Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer / 中华肿瘤杂志

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.

Interpretation of the International Myopia Institute White Papers Ⅱ / 国际眼科杂志(Guoji Yanke Zazhi)

Worldwide, the incidence rate of myopia is maintained in a high level. Especially, the morbidity is rising continuously among children and adolescents. The progression of myopia affects visual acuity, vision related quality of life and productivity. Moreover, high myopia and its related ocular complications also aggravate the family and social burden. Therefore, the mechanism of myopia, related complications and methods of myopia prevention and control need further exploration. International Myopia Institute(IMI)published the second-edition white papers in April 2021. These white papers included reflections on the implications for clinical practice, the impact of myopia, the risk factors of myopia, the relationship among accommodation and binocular vision with myopia, pathologic myopia, prevention of myopia and digest. Comparing to the first edition, more than thousands of articles and conference abstracts were considered in white papers II, highlighting the latest research and progress related to myopia prevention and control. This article briefly summarizes and interprets the contents of the above white papers, including overview of myopia, impact of myopia, risk factors in myopia, ocular changes in the progress of myopia, and myopia prevention and control, hoping to provide advice for the clinical and scientific research work relating to myopia prevention and control.

Programmed Intermittent Epidural Bolus in Comparison with Continuous Epidural Infusion for the Effects of Enhanced Recovery after Cesarean Section / 中山大学学报(医学科学版)

ObjectiveTo compare the effects of programmed intermittent epidural bolus （PIEB） and continuous epidural infusion （CEI） on enhanced recovery after cesarean section. MethodsTotally 120 women scheduled to undergo elective cesarean section under combined spinal and epidural anesthesia， aged 18-45 years， with single fetus， full-term pregnancy （≥37 weeks）， ASA grade II or III， were recruited， with 60 cases in each group. At the end of the surgery， after a similar epidural loading dose， patients were randomLy assigned to receive either PIEB （6 mL·h-1 beginning 30 minutes after the loading dose） or CEI （6 mL·h-1， beginning immediately after the loading dose） for the maintenance of analgesia with 0.1% ropivacaine. At 2， 6， 12， 24 and 36 h postoperatively， VAS score was used to evaluate the composite pain， and Bromage Score was used to evaluate the degree of lower extremity motor block. The time to first flatus， time to first ambulation and the satisfaction scores were also recorded. ResultsThe VAS scores at 12， 24 and 36 h postoperatively and the lower extremity motor block scores at 6， 12 and 24 h postoperatively in the PIEB group were significantly lower than those in the CEI group （P < 0.01）. The epidural analgesic dosage was less in the PIEB group than that of the CEI group （P=0.002）. The time to first flatus and time to first ambulation were significantly shorter than those in the CEI group （P < 0.05）. The satisfaction scores were significantly higher in the PIEB group than in the CEI group （P < 0.05）. There was no significant difference in the first urination time after urinary catheter removal and the length of hospital stay between the two groups （P > 0.05）. ConclusionCompared with CEI， PIEB provides better postoperative analgesia， less motor block scores， lower epidural analgesic dosage， shorter the time to first flatus and defecation and time to first ambulation， and greater patient satisfaction， which is more consistent with the ERAS concept of analgesia.

Pharmacodynamics of human interferon α1b against severe acute respiratory syndrome coronavirus 2 Omicron strain in vitro / 中国生物制品学杂志

@#Objective To evaluate the pharmacodynamics of human interferon(IFN)α1b against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron strain in vitro.Methods Total four drugs human IFNα1b bulk,human IFNα1b eye drops,human IFNα1b spray and Remdesivir were detected for cytotoxicity by CCK-8 assay.The inhibitory effect of human IFNα1b on SARS-CoV-2 Omicron strains(BA.5/BA.2/BA.1)was determined by qPCR.Results Human IFNα1b bulk of the maximum concentration(1 × 107IU/mL)and Remdesivir of the maximum concentration(150 μmol/L)did not achieve half cytotoxicity to Vero cells;The median cytotoxicity concentrations(CC_(50))of human IFNα1b eye drops and human IFNα1b sprays were 29 958 and 37 550 IU/mL,respectively,showing toxicity to Vero cells.The median effective concentrations(EC_(50))of human IFNα1b against virus strains BA.1,BA.2 and BA.5 after incubation for 2 h in advance were 9.30,13.38 and 12.33 IU/mL and those of Remdesivir were 0.314 7,0.291 0 and0.300 3 μmol/L.When incubation with virus simultaneously,the EC_(50)of human IFNα1b to BA.1,BA.2 and BA.5 were19.68,10.91 and 18.84 IU/mL and those of the control drug Remdesivir were 0.320 5,0.274 4 and 0.304 1 μmol/L,respectively.Conclusion At the cell level in vitro,human IFNα1b of very low activity showed a good inhibitory effect on SARS-CoV-2 Omicron strain,which was expected to be a clinical specific drug for the treatment of SARS-CoV-2 Omicron strain infection.

Analysis of Chinese Medical Syndrome Features of Ischemic Stroke Based on Similarity of Symptoms Subgroup / 中国结合医学杂志

OBJECTIVE@#To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients.@*METHODS@#By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup.@*RESULTS@#Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens.@*CONCLUSIONS@#There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.

Antinociceptive effect of N-(9,13b-dihydro-1H-dibenzo[c, f]imidazo[1,5-a]azepin-3-yl)-2-hydroxybenzamide on different pain models in mice

Abstract N-(9,13b-dihydro-1H-dibenzo[c,f]imidazo[1,5-a]azepin-3-yl)-2-hydroxybenzamide (DDIAHB) is a new drug developed through molecular modelling and rational drug design by the molecular association of epinastine and salicylic acid. The present study was designed to assess the possible antinociceptive effects of DDIAHB on different pain models in male ICR mice. DDIAHB exerted the reductions of writhing numbers and pain behavior observed during the second phase in the formalin test in a dose-dependent manner. Moreover, DDIAHB increased the latency in the hot-plate test in a dose-dependent manner. Furthermore, intragastric administration DDIAHB caused reversals of decreased pain threshold observed in both streptozotocin-induced diabetic neuropathy and vincristine-induced peripheral neuropathy models. Additionally, intragastric pretreatment with DDIAHB also caused reversal of decreased pain threshold observed in monosodium urate-induced pain model. We also characterized the possible signaling molecular mechanism of the antinociceptive effect-induced by DDIAHB in the formalin model. DDIAHB caused reductions of spinal iNOS, p-STAT3, p-ERK and p-P38 levels induced by formalin injection. Our results suggest that DDIAHB shows an antinociceptive property in various pain models. Moreover, the antinociceptive effect of DDIAHB appear to be mediated by the reductions of the expression of iNOS, p-STAT3, p-ERK and p-P38 levels in the spinal cord in the formalin-induced pain model.

Effect of Polysaccharides from Root， Stem， Leaf and Fruit of Schisandra chinensis on Exercise Endurance in D-galactose-induced Aging Mice / 中国实验方剂学杂志

ObjectiveTo observe the effect of polysaccharides from root， stem， leaf and fruit of Schisandra chinensis on exercise endurance in the aging mice induced by D-galactose. MethodMale ICR mice were randomly assigned into six groups： blank control group， model group， root polysaccharide group， stem polysaccharide group， leaf polysaccharide group and fruit polysaccharide group. The mice were administrated with distilled water or root， stem， leaf and fruit polysaccharide （total sugar content of 35 mg·kg-1） by gavage. Thirty minutes after the administration， the blank control group was subcutaneously injected with normal saline， and the other groups with D-galactose （300 mg·kg-1）， once daily for 6 weeks. The anti-fatigue effects were evaluated by rotarod test， forelimb grip strength test， and weight-loaded swimming test. The fatigue and oxidation indicators such as blood urea nitrogen （BUN）， serum lactic acid （LD）， lactic dehydrogenase （LDH）， creatine kinase （CK）， superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， and reactive oxygen species （ROS） were measured by chemical colorimetry. The protein levels of pro-apoptotic protein B cell lymphoma-2 （Bcl-2）-associated X protein （Bax）， anti-apoptotic Bcl-2 and cleaved cysteinyl aspartate-specific protease-3 （cleaved Caspase-3） in mouse skeletal muscle were detected by Western blot. ResultIn the rotarod test， the time on rod was shorter in the model group than in the blank control group （P<0.01） and the root， stem and fruit polysaccharide groups （P<0.01）. In the forelimb grip strength test， the forelimb grip strength in the model group was lower than that in the blank control group （P<0.01） and the root， stem， leaf and fruit polysaccharide groups （P<0.01）. In the weight-loaded swimming test， the weight-loaded swimming time in the model group was shorter than that in the blank control group （P<0.01） and the root， stem， leaf and fruit polysaccharide groups （P<0.01）. Compared with those in the blank control group， the BUN， LD， LDH and CK levels significantly increased in the model group （P<0.05， P<0.01）. The increases in BUN and LDH levels were decreased by the root， stem and fruit polysaccharides （P<0.05， P<0.01） and those in LD and CK by the root， stem， leaf and fruit polysaccharides （P<0.05， P<0.01）. Compared with the blank control group， the model group showed decreased SOD and GSH-Px activities （P<0.01） and increased MDA and ROS content （P<0.01）. Compared with the model group， the root， stem， and fruit polysaccharide increased the SOD activity （P<0.05， P<0.01） and decreased ROS content （P<0.01）. The root and stem polysaccharides decreased the MDA content （P<0.01） and increased the GSH-Px activity （P<0.05， P<0.01）. Compared with the blank control group， the model group showed up-regulated protein levels of Bax and cleaved Caspase-3 and down-regulated protein level of Bcl-2 （P<0.01）. Compared with the model group， the root， and stem polysaccharides down-regulated the protein levels of cleaved Caspase-3 （P<0.05） and up-regulated protein level of Bcl-2 （P<0.01）. ConclusionThe polysaccharides from the root， stem， leaf， and fruit of S. chinensis have anti-fatigue effect in D-galactose-induced aging mice. The polysaccharides may exert such effect by improving the antioxidant capacity and inhibiting the apoptosis of skeletal muscle cells.

Incidence of extrauterine growth retardation and its risk factors in very preterm infants during hospitalization: a multicenter prospective study / 中国当代儿科杂志

OBJECTIVES@#To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China.@*METHODS@#A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined.@*RESULTS@#The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05).@*CONCLUSIONS@#It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.

Effect and influence factors of cardiopulmonary resuscitation in children with congenital heart disease in pediatric intensive care unit / 中华儿科杂志

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ2=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ2=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.

Impact of the COVID-19 pandemic on intention to use traditional Chinese medicine: A cross-sectional study based on the theory of planned behavior / 中西医结合学报

OBJECTIVE@#Coronavirus disease 2019 (COVID-19) has become an increasingly severe public health emergency. Although traditional Chinese medicine (TCM) has helped to combat COVID-19, public perception of TCM remains controversial. We used the theory of planned behavior (TPB) to identify factors that affect the intention to use TCM.@*METHODS@#A cross-sectional web-based survey of 10,824 individuals from the general public was conducted between March 16 and April 2, 2020. The participants were recruited using a snowball sampling method. Data were collected using a self-administered questionnaire, based on the TPB. The questionnaire consisted of demographic characteristics and TPB structures. Structural equation modeling was used to identify predictors of intention.@*RESULTS@#The results indicated the model explained 77.5% and 71.9% of intention and attitude variance. Intention to use TCM had the strongest relationship with attitude (P < 0.001), followed by past behavior (P < 0.001), subjective norms (P < 0.001) and perceived behavioral control (P < 0.001). Attitudes toward TCM were significantly affected by perceived behavioral control (P < 0.001), subjective norms (P < 0.001) and cognition of TCM (P < 0.001).@*CONCLUSION@#Attitude is a key factor in determining the intention to use TCM, followed by past behaviors, subjective norms and perceived behavioral control. Our results offer important implications for health policy makers to promote the use of TCM.

Clinical Features and Prognosis of Acute Lymphoblastic Leukemia Children with P2RY8-CRLF2 Gene Rearrangement / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical features and prognostic factors of acute lymphoblastic leukemia (ALL) children with P2RY8-CRLF2 gene rearrangement.@*METHODS@#A total of 108 children with B-cell ALL (B-ALL) were diagnosed and systematically treated according to Chinese Children's Leukemia Group (CCLG) -ALL 2008 in our hospital from January 2016 to December 2016. The 108 patients were divided into two groups according to the result of mutiplex polymerase chain reaction: group with P2RY8-CRLF2 gene rearrangement and group without P2RY8-CRLF2 gene rearrangement. The ALL children with P2RY8-CRLF2 gene rearrangement were all treated by CCLG-ALL 2008 high-risk group (HR) regimens, and the ALL children in group without P2RY8-CRLF2 gene rearrangement received different intensity chemotherapy according to clinical risk classification.@*RESULTS@#Five (4 male and 1 female) out of 108 patients with B-ALL had P2RY8-CRLF2 gene rearrangement. In the 5 B-ALL patients with P2RY8-CRLF2 gene rearrangement, the median age of the was 4 (2-6) years old and the median WBC count was 26.2 (2.46-525.1)×10@*CONCLUSION@#The early treatment response and prognosis of ALL children with P2RY8-CRLF2 gene rearrangement are worse, and more effective protocol is needed for this subtype patients.

Clinical Effect and Safety of CCLG-ALL 2008 (high risk group) Protocol in the Treatment of Childhood Mixed Phenotype Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical effect and safety of Chinese Children's Leukemia Group (CCLG)-ALL 2008 (high risk group) protocol in the treatment with childhood Mixed phenotype acute leukemia (MPAL).@*METHODS@#The clinical data of 15 new diagnosed patients with MPAL treated in our hospital from January 2013 to December 2017 were retrospectively analyzed, and received CCLG-ALL 2008 (high risk group) protocol chemotherapy.@*RESULTS@#One patient gave up treatment after diagnosed, and 14 children with MPAL after induction remission chemotherapy, 3 patients gave up, and 5 patients received consolidation chemotherapy, and 6 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). The complete remission (CR) rate was 85.7% at d33 of induction remission chemotherapy. The serious adverse event and treatment-related mortality (TRM) rate was 71.4% and 14.3%, respectively. The recurrence rate was 21.4% and the median time of relapse was 12(9.7-18.4) months. Except for 4 patients who gave up treatment, the 5-year event-free survival (EFS) rate in the other 11 patients was (54.5±15.0)%. The 5 years EFS of 4 patients who received consolidation chemotherapy was significantly lower than the 6 patients who received allo-HSCT after CR (25.0%±21.7% vs 83.3%±15.2%, P=0.033).@*CONCLUSION@#The CCLG-ALL2008 (for high-risk group) protocol in treatment of children with MPAL can get a high CR rate, but also with a high incidence of SAE. The patients received allo-HSCT after CR may have a good prognosis.

The changes of nociception and the signal molecules expression in the dorsal root ganglia and the spinal cord after cold water swimming stress in mice

Several studies have previously reported that exposure to stress provokes behavioral changes, including antinociception, in rodents. In the present study, we studied the effect of acute cold-water (4°C) swimming stress (CWSS) on nociception and the possible changes in several signal molecules in male ICR mice.Here, we show that 3 min of CWSS was sufficient to produce antinociception in tailflick, hot-plate, von-Frey, writhing, and formalin-induced pain models. Significantly, CWSS strongly reduced nociceptive behavior in the first phase, but not in the second phase, of the formalin-induced pain model. We further examined some signal molecules' expressions in the dorsal root ganglia (DRG) and spinal cord to delineate the possible molecular mechanism involved in the antinociceptive effect under CWSS.CWSS reduced p-ERK, p-AMPKα1, p-AMPKα2, p-Tyk2, and p-STAT3 expression both in the spinal cord and DRG. However, the phosphorylation of mTOR was activated after CWSS in the spinal cord and DRG. Moreover, p-JNK and p-CREB activation were significantly increased by CWSS in the spinal cord, whereas CWSS alleviated JNK and CREB phosphorylation levels in DRG. Our results suggest that the antinociception induced by CWSS may be mediated by several molecules, such as ERK, JNK, CREB, AMPKα1, AMPKα2, mTOR, Tyk2, and STAT3 located in the spinal cord and DRG.

Preliminary adipose removal did not prevent diet-induced metabolic disorders in mice / 中华医学杂志(英文版)

BACKGROUND@#Obesity is a fundamental factor in metabolic disorders such as hyperlipidemia, insulin resistance, fatty liver, and atherosclerosis. However, effective preventive measures are still lacking. This study aimed to investigate different surgical protocols for removing partial adipose tissue before the onset of obesity and determine whether, and by which protocol, preliminary adipose removal could exert potent preventive effects against diet-induced metabolic disorders.@*METHODS@#Male low-density lipoprotein receptor (LDL-R) knockout (KO) mice were randomly divided into four groups and subjected to epididymal fat removal (Epi-FR) surgery, subcutaneous fat removal (suQ-FR) surgery, both subcutaneous and epididymal fat removal (Epi + suQ-FR) surgery, or sham-operation. After 1 week of recovery, all mice were given a high-fat diet (HFD) for 10 weeks to induce metabolic disorders.@*RESULTS@#In the Epi-FR group and the sham-operated group, the mean numbers of the residual subcutaneous fat were 28.59 mg/g and 18.56 mg/g, respectively. The expression of relative genes such as Pparg, Cebpa, Dgat2, Fabp4 and Cd36 in the residual subcutaneous fat increased 2.62, 3.90, 3.11, 2.06, 1.78 times in the Epi-FR group compared with that in the sham-operated group. Whereas in the other fat-removal groups, the residual fat depots had no significant change in either size or gene expression, as compared with those of the sham-operated group. Plasma lipid and glucose levels and insulin sensitivity, as detected by the glucose tolerance test, were not significantly alleviated in the three fat removal groups. Liver mass or lipid content was not attenuated in any of the three fat removal groups. The atherosclerosis burdens in the entire inner aorta and aortic root did not decrease in any of the three fat removal groups.@*CONCLUSIONS@#Our data suggest that removal of epididymal adipose or subcutaneous adipose alone or in combination before the onset of obesity did not protect against hyperlipidemia, insulin resistance, fatty liver, or atherosclerosis in LDL-R KO mice fed with a HFD. Hence, adipose removal possibly does not represent a potential approach in preventing obesity-related metabolic disorders in the obesity-susceptible population.

Anwulignan alleviates liver damages in exhausted mice by activating NRF2 / 药学学报

Excessive exercise makes the body consume more oxygen and produce excessive free radicals. The increased free radicals lead to oxidative stress injury and dysfunctions in liver tissue. Our previous study showed that Anwulignan, an active monomer in Schisandra sphenanthera Rehd. et Wils. (Schisandra), had anti-fatigue effects in mice. However, whether Anwulignan has a protective effect on liver damage in exhausted mice and the mechanism underlying remain elusive. An exhaustive swimming mice model was used to study the protective effects of Anwulignan on liver damage. The involvement of the nuclear factor (erythroid-derived 2)-like 2 (NRF2)/antioxidant responsive element (ARE) antioxidative pathway in Anwulignan-mediated anti-fatigue was analyzed using NRF2 inhibitor ML385 in HepG2 cells treated with H2O2. Animal welfare and experimental process follow the regulations of the Animal Ethics Committee of Beihua University. Anwulignan significantly lowered serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, reduced liver tissue damages, increased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), and decreased malondialdehyde (MDA) and 8-hydroxy-2 deoxyguanosine (8-OHdG) contents in the livers of exhausted mice, demonstrating a strong antioxidant effect. Furthermore, Anwulignan up-regulated the NRF2/ARE antioxidant pathway in liver tissue, increased B-cell lymphoma 2 (Bcl-2) expression, and decreased Bcl-2-like protein 4 (Bax) and caspase3 expression. In HepG2 cells, Anwulignan improved the cell viability and SOD activity, reduced reactive oxygen species (ROS) and MDA contents, up-regulated the expression of the NRF2/ARE signaling pathway and Bcl-2, and decreased Bax and caspase3 expression in the cells. Furthermore, pretreated ML385 partly abolished all these effects of Anwulignan. Anwulignan protects the liver from damage in the exhausted mice by its antioxidant effects and related to its activation of the NRF2 pathway.

Suppression of OCT2/MRP2 decreases kidney injury and enhances the chemosensitivity of co-administration of cisplatin and astragaloside IV / 药学学报

Kidney injury and decreased chemosensitivity of tumor cells are obstacles with cisplatin (CDDP) chemotherapy. Down-regulation of the organic cation transporter 2 (OCT2) and multidrug resistance-associated protein 2 (MRP2) is a key means to alleviate CDDP-induced kidney injury and increase chemosensitivity. Astragaloside IV (AS IV) is obtained from the well-known traditional Chinese herb Astragalus membranaceus. This study explored the role of AS IV in preventing kidney injury and enhancing the antitumor effect of CDDP by suppressing OCT2 expression in kidney and MRP2 in tumors. This project was reviewed and approved by the Animal Ethics Committee of the First Hospital of Jilin University. The effects of AS IV on CDDP inhibition of tumor growth and promotion of apoptosis were assessed in Lewis lung tumor (LLC)-bearing mice by H&E and TUNEL staining. Kidney injury was assessed by serum biochemical parameters and H&E staining. We used Western blotting and immunohistochemistry assays to detect OCT2 and MRP2 expression in kidney and tumor. The concentration of CDDP in kidney and tumor was measured by HPLC-MS/MS. AS IV enhanced CDDP chemosensitivity by increasing tumor cell apoptosis and slowing tumor growth, and decreased kidney injury as evidenced by lower blood creatinine (Cr) and blood urea nitrogen (BUN). Co-administration of AS IV suppressed MRP2 overexpression induced by CDDP in tumor tissues and may be an important mechanism for enhancing CDDP chemosensitivity. Moreover, AS IV reduced CDDP-induced kidney injury in mice along with suppression of OCT2 expression in kidney. The concentration of CDDP was increased in tumor but decreased in kidney. In total, AS IV not only enhanced the antitumor effect of CDDP by suppressing MRP2 expression in tumor cells, but also decreased kidney injury induced by CDDP. The results provide new insight into the combined use of a chemotherapy drug and natural ingredients to treat cancer.

Extract from Modified Xiao Xianxiongtang Inhibits Epithelial-mesenchymal Transition and Invasion and Migration Mediated by TGF-β1 of Human Gastric Cancer MGC-803 Cells via Wnt5a/Ca2+/NFAT Signaling Pathway / 中国实验方剂学杂志

Objective:This studu aims to investigate the effect of aqueous extract of modified Xiao Xianxiongtang on the epithelial mesenchymal transition（EMT） and the change of its invasion and migration ability of human gastric cancer MGC-803 cells mediated by transforming growth factor-<italic>β</italic>₁（TGF-<italic>β</italic>₁），and to explore the mechanism of regulating Wnt5a/Ca²⁺/ activated T-cell nuclear factor（NFAT） signaling pathway to inhibit EMT and invasion and metastasis of MGC-803 cells. Method:TGF-<italic>β</italic>₁（10 μg·L^-1）was used to induce EMT and the invasion and metastasis model of human gastric cancer MGC-803 cells. Transwell chamber experiment， scratchhealing experiment， Western blot and immunofluorescence assay were used to detect cell invasion and migration ability， expression of EMT marker protein and key protein expression of Wnt5a/Ca²⁺/NFAT signaling pathway， and intracellular Ca²⁺ concentration. Result:Compared with the blank group， TGF-<italic>β</italic>₁ could significantly enhance the invasion and migration ability of MGC-803 cells（<italic>P</italic><0.01）， down-regulate the level of E-cadherin（<italic>P</italic><0.01）， up-regulate protein expressions of N-cadherin， Snail and Vimentin（<italic>P</italic><0.01）， and induce cell Wnt5a， calcineurin （CaN）， total protein of activated T-cell nuclear factor 1（NFAT1）， up-regulation of phosphorylated proteins p-NFAT1 and NFAT1 nucleoprotein and intracellular accumulation of Ca²⁺（<italic>P</italic><0.01）. Compared with the TGF-<italic>β</italic>₁ group， modified Xiao Xianxiongtang （10， 20， 40 mg·L^-1） could significantly inhibit this phenomenon，and 40 mg·L^-1 had the best effect（<italic>P</italic><0.05，<italic>P</italic><0.01）.The specific inhibitors of Wnt5a/Ca²⁺/NFAT signaling pathway （<italic>R</italic>）-（+）-Bay-K-8644 and modified Xiao Xianxiongtang （40 mg·L^-1） could significantly inhibit theinvasion and migration of MGC-803 cells mediated by TGF-<italic>β</italic>₁， up-regulate the level of E-cadherin， and down-regulate expressions of N-cadherin， Snail， Vimentin， Wnt5a， CaN and NFAT1 proteins and reduce the intracellular accumulation of Ca²⁺（<italic>P</italic><0.05，<italic>P</italic><0.01）.Moreover， （<italic>R</italic>）-（+）-Bay-K-8644 combined with modified Xiao Xianxiongtang （40 mg·L^-1） had stronger inhibitory effect（<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:These results suggest that modified Xiao Xianxiongtang can inhibit the EMT mediated by TGF-<italic>β</italic>₁ via Wnt5a/Ca²⁺/NFAT signaling pathway，thereby reducing the invasion and migration ability of MGC-803 cells.

The changes of nociception and the signal molecules expression in the dorsal root ganglia and the spinal cord after cold water swimming stress in mice

Several studies have previously reported that exposure to stress provokes behavioral changes, including antinociception, in rodents. In the present study, we studied the effect of acute cold-water (4°C) swimming stress (CWSS) on nociception and the possible changes in several signal molecules in male ICR mice.Here, we show that 3 min of CWSS was sufficient to produce antinociception in tailflick, hot-plate, von-Frey, writhing, and formalin-induced pain models. Significantly, CWSS strongly reduced nociceptive behavior in the first phase, but not in the second phase, of the formalin-induced pain model. We further examined some signal molecules' expressions in the dorsal root ganglia (DRG) and spinal cord to delineate the possible molecular mechanism involved in the antinociceptive effect under CWSS.CWSS reduced p-ERK, p-AMPKα1, p-AMPKα2, p-Tyk2, and p-STAT3 expression both in the spinal cord and DRG. However, the phosphorylation of mTOR was activated after CWSS in the spinal cord and DRG. Moreover, p-JNK and p-CREB activation were significantly increased by CWSS in the spinal cord, whereas CWSS alleviated JNK and CREB phosphorylation levels in DRG. Our results suggest that the antinociception induced by CWSS may be mediated by several molecules, such as ERK, JNK, CREB, AMPKα1, AMPKα2, mTOR, Tyk2, and STAT3 located in the spinal cord and DRG.

Mechanism of oxymatrine in treatment of collagen-induced arthritis in mice / 中国中药杂志

Sophorae Flavescentis Radix, the root of Sophora flavescens Ait., has been widely applied in the medical field due to its anti-inflammatory, analgesic, bacteriostatic, antiviral, antitumor, and other pharmacological effects. The present study investigated the anti-rheumatoid arthritis effect of oxymatrine(OMT), the active component of Sophorae Flavescentis Radix by observing its effect on the function of B lymphocytes in collagen-induced arthritis(CIA) mice through the Toll-like receptor 9(TLR9)/myeloid differentiation factor 88(MyD88)/signal transducer and activator of transcription 3(STAT3) pathway. The CIA model in DBA/1 J mice was induced by bovine type Ⅱ collagen and complete Freund's adjuvant(CFA). Fifteen days after the primary immunization, mice were treated with OMT for 30 days by intraperitoneal injection. Paw swelling and arthritis index(AI) score were evaluated every 3 days. Joint histopathologic changes were observed by HE staining. Magnetic-activated cell sorting(MACS) was used to isolate B lymphocytes from the spleen of CIA mice spleen. The serum expression level of interleukin(IL)-21 was examined by the enzyme-linked immunosorbent assay(ELISA). The expression of TLR9, STAT3, p-STAT3, and IL-21 in B lymphocytes was detected by Western blot. The mRNA expression of TLR9, STAT3, and IL-21 in B lymphocytes was detected by real-time fluorescence-based quantitative PCR(qRT-PCR). The results showed that OMT could significantly alleviate the paw swelling, decrease the AI score, relieve synovial inflammatory cell infiltration and hyperplasia, reduce the level of inflammatory cytokines, and inhibit the expression of TLR9, STAT3, p-STAT3, and IL-21 of B lymphocytes in CIA mice. Therefore, OMT may alleviate rheumatoid arthritis by regulating TLR9/MyD88/STAT3 pathway in B lymphocytes, providing a valuable reference for the application of OMT in the clinical treatment of rheumatoid arthritis.

Role of cardiac magnetic resonance imaging in myocarditis patients with biopsy negative: a retrospective case series study / 中华心血管病杂志

Objective: To analyze the cardiac magnetic resonance (CMR) imaging feature of clinically diagnosed myocarditis patients with negative endocardial biopsy (EMB) results, and to further demonstrate the diagnostic value of CMR in these patients. Methods: This was a retrospective case series study. Fourteen patients, who were clinically diagnosed as myocarditis according to 2013 European Society of Cardiology (ESC) clinical diagnostic criteria for myocarditis, but with negative EMB results, were enrolled. All patients underwent CMR examinations. The morphological, functional and histological changes of the heart were assessed based on black blood sequence, cine sequence, T2W-STIR sequence and contrast agent late gadolinium enhancement,(LGE). Results: There were 10 males and 4 females in this cohort, the age was (25.6±13.2) years. The interval between symptom onset and CMR was 21 (13, 60) days, and the interval between symptom onset and EMB was 19 (9, 40) days. There were 13 patients with abnormal CMR results including myocardial oedema, fibrosis, decreased ejection fraction, pericardial effusion or increased cardiac chamber dimension. Nine out of 14 patients had CMR morphological and/or functional abnormalities, including 1 case of left atrium enlargement, 1 case of left ventricle enlargement, 3 cases of right ventricle enlargement, 4 cases of increased left ventricular end diastolic volume index. Left ventricular ejection fraction was<50% in three cases, right ventricular ejection fraction was<40% in 5 cases, and pericardial effusion depth>3 mm was detected in 3 cases. Of the 14 patients, 11 had histological changes, of which 6 had T2 ratio≥2. Among the 10 patients (10/14) with positive LGE, the most common patterns were subepicardial LGE of the lateral wall and/or midwall LGE of the septum (n=9); 2 cases showed extensively subendocardial LGE of the left ventricular wall. No LGE involved in the right ventricular wall in the whole cohort. Conclusion: CMR plays a complementary role in the diagnosis of myocarditis in clinically diagnosed myocarditis patients with negative EMB findings.