CD38 deficiency prevents diabetic nephropathy by inhibiting lipid accumulation and oxidative stress through activation of the SIRT3 pathway.

Diabetic nephropathy (DN) is one of the most common complications of diabetes. Our previous study showed that CD38 knockout (CD38KO) mice had protective effects on many diseases. However, the roles and mechanisms of CD38 in DN remain unknown. Here, DN mice were generated by HFD feeding plus streptozotocin (STZ) injection in male CD38KO and CD38flox mice. Mesangial cells (SV40 MES 13 cells) were used to mimic the injury of DN with palmitic acid (PA) treatment in vitro. Our results showed that CD38 expression was significantly increased in kidney of diabetic CD38flox mice and SV40 MES 13 cells treated with PA. CD38KO mice were significantly resistant to diabetes-induced renal injury. Moreover, CD38 deficiency markedly decreased HFD/STZ-induced lipid accumulation, fibrosis and oxidative stress in kidney tissue. In contrast, overexpression of CD38 aggravated PA-induced lipid accumulation and oxidative stress. CD38 deficiency increased expression of SIRT3, while overexpression of CD38 decreased its expression. More importantly, 3-TYP, an inhibitor of SIRT3, significantly enhanced PA-induced lipid accumulation and oxidative stress in CD38 overexpressing cell lines. In conclusion, our results demonstrated that CD38 deficiency prevented DN by inhibiting lipid accumulation and oxidative stress through activation of the SIRT3 pathway.

Effects of Different Brewing Technologies on Polyphenols and Aroma Components of Black Chokeberry Wine.

The black chokeberry is a shrub of the Rosaceae family, which is characterized by strong acidity and astringency and is widely processed into wine and alcoholic beverages. However, due to the characteristics of black chokeberries, the wine brewed by traditional methods often has a strong sour taste, weak aroma, and poor sensory quality. In order to improve the sensory quality and explore the effects of different brewing technologies on polyphenols of black chokeberry wine, five brewing technologies (traditional fermentation, frozen fruit fermentation, co-fermentation, carbonic maceration, and co-carbonic maceration) were used in this study. The results showed that compared with the traditional method, the four alternative brewing technologies could reduce acidity, increase the contents of several major polyphenols, and enrich floral scents and fruity aroma, thus significantly improving the sensory qualities of black chokeberry wine. The proposed brewing technologies would be applied to the production of quality black chokeberry or other fruit wines.

Leaf Removal at Véraison and Foliar K+ Application to Beibinghong Vines Improved Berry Quality under Cold-Climate Conditions.

(1) Background: Beibinghong is a grapevine variety that is well distributed in Northeastern China due to its adaptation to extreme cold conditions and vine diseases. Nonetheless, Beibinghong wines are extremely acidic and rich in phenolic compounds. The aim of this research was to study the effects of leaf removal at véraison and foliar K+ applications on Beibinghong vines to reduce the acidity and increase their polyphenol content. (2) Methods: Beibinghong berries were harvested when they reached close to 20 °Brix, and the physicochemical parameters were determined. (3) Results: Leaf removal at véraison plus K+ foliar applications to Beibinghong vines decreased the titratable acidity and increased the total phenolic and phenolic acid contents compared with the control. Moreover, the titratable acidity in the Beibinghong berries was negatively related to their total contents of phenols, proanthocyanidins, and anthocyanins. (4) Conclusions: Leaf removal at véraison performed with foliar K+ applications to vines could be an interesting alternative for Beibinghong production under cold-climate viticulture because it allows for a decrease in the acidity and an increase in the phenolic content of the berries, without incurring the risk of sunburn.

Study on the curative effect of Huoluoxiaolingdan formula combined with ginkgolide injection in treatment of blood stasis and collateral obstruction syndrome in convalescent period of cerebral infarction / 中国药师

Objective To investigate the efficacy and safety of Huoluoxiaolingdan formula combined with ginkgolide injection in the treatment of ischemic stroke patients with blood stasis blockage syndrome.Methods The ischemic stroke patients with blood stasis blockage syndrome who were treated in Suzhou First People's Hospital from June 2017 to August 2019 were randomly divided into test group and control group.The control group was given ginkgolide injection,and the test group was given Huoluoxiaolingdan formula additionally.Both groups were treated for 2 weeks.The efficacy and adverse drug reactions of the two groups were evaluated,and the changes of clinical scores,hemorheology,blood lipids and inflammatory factors before and after treatment were compared between the two groups.Results A total of 194 patients were included,there were 97 cases in each group.The total effective rate of test group was 91.75％,which was significantly higher than that of control group(79.38％)(P＜0.05),and the incidence of adverse reactions was significantly lower than that in the control group(P＜0.05).After treatment,NIHSS,CSS and ASS in both groups were lower than before treatment(P＜0.05),while BI was higher than before treatment(P＜0.05).The levels of ηp,ηb,Fib and EEP in test group were significantly lower than those in control group(P＜0.05).HDL-C level of test group was significantly higher than that of control group,TC,LDL-C and TG levels were lower than that of control group(P＜0.05).The levels of IL-4 in test group were significantly higher than those in control group,and the levels of IL-1 β,IL-8 and TNF-α were lower than those in control group(P＜0.05).The above indexes in the test group was significantly better than that in control group(P＜0.05).Conclusion Huoluoxiaolingdan formula combined with ginkgolide injection can significantly improve the efficacy of patients with blood stasis blockage syndrome during the recovery period of ischemic stroke,improve clinical symptom score,correct abnormal hemorheology,reduce blood lipid level,inhibit the progression of inflammation,and alleviate adverse reactions,which has high clinical application value.

Mechanism of Naozhenning granules in regulating mitochondrial energy metabolism in multiple cerebral concussion rats / 中国药房

OBJECTIVE To explore the mechanism of Naozhenning granules in regulating mitochondrial energy metabolism in hippocampal tissue of multiple cerebral concussion （MCC） model rats. METHODS SPF grade Wistar rats were used to prepare MCC models using the “free fall impact method”. The successfully modeled rats were divided into model group， piracetam group， and Naozhenning granule low-dose， medium-dose and high-dose groups， and a normal group was also set up， with 8 rats in each group. Rats in each treatment group orally administered corresponding drugs at doses of 0.324 g/kg for the piracetam group and 2.25， 4.5 and 9 g/kg for the Naozhenning granule low-dose， medium-dose and high-dose groups； the normal group and model group were given equal volumes of normal saline； once a day， for 14 consecutive days. The motor exploration ability， learning and memory ability of rats were tested； the adenosine triphosphate （ATP） content in the hippocampal tissue of rat was detected； the changes in the mitochondrial structure of hippocampal tissue was observed； the fluorescence intensity of mitochondrial dynamin- related protein 1 （Drp1）， mitochondrial fission protein 1 （Fis1）， mitochondrial fusion 1 （Mfn1）， and optic atrophy protein 1 （Opa1） were detected in the hippocampal tissue of rat； the protein expression levels of peroxisome proliferator activated receptor gamma coactivator-1α（PGC-1α）， nuclear respiratory factor-1（NRF-1），mitochondrial transcription factor A（TFAM）， Wnt-3a，β-catenin in hippocampal tissue of rat were detected. RESULTS Compared with the normal group， the total exercise distance， number of central grid entries， number of upright positions， new object recognition index， mitochondrial ATP content， fluorescence intensity of Mfn1 and Opa1， the protein expression levels of PGC-1α、NRF-1、TFAM、Wnt-3a、 β-catenin in the model group were significantly reduced （P＜0.01）， while the rest time and fluorescence intensity of Drp1 and Fis1 in hippocampal tissue were significantly increased （P＜0.01）. The results of transmission electron microscopy showed that the mitochondria in the hippocampal tissue were significantly swollen， with a large number of broken and reduced cristae， and some mitochondria had myeloid changes in the membrane. Compared with the model group， the levels/contents of the above indicators in rats of each administration group showed varying degrees of reversal， and most of the differences were statistically significant （P＜0.05 or P＜0.01）； the degree of mitochondrial swelling in the hippocampal tissue was reduced， with a small amount of broken and reduced cristae， fuzzy fractures appeared in local areas of the rough endoplasmic reticulum. CONCLUSIONS Naozhenning granules can improve the motor exploration， learning and memory abilities of MCC model rats， repair neuronal damage， and exert neuroprotective effects. Its mechanism may be related to activating Wnt/β-catenin signaling pathway，maintaining the balance of mitochondrial division and fusion，and promoting mitochondrial biosynthesis.

Analysis on Mechanism of Huangwu Ganfu Ointment in Relieving Knee Osteoarthritis Pain Based on Network Pharmacology and Experimental Verification / 中国中医药信息杂志

Objective To analyze the mechanism of Huangwu Ganfu Ointment in relieving pain of knee osteoarthritis(KOA)based on network pharmacology;To verify it in animal experiments.Methods The active components of Huangwu Ganfu Ointment were obtained by TCMSP database,PubChem database and SwissADME platform,the effective components were screened,and the targets were obtained from SEA database.KOA disease-related targets were obtained from GeneCards,OMIM and other databases,and the intersection targets were obtained.A effective component-target-disease network was constructed using Cytoscape 3.9.0 Software.Protein-protein interaction(PPI)network was constructed by STRING database and core targets were screened.GO and KEGG enrichment analysis of intersection targets were analyzed using DAVID platform.The KOA rat model with cold and damp syndrome was established,and the intervention of Huangwu Ganfu Ointment was carried out.The efficacy was observed and the core target expressions were detected.Results Totally 104 effective components were screened from Huangwu Ganfu Ointment,and 59 potential targets were obtained for treating KOA.PPI network interaction analysis obtained the important targets of IL6,IL1B and PTGS2.KEGG enrichment results showed that Huangwu Ganfu Ointment may involve 84 signaling pathways such as IL-17,TNF,TRP and NF-κB in the treatment of KOA,most of which were related to inflammation.The results of animal experiments showed that Lecuesne MG scores increased in the model rats(P<0.05),and paw withdrawal threshold(PWT)significantly decreased(P<0.05).Compared with model group,PWT in Huangwu Ganfu Ointment medium-and high-dosage groups were significantly recovered,and synovitis Krenn score decreased(P<0.05).The Mankin score of cartilage tissue of Huangwu Ganfu Ointment high-dosage group decreased(P<0.05).The contents of IL-6 and IL-1β in all Huangwu Ganfu Ointment groups decreased(P<0.01).Huangwu Ganfu Ointment medium-and high-dosage groups could down-regulate the expression of TRPV1 protein(P<0.05,P<0.01).Conclusion The mechanism of Huangwu Ganfu Ointment in alleviating the pain of KOA may be related to reducing inflammatory response,reducing the release of inflammatory factors of IL-1β and IL-6,alleviating inflammatory pain sensitivity of KOA,and down-regulating the expression level of TRPV1.

Mechanism of Huangwu Ganfu Ointment in Treatment of Peripheral Inflammatory Hyperalgesia of Knee Osteoarthritis Based on TRPV1 / 中国实验方剂学杂志

ObjectiveTo observe the regulatory effect of Huangwu Ganfu ointment on transient receptor potential anchor protein 1 （TRPV1） receptor expression， macrophage polarization， and p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway in synovial tissue of knee osteoarthritis （KOA） rats with yang deficiency and cold coagulation syndrome and explore the mechanism of relieving peripheral inflammatory hyperalgesia of KOA. MethodForty-eight male SD rats were randomly divided into blank group， model group， high-dose， middle-dose， and low-dose groups of Huangwu Ganfu ointment （9.3， 4.65， 2.325 g·kg-1）， and celecoxib group （20.82 mg·kg-1）. The KOA rat model of yang deficiency and cold coagulation syndrome was established through climate box and swimming for two weeks combined with an injection of sodium iodoacetate （MIA） in the articular cavity. After continuous administration for four weeks， the general condition of rats in each group was observed， and the pain withdrawal threshold （PWT） and joint diameter induced by mechanical stimulation were recorded. The expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， nerve growth factor （NGF）， and calcitonin gene-related peptide （CGRP） inflammatory factor were detected by enzyme-linked immunosorbent assay （ELISA）， and the histopathological changes of synovial tissue of the knee joint were observed by hematoxylin-eosin （HE） staining. Western blot was used to detect the protein expression of TRPV1， p38 MAPK， and p-p38 MAPK in synovial tissue of the knee joint， and immunofluorescence （IF） was used to evaluate the polarization of M1/M2 macrophages. ResultCompared with that in the blank group， the overall mental state of the model group was worse， and the autonomous activity was decreased. The body mass was lower， and the joint diameter was increased. The X-ray showed that the osteophyte at the edge of the joint proliferated， and the articular surface was obviously rough. The articular cavity was significantly narrowed， and the PWT was significantly decreased （P<0.01）. The contents of IL-1β， TNF-α， CGRP， and NGF in serum and synovium Krenn score increased significantly （P<0.01）. The protein expression of TRPV1 and p-p38 MAPK/p38 MAPK increased significantly （P<0.01）， and the proportion of M1 macrophages and M1/M2 increased （P<0.01）， while the proportion of M2 macrophages decreased （P<0.01）. Compared with model group， the body mass in the low， middle， and high dose groups of Huangwu Ganfu ointment increased to different degrees （P<0.05， P<0.01）. The diameter of the knee joint in the high dose group of Huangwu Ganfu ointment and celecoxib group decreased （P<0.01）. The recovery of PWT in the high and middle dose groups of Huangwu Ganfu ointment groups was more obvious （P<0.05）. The contents of IL-1β and CGRP in the serum of rats in each administration group were significantly decreased （P<0.01）， and the content of serum TNF-α in the celecoxib group and high dose group of Huangwu Ganfu ointment decreased significantly （P<0.05）. The content of serum NGF in the middle dose group of Huangwu Ganfu ointment decreased significantly （P<0.05）， and the synovium Krenn score decreased in the high dose group of Huangwu Ganfu ointment （P<0.05）. In addition， the protein expression of TRPV1 and p-p38 MAPK/p38 MAPK in synovial tissue decreased significantly in all groups of Huangwu Ganfu ointment （P<0.01）. The proportion of M1 macrophages in synovial tissue in the celecoxib group and all groups of Huangwu Ganfu ointment decreased （P<0.01）， and the proportion of M2 macrophages in the high dose group of Huangwu Ganfu ointment increased （P<0.05）. The M1/M2 in the middle and high dose groups of Huangwu Ganfu ointment decreased （P<0.05）. ConclusionHuangwu Ganfu ointment can mediate the polarization of macrophages to reduce the inflammatory reaction of KOA， alleviate the release of inflammatory pain mediators， and lower the protein expression of TRPV1. The mechanism may be related to the p38 MAPK signaling pathway， so as to improve the peripheral hyperalgesia of KOA.

Effect of Naozhenning Granules on Energy Metabolism of Cortical Mitochondria in Rat Model of Post-concussion Syndrome / 中国实验方剂学杂志

ObjectiveTo explore the effects of Naozhenning granules on the memory function and neuron cells in the rat model of post-concussion syndrome based on mitochondrial biosynthesis. MethodSPF-grade Wistar rats were used to establish the multiple cerebral concussion （MCC） model by the weight-drop method. The successfully modeled rats were assigned into model， piracetam （0.324 g·kg-1）， and low-， medium-， and high-dose （2.25， 4.5， and 9 g·kg-1， respectively） Naozhenning groups. The rats were administrated with corresponding drugs by gavage and those in the blank group and model group were administrated the same volume of normal saline once a day for 14 days. The general state of rats was observed before and after treatment. The open field test and new object recognition test were conducted to examine the motor and memory abilities of rats. Hematoxylin-eosin staining was employed to observe the pathological changes of cortical neurons in rats. Western blot and real-time polymerase chain reaction were employed to determine the protein and mRNA levels， respectively， of peroxisome proliferator-activated receptor γ-coactivator-1α （PGC-1α）， nuclear respiratory factor-1 （NRF-1）， and transcription factor A mitochondrial （TFAM） in rat cortex. ResultCompared with the blank group， the model group showed anxious and manic mental status， yellow and messy fur， and reduced food intake. In the open field experiment， the model group showed reduced total movement distance， times of entering the central grid， and times of rearing decreased and increased resting time compared with the blank group （P<0.01）. The model group had lower recognition index of new objects than the blank group （P<0.01）. In addition， the modeling caused reduced neurons with sparse distribution and deformed， broken， and irregular nucleoli and down-regulated the mRNA and protein levels of PGC-1α， NRF-1， and TFAM in the cortex （P<0.01）. Compared with the model group， piracetam and Naozhenning improved the mental state， coat color， food intake， and activities of rats. In the open field test， piracetam and Naozhenning increased the total movement distance， the times of entering the central grid， and the times of rearing and shortened the resting time （P<0.05， P<0.01）. The piracetam and Naozhenning groups had higher recognition index of new objects than the model group （P<0.05， P<0.01）. Compared with the model group， the piracetam and Naozhenning groups showed increased neurons with tight arrangement and large and round nuclei， and some cells with irregular morphology and turbid cytoplasm. Furthermore， piracetam and medium-dose Naozhenning upregulated the protein levels of PGC-1α， NRF-1， and TFAM （P<0.01）. Low-dose Naozhenning upregulated the protein levels of NRF-1 and TFAM （P<0.01）， and high-dose Naozhenning upregulated the protein levels of PGC-1α and TFAM in the cortex （P<0.01）. The mRNA levels of PGC-1α， NRF-1， and TFAM in the cortex were upregulated in the piracetam group and Naozhenning groups （P<0.05， P<0.01）. ConclusionNaozhenning granules can improve the motor， memory， and learning， repair the neuronal damage， and protect the nerve function in the rat model of MCC by promoting mitochondrial biosynthesis.

Effect of Zuoguiwan on Pancreatic Islet Function in Offspring of Maternal Rats with GDM / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Zuoguiwan on pancreatic islet function in offspring of gestational diabetes mellitus （GDM） maternal rat model and explore the mechanisms of Zuoguiwan in improving pancreatic islet function based on postpartum pancreatic regeneration. MethodHealthy female SD rats with normal blood glucose levels were paired with male rats in a 2∶1 ratio and housed together. Pregnancy was confirmed based on vaginal plugs or vaginal smears. The pregnant rats were divided into the following groups： normal group， model group， insulin group （insulin Detemir， 20 U·kg-1）， low-dose Zuoguiwan group （1.89 g·kg-1）， and high-dose Zuoguiwan group （3.78 g·kg-1）. The GDM rat model was induced using streptozotocin in rats except for those in the normal group. The model was confirmed by blood glucose testing in the maternal rats. Except for the normal and model groups， the other groups received daily administration of corresponding treatments. At 21 days after birth， fasting blood glucose （FBG） and fasting serum insulin （FINS） levels were measured in 6 offspring from each group. The homeostasis model assessment of insulin resistance （HOMA-IR） was calculated， and an oral glucose tolerance test （OGTT） was performed on additional 12 offspring from each group. Blood samples were taken from the abdominal aorta of the offspring at postnatal day 22， and enzyme-linked immunosorbent assay （ELISA） was used to measure insulin， glucagon （GC）， pancreatic polypeptide （PPY）， and somatostatin （SS） levels in the serum. Hematoxylin-eosin （HE） staining was performed to observe pathological changes in the pancreatic tissue of the offspring. Immunofluorescence （IF） was used to observe the area and structure of the pancreatic islets. Western blot was used to detect the expression of key proteins involved in the development and functional expression of pancreatic β-cells， namely pancreatic and duodenal homeobox factor 1 （Pdx1）， Nkx6.1， and Glucose transporter 2 （Glut2）. ResultCompared with the normal group， the model group showed significant increases in FBG and FINS levels， and HOMA-IR （P<0.01）. Compared with the model group， the insulin group showed significant decreases in FBG levels and HOMA-IR （P<0.01）， the low-dose Zuoguiwan group showed a significant decrease in FBG levels （P<0.05）， and the high-dose Zuoguiwan group showed significant decreases in FBG and FINS levels， and HOMA-IR （P<0.01）. Compared with the normal group， the model group showed significant increases in OGTT 60-min blood glucose levels and AUC index （P<0.05， P<0.01）. Compared with the model group， the high-dose Zuoguiwan group showed significant decreases in OGTT60-min blood glucose levels and area under the curve（AUC） index （P<0.05， P<0.01）. HE staining of pancreatic tissue showed that compared with the normal group， the model group had a reduced number of islets and a loose arrangement of acinar cells. Compared with the model group， the groups with drug treatment showed increased number of islets and a compact arrangement of acinar cells. Compared with the normal group， the model group had significantly increased levels of insulin， GC， PPY， and SS in the serum （P<0.01）. Compared with the model group， the low-dose and high-dose Zuoguiwan groups and the insulin group showed significantly decreased serum levels of insulin， GC， PPY， and SS （P<0.05， P<0.01）. IF results showed that compared with the normal group， the model group had a significantly lower positive rate of insulin （P<0.05）. Compared with the model group， the low-dose and high-dose Zuoguiwan groups showed a significant increase in the positive rate of insulin （P<0.05）. There was no significant difference in the positive rate of GC among the groups. In terms of the proportion of insulin and GC in individual islets， compared with the normal group， the model group showed a significant decrease in the proportion of insulin （P<0.01） and a significant increase in the proportion of GC （P<0.01）. Compared with the model group， the low-dose and high-dose Zuoguiwan groups showed significantly increased proportion of insulin （P<0.01） and significantly decreased proportion of GC （P<0.01）. Compared with the normal group， the model group showed significantly decreased expression levels of Pdx1， Nkx6.1， and Glut2 proteins in the pancreatic tissue of GDM offspring （P<0.05）. Compared with the model group， the insulin group and the low-dose Zuoguiwan group showed significant increases in the expression levels of Pdx1 and Nkx6.1 proteins in the pancreatic tissue of GDM offspring （P<0.05）， and the low-dose and high-dose Zuoguiwan groups showed significant increases in the expression levels of Glut2 protein （P<0.05）. ConclusionZuoguiwan can promote pancreatic islet development in offspring of GDM maternal rat model， improve pancreatic islet morphology and function， and alleviate insulin resistance. Its mechanism of action may be related to the regulation of Pdx1， Nkx6.1， and Glut2 protein expression in the pancreatic tissue of offspring.

The Humanistic Significance of the Application of Peer Education Mode in Urological Tumors Patients during Perioperative Period / 中国医学伦理学

【Objective:】 To study the application and effect of peer education mode in the nursing of patients with urinary tumor, and explore the ways to improve the quality of clinical care and the humanistic significance of this mode in clinical nursing. 【Methods:】 84 patients with urological tumors who received surgical treatment in urology department of a third-class hospital from March 2021 to December 2021 were randomly divided into the control group and the experimental group, with 42 patients in each group. The subjects in control group adopted routine intervention mode.The subjects in experimental group integrated the peer education program into the routine nursing mode.SAS and SDS scales were used to evaluate patients’ state of anxiety and depression, and the degree of nursing satisfaction. 【Results:】 The scores of SAS and SDS in the experimental group were significantly lower than that of the experimental group before intervention and the control group after intervention (P<0.05).The number of very satisfied, moderately satisfied and dissatisfied cases in the control group was 12, 29 and 1 respectively, and in the experimental group was 19, 23 and 0 respectively. The difference was statistically significant (P<0.05). 【Conclusion:】 Adopting peer education with humanistic care significance can effectively alleviate patients’ preoperative anxiety, depression and other adverse mental state, reduce preoperative stress, and provide a new way for nursing quality.

Construction of a competing risk model for disease-free survival of patients with non-muscle invasive bladder cancer / 现代泌尿外科杂志

【Objective】 To construct an easy-to-use individual survival prognostic tool based on competing risk analyses to predict the risk of 1-, 2- and 3- year recurrence for patients with non-muscle invasive bladder cancer (NMIBC). 【Methods】 The follow-up data of 419 NMIBC patients were obtained. The patients were randomly divided into training cohort (n=293) and validation cohort (n=126). The variables included age at diagnosis, sex, history of smoking, tumor number, tumor size, histolo-gic grade, pathological stage, and bladder perfusion drug. The cumulative incidence function (CIF) of recurrence was estimated using all variables in the training cohort and potential prognostic variables were determined with Gray’s test. The Fine-Gray subdistribution proportional hazard approach was used as a multivariate competitive risk analysis to identify independent pro-gnostic variables. A competing risk nomogram was developed to predict the recurrence. The performance of the competing risk model was evaluated with the area under the receiver operating characteristic curve (AUC), calibration curve, and Brier score. 【Results】 Five independent prognostic factors including age, number of tumors, tumor size, histologic grade and pathological stage were used to construct the competing risk model. In the validation cohort, the AUC of 1-, 2- and 3- year recurrence were 0.895 (95%CI: 0.831-0.959), 0.861(95%CI: 0.774-0.948) and 0.827(95%CI: 0.721-0.934), respectively, indicating that the model had a high predictive performance. 【Conclusion】 We successfully constructed a competing risk model to predict the risk of 1-, 2- and 3-year recurrence for NMIBC patients. It may help clinicians to improve the postoperative management of patients.

Changes of ferroptosis in hippocampal neurons of rats with multiple cerebral concussion / 中华行为医学与脑科学杂志

Objective:To observe the ferroptosis in hippocampal neurons of rats with multiple cerebral concussion (MCC) .Methods:Ninety clean grade male Wistar rats with a body mass of (250±10) g were randomly divided into control group (12 rats) and model group (78 rats) according to the random number table method. The rat of MCC model was prepared by hitting the frontotemporal lobe of rats with free fall method once a day for 3 consecutive days.Then the MCC model rats were randomly divided into 12 h, 24 h, 48 h, 72 h, 7 d and 14 d groups with 12 rats in each group. The balance beam experiment was used to detect the motor coordination function of the rats. The levels of interleukin-β(IL-1β), interleukin-6(IL-6), serum glutathione (GSH), neuron-specific enolase (NSE) in serum of rats were detected by ELISA.The content of iron ion in hippocampus was detected by colorimetry. The mRNA and protein levels of glutathione peroxidase 4(GPX4), ferritin heavy (FTH) and ferritin light(FTL) in the hippocampus were detected by RT-PCR and Western blot. Prussian blue staining was used to observe the iron deposition in brain tissue.The ultrastructural changes of hippocampal neurons and mitochondria were observed by transmission electron microscope. SPSS 24.0 statistical software was used for one-way ANOVA among groups, and LSD test was used for multiple pairwise comparison.Results:In the balance beam experiment, the passing time and motor coordination score of rats in each group were significantly different ( F=30.08, 60.34, both P<0.05). The passing time and motor coordination score of rats in the 48 h group ((87.00±4.74) s, (4.75±0.43)) were significantly higher than those in the control group ((35.13±6.99) s, (0.75±0.23)) (both P<0.05). There was significant difference in the total iron ion content, Fe 2+ content and Fe 3+ content in hippocampus of rats in each group ( F=25.20, 94.42, 40.25, all P<0.05), and the content of Fe 2+ in hippocampus of 48 h group was significantly higher than that of the control group ((10.17±0.05) ng/μL, (8.65±0.01) ng/μL)( P<0.05). In the results of RT-PCR and Western blot, the mRNA and protein levels of GPX4, FTH and FTL in hippocampus of each group were significantly different ( F=37.94, 82.09, 49.01, 71.63, 28.94, 15.78, all P<0.05). The mRNA level and protein level of GPX4 ((1.09±0.01), (0.23±0.01) )and FTL ((1.60±0.03), (0.64±0.02)) in 24 h group were significantly higher than those of the control group (GPX4: (1.00±0.02), (0.17±0.01)), FTL: ((1.00±0.04), (0.32±0.01))(all P<0.05). The mRNA level and protein level of FTH ((0.24±0.03), (0.07±0.01)) in 24 h group were significantly lower than those of the control group((1.00±0.01), (0.67±0.03))(both P<0.05). The results of electron microscope showed that the hippocampal neuronal cells of the model rats were reduced, the nucleolus was broken and the nuclear membrane was shrunk in varying degrees, the mitochondria were swollen and deformed and there were vacuoles, and the cristae in the mitochondria decreased or disappeared. Conclusion:The levels of inflammatory reaction and oxidative stress in the multiple cerebral concussion model rats increase, and the hippocampal neurons show the characteristics of ferroptosis, especially at 24 h and 48 h.

Effect of Naozhenning on Hippocampal Mitochondrial Function in Model Rats with Post-concussion Syndrome / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Naozhenning on learning and memory ability and neuron damage in hippocampal CA1 region of post-concussion syndrome model rats based on mitochondrial function. MethodMultiple cerebral concussion （MCC） was induced in SPF Wistar rats with the free-fall impact method. Then the model rats were randomly classified into model group （equivalent volume of distilled water）， piracetam （0.43 g·kg-1， ig） group， and low-， medium-， and high-dose NZN （5.4， 10.8， 21.6 g·kg-1， respectively， ig） groups， with 10 rats in each group， and another 10 normal rats were included in the normal control group （equivalent volume of distilled water）. The administration lasted 14 days and then relevant indexes were detected. Morris water maze test was used to observe the changes of learning and memory ability in each group， such as escape latency， residence time in primary quadrant， and times of crossing platform. The pathological changes of hippocampal CA1 region were observed based on hematoxylin-eosin （HE） staining and Nissl staining. The ultrastructure of mitochondria was observed under the transmission electron microscope （TME） and the activity of mitochondrial respiratory chain complex Ⅰ was detected by colorimetry. The content of adenosine triphosphate （ATP） was determined by fluorescence probe and mitochondrial membrane potential （MMP） by fluorescein enzyme-linked fluorescence immunoassay. ResultCompared with the normal control group， the model group showed long escape latency， short residence time in target quadrant， few times of crossing the platform， significant decrease in counts of neurons and Nissl bodies in hippocampal CA1 region， damage of neuronal morphology and mitochondrial structure， and significant reduction of MMP and the content of mitochondrial ATP and respiratory chain complex I （P<0.05， P<0.01）. The NZN groups demonstrated short escape latency， long residence time in target quadrant， increased times of crossing the platform， small number of neurons and Nissl bodies in hippocampal CA1 region， alleviated damage of neuronal morphology and mitochondrial structure， and increase in MMP and the content of mitochondrial ATP and respiratory chain complex I （P<0.05， P<0.01）. ConclusionNZN can improve the learning and memory ability of MCC rats by improving mitochondrial structure and function and alleviating hippocampal neuron injury.

Effect and Safety of Cinnamaldehyde on Immunosuppressed Mice with Invasive Pulmonary Candidiasis / 中国结合医学杂志

OBJECTIVE@#To evaluate the effect and safety of cinnamaldehyde on immunosuppressed mice with invasive pulmonary candidiasis.@*METHODS@#An immunosuppressed BALB/c mouse model was established by intraperitoneal administration of cyclophosphamide (200 mg/kg) once daily for 2 days. The immunosuppressed mouse with invasive pulmonary candidiasis model was further established by nasal perfusion of Candida albicans suspension. In the cinnamaldehyde treatment group, immunosuppressed mice with invasive pulmonary candidiasis were orally given cinnamaldehyde 240 mg/(kg·d) for 14 consecutive days. Fluconazole and 0.9% saline were used as the positive and negative controls, respectively. The mice in the cinnamaldehyde safety evaluation group were orally administered cinnamaldehyde 480 mg/(kg·d) for 42 days to observe the safety of the drug. Microscopic identification, fungal culture, histopathological examination, and (1,3)-beta-D-glucans detection were conducted to analyze the effect of cinnamaldehyde on C. albicans.@*RESULTS@#The fungal clearance rate in the cinnamaldehyde treatment group was higher than that in the fluconazole control group (80.00% vs. 56.67%, P<0.05). The level of (1,3)-β-D-glucan in the cinnamaldehyde treatment group was lower than that in the fluconazole positive control group (1160.62 ±89.65 pg/mL vs. 4285.87 ± 215.62 pg/mL, P<0.05). The survival rate of mice in the cinnamaldehyde safety evaluation group was 100%, and no significant pathological changes of kidney, lung and liver were observed.@*CONCLUSIONS@#Cinnamaldehyde was effective and safe in treating immunosuppressed BALB/c mice with invasive pulmonary candidiasis. It would be a potentially novel drug for anti-candidiasis infection.

Ginsenoside 20(S)-Rg3 upregulates tumor suppressor VHL gene expression by suppressing DNMT3A-mediated promoter methylation in ovarian cancer cells / 南方医科大学学报

OBJECTIVE@#To explore the mechanism by which ginsenoside 20(S)-Rg3 upregulates the expression of tumor suppressor von Hippel-Lindau (VHL) gene in ovarian cancer cells.@*METHODS@#Ovarian cancer cell line SKOV3 treated with 20(S)-Rg3 were examined for mRNA and protein levels of VHL, DNMT1, DNMT3A and DNMT3B by real-time PCR and Western blotting, respectively. The changes in VHL mRNA expression in SKOV3 cells in response to treatment with 5-Aza-CdR, a DNA methyltransferase inhibitor, were detected using real-time PCR. VHL gene promoter methylation was examined with methylation-specific PCR and VHL expression levels were determined with real-time PCR and Western blotting in non-treated or 20(S)-Rg3-treated SKOV3 cells and in 20(S)-Rg3-treated DNMT3A-overexpressing SKOV3 cells. VHL and DNMT3A protein levels were detected by immunohistochemistry in subcutaneous SKOV3 cell xenografts in nude mice.@*RESULTS@#Treatment of SKOV3 cells with 20(S)-Rg3 significantly upregulated VHL and downregulated DNMT3A expressions at both the mRNA and protein levels (@*CONCLUSIONS@#Ginsenoside 20(S)-Rg3 upregulates VHL expression in ovarian cancer cells by suppressing DNMT3A-mediated DNA methylation.

Effect of Modified Shengmaiyin on Children with Acute Lymphocyte Leukemia of Deficiency of Both Qi and Blood / 中国实验方剂学杂志

Objective:To observe the regulatory effect of modified Shengmaiyin adjuvant chemotherapy on the nutritional status and immune function of children with acute lymphocyte （ALL）. Method:One hundred children with ALL chemotherapy were randomly divided into observation group and control group. Both groups were given VDLD regimen as the induction therapy and CAM regimen as the early therapy. Control group was given Shengmaiyin orally， 10 mL/time， 3 times/day. Observation group was given modified Shengmaiyin orally， 1 does/day. The course of treatment for both groups was 3 months. Micro-nutrition assessment （MNA） was carried out before and after treatment， and serum total protein （TB）， albumin （ALB）， prealbumin （PAB）， T cell CD4⁺， CD8⁺， immunoglobulin G （IgG）， IgM， IgA levels were detected before and after treatment. The ratio of CD4⁺/CD8⁺ was calculated. The traditional Chinese medicine （TCM） syndrome before and after treatment and the piper fatigue scale （PFS-R） and universal core scale of children's quality of life （PedsQL） were scored. The changes of white blood cells （WBC）， red blood cells （RBC）， hemoglobin （Hb） and platelets （PLT） were evaluated before and after treatment. Result:The nutritional status of the observation group was better than that of the control group after treatment （<italic>Z</italic>=2.018， <italic>P</italic><0.05）. The observed fatigue was lighter than that of the control group （<italic>Z</italic>=2.029， <italic>P</italic><0.05）. The MNA score of the observation group was higher than that of the control group （<italic>P</italic><0.01）. The scores of PFS-R and deficiency of both Qi and blood were lower than those of the control group （<italic>P</italic><0.01）. The CD4⁺levels and CD4⁺/CD8⁺ levels of TB， ALB and PAB in the observation group were higher than those in the control group （<italic>P</italic><0.01）， while the CD8⁺ was lower than the control group （<italic>P</italic><0.01）. The IgM and IgA levels in the observation group were higher than those in the control group （<italic>P</italic><0.01）. The RBC， Hb and PLT levels of the observation group were higher than those of the control group （<italic>P</italic><0.01）. Conclusion:Modified Shengmaiyin can be used as adjuvant therapy for children with ALL chemotherapy by improving nutritional status， immune function and immune balance， reducing clinical symptoms， promoting the recovery of hematopoietic system and improving the quality of life.

Research progress of Sect. Euthya medicinal plants in Paris L. from Shaanxi Province / 国际中医中药杂志

Medicinal plant Paris L. has high medicinal value. There are 8 varietas of 4 kinds of Sect. Euthya which could be used as Chinese medicine. Sect. Euthya with stout rhizomes are the source of Chinese herb Paris L. and the core source of the medicinal plants in every place of origin. Shaanxi Province is one of the major areas. This paper summarizesand analizes the research progress of Paris L. grew in Shaanxi Province including its medicinal status, effective component, pharmacological, endophytic microorganisms sequencing, resource distribution and utilization, as well as the standardized production and planting and provides suggestions for the further research and rational exploitation and utilization of medicinal plant resources of Paris L. in Shaanxi Province.

Mechanism and application of acid-sensitive peptides in drug delivery / 药学学报

As a part of novel drug delivery carriers, peptides have diverse biological activities, low immunogenicity and good biocompatibility. In recent years, studies on the delivery carriers modified by peptides have attracted much attention. Among them, the peptides with acid sensitivity can change their secondary structures under slightly acidic microenvironment of the tumor or in lysosome. Therefore, the carriers made or modified by acid-sensitive peptides can specifically release the loaded drug in the tumor tissue, enhance the cell internalization of drugs and improve its therapeutic effects. In accordance with acid-sensitive peptides studied, the side chains, number of polar residues, sequence and secondary structure of the peptides might be involved in the acid sensitivity. In this review, we summarize the acid-sensitive peptides from recent literatures, analyze the connection between the structure and the acid sensitivity, and focus on the mechanism and application of acid-sensitive peptides in drug delivery. This provides the basis for further development and utilization for acid-sensitive peptides for efficient drug delivery.

Effect of miR-145 on Migration and Invasion of Ovarian Cancer Cells / 中国医学科学院学报

Objective To evaluate the effect of miR-145 on migration and invasion of ovarian cancer cells.Methods The effect of miR-145 overexpression on the expression levels of miR-145 and zeb-2 were detected with qRT-PCR and Western blotting.The changes of migration and invasion were examined using Transwell assay.Target genes of miR-145 were predicted by bioinformatics software.Dual-luciferase reporter assay were used to verify zeb-2 as a direct target of miR-145.zeb-2 siRNA was transiently transfected in SKOV3 and 3AO cells,Transwell was used to examine migration and invasion abilities.Results The migration and proliferation of SKOV3(=10.752,=0.000;=5.617,=0.005)and 3AO cells(=10.111,=0.001;=21.746,=0.000)decreased significantly after overexpression of miR-145.The results of dual-luciferase reporter assay showed that the relative luciferase activity of co-transfected miR-145 mimic and WT 3'UTR expression vectors was significantly lower than that of co-transfected mimic control and WT 3'UTR expression vectors(SKOV3:=4.572,=0.010;3AO:=3.528,=0.024).There was no significant difference in relative luciferase activity between co-transfected miR-145 mimic/MUT 3'UTR expression vector cells and co-transfected mimic control/MUT 3'UTR expression vector cells(SKOV3:=0.227,=0.831;3AO:=0.040,=0.970).Real-time quantitative PCR showed that the zeb-2 expressions in SKOV3(=1.490,=0.211)and 3AO cells(=0.114,=0.914)were not significantly different from negative control after 48 h of miR-145 overexpression.Western blot analysis showed that the expression of zeb-2 protein in SKOV3(=3.769,=0.020)and 3AO cells(=4.452,=0.011)decreased significantly compared with negative control after 72 h of miR-145 overexpression.Seventy-two hours after transfection of zeb-2 siRNA,Western blotting showed that the expression of zeb-2 protein in SKOV3(=4.660,=0.010)and 3AO cells(=4.594,=0.010)was significantly down-regulated.Transwell assay showed that the migration and invasion abilities of SKOV3(=18.655,=0.000;=18.026,=0.000)and 3AO cells(=5.500,=0.005;=8.780,=0.001)were significantly decreased.Conclusion miR-145 may inhibit the migration and invasion of ovarian cancer cells by targeting zeb-2.

Application of warm liquid in proximal femoral nail antirotation(PFNA) internal fixation / 中国骨伤

OBJECTIVE@#To investigate the effect and application of warm fluid in patients with proximal femoral nail antirotation(PFNA) internal fixation.@*METHODS@#From November 2012 to December 2016, 80 patients with femoral intertrochanteric fracture were treated with PFNA internal fixation, including 35 males and 45 females, aged from 62 to 90 years old. The patients were divided into two groups. In the control group 40 patients were infused and rinsed at the normal temperature liquid(22 to 24 °C) during the operation; in the experimental group 40 patients were infused and rinsed at warm liquid(36.5 to 37.5 °C). The amount of bleeding, the temperature, the occurrence of shiver and the C-reaction protein in the two groups were analyzed.@*RESULTS@#The incidence of hypothermia and shiver in the experimental group was significantly lower than that in the control group(<0.05). The amount of intraoperative bleeding and C-reaction protein were significantly decreased(<0.05).@*CONCLUSIONS@#The application of warm liquid infusion and flushing in PFNA internal fixation can effectively reduce the incidence of hypothermia and shiver, reduce the amount of bleeding in the operation and the infection rate of the surgical site, improve the comfort of the patients, and ensure the safety of the patients.