.147×pre-thrombolysis NIHSS score.The optimal cutoff value for the TyG index was 9.37.The ROC areas under the curve for predicting unfavorable prognosis in AIS patients at 90 days post-thrombolysis were 0.713 for TyG index,0.705 for pre-thrombolysis NIHSS score,and 0.787 for the combined variable(Y),with the combined variable(Y)exhibiting the largest ROC curve area.Conclusion TyG index≥9.37 and pre-thrombolysis high NIHSS score are independent risk factors for poor prognosis.The combined variable the combined variable(Y)has higher predictive efficiency than the separate variables.

Quality evaluation of Tongshu gel paste based on multi-index component quantification / 中国药师

Objective To evaluate the quality of Tongshu gel paste based on thin layer chromatography(TLC)identification and high performance liquid chromatography(HPLC)quantitative analysis of multi-index components.Methods Qualitative identification of tetrahydropalmatine,paeoniflorin,tetrandrine,linderane,Rhizoma atractylodis and Fructus aurantii in the modified Tongshu gel paste was carried out by TLC.The main active contents of tetrahydropalmatine,paeoniflorin,tetrandrine and linderane in the preparation were determined by HPLC.Results The TLC spots of the six herbs in the prescription were clear and negative without interference.The linear ranges of tetrahydropalmatine,paeoniflorin,tetrandrine and linderane were 4.30-272.50 μg/mL(r=0.999 9),21.10-1 350.00 μg/mL(r=0.999 8),4.10-262.40 μg/mL(r=0.999 8)and 3.60-232.50 μg/mL(r=0.998 6),respectively.The range of average recovery for each component was 98.96％-99.52％,and all RSDs were less than or equal to 1.54％(n=9).Conclusion The multi-index TLC qualitative identification and HPLC quantitative method established by research have high specificity,simple operation and can be used for quality evaluation of the improved formulation of this prescription.

Early coagulation function changes of penetrating intestinal firearm injury of pigs in high-altitude environment / 中华创伤杂志

Objective:To explore the early coagulation function changes of penetrating intestinal firearm injury of pig in high-altitude environments.Methods:Twenty healthy long white piglets were selected and divided into the plain group and the high-altitude group using the random number table method, with 10 pigs in each group. Pigs in the plain group were placed in a plain environment at an altitude of 800 meters, while pigs in the high-altitude group were placed in an experimental chamber simulating an altitude of 6 000 meters for 48 hours. Both groups received pistol gunshot to have firearm penetrating wounds to the abdominal intestinal tract and then returned to the plain observation room. At 0, 2, 4, 8, 12 and 24 hours after injury, coagulation in the peripheral blood and fibrinolytic indexes [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fbg), D-dimer (D-D), and fibrinogen degradation product (FDP)], thromboelastogram (TEG) [reaction time (R), clotting time (K), clot formation rate (α), maximum amplitude (MA) and coagulation composite index (CI) ], platelet parameters [platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and platelet-large cell ratio (P-LCR)] in the two groups were detected separately.Results:The PT values at 0 and 2 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 8, 12 and 24 hours than those in the plain group ( P<0.01); there was no significant difference at 4 hours between the two groups ( P>0.05). The APTT values at 0, 2 and 4 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The TT values at 0, 2 and 4 hours after the injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 12 and 24 hours after injury than those in the plain group ( P<0.01); there was no significant difference at 8 hours after injury between the two groups ( P>0.05). The Fbg, D-D and FDP values at 0, 2, 4, 8, 12 and 24 hours after injury were higher in the high-altitude group than those in the plain group ( P<0.01). The R values at 0, 2 and 4 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The K values at 0, 2, 4 and 8 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 12 and 24 hours after injury than those in the plain group ( P<0.05 or 0.01). The α angles at 0, 2 and 4 hours after injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The MA values at 0, 2 and 4 hours after the injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The CI values at 0, 2 and 4 hours after injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The PLT values at 0, 2, 4 and 8 hours after injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 12 and 24 hours after injury than those in the plain group ( P<0.05 or 0.01). The MPV values at 0, 2, 4, 8, 12 and 24 hours after injury in the high-altitude group were significantly higher than those in the plain group ( P<0.01). The PDW values at 2, 4, 8, 12 and 24 hours after injury in the high-altitude group were significantly higher than those in the plain group ( P<0.05 or 0.01), while there was no significant difference in PDW at 0 hour after injury between the two groups ( P>0.05). The P-LCR values at 0, 2, 4, 8, 12 and 24 hours after injury in the high-altitude group were all significantly higher than those in the plain group ( P<0.01). Conclusion:Compared with the plain environments, pig intestinal firearm penetrating injury in the high-altitude environments is more prone to early hypercoagulable state accompanied by mild hyperfibrinolysis, and faster to reach a hypocoagulable state accompanied by obvious hyperfibrinolysis.

Pediatric Classic Prescription Xiaoruwan Based on Ancient Literature / 中国实验方剂学杂志

Xiaoruwan is one of the classic prescriptions included in the Catalogue of Ancient Classic Prescriptions （the Second Batch of Pediatrics） published by the National Administration of Traditional Chinese Medicine（TCM） in 2022 with definite clinical efficacy， but it has not been converted into Chinese patent medicine preparations. The authors collected 173 pieces of data based on ancient literature on Xiaoruwan by the method of bibliometrics and selected 99 pieces of effective data， involving 46 ancient books of TCM. The study analyzed the historical development origin， prescription names， formulation rules， dosage， drug origin， preparation method and usage， indications and functions， and other aspects of Xiaoruwan. The results showed that Xiaoruwan was presumably derived from Ying Hai Miao Jue Lun（《婴孩妙诀论》） written by TANG Minwang， a doctor in the Song Dynasty. In the records of ancient medical books， there are names such as Xiaoshiwan，Yangshi Xiaoruwan， and Kuaige Xiaoshiwan， but they are mainly recorded in the name of Xiaoruwan. The prescription was composed of Cyperi Rhizoma， Amomi Fructus， Citri Reticulatae Pericarpium， Massa Medicata Fermentata， Hordei Fructus Germinatus， and Glycyrrhizae Radix et Rhizoma. In terms of processing method， Cyperi Rhizoma， Massa Medicata Fermentata， and Hordei Fructus Germinatus are fried， Glycyrrhizae Radix et Rhizoma is processed， and raw materials of Amomi Fructus and Citri Reticulatae Pericarpium are used directly. In terms of function， it is effective in warming the middle， improving digestion， stopping vomiting， and digesting milk and food. The main indications include vomiting， diarrhea， night crying， and other diseases caused by milk and food stagnation. The dosage of the most used prescription in the records of ancient books is Cyperi Rhizoma 41.30 g， Amomi Fructus 20.65 g， Citri Reticulatae Pericarpium 20.65 g， Massa Medicata Fermentata 20.65 g， Hordei Fructus Germinatus 20.65 g， and Glycyrrhizae Radix et Rhizoma 20.65 g， which are prepared into pills. In the taking method， it is recommended to take it with warm boiled water or ginger soup after meals. The study summarized the historical evolution of Xiaoruwan and identified the key information， with a view to providing a reference for the modern development and research of Xiaoruwan.

Effect of Angelica dahurica coumarins on the transport behavior of puerarin across blood-brain barrier in vitro and in vivo / 药学学报

A BBB co-culture cell model consisting of rat brain microvascular endothelial cells (BMEC) and astrocytes (AS) was established to study the effect of Angelica dahurica coumarins on the transport behavior of puerarin across blood-brain barrier (BBB) in vitro and in vivo. The barrier function of this model was evaluated by measuring the transendothelial resistance, phenol red permeability and BBB related protein expression. The permeability assay and western blot methods were performed to study the effects of Angelica dahurica coumarins on the BBB permeability and the expression of BBB related protein. The animal experiment protocols in this study were approved by the Animal Ethics Committee of Xi'an Jiaotong University (Animal Ethics No.: 2021-1329). The results showed that the established BMEC/AS co-culture model could be used to evaluate drug transport across BBB in vitro. After combined with Angelica dahurica coumarins, the transport capacity of puerarin was significantly increased in vitro and in vivo. Additionally, Angelica dahurica coumarins enhanced BBB permeability and inhibited the protein expression of P-glycoprotein (P-gp), zonula occludens-1 (ZO-1) and occludin. Angelica dahurica coumarins might increase BBB permeability by inhibiting the expression of P-gp and tight junction protein, thereby increasing the content of puerarin in brain tissue.

Scientific basis of acupuncture on mesenchymal stem cells for treating ischemic stroke / 中国针灸

The scientific basis of acupuncture on mesenchymal stem cells (MSCs) for treating ischemic stroke (IS) is discussed. MSCs transplantation has great potential for the treatment of tissue damage caused by early stage inflammatory cascade reactions of IS, but its actual transformation is limited by various factors. How to improve the homing efficiency of MSCs is the primary issue to enhance its efficacy. As such, the possible mechanisms of acupuncture and MSCs transplantation in inhibiting inflammatory cascade reactions induced by IS are explored by reviewing literature, and a hypothesis that acupuncture could promote the secretion of stromal cell-derived factor-1α (SDF-1α) from ischemic foci to regulate SDF-1α/CXC chemokine receptor 4 (CXCR4) axis, thereby improving the homing efficiency of MSCs transplantation, exerting its neuroprotective function, and improving the bed transformation ability, is proposed.

Inositol 1,4,5-triphosphate receptor 3 promotes renal cyst development in autosomal dominant polycystic kidney disease / 生理学报

The purpose of the present study was to determine the role of inositol 1,4,5-trisphosphate receptor 3 (IP3R3) in renal cyst development in autosomal dominant polycystic kidney disease (ADPKD). 2-aminoethoxy-diphenyl borate (2-APB) and shRNA were used to suppress the expression of IP3R3. The effect of IP3R3 on cyst growth was investigated in Madin-Darby canine kidney (MDCK) cyst model, embryonic kidney cyst model and kidney specific Pkd1 knockout (PKD) mouse model. The underlying mechanism of IP3R3 in promoting renal cyst development was investigated by Western blot and immunofluorescence staining. The results showed that the expression level of IP3R3 was significantly increased in the kidneys of PKD mice. Inhibiting IP3R3 by 2-APB or shRNA significantly retarded cyst expansion in MDCK cyst model and embryonic kidney cyst model. Western blot and immunofluorescence staining results showed that hyperactivated cAMP-PKA signaling pathway in the growth process of ADPKD cyst promoted the expression of IP3R3, which was accompanied by a subcellular redistribution process in which IP3R3 was translocated from endoplasmic reticulum to intercellular junction. The abnormal expression and subcellular localization of IP3R3 further promoted cyst epithelial cell proliferation by activating MAPK and mTOR signaling pathways and accelerating cell cycle. These results suggest that the expression and subcellular distribution of IP3R3 are involved in promoting renal cyst development, which implies IP3R3 as a potential therapeutic target of ADPKD.

Initial Treatment of Aumolertinib in Combination with Bevacizumab for Advanced NSCLC with Primary EGFR T790M Mutation: A Report of Three Cases and Literature Review / 中国肺癌杂志

With the development of sequencing technology, the detection rate of non-small cell lung cancer (NSCLC) with primary epidermal growth factor receptor (EGFR) T790M mutation is increasing. However, the first-line treatment for primary EGFR T790M-mutated NSCLC still lacks standard recommendations. Here, we reported three advanced NSCLC cases with EGFR-activating mutation and primary T790M mutation. The patients were initially treated with Aumolertinib combination with Bevacizumab; among which, one case was discontinued Bevacizumab due to bleeding risk after treatment for three months. Treatment was switched to Osimertinib after ten months of treatment. Another case switched to Osimertinib and discontinued Bevacizumab after thirteen months of treatment. The best effect response in all three cases was partial response (PR) after initial treatment. Two cases progressed after first-line treatment and progression-free survival (PFS) was eleven months and seven months respectively. The other one patient had persistent response after treatment, and the treatment duration has reached nineteen months. Two cases had multiple brain metastases before administration and the best response to intracranial lesions was PR. The intracranial PFS was fourteen months and not reached (16+ months), respectively. There were no new adverse events (AEs), and no AEs of grade three or above were reported. In addition, we summarized the research progress of Osimertinib in the treatment of NSCLC with primary EGFR T790M mutation. In conclusion, Aumolertinib combined with Bevacizumab in the treatment of advanced NSCLC with primary EGFR T790M mutation has a high objective response rate (ORR) and control ability of intracranial lesions, which can be used as one of the initial options for first-line advanced NSCLC with primary EGFR T790M mutation.
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A clinical application study of digital manufacturing simple intraoral Gothic arch-tracing device in determining the centric relation of complete dentures / 北京大学学报(医学版)

OBJECTIVE@#To verify the consistency between the digital manufacturing simple intraoral Gothic arch-tracing device and the traditional intraoral Gothic arch-tracing device in determining the centric relation of complete dentures restoration.@*METHODS@#Ten outpatients with edentulous jaws were selec-ted, and the centric relation of the patients was determined by digital manufacturing of simple intraoral Gothic arch-tracing device (T1) and traditional intraoral Gothic arch-tracing device (T2); the difference of clinical operation time between the two methods was recorded; the upper and lower edentulous jaw plaster models were scanned with two kinds of centric relation, the Standard Triangle Language (STL) files imported into Geomagic studio software to apply the best fitting of multiple points of the both upper jaw models, the fitted STL files imported into the 3 shape viewer software, and the maximum position deviations of the vertical, labial (buccal) and lingual directions of the mandibular midline area and molar areas in T1 and T2 groups measured. During the clinical complete dentures try-in, we observed whether there was midline deviation in the mouth of T1 group and T2 group, and whether the occlusion of posterior teeth was stable or not.@*RESULTS@#The mean time spent on determining the centric relation of T1 and T2 groups was (41.90±2.64) min, (57.50±2.37) min respectively. Paired t test was conducted in the two groups, P < 0.01 with significant statistical difference; The mean maximum position deviation between T1 group and T2 group of the midline mandibular region in labial lingual direction was (0.32±0.14) mm, that was (0.40±0.23) mm in vertical direction; the mean maximum position deviation of molar area in buccal lingual direction was (0.35±0.23) mm and that was (0.33±0.20) mm in vertical direction. In the vertical and horizontal directions, the maximum position deviation of mandibles between group T1 and group T2 was controlled within 0.5 mm. In the process of clinical complete dentures try-in, there was no deviation from the center line of dentures. There was not warping, swinging and other poor stability phenomena in T1 and T2 groups.@*CONCLUSION@#The digital manufacturing of simple intraoral Gothic arch-tracing device can be used to determine the centric relation of complete dentures, which can not only save time of clinical operation, but also ensure the accuracy of the centric relation.

Establishment of leukemia cell model with inducible AML1-ETO expression and its effect on fatty acid metabolism in leukemia cells / 中华血液学杂志

Objective: To investigate the effect of the AML1-ETO (AE) fusion gene on the biological function of U937 leukemia cells by establishing a leukemia cell model that induces AE fusion gene expression. Methods: The doxycycline (Dox) -dependent expression of the AE fusion gene in the U937 cell line (U937-AE) were established using a lentivirus vector system. The Cell Counting Kit 8 methods, including the PI and sidanilide induction, were used to detect cell proliferation, cell cycle-induced differentiation assays, respectively. The effect of the AE fusion gene on the biological function of U937-AE cells was preliminarily explored using transcriptome sequencing and metabonomic sequencing. Results: ①The Dox-dependent Tet-on regulatory system was successfully constructed to regulate the stable AE fusion gene expression in U937-AE cells. ②Cell proliferation slowed down and the cell proliferation rate with AE expression (3.47±0.07) was lower than AE non-expression (3.86 ± 0.05) after inducing the AE fusion gene expression for 24 h (P<0.05). The proportion of cells in the G(0)/G(1) phase in the cell cycle increased, with AE expression [ (63.45±3.10) %) ] was higher than AE non-expression [ (41.36± 9.56) %] (P<0.05). The proportion of cells expressing CD13 and CD14 decreased with the expression of AE. The AE negative group is significantly higher than the AE positive group (P<0.05). ③The enrichment analysis of the transcriptome sequencing gene set revealed significantly enriched quiescence, nuclear factor kappa-light-chain-enhancer of activated B cells, interferon-α/γ, and other inflammatory response and immune regulation signals after AE expression. ④Disorder of fatty acid metabolism of U937-AE cells occurred under the influence of AE. The concentration of the medium and short-chain fatty acid acylcarnitine metabolites decreased in cells with AE expressing, propionyl L-carnitine, wherein those with AE expression (0.46±0.13) were lower than those with AE non-expression (1.00±0.27) (P<0.05). The metabolite concentration of some long-chain fatty acid acylcarnitine increased in cells with AE expressing tetradecanoyl carnitine, wherein those with AE expression (1.26±0.01) were higher than those with AE non-expression (1.00±0.05) (P<0.05) . Conclusion: This study successfully established a leukemia cell model that can induce AE expression. The AE expression blocked the cell cycle and inhibited cell differentiation. The gene sets related to the inflammatory reactions was significantly enriched in U937-AE cells that express AE, and fatty acid metabolism was disordered.

Analysis of on-demand adherence and related factors in men who have sex with men who access HIV pre-exposure prophylaxis services via the internet / 中华流行病学杂志

Objective: To understand the compliancy to on-demand HIV pre-exposure prophylaxis (PrEP) and related factors in men who have sex with men (MSM) accessing to PrEP service through an Internet platform. Methods: A cross-sectional study method was used to recruit survey respondents through the Heer Health platform from July 6 to August 30, 2022, and a questionnaire survey on the current status of medication use was conducted in MSM who use PrEP through the platform and take medication on demand. The MSM's information collected in the survey mainly included socio-demographic characteristics, behavioral characteristics, risk perception characteristics, PrEP awareness and the status of dose taking. Univariate and multivariate logistic regression analyses were used to evaluate factors related with compliancy to PrEP. Results: A total of 330 MSM who met the recruitment criteria were included during the survey period, with a valid response rate of 96.7% (319/330) to the questionnaire survey. The age of the 319 MSM was (32.5±7.3) years. Most of them had education level of junior college or college and above (94.7%, 302/319), most of them were unmarried (90.3%, 288/319), most of them had full-time works (95.9%, 306/319), and 40.8% of them had average monthly income ≥10 000 yuan (130/319). The proportion of the MSM with good compliancy to PrEP was 86.5% (276/319). The results of univariate and multivariate logistic analyses showed that the MSM with good awareness of PrEP had relatively better compliancy to PrEP compared with those with poor awareness of PrEP (aOR=2.43, 95%CI:1.11-5.32). Conclusions: The compliancy to on-demand PrEP was good in MSM who accessed to the services through Internet platform, but there is still a need to strengthen PrEP promotion in MSM for the further improvement of PrEP compliancy and reduction of the risk for HIV infection in this population.

A risk prediction model of cervical cancer developed based on nested case-control design / 中华流行病学杂志

Objective: To construct a cervical cancer risk prediction model based on nested case-control study design and Yinzhou Health Information Platform in Ningbo, and provide reliable reference for self-risk assessment of cervical cancer in local women. Methods: In local women aged 25-75 years old who had no history of cervical cancer registered in Yinzhou before October 31, 2018, a follow up was conducted for at least three years, the patients who developed cervical cancer during the follow up period were selected as the case group and matched with a control group at a ratio of 1∶10. The prediction indicators before the onset was used in model construction. Variables were selected by Lasso-logistic regression, the variables with non-zero β were selected to fit the logistic regression model and Bootstrap was used for internal validation. The discrimination of the model was evaluated by area under the receiver operating characteristic curve(AUROC), and the calibration was evaluated by calibration curve and Hosmer-Lemeshow test. Results: The prediction indicators included in the final model were age, smoking status, history of cervicitis, history of adenomyosis, HPV testing, and thinprep cytologic test. The AUROC calculated in the internal validation was 0.740 (95%CI:0.739-0.740), and the calibration curve was almost identical with the ideal curve, P=0.991 in Hosmer-Lemeshow test, indicating that the model discrimination and calibration were good. Conclusions: In this study, a simple and practical cervical cancer risk prediction model was developed. The model can be used in general population with strong interpretability, good discrimination and calibration in internal validation, which can provide a reference for women to assess their risk of cervical cancer.

Effect of pancreatic extracorporeal shock wave lithotripsy on chronic pancreatitis stones / 中华外科杂志

Objective: To analyze the therapeutic effect and safety of pancreatic extracorporeal shock wave lithotripsy(P-ESWL) for patients with chronic pancreatitis complicated by stones of the pancreatic duct and to investigate the influencing factors. Methods: A retrospective analysis was performed on clinical data from 81 patients with chronic pancreatitis complicated by pancreatic duct calculus treated with P-ESWL in the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi 'an Jiaotong University from July 2019 to May 2022. There were 55 males(67.9%) and 26 females(32.1%). The age was (47±15)years (range: 17 to 77 years). The maximum diameter(M(IQR)) of the stone was 11.64(7.60) mm, and the CT value of the stone was 869 (571) HU. There were 32 patients (39.5%) with a single pancreatic duct stone and 49 patients(60.5%) with multiple pancreatic duct stones. The effectiveness, remission rate of abdominal pain, and complications of P-ESWL were evaluated. Student's t test, Mann Whitney U test, χ2 test, or Fisher's exact test was used to compare the characteristics between the effective and ineffective groups of lithotripsy. The factors influencing the effect of lithotripsy were analyzed by univariate and multivariate logistic regression analysis. Results: Eighty-one patients with chronic pancreatitis were treated with P-ESWL 144 times, with an average of 1.78 (95%CI:1.60 to 1.96) times per person. Among them, 38 patients(46.9%) were treated with endoscopy. There were 64 cases(79.0%) with effective removal of pancreatic duct calculi and 17 cases(21.0%) with ineffective removal. Of the 61 patients with chronic pancreatitis accompanied by abdominal pain, 52 cases(85.2%) had pain relief after lithotripsy. After lithotripsy treatment, 45 patients(55.6%) developed skin ecchymosis, 23 patients(28.4%) had sinus bradycardia, 3 patients(3.7%) had acute pancreatitis, 1 patient(1.2%) had a stone lesion, and 1 patient(1.2%) had a hepatic hematoma. Univariate and multivariate logistic regression analysis showed that the factors affecting the efficacy of lithotripsy included the age of patient(OR=0.92, 95%CI: 0.86 to 0.97), the maximum diameter of the stone(OR=1.12,95%CI:1.02 to 1.24) and the CT value of the stone(OR=1.44, 95%CI: 1.17 to 1.86). Conclusions: P-ESWL is effective in the treatment of patients with chronic pancreatitis complicated by calculi of the main pancreatic duct.Factors affecting the efficacy of lithotripsy include patient's age, maximum stone diameter, and CT value of calculi.