Acteoside promotes autophagy and apoptosis of hepatoma cells by regulating JNK signaling pathway / 中国中药杂志

This study explored the molecular mechanism of acteoside against hepatoma 22(H22) tumor in mice through c-Jun N-terminal kinase(JNK) signaling pathway. H22 cells were subcutaneously inoculated in 50 male BALB/c mice, and then the model mice were classified into model group, low-dose, medium-dose, and high-dose acteoside groups, and cisplatin group. The administration lasted 2 weeks for each group(5 consecutive days/week). The general conditions of mice in each group, such as mental status, diet intake, water intake, activity, and fur were observed. The body weight, tumor volume, tumor weight, and tumor-inhibiting rate were compared before and after administration. Morphological changes of liver cancer tissues were observed based on hematoxylin and eosin(HE) staining, and the expression of phosphorylated(p)-JNK, JNK, B-cell lymphoma-2(Bcl-2), Beclin-1, and light chain 3(LC3) in each tissue was detected by immunohistochemistry and Western blot. qRT-PCR was performed to detect the mRNA expression of JNK, Bcl-2, Beclin-1, and LC3. The general conditions of mice in model and low-dose acteoside groups were poor, while the general conditions of mice in the remaining three groups were improved. The body weight of mice in medium-dose acteoside group, high-dose acteoside group, and cisplatin group was smaller than that in model group(P<0.01). The tumor volume in model group was insignificantly different from that in low-dose acteoside group, and the volume in cisplatin group showed no significant difference from that in high-dose acteoside group. Tumor volume and weight in medium-dose and high-dose acteoside groups and cisplatin group were lower than those in the model group(P<0.001). The tumor-inhibiting rates were 10.72%, 40.32%, 53.79%, and 56.44% in the low-dose, medium-dose, and high-dose acteoside groups and cisplatin group, respectively. HE staining showed gradual decrease in the count of hepatoma cells and increasing sign of cell necrosis in the acteoside and cisplatin groups, and the necrosis was particularly obvious in the high-dose acteoside group and cisplatin group. Immunohistochemical results suggested that the expression of Beclin-1, LC3, p-JNK, and JNK was up-regulated in acteoside and cisplatin groups(P<0.05). The results of immunohistochemistry, Western blot, and qRT-PCR indicated that the expression of Bcl-2 was down-regulated in the medium-dose and high-dose acteoside groups and cisplatin group(P<0.01). Western blot showed that the expression of Beclin-1, LC3, and p-JNK was up-regulated in acteoside and cisplatin groups(P<0.01), and there was no difference in the expression of JNK among groups. qRT-PCR results showed that the levels of Beclin-1 and LC3 mRNA were up-regulated in the acteoside and cisplatin groups(P<0.05), and the level of JNK mRNA was up-regulated in medium-dose and high-dose acteoside groups and cisplatin group(P<0.001). Acteoside promotes apoptosis and autophagy of H22 cells in mice hepatoma cells by up-regulating the JNK signaling pathway, thus inhibiting tumor growth.

Trajectory and impact factors of cycle threshold values of virus load in respiratory tract in children infected with severe acute respiratory syndrome coronavirus 2 Omicron variants / 中华传染病杂志

Objective:To investigate the clinical characteristics of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants, and the impact factors of duration of cycle threshold (Ct) values turning to ≥35 detected by nucleotide test.Methods:Children aged 0 to 14 years with clinical symptoms of Omicron variants infection who admitted to designated hospital in Shanghai City (Renji Hospital, South Branch, Shanghai Jiao Tong University School of Medicine) from April 7 to June 2, 2022 were enrolled. The daily nasopharyngeal swab specimens were used for SARS-CoV-2 nucleic acid detecting by polymerase chain reaction and the results were expressed as Ct values. The T Ct≥ x was defined as from the symptom onset or first positive nucleic acid test results (the earlier data) to Ct≥ x of the open reading frame 1ab ( ORF1 ab) gene, which was the time duration from the initial to a specific Ct value.Clinical data were collected, including age, sex, vaccination and comorbidities.Cox model was performed to analyzed the impact factors of T Ct≥35. Results:A total of 871 pediatric cases with a median age of two years (ranging from one month to 14 years old) were included. Among them, 474 cases (54.4%) were male, and 89 cases (10.2%) had underlying diseases including congenital heart disease, solid tumors and epilepsy. There were 572(65.7%) mild cases, 298(34.2%) common cases, one (0.1%) severe case and no critical cases or deaths. The T Ct≥35 was 12(10, 14) days. Cox model indicated that compared to children aged one to 12 months, children aged 37 to 84 months and 85 to 168 months had shorter T Ct≥35 (hazard ratio ( HR)=1.55 and 1.84, respectively, both P<0.001). After adjusted with age, comparing to unvaccinated patients, patients with one or two shots vaccine had shorter T Ct≥35 (adjected hazard ratio (a HR)=1.49, P=0.011), and common patients had longer T Ct≥35 than mild patients (a HR=0.78, P=0.002), and patients with comorbidities had longer T Ct≥35than patients without comorbidities (a HR=0.38, P<0.001).The duration of T Ct≥28, T Ct≥30, T Ct≥33 and T Ct≥35 in children without underlying diseases were 7(6, 9) d, 9(7, 10) d, 10(8, 11) d and 12(10, 14) d, respectively. Conclusions:Age, vaccination, disease severity and underlying diseases could affect the duration of SARS-CoV-2 nucleotide turning to negative (Ct value≥35) in children infected with Omicron variants.

Application of prostatic exosomal protein in the diagnosis of histological prostatitis in patients with benign prostatic hyperplasia / 现代泌尿外科杂志

【Objective】 To investigate the feasibility of prostatic exosomal protein (PSEP) detection kit in the diagnosis of histological prostatitis (HP) in patients with benign prostatic hyperplasia (BPH), and to explore the correlation between PSEP and other clinical parameters. 【Methods】 A total of 104 patients with BPH or BPH plus HP treated during Nov.2021 and Nov.2022 were involved. The patients were instructed to fill out the International Prostate Symptom Score (IPSS) scale independently before surgery. Clinical data such as prostate volume, residual urine volume, free prostate specific antigen (fPSA), total prostate specific antigen (tPSA), and fPSA/tPSA were collected. Preoperative midstream morning urine was collected for PSEP detection. 【Results】 The sensitivity and specificity of PSEP in the diagnosis of BPH were 93.51% and 70.37%, respectively, which were highly consistent with the postoperative pathological diagnosis results (Kappa=0.663). Serum PSEP level was positively correlated with tPSA level (r=0.242, P=0.040). 【Conclusion】 PSEP has a high clinical diagnostic value in the diagnosis of HP, which can provide a reliable basis for the diagnosis of HP in BPH patients and improve the diagnosis rate.

Effect of dexmedetomidine on perioperative neurocognitive disorders in elderly frail patients undergoing hip joint surgery / 中华麻醉学杂志

Objective:To evaluate the effect of dexmedetomidine on perioperative neurocognitive disorders in elderly frail patients undergoing hip joint surgery.Methods:Sixty elderly patients of either sex, aged≥ 60 yr, weighing 40-100 kg, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, with the Frail Scale score 3-5 points, scheduled for elective hip surgery under spinal-epidural anesthesia, were divided into 2 groups ( n=30 each) using the random number table method: control group (group C) and dexmedetomidine group (group D). Dexmedetomidine was intravenously infused at a dose of 0.5 μg/kg at 10 min before anesthesia followed by a continuous infusion of 0.2 μg·kg -1·h -1 until 10 min before the end of surgery in group D. The equal volume of 0.9% sodium chloride solution was given at the corresponding time point in group C. Blood samples from the median cubital vein were collected before surgery (T 1) and at 1 and 3 days after surgery (T 2, 3) for determination of concentrations of serum S100β and neuron-specific enolase by enzyme-related immunosorbent assay. Postoperative delirium was assessed within 3 days after surgery using the Confusion Assessment Method. Cognitive function was evaluated by Mini-Mental State Examination at T 1 and 30 days after surgery. Results:Compared with the baseline at T 1, the concentrations of serum S100β and NSE were significantly increased at T 2 and T 3 in two groups ( P<0.05). Compared with group C, the concentrations of serum S100β and neuron-specific enolase and incidence of postoperative delirium and postoperative cognitive dysfunction were significantly decreased at T 2 and T 3 in group D( P<0.05). Conclusions:Dexmedetomidine can effectively decrease the occurrence of perioperative neurocognitive disorders in elderly frail patients undergoing hip joint surgery.

Effect of sodium bicarbonate Ringer′s solution on acute kidney injury following laparoscopic hepatectomy in elderly patients / 中华麻醉学杂志

Objective:To evaluate the effect of sodium bicarbonate Ringer′s solution on acute kidney injury(AKI) following laparoscopic hepatectomy in elderly patients.Methods:A total of 362 American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ elderly patients, aged 65-79 yr, with body mass index of 18-28 kg/m 2, scheduled for elective laparoscopic hepatectomy, were divided into 2 groups( n=181 each) using a random number table method: bicarbonate Ringer′s solution group(BR group) and lactated Ringer′s solution group(LR group). Bicarbonate Ringer′s solution and lactated Ringer′s solution were intravenously infused in BR group and LR group, respectively. All operations were performed under general anesthesia combined with abdominal fascia block, and the methods of controlled low central venous pressure and intermittent hepatic inflow occlusion were applied to reduce intraoperative bleeding. Radial artery blood samples were collected for blood gas analysis at 5 min before anesthesia induction(T 0), 20 min after occluding liver hilus(T 1), 10 min after hepatectomy and hemostasis(T 2), at the end of surgery(T 3) and at postanesthesia care unit discharge(T 4), and lactate value(Lac) was recorded. Blood samples from cubital vein were collected on admission to hospital(T A) and at 24(T 24) and 48 h after operation(T 48) for determination of serum creatinine(Cr) concentrations. Doppler-based renal resistive index(RRI) was measured at T A, T 4, T 24 and T 48. The incidence of AKI was calculated within 48 h after operation according to the Kidney Disease: Improving Global Outcomes criteria in 2012 for Cr concentration. Adverse reactions(such as nausea and vomiting) and complications(such as incision infection) within 48 h after operation were recorded. Results:Compared with the baseline at T 0, Lac concentrations were significantly increased at T 1-4 in both groups( P<0.01). Cr concentrations were significantly increased at T 24 and T 48, and RRI was increased at T 4, T 24 and T 48 than at T A in both groups( P<0.01). Compared with group LR, the incidence of AKI within 48 h after operation, Lac concentrations at T 3, 4, Cr concentrations at T 24 and T 48, and RRI at T 4, T 24 and T 48 were significantly decreased in group BR( P<0.05 or 0.01). There was no significant difference in the incidence of nausea, vomiting, incision infection, delirium, bile leakage and pulmonary infection within 48 h after operation among the two groups( P>0.05). Conclusions:Sodium bicarbonate Ringer′s solution can decrease the development of AKI following laparoscopic hepatectomy in elderly patients.

Effect of transcutaneous electrical acupoint stimulation on postoperative acute lung injury in pediatric patients undergoing living-related liver transplantation / 中华麻醉学杂志

Objective:To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative acute lung injury (ALI) in the pediatric patients undergoing living-related liver transplantation.Methods:Sixty pediatric patients of either sex, aged 4-24 months, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with New York Heart Association (NYHA) class Ⅰ or Ⅱ, with Child-Pugh B or C, scheduled to undergo elective left external lobe piggyback living-related liver transplantation, were divided into 2 groups ( n=30 each) using a computer-generated table of random numbers: control group (group C) and TEAS group (group T). In group T, bilateral Zusanli (ST36), Neiguan (PC6), and Feishu (BL13) acupoints were stimulated with disperse-dense waves at the initial intensity of 0.5 mA and frequency of 2/15 Hz, the current intensity was gradually increased until local slight muscle shaking appeared, and continuous stimulation lasted for 30 min at a 30-min interval (a cycle) until the end of operation. TEAS was performed for 30 min at the same time every day up to 1 week after surgery. Stimulus locations in group C were selected at 0.5 cm lateral to the acupoints, and the electrodes with inert medium were attached to the location, with no effective current output from acupuncture treatment instrument. The peak inspiratory pressure, plateau pressure, and pulmonary compliance were recorded before skin incision (T 0), at 30 min after portal vein occlusion (T 1), at 1 h after portal vein opening (T 2), at the end of operation (T 3), and the difference between peak inspiratory pressure and plateau pressure was calculated. Blood samples from the jugular vein were collected at T 0-3 to determine the levels of plasma club cell protein 16 (CC16), surfactant protein D (SP-D), soluble receptor for advanced glycation end products (sRAGE), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) by enzyme-linked immunosorbent assay. Blood samples from the radial artery were collected at T 0-3 for blood gas analysis, PaO 2 and A-aDO 2 were recorded, and oxygenation index (OI) and respiratory index (RI) were calculated. The indwelling time of postoperative tracheal tube and length of ICU stay were also recorded. The lung injury was assessed and scored using ultrasound at 48 h after surgery. The occurrence of ALI within 1 week after operation was also recorded. Results:Compared with baseline at T 0, OI was significantly decreased, RI was increased, and plasma IL-10 concentrations were increased at T 2, 3, and the plasma concentrations of TNF-α, CC16, sRAGE and SP-D were increased at T 1-3 in both groups ( P<0.05). Compared with group C, OI was significantly increased, RI was decreased, the plasma concentrations of sRAGE were decreased, and the plasma concentrations of IL-10 were increased at T 2, 3, and the concentrations of plasma TNF-α, CC16 and SP-D were decreased at T 1-3, the indwelling time of postoperative tracheal tube and length of ICU stay were shortened, the ultrasound score of lung injury was decreased ( P<0.05), and no significant change was found in the incidence of ALI in group T ( P>0.05). Conclusions:TEAS can alleviate ALI in the pediatric patients after living-related liver transplantation.

Research progress of ProTide technology and its application in the development of antiviral drugs / 药学学报

ProTide technology is a kind of prodrug design strategy invented by the team of Christopher McGuigan. ProTides are aryloxyphosphoramidates (or aryloxyphosphonamidates) which contain a phosphorus atom combined with an amino acid ester and an aryloxy group. These prodrugs can efficiently cross the cell membrane and escape from the first rate-limiting step of phosphorylation, which afford effective solutions to the drawbacks of current nucleoside analogues. At present, ProTide technology has been extensively applied in the field of antiviral research. It has been successful in providing a number of approved drugs and clinical candidates, such as sofosbuvir and so much more, highlighting the promising future in drug discovery. This review summarizes the brief history and characteristics of ProTide technology, as well as its application in the exploration of antiviral drugs.

Integration of plasma metabolomics and spectrum-effect correlation for profiling the mechanism and pharmacodynamic substances on attenuating hepatic fibrosis of Bupleuri Radix and Paeoniae Radix Alba before and after vinegar-processing and compatibility / 药学学报

Plasma metabolomics based on UHPLC-Q-TOF-MS/MS technique was developed for profiling the mechanism on attenuating hepatic fibrosis of Bupleuri Radix (BR) and Paeoniae Radix Alba (PRA) before and after vinegar-processing and compatibility, and to screen potential pharmacodynamic substances by spectrum-effect correlation method in this study. Firstly, SD rats with CCl4-induced hepatic fibrosis were used as an in vivo model. The blood and tissue samples were collected for the analyses of pharmacodynamic indexes and plasma metabolomics after six weeks’ administration of BR, vinegar-processed BR (VPBR), PRA, vinegar-processed PRA (VPPRA), BR-PRA herb-pair, and VPBR-VPPRA herb-pair. The experiment was approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine (No.202103A002). The results of pharmacodynamics indicated that the levels of alanine aminotransferase (ALT, P < 0.01), aspartate aminotransferase (AST, P < 0.01), and hydroxyproline (HYP, P < 0.01) were decreased significantly, while the level of glutathione peroxidase (GSH-Px, P < 0.05) was increased obviously after administration of all treatment groups. Next, UHPLC-Q-TOF-MS/MS was performed to characterize the endogenous metabolites. A total of 20 differential endogenous metabolites related to the pathogenesis of hepatic fibrosis were identified in positive and negative ion modes, mainly involving five metabolic pathways of retinol metabolism, glycerol phospholipid metabolism, glyceride metabolism, fatty acid biosynthesis, and arachidonic acid metabolism. Meanwhile, a concept named correction rate was introduced to evaluate the back-regulation effects of all treatment groups on differential metabolites, and 10 differential metabolites were corrected by all treatment groups. The correction effects of the vinegar-processed herb groups were better than those of the crude ones, and the correction effects of the herb-pair groups were better than those of the single ones. Interestingly, the best correction effect was found in the VPBR-VPPRA herb-pair group, which further verified the efficacy improvement through vinegar-processing and compatibility. Partial least square method and VIP analysis combined with spectrum-effect correlation were applied for screening pharmacodynamic markers, and 38 ingredients with higher correlation with four classical pharmacodynamic indexes (ALT, AST, HYP, and GSH-Px) were identified as pharmacodynamic markers of the anti-hepatic fibrosis effects of BR and PRA before and after vinegar-processing and compatibility. The results of the investigation could not only lay a foundation for clarifying the pharmacodynamic materials and mechanism of vinegar-processing and compatibility of BR and PRA in the treatment of hepatic fibrosis as well as provide a theoretical basis for demonstrating the scientific connotation of processing and compatibility, but also provide a reference for further drug design and development of BR and PRA in clinic.

Effect of Qiling Baitouweng Tang on Proliferation and Apoptosis in Diffuse Large B-cell Lymphoma Through JAK2/STAT3 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Qiling Baitouweng Tang （QLBTWT） on proliferation and apoptosis， Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway and interleukin-10 （IL-10） in diffuse large B-cell lymphoma （DLBCL）. MethodWith human DLBCL cells OCI-LY10 and U2932 as research objects， cell proliferation was detected by cell counting kit-8 （CCK-8） assay. After treatment with 0， 4.6， 9.3， 18.7， 37.5， 75， 150 mg·L-1 QLBTWT for 24 h， the half-inhibitory concentration （IC50） of OCL-LY10 and U2932 cells was calculated to be 9.33， 16.13 mg·L-1， respectively， based on which， 9.5， 19， 38 mg·L-1 QLBTWT were selected for subsequent experiments. After 0， 9.5， 19， 38 mg·L-1 QLBTWT treatment for 24 h， the zymogen activities of Caspase-3， Caspase-8 and Caspase-9 in OCI-LY10 and U2932 cells were detected using corresponding activity assay kits （colorimetric）， and the IL-10 expression was detected by enzyme-linked immuno sorbent assay （ELISA）. The apoptosis rate and cell cycle of OCI-LY10 and U2932 cells treated with different concentrations of QLBTWT for 24 h were detected by flow cytometry. The expressions of apoptosis-related proteins ［B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved poly adenosine diphosphate ribose polymerase （cleaved PARP）， cleaved Caspase-3］， JAK2， STAT3， phospho-JAK2 （p-JAK2）， phospho-STAT3 （p-STAT3） pathway proteins， and c-Myc protein in OCL-LY10 and U2932 cells after 24 h treatment with 0， 9.5， 19， 38 mg·L-1 QLBTWT were all tested by Western blot. ResultAfter QLBTWT treatment on OCI-LY10 and U2932 cells for 24 h， cell proliferation was inhibited in each QLBTWT group compared with that in the control group （P<0.05， P<0.01）. The zymogens of Caspase-3， Caspase-8 and Caspase-9 were activated （P<0.01）， and there was an increase in cell apoptosis （P<0.05， P<0.01） and cell cycle arrest at Gap phase1 （G1） phase in 9.5， 19 and 38 mg·L-1 QLBTWT group （P<0.05， P<0.01）. After 9.5， 19 and 38 mg·L-1 QLBTWT treatment on OCI-LY10 and U2932 cells for 24 h， the expressions of Bcl-2， p-JAK2 and p-STAT3 proteins were decreased （P<0.01）， and the expressions of Bax， cleaved PARP and cleaved Caspase-3 proteins were increased （P<0.01）， but no significant change was observed in the expressions of JAK2 and STAT3 proteins. Compared with the conditions in the control group， the expressions of c-Myc， p-JAK2， and p-STAT3 proteins were down-regulated in 19 mg·L-1 QLBTWT group and 19 mg·L-1 QLBTWT+10 μg·L-1 IL-10 group （P<0.05， P<0.01）， and up-regulated in 10 μg·L-1 IL-10 group （P<0.05， P<0.01）， while there was no difference in JAK2/STAT3 proteins. ConclusionQLBTWT can inhibit proliferation and induce apoptosis of human DLBCL cells OCI-LY10 and U2932， and the potential mechanism may be related to the regulation of JAK2/STAT3 signaling pathway.

Effects of 0.05% cyclosporine eye drops(Ⅱ)on corneal nerves of patients with moderate to severe dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the efficacy of domestic cyclosporine A(CsA)in dry eye and its effect on sub-basal nerves(SBN)by observing quantitative and morphological changes in corneal SBN of patients with moderate to severe dry eye before and after the treatment with 0.05% CsA eye drops(Ⅱ).METHODS: In this prospective study, a total of 20 patients(20 eyes)with moderate to severe dry eye who admitted to the ophthalmology department of the Affiliated Eye Hospital of Nanchang University from December 2020 to January 2022 were selected. They were treated with domestic CsA and followed up for 3mo. Clinical evaluation was carried out at baseline and at 3mo after treatment. The changes in clinical symptoms, signs and morphology and quantity of SBN were observed.RESULTS: The ocular surface disease index(OSDI)score, the tear break-up time(TBUT), Schirmer Ⅰ, corneal fluorescein staining(CFS)score were significantly improved at 3mo after treatment. Confocal microscopy data analysis showed that SBN density increased from 13.49±5.43 mm/mm2 to 14.93±5.34 mm/mm2(P&#x0026;#x003C;0.001), nerve curvature scores decreased from 2.86±0.92 to 2.31±0.75(P&#x0026;#x003C;0.001), number of beaded structure decreased from 1.45±0.67/100μm to 1.07±0.45/100μm(P&#x0026;#x003C;0.001), and the number of dendritic cell(DC)decreased from 5.83±3.28 per frame to 3.67±2.24 per frame at 3mo after treatment(P&#x0026;#x003C;0.001). The number of DC was positively correlated with the number of branch nerves, the grade of nerve curvature and the number of nerve bead.(rs=0.27, P=0.045; rs=0.407, P&#x0026;#x003C;0.01; rs=0.486, P&#x0026;#x003C;0.01).CONCLUSIONS: Nerve injury was positively correlated with corneal inflammation caused by dry eye, and 0.05%CsA eye drops(II)could effectively inhibit inflammation and improve the morphology and quantity of corneal SBN. Observation of corneal SBN via in vivo confocal microscopy can be used as an effective method to evaluate the therapeutic effect of dry eye patients.

Analysis on the status quo of the awareness rate of core knowledge of cancer prevention and treatment and its influencing factors among residents in Liaoning Province in 2021 / 中华预防医学杂志

Objective: To analyze the status quo of the knowledge and related factors of cancer prevention and treatment among residents in Liaoning Province in 2021. Methods: From August to November 2021, through network sampling method, 17 474 permanent residents aged 15-69 years in Liaoning Province were surveyed. The WeChat public account was used to collect information such as demographic characteristics and core knowledge of cancer prevention and treatment. The Chi-square test was used to compare the difference of the level of the cancer prevention and treatment knowledge among different groups. The multivariate logistic regression model was used to analyze the related factors. Results: Among the 17 474 subjects, 43.1% (7 528) were male and 58.7% (10 262) were urban residents. The overall awareness rate was 72.3%, and the awareness rate of cancer cognition, prevention, early diagnosis and treatment, cancer management and rehabilitation were 71.4%, 67.6%, 72.7%, 83.4% and 63.5%, respectively. The multivariate logistic regression model showed that the residents who were man (OR: 0.850, 95%CI: 0.781-0.925), in rural areas (OR: 0.753, 95%CI: 0.694-0.817), 55-59 years old (OR: 0.851, 95%CI: 0.751-0.963), quitters (OR: 0.721, 95%CI: 0.640-0.813) and smoker (OR: 0.724, 95%CI: 0.654-0.801) had lower awareness rates, while the residents who were 35-54 years old (OR: 1.312, 95%CI: 1.202-1.432), with an educational level of junior high school/senior high school/college degree or above (OR: 1.834-5.130, 95%CI: 1.575-6.047), technical personnel (OR: 1.592, 95%CI: 1.367-1.854), civil servant/institution staff (OR: 1.282, 95%CI: 1.094-1.503), enterprise/business/service staff (OR: 1.218, 95%CI: 1.071-1.385), retired (OR: 1.324, 95%CI: 1.114-1.573) and with family history of cancer (OR: 1.369, 95%CI: 1.266-1.481) had higher awareness rates. Conclusion: The level of the awareness of core knowledge of cancer prevention and treatment among residents in Liaoning Province has met the requirements of the Healthy China Action. Region, gender, education level, age, family history of cancer and smoking are relevant factors.

REEP1 Preserves Motor Function in SOD1G93A Mice by Improving Mitochondrial Function via Interaction with NDUFA4 / 神经科学通报·英文版

A decline in the activities of oxidative phosphorylation (OXPHOS) complexes has been consistently reported in amyotrophic lateral sclerosis (ALS) patients and animal models of ALS, although the underlying molecular mechanisms are still elusive. Here, we report that receptor expression enhancing protein 1 (REEP1) acts as an important regulator of complex IV assembly, which is pivotal to preserving motor neurons in SOD1G93A mice. We found the expression of REEP1 was greatly reduced in transgenic SOD1G93A mice with ALS. Moreover, forced expression of REEP1 in the spinal cord extended the lifespan, decelerated symptom progression, and improved the motor performance of SOD1G93A mice. The neuromuscular synaptic loss, gliosis, and even motor neuron loss in SOD1G93A mice were alleviated by increased REEP1 through augmentation of mitochondrial function. Mechanistically, REEP1 associates with NDUFA4, and plays an important role in preserving the integrity of mitochondrial complex IV. Our findings offer insights into the pathogenic mechanism of REEP1 deficiency in neurodegenerative diseases and suggest a new therapeutic target for ALS.

Establishment of a Patient-Derived T-Cell Acute Lymphoblastic Leukemia Xenograft Model in Novel Immunodeficient NCG Mice / 中国实验血液学杂志

OBJECTIVE@#The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model.@*METHODS@#Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model.@*RESULTS@#On the 10th day after inoculation, hCD45+ leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3+ leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks.@*CONCLUSION@#Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.

FOXA1 in prostate cancer / 亚洲男科学杂志(英文版)

Most prostate cancers initially respond to androgen deprivation therapy (ADT). With the long-term application of ADT, localized prostate cancer will progress to castration-resistant prostate cancer (CRPC), metastatic CRPC (mCRPC), and neuroendocrine prostate cancer (NEPC), and the transcriptional network shifted. Forkhead box protein A1 (FOXA1) may play a key role in this process through multiple mechanisms. To better understand the role of FOXA1 in prostate cancer, we review the interplay among FOXA1-targeted genes, modulators of FOXA1, and FOXA1 with a particular emphasis on androgen receptor (AR) function. Furthermore, we discuss the distinct role of FOXA1 mutations in prostate cancer and clinical significance of FOXA1. We summarize possible regulation pathways of FOXA1 in different stages of prostate cancer. We focus on links between FOXA1 and AR, which may play different roles in various types of prostate cancer. Finally, we discuss FOXA1 mutation and its clinical significance in prostate cancer. FOXA1 regulates the development of prostate cancer through various pathways, and it could be a biomarker for mCRPC and NEPC. Future efforts need to focus on mechanisms underlying mutation of FOXA1 in advanced prostate cancer. We believe that FOXA1 would be a prognostic marker and therapeutic target in prostate cancer.

Anti-fatigue effect of Lubian on kidney Yin deficiency and kidney Yang deficiency mice and mechanism based on PI3K-Akt pathway / 中国中药杂志

This study aimed to investigate the anti-fatigue effect and mechanism of Lubian(Cervi Penis et Testis) on kidney Yin deficiency and kidney Yang deficiency mice. After one week of adaptive feeding, 88 healthy male Kunming mice were randomly divided into a blank group, a kidney Yin deficiency model group, a kidney Yin deficiency-Panacis Quinquefolii Radix(PQR) group, kidney Yin deficiency-Lubian treatment groups, a kidney Yang deficiency model group, a kidney Yang deficiency-Ginseng Radix et Rhizoma(GR) group, and kidney Yang deficiency-Lubian treatment groups, with eight mice in each group. The kidney Yin deficiency model and kidney Yang deficiency model were prepared by daily regular oral administration of dexamethasone acetate and hydrocortisone, respectively, and meanwhile, corresponding drugs were provided. The mice in the blank group received blank reagent. The treatment lasted 14 days. The exhaustive swimming time was measured 30 min after drug administration on the 14th day. On the 15th day, blood was collected from eyeballs and the serum was separated to determine the content of lactic acid(LD), blood urea nitrogen(BUN), lactate dehydrogenase(LDH), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP). The liver was dissected to determine the content of liver glycogen and the protein expression of phosphoinositide 3-kinase(PI3K) and protein kinase B(Akt). Compared with the kidney Yang deficiency model group, the kidney Yang deficiency-Lubian treatment groups showed increased body weight(P<0.05), relieved symptoms of Yang deficiency, decreased cGMP content(P<0.01), increased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), reduced LD(P<0.01), elevated BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K and Akt in the liver(P<0.05). Compared with the kidney Yin deficiency model group, the kidney Yin deficiency-Lubian treatment groups showed increased body weight(P<0.01), relieved symptoms of Yin deficiency, increased content of cGMP(P<0.01), decreased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), decreased LD(P<0.01), decreased BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K(P<0.05) and Akt in the liver(P<0.05). To sum up, Lubian can regulate Yin deficiency and Yang deficiency and increase glycogen synthesis by affecting the PI3K-Akt pathway, thereby exerting an anti-fatigue role.

Study of clinical characteristics in patients with gp210 antibody-positive primary biliary cholangitis / 中华肝脏病杂志

Objective: To analyze the clinical characteristics and prognostic value of liver function in a large samples of patients with anti-glycoprotein 210 (gp210 antibody) positive primary biliary cholangitis (PBC). Methods: A retrospective study was performed on 931 PBC cases in Beijing You'an Hospital affiliated to Capital Medical University from 2010 to 2019. According to the detection of gp210 antibody, 318 cases were divided into gp210 antibody positive group (positive group) and 613 cases were divided into gp210 antibody negative group (negative group). The differences in demographic, medical history, clinical indicators, B-ultrasound and pathological indicators as well as the histopathological basis were compared between the two groups. SPSS 16.0 software was used for statistical analysis. Measurement data were analyzed by t-test or rank sum test, and enumeration data by χ2 test. Multivariate analysis was used for logistic test, and and survival analysis was used for prognosis. Results: The positive and the negative groups were compared. The ratio of male to female was significantly higher in positive than negative group (1:5.35 vs. 1:9.73, P＜0.05), and the difference was statistically significant. The proportion of hormone use in history of past diagnosed and treated was higher in positive than negative group (12.9% vs. 3.47%, P＜0.05), and the difference was statistically significant. The detection of biochemical indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT) were higher in positive than the negative group (51.1 U/L vs. 41.1 U/L, 62.6 U/L vs. 49.6 U/L, 24.1 μmol/L vs. 17.9 μmol/L, 228.3 U/L vs. 169.6 U/L, 203.9 U/L vs. 147.6 U/L), (P＜0.05), and the differences were statistically significant. Antinuclear antibody (ANA)-positive rate, high titer ratio and immunoglobulin G (IgG) levels were higher in positive than negative group (95.2% vs. 81.6%, 69.7% vs. 48.8%, 17.2 g/L vs. 16.2 g/L), (P＜0.05), and the differences were statistically significant. The incidence of liver failure was higher in positive than negative group (P＜0.05). CK7 and inflammation score were higher in positive group than negative group in liver histopathological observations (0.83±0.53 vs. 0.28±0.47; 1.06±0.39 vs. 0.54±0.65), (P＜0.05), and the differences were statistically significant. Conclusion: The illness condition of patients with gp210 antibody positive PBC is more severe than patients with gp210 antibody negative PBC, and the incidence of liver failure is significantly increased. Cholangiocytes may be the histopathological basis of the clinical characteristics of gp210 antibody positive PBC patients.

Feasibility analysis of immediate implant placement in the maxillary molar region / 中华口腔医学杂志

Objective: To study the clinical outcomes and feasibility of immediate implantation after flap surgery and minimally invasive extraction in the maxillary molar area and to provide a reference for it. Methods: Forty-one patients (41 molars in total) with maxillary molars that could not be preserved, treated from June 2018 to June 2020 at the Department of Oral and Maxillofacial Surgery at the Affiliated Hospital of Qingdao University, were selected. There are 24 males and 17 females with the age of (49.7±1.8) years (range 18-66 years). Pre-operative cone-beam CT (CBCT) was taken for measurement and analysis. After flap surgery and minimally invasive tooth extraction, the inflammatory granulation tissues attached to the soft and hard tissues were completely scraped and clipped, followed by the preparation of the implants in the correct three-dimensional position. Torque value and implant stability quotient (ISQ) were recorded after implant placement and with non-submerged healing. CBCT examination was taken 6 months after surgery and ISQ value was checked before crown restoration. CBCT examination was also taken 1 year after the permanent restoration. The survival rate of 6 months after surgery, the success rate of 1 year after permanent restoration, and the size of jump gaps immediately after surgery, 6 months after surgery, 1 year after permanent restoration respectively, were performed. The ISQ values were compared immediately and 6 months after surgery. Results: A total of 41 implants were placed in 41 patients. Six months after surgery, the survival rate was 100% (41/41). Twelve months after permanent restoration, the success rate of the implant restoration was 100% (41/41). The torque value after implant implantation was (42.77±0.79) N·cm. The buccal and palatal jump gaps were (3.15±0.16) mm and (2.86±0.18) mm immediately after surgery, respectively. The mesial and distal jump gaps were (2.94±0.19) mm and (3.77±0.21) mm, respectively. CBCT showed that no jump gap around the implants at 6 months after surgery and 1 year after permanent restoration. The ISQ values at immediately and 6 months after surgery were (74.78±0.59) and (80.20±0.49) respectively, and the difference was statistically significant (t=-9.03, P<0.001). Conclusions: Immediate dental implantation in the correct three-dimensional position could achieve good osseointegration by means of flap surgery, minimally invasive extraction and thorough removal of inflammatory tissue on the surface of soft and hard tissues. The clinical outcomes were satisfactory.

Effect of intensive isometric strength training of hip adductor on functional ankle instability / 中国康复理论与实践

Objective To explore the effect of intensive hip adductor isometric strength training on the balance ability of functional ankle joint instability. Methods From November, 2019 to January, 2020, 18 college students with functional ankle instability were recruited from a university in Shenzhen and randomly divided into control group (n = 9) and experimental group (n = 9). Both groups received ankle stability training, and the experimental group received isometric muscle strength training of hip adductor in addition, one hour a time, three times a week, for four weeks. The Cumberland Ankle Instability Assessment Questionnaire (CAIT), Y Balance Test (YBT), Balance-check balance equipment and Back-check hip adductor maximum isometric strength test were performed before and after training. Results After training, the scores of CAIT, YBT and balance-check increased in both groups (t > 2.540, P < 0.05); the strength of adductor hip muscle significantly increased in the experimental group (t = 8.485, P < 0.001). The d-value of CAIT score, YBT distance, the score of Balance-check, and the strength of adductor hip muscle were more in the experimental group than in the control group (t > 2.168, P < 0.05); the d-value of the average rotation speed, the maximum rotation speed and the balance level were less in the experimental group than in the control group (t > 2.804, P < 0.05). Conclusion Hip adductor isometric muscle strength training may promote the recovery of the balance after functional ankle instability.

The Legal Correspondence of Sexual Self-Defense Capability Assessment / 法医学杂志

OBJECTIVES@#To understand the legal application and case deposition of assessment opinions of sexual self-defense capability, and to explore the necessity of legal correspondence in the sexual defense capability assessment.@*METHODS@#According to the self-made questionnaire, the cases of sexual self-defense capability assessment completed by the Academy of Forensic Science from January 1, 2012 to December 31, 2018 were statistically analyzed through telephone interviews and referrals.@*RESULTS@#Among the 69 cases, 3 cases (4.3%) had complete sexual self-defense capability, 30 cases (43.5%) had weakened sexual self-defense capability, 32 cases (46.2%) had no sexual self-defense capability, and 4 cases (5.8%) were not suitable for assessment. Among the 30 cases with weakened sexual self-defense ability, 15 cases were filed and investigated by public security authorities for rape and 15 cases were not. The inconsistent rate of disposition was 1∶1. Among the 15 rape cases filed and investigated by the public security authorities, 10 cases were arrested and prosecuted by the procuratorate and sentenced to fixed-term imprisonment by the court, while the other 5 cases were not arrested and prosecuted by the procuratorate, with an inconsistent rate of disposition being 2∶1.@*CONCLUSIONS@#The legal application of the assessment opinion on the weakening of sexual self-defense capability is inconsistent, and the judicial disposition is confusing. It is imperative to unify and correspond the classification of sexual self-defense capability with the legal requirements.

Rabdosia serra alleviates dextran sulfate sodium salt-induced colitis in mice through anti-inflammation,regulating Th17/Treg balance,maintaining intestinal barrier integrity,and modulating gut microbiota / 药物分析学报

Rabdosia serra(R.serra),an important component of Chinese herbal tea,has traditionally been used to treat hepatitis,jaundice,cholecystitis,and colitis.However,the chemical composition of R.serra and its effect against colitis remain unclear.In this study,the chemical composition of the water extract of R.serra was analyzed using ultra performance liquid chromatography coupled with a hybrid linear ion trap quadrupole-orbitrap mass spectrometer(UPLC-LTQ-Orbitrap-MS).A total of 46 compounds,comprising ent-kaurane diterpenoids,flavonoids,phenolic acids,and steroids,were identified in the water extract of R.serra,and the extract could significantly alleviate dextran sulfate sodium salt-induced colitis by improving colon length,upregulating anti-inflammatory factors,downregulating proinflammatory fac-tors,and restoring the balance of T helper 17/T regulatory cells.R.serra also preserved intestinal barrier function by increasing the level of tight junction proteins(zonula occludens 1 and occludin)in mouse colonic tissue.In addition,R.serra modulated the gut microbiota composition by increasing bacterial richness and diversity,increasing the abundance of beneficial bacteria(Muribaculaceae,Bacteroides,Lactobacillus,and Prevotellaceae_UCG-O01),and decreasing the abundance of pathogenic bacteria(Turi-cibacter,Eubacterium_fissicatena_group,and Eubacterium_xylanophilum_group).Gut microbiota depletion by antibiotics further confirmed that R.serra alleviated colitis in a microbiota-dependent manner.Overall,our findings provide chemical and biological evidence for the potential application of R.serra in the management of colitis.