Aim To study the mechanism of action of licorice in alleviating cisplatin liver injury.Methods Forty-eight SD rats were randomly divided into a blank group,a model group,a positive control group and lico-rice administration groups(450,900 and 1 800 mg·kg-1).After 5 days of prophylactic administration,8 mg·kg-1 of cisplatin was injected intraperitoneally in-to the model,positive control,and licorice administra-tion groups to establish an acute liver injury model.LC-MS/MS untargeted metabolomics was used to ana-lyze the differential metabolites and metabolic pathways of licorice to alleviate cisplatin acute liver injury.Re-sults PLS-DA score plots showed significant separa-tion of metabolomics samples.The analysis yielded 119 differential metabolites associated with cisplatin liver injury,of which 31 differential metabolites were signifi-cantly regressed after licorice intervention and were mainly involved in D-arginine and D-ornithine metabo-lism;parathyroid hormone synthesis,secretion,and ac-tion;tyrosine metabolism;biosynthesis of phenylala-nine,tyrosine,and tryptophan;β-alanine metabolism;and amino acid and nucleotide sugar metabolism.Con-clusions Metabolomics analysis indicates that licorice can alter the metabolic profile of cisplatin-induced he-patic injury rats,and its mechanism of action may be related to its improvement of the levels of differential metabolites and its involvement in the regulation of a-mino acid metabolism and other related pathways.

The purpose of this study is to investigate whether chrysin reduces cerebral ischemia-reperfusion injury(CIRI) by inhi-biting ferroptosis in rats. Male SD rats were randomly divided into a sham group, a model group, high-, medium-, and low-dose chrysin groups(200, 100, and 50 mg·kg~(-1)), and a positive drug group(Ginaton, 21.6 mg·kg~(-1)). The CIRI model was induced in rats by transient middle cerebral artery occlusion(tMCAO). The indexes were evaluated and the samples were taken 24 h after the operation. The neurological deficit score was used to detect neurological function. The 2,3,5-triphenyl tetrazolium chloride(TTC) staining was used to detect the cerebral infarction area. Hematoxylin-eosin(HE) staining and Nissl staining were used to observe the morphological structure of brain tissues. Prussian blue staining was used to observe the iron accumulation in the brain. Total iron, lipid pero-xide, and malondialdehyde in serum and brain tissues were detected by biochemical reagents. Real-time quantitative polymerase chain reaction(RT-qPCR), immunohistochemistry, and Western blot were used to detect mRNA and protein expression of solute carrier fa-mily 7 member 11(SLC7A11), transferrin receptor 1(TFR1), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long chain family member 4(ACSL4), and prostaglandin-endoperoxide synthase 2(PTGS2) in brain tissues. Compared with the model group, the groups with drug intervention showed restored neurological function, decreased cerebral infarction rate, and alleviated pathological changes. The low-dose chrysin group was selected as the optimal dosing group. Compared with the model group, the chrysin groups showed reduced content of total iron, lipid peroxide, and malondialdehyde in brain tissues and serum, increased mRNA and protein expression levels of SLC7A11 and GPX4, and decreased mRNA and protein expression levels of TFR1, PTGS2, and ACSL4. Chrysin may regulate iron metabolism via regulating the related targets of ferroptosis and inhibit neuronal ferroptosis induced by CIRI.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Ferroptosis ; Signal Transduction ; Brain Ischemia/metabolism* ; Cyclooxygenase 2/metabolism* ; RNA, Messenger ; Cerebral Infarction ; Reperfusion Injury/metabolism* ; Malondialdehyde ; Infarction, Middle Cerebral Artery

OBJECTIVE: The study explores the effects of electroacupuncture (EA) at the governing vessel (GV) on proteomic changes in the hippocampus of rats with cognitive impairment. METHODS: Healthy male rats were randomly divided into 3 groups: sham, model and EA. Cognitive impairment was induced by left middle cerebral artery occlusion in the model and EA groups. Rats in the EA group were treated with EA at Shenting (GV24) and Baihui (GV20) for 7 d. Neurological deficit was scored using the Longa scale, the learning and memory ability was detected using the Morris water maze (MWM) test, and the proteomic profiling in the hippocampus was analyzed using protein-labeling technology based on the isobaric tag for relative and absolute quantitation (iTRAQ). The Western blot (WB) analysis was used to detect the proteins and validate the results of iTRAQ. RESULTS: Compared with the model group, the neurological deficit score was significantly reduced, and the escape latency in the MWM test was significantly shortened, while the number of platform crossings increased in the EA group. A total of 2872 proteins were identified by iTRAQ. Differentially expressed proteins (DEPs) were identified between different groups: 92 proteins were upregulated and 103 were downregulated in the model group compared with the sham group, while 142 proteins were upregulated and 126 were downregulated in the EA group compared with the model group. Most of the DEPs were involved in oxidative phosphorylation, glycolipid metabolism and synaptic transmission. Furthermore, we also verified 4 DEPs using WB technology. Although the WB results were not exactly the same as the iTRAQ results, the expression trends of the DEPs were consistent. The upregulation of heat-shock protein β1 (Hspb1) was the highest in the EA group compared to the model group. CONCLUSION EA can effect proteomic changes in the hippocampus of rats with cognitive impairment. Hspb1 may be involved in the molecular mechanism by which acupuncture improves cognitive impairment.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Electroacupuncture ; Proteomics ; Cognitive Dysfunction/therapy* ; Hippocampus

This study aims to study the effective substance and mechanism of Ziziphi Spinosae Semen extract in the treatment of insomnia based on serum metabolomics and network pharmacology. The rat insomnia model induced by p-chlorophenylalanine(PCPA) was established. After oral administration of Ziziphi Spinosae Semen extract, the general morphological observation, pentobarbital sodium-induced sleep test, and histopathological evaluation were carried out. The potential biomarkers of the extract in the treatment of insomnia were screened by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS) combined with multivariate analysis, and the related metabolic pathways were further analyzed. The "component-target-pathway" network was constructed by ultra-high performance liquid chromatography coupled with quadrupole-Exactive mass spectrometry(UHPLC-Q-Exactive-MS/MS) combined with network pharmacology to explore the effective substances and mechanism of Ziziphi Spinosae Semen in the treatment of insomnia. The results of pentobarbital sodium-induced sleep test and histopathological evaluation(hematoxylin and eosin staining) showed that Ziziphi Spinosae Semen extract had good theraputic effect on insomnia. A total of 21 endogenous biomarkers of Ziziphi Spinosae Semen extract in the treatment of insomnia were screened out by serum metabolomics, and the metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and nicotinate and nicotinamide metabolism were obtained. A total of 34 chemical constituents were identified by UHPLC-Q-Exactive-MS/MS, including 24 flavonoids, 2 triterpenoid saponins, 4 alkaloids, 2 triterpenoid acids, and 2 fatty acids. The network pharmacological analysis showed that Ziziphi Spinosae Semen mainly acted on target proteins such as dopamine D2 receptor(DRD2), 5-hydroxytryptamine receptor 1 A(HTR1 A), and alpha-2 A adrenergic receptor(ADRA2 A) in the treatment of insomnia. It was closely related to neuroactive ligand-receptor interaction, serotonergic synapse, and calcium signaling pathway. Magnoflorine, N-nornuciferine, caaverine, oleic acid, palmitic acid, coclaurine, betulinic acid, and ceanothic acid in Ziziphi Spinosae Semen may be potential effective compounds in the treatment of insomnia. This study revealed that Ziziphi Spinosae Semen extract treated insomnia through multiple metabolic pathways and the overall correction of metabolic disorder profile in a multi-component, multi-target, and multi-channel manner. Briefly, this study lays a foundation for further research on the mechanism of Ziziphi Spinosae Semen in treating insomnia and provides support for the development of innovative Chinese drugs for the treatment of insomnia.
Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Metabolomics ; Network Pharmacology ; Rats ; Seeds/chemistry* ; Sleep Initiation and Maintenance Disorders/drug therapy* ; Tandem Mass Spectrometry ; Ziziphus/chemistry*

OBJECTIVE: To explore the influencing factors of the residual back pain in patient with osteoporotic vertebral compression fractures(OVCFs) in the early and late stages after percutaneous vertebral augmentation(PVA), and analyze the correlation between these factors and the residual back pain after PVA. METHODS: From March 2018 to December 2019, 312 patients with OVCFs who treated with PVA were collected. According to the inclusion and exclusion criteria, a total of 240 patients were included in this retrospective study. There were 59 males and 181 females, aged from 50 to 95 years old with an average of (76.11±10.72) years old, and 50 cases of fractures located in the thoracic region (T₅-T₁₀), 159 cases in the thoracolumbar region (T₁₁-L₂), and 31 cases in the lumbar region (L₃ and below). The first day after PVA was regarded as the early postoperative period, and the seventh day was regarded as the late postoperative period. According to the visual analogue scale (VAS), the patients were divided into 4 groups:early postoperative pain relief group(group A, VAS≤4 scores), there were 121 patients, including 29 males and 92 females, aged from 50 to 90 years with an average of (75.71±11.00) years;early postoperative pain relief was not an obvious group (group B, VAS >4 scores), there were 119 patients, including 30 males and 89 females, aged from 53 to 95 years with an average of (76.51±10.46) years; late postoperative pain relief group (group C, VAS≤ 4 scores), there were 172 patients, including 42 males and 130 females, aged from 50 to 95 years with an average of (76.20±10.68) years; late postoperative pain relief was not obvious group (group D, VAS>4 scores), there were 68 patients, including 17 males and 51 females, aged from 53 to 94 years old with an average of (75.88±10.91) years old. The age, gender, bone mineral density(BMD), injured vertebral segment, preoperative thoracolumbar fascial condition, surgical methods, single or bilateral puncture, the amount of bone cement injection, anterior vertebral height recovery rate and central vertebral height recovery rate in the 4 groups were analyzed by univariate analysis. The statistically significant factors were put into a Logistic regression to analyze the correlation between these factors and residual back pain after PVA. RESULTS: Univariate analysis showed that the residual back pain in the early stage after PVA was correlated with BMD, preoperative thoracolumbar fascial injury, single or bilateral puncture, the amount of bone cement injection, anterior vertebral height recovery rate and central vertebral height recovery rate(P<0.05). The residual back pain in the late postoperative period was related to BMD, injured vertebral segment, surgical methods, the amount of bone cement injection, anterior vertebral height recovery rate and central vertebral height recovery rate(P<0.05). Multivariate Logistic regression analysis showed that thoracolumbar fascial injury(OR=4.938, P=0.001), single or bilateral puncture(OR=5.073, P=0.002) were positively correlated with the residual back pain in the early stage after PVA(B>0), which were risk factors;the BMD (OR=0.211, P=0.000) and anterior vertebral height recovery rate (OR=0.866, P=0.001) were negatively correlated with the residual back pain in the early stage after PVA(B<0), which were protective factors. In the late stage after PVA, the BMD(OR=0.448, P=0.003), the amount of bone cement injection (OR=0.648, P=0.004) and anterior vertebral height recovery rate (OR=0.820, P=0.000) were negatively correlated with residual back pain(B<0), which were protective factors. CONCLUSION The decrease of BMD, injury of the thoracolumbar fascia, single or bilateral puncture, poor recovery of anterior vertebral height and insufficient injection of bone cement are closely related to the occurrence of residual back pain after PVA, which affect the relief of residual back pain in the early and late postoperative periods.
Aged ; Aged, 80 and over ; Back Pain ; Bone Cements ; Disease Progression ; Female ; Fractures, Compression/etiology* ; Humans ; Male ; Middle Aged ; Osteoporotic Fractures/surgery* ; Pain, Postoperative/etiology* ; Retrospective Studies ; Spinal Fractures/surgery* ; Treatment Outcome ; Vertebroplasty/methods*

BACKGROUND: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. METHODS: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. RESULTS: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. CONCLUSION: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; Bendamustine Hydrochloride/therapeutic use* ; China ; Humans ; Lymphoma, Non-Hodgkin/drug therapy* ; Neoplasm Recurrence, Local/drug therapy* ; Prospective Studies ; Rituximab/therapeutic use*

OBJECTIVE: To evaluate the clinical efficacy and safety of Congrong Shujing Granules ( , CSGs) in treating patients with Parkinson's disease (PD) and Chinese medicine (CM) syndrome of Shen (Kidney) essence deficiency, and to investigate the potential mechanism involving efficacy through a transcriptome sequencing approach. METHODS: Eligible PD patients with syndrome of Shen essence defificiency were randomly assigned to a treatment group or a control group by a random number table, and were treated with CSGs combined with Western medicine (WM), or placebo combined with WM, respectively. Both courses of treatment lasted for 12 weeks. The Unifified Parkinson's Disease Rating Scale (UPDRS) score, the PD Question-39 (PDQ-39) score, CM Syndrome Scale score, and drug usage of all patients were evaluated before and after treatment. Safety was evaluated by clinical laboratory tests and electrocardiographs. Blood samples from 6 patients in each group were collected before and after the trial and used for transcriptomic analysis by gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Differentially expressed genes were validated using reverse transcription-polymerase chain reaction. RESULTS: A total of 86 PD patients were selected from the Third Affifiliated People's Hospital of Fujian University of Traditional Chinese Medicine between January 2017 and December 2017. Finally, 72 patients completed the trial, including 35 in the treatment group and 37 in the control group. When compared with the control group after treatment, patients in the treatment group showed signifificant decreases in UPDRS sub-II score, PDQ-39 score, CM syndrome score, and Levodopa equivalent dose (P<0.05). During the treatment course, no signifificant changes were observed in safety indicators between the two groups (P>0.05). A possible mechanism of clinical effificacy was proposed that involved regulating cell metabolism-related processes and ribosome-related pathways. Treatment with CSGs had shown to affect relevant gene loci for PD, including AIDA, ANKRD36BP2, BCL2A1, BCL2L11, FTH1P2, GCH1, HPRT1, NFE2L2, RMRP, RPS7, TGFBR1, WIPF2, and COX7B. CONCLUSIONS CSGs combined with WM can be used to treat PD patients with CM syndrome of Shen essence defificiency with a good safety. The possible mechanism of action and relevant gene loci were proposed. (Registration No. ChiCTR-IOR-16008394).

Objective:To make a new simple respirator and observe the oxygen therapy effect of the respirator on patients with severe and critical coronavirus disease 2019 (COVID-19).Methods:Based on the infectivity and hospital requirements of COVID-19, a new simple respirator was designed by the medical staff of the Department of Anesthesiology of the Second Affiliated Hospital of Nanchang University, which was applied on the 22 patients with severe and critical COVID-19 who needed oxygen therapy admitted to the Cancer Center of Tongji Medical College of Huazhong University of Science and Technology from February 15th to March 15th in 2020. The new simple respirator contained two National Utility Model Patents (a respirator: ZL 2015 2 0410623.6, a fluid switch and oxygen suction device: ZL 2017 2 0873509.6), which was mainly composed of anesthesia mask and filter, L-shaped connecting tube, soft breathing bladder, connecting tube and elastic fixing belt. When in use, the anesthesia mask was fixed to the patient's mouth and nose with elastic straps, the connecting tube was inserted into the oxygen meter interface, the oxygen flow was adjusted to 6-10 L/min, and the L-shaped connecting tube was opened immediately after the soft breathing bag was full. The carbon dioxide and excess oxygen in the body was discharged from exhaust port. The oxygen flow was lowered to 2-3 L/min, the patient's respiratory rate (RR) was observed through the soft breathing bag fluctuations, and the oxygen flow was adjusted at any time. The changes of pulse oxygen saturation (SpO 2), RR and heart rate (HR) before and after application of new simple respirator were observed, and the blood gas test results of part of the patients were collected. Results:Twenty-two patients with severe and critical COVID-19 had significantly higher SpO 2 at 10 minutes after application of the new simple ventilator than before application (0.994±0.007 vs. 0.952±0.017, P < 0.01), and RR was significantly lower than that before application (times/min: 27.59±3.63 vs. 29.64±3.81, P < 0.01); after 1 day of application, each index was further improved. All 13 patients who received blood gas analysis indicated no carbon dioxide accumulation. Conclusions:The new simple respirator can significantly improve the oxygen therapy effect of patients with severe and critical COVID-19. At the same time, 2019 novel coronavirus (2019-nCoV) can be filtered through the filter to reduce the formation of aerosol and protect the medical staff and patients.

Objective: This study aimed to measure the basal energy expenditure (BEE) of Chinese healthy adults and establish an accurate predictive equation for this population. Methods: In total, 470 Chinese healthy adults had their BEE measured using the Cosmed K4b portable metabolic system. Multiple linear regression analysis was applied to develop new optimal equations for predicting BEE. The bias, accuracy rate, concordance correlation coefficient (CCC), and root mean square error (RMSE) were used to evaluate the accuracy of the predictive equations. Results: There was a significant difference in BEE between males and females, with 5,954 kJ/d and 5,089 kJ/d, respectively. People living in rural areas expended significantly higher BEE (5,885 kJ/d) than those in urban areas (5,279 kJ/d). Previous equations developed by Henry, Schofield, Harris-Benedict (H-B), and Liu overestimated the BEE of Chinese healthy adults. The new equations derived from the present study displayed the smallest average bias and RMSE from the measured basal energy expenditure (mBEE). The CCC of the new equations was higher than other predictive equations, but it was lower than 0.8. There was no significant difference in the accuracy rate among all predictive equations. Conclusions Sex and regional differences in BEE were observed in Chinese healthy adults. Neither the widely used previous predictive equations nor the one derived in the present study were accurate enough for estimating the BEE of Chinese healthy adults. Further study is required to develop more accurate equations for predicting the BEE of Chinese healthy adults aged between 20-45 years.
Adult ; Basal Metabolism ; Calorimetry ; methods ; China ; Female ; Humans ; Male ; Young Adult

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine (CM) improving pregnancy outcomes after surgery for endometriosis-associated infertility. METHODS: A multicenter, randomized, double-blind placebo parallel controlled clinical trial was designed. A total of 202 patients who had laparoscopy for endometriosis-associated infertility with qi stagnation and blood stasis syndrome were included and randomly divided into the CM treatment group and placebo control group at a ratio of 1:1 using a central block randomization from May 2014 to September 2017, 101 patients in each group. The two groups received continuous intervention at 1-5 days after surgery, for 6 menstrual cycles. Before ovulation, the CM group was treated Huoxue Xiaoyi Granule (); after ovulation, Bushen Zhuyun Granule ( was involved. The control group was treated with placebo. Transvaginal ultrasonography was performed every menstrual cycle during the treatment, and female hormone levels in the follicular and luteal phases were measured during the 1st, 3rd and 6th menstrual cycles. The analysis was continued until pregnancy. The primary outcomes were clinical pregnancy rate and pregnancy outcome, and the secondary outcomes were follicular development and endometrial receptivity. Safety evaluations were performed before and after treatment. RESULTS: (1) Clinical pregnancy and live birth rates: the clinical pregnancy and live birth rates of the CM group were significantly higher than those of the placebo group [44.6% (45/101) vs. 29.7% (30/101), 34.7% (35/101) vs. 20.8% (21/101), both P<0.05]. (2) Follicle development: the incidence of dominant follicles, rate of cumulative cycle ovulation, and rate of cumulative cycle mature follicle ovulation were significantly higher in the CM group than those in the placebo group [93.8% (350/373) vs. 89.5% (341/381), 80.4% (275/342) vs. 69.1% (253/366), 65.8% (181/275) vs 56.1% (142/253), P<0.05 or P<0.01]). The incidence of cumulative cycle luteinized unruptured follicle syndrome was significantly lower in the CM group than in the placebo group [11.7% (40/342) vs. 17.8% (65/366), P<0.05). (3) Endometrial receptivity: after treatment, both endometrial types and endometrial blood flow types in the CM group were mainly types A and B, while those in the placebo group were mainly types B and C, with a significant difference between the two groups (both P<0.05). (4) Adverse events: the incidence of adverse events between the two groups was not significantly different (P>0.05). CONCLUSION Strategies for activating blood circulation-regulating Gan (Liver)-tonifying Shen (Kidney) sequential therapy can effectively improve the clinical pregnancy rate and live birth rate of endometriosis-associated infertility with qi stagnation and blood stasis after laparoscopy, improve follicular development, promote ovulation, improve endometrial receptivity, while being a safe treatment option. (Trial registration No. NCT02676713).