Objective To evaluate the efficacy and safety of hydroxychloroquine sulfate (HCQ) on pregnancy outcomes in patients with systemic lupus erythematosus (SLE). Methods One hundred and sixty-six pregnant patients with SLE from Janurary 2010 to December 2015 were studied retrospectively . Fifty-two patients were excluded due to new-onset during pregnancy, active disease or termination of pregnancy as a result of continuous intaking of immunosuppressant. The remaining 114 SLE patients in stable condition before pregnancy were divided into the following two groups: prednisone combined with HCQ and prednisone alone. The effects of HCQ on disease activity and pregnancy outcome were analyzed. Differences between groups were analyzed by chi-square test. Results A total of 90 patients (78.9%) had successful pregnancy. Among 71 patients treated with prednisone combined with HCQ, 60 patients (84.5%) had no disease flare and 62 cases (87.3%) had successful pregnancy. Among 43 patients treated with prednisone alone, 28 patients (65.1%) had no disease flare and 28 cases (65.1%) had successful pregnancy. No abnormality of neither visual field nor fundus was observed among patients treated with HCQ. No congenital abnormalities were found among new born infants. Conclusion HCQ intake during pregnancy in SLE patients can reduce disease flare and improve the pregnancy outcome, indicating that HCQ is safe for SLE patients during pregnancy.

Objective To observe the effect of intermedin (IMD) preconditioning on cyclin D1, cyclin E and CDKs expression, and explore its role in.promoting kidney tissue regeneration after renal ischemiareperfusion injury. Methods One hundred and forty-four healthy male Wistar rats were randomly divided into four groups: sham operation (S) group, ischemia-reperfusion injury (IR) group, empty plasmid (EP) group and IMD group. In the IR group, after the right kidney was excised, the aorta abdominalis and left renal artery were bluntly dissected in EP and IMD group, empty plasmid and IMD plasmid were transfected into the left kidney using ultrasound-micro-bubble (SonoVue) mediated system, respectively. One week later, renal IRI model was made by clasping the left renal artery for 45 min. After 1, 2, 3, 4, 7 and 14 day of reperfusion, the kidney in each group was collected to detect the expression of cyclin D1, cyclin E, CDK4 and CDK2 by western blot analysis or enzyme-linked immunosorbent assay (ELISA). Results Compared with S group, the expression of cyclin D1, cyclin E, CDK4 and CDK2 was significantly up-regulated in day 1, 2,3, 4, 7 and 14 in IR group. And the above index increased gradually after reperfusion, and reached the peak at day 7 (F=54.92, 69.60, 61.28, 77.38, P＜0.05). While in IMD group, these indexes reached the peak at day 1, then progressively declined, and could not be detected at day 14 (compared with the IR group, F=54.92, 69.60, 61.28, 77.38, P＜0.05). Conclusion IMD preconditioning can up-regulate the expression of cyclin D1, cyclin E, CDK2 and CDK4 in the early phase of renal ischemia-reperfusion injury that may accelerate repair of renal tissue, at least by part, by enhancinge cell proliferation.

Objective To establish the animal model of comorbidity of knee osteoarthritis(KOA)and hypertension with pattern of liver and kidney deficiency and evaluate its characteristics of comorbidity and pattern.Methods Wistar-Kyoto(WKY)rats and spontaneously hypertensive rats(SHR)were assigned to the WKY control group(control group),hypertension combined with KOA sham-operation group(sham-operation group),hypertension combined with KOA group(model group),hypertension combined with KOA and liver-kidney deficiency pattern group(LKD group).The animal model of KOA combined with hypertension was prepared by anterior cruciate ligament transection(ACLT)in spontaneously hypertensive rats.ACLT combined with intramuscular injection of hydrocortisone was performed to prepare an animal model of KOA with liver-kidney deficiency(LKD)pattern type,combined with hypertension.Then,the related indexes of LKD syndrome were detected in turn,including the contents of thyroid stimulating hormone(TSH),testosterone(T),corticosterone(CORT),adrenocorticotropic hormone(ACTH)in serum,and enzyme activities of alanine transaminase(ALT),aspartate transaminase(AST),and alkaline phosphatase(ALP)in serum,the mass ratio of liver,kidney,spleen,thymus to the brain,body weight,anal temperature,activity situation,and emotion.Systolic blood pressure,diastolic blood pressure,and other blood pressure-related indices were also detected.The levels of serum tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β),plantar mechanical pain sensitivity threshold,weight difference score of both hind limbs,hind limb joint swelling,and quadruped gait parameters were also measured.Furthermore,hematoxylin-eosin,safranine-fast green,and Masson staining were performed to observe pathological changes,cartilage degeneration,and bone destruction of the knee joint,and the microstructure parameters of the tibia were detected by Micro-CT imaging.Results Compared to the model group,the contents of serum TSH,ACTH,T,CORT and the mass ratio of the kidney,spleen,and thymus to the brain in the LKD group decreased(P<0.05).Compared to the control group,the systolic blood pressure and diastolic blood pressure of the other three groups increased significantly(P<0.05).Compared to the sham-operation group,serum TNF-α and IL-1β levels increased,plantar mechanical pain threshold decreased,weight difference score of both hind limbs and joint swelling of the affected limb increased(P<0.05),and gait parameters(e.g.,gait length and standing time of the affected limbs)became abnormal in the model and LKD groups.Simultaneously,the cartilage surface defect of the rat knee joint was severe,the arrangement of the surface chondrocytes was altered,the cartilage layer became thinner,the muscle fibers increased,and the cartilage ossification was severe.Furthermore,the relative volume,thickness,and number of trabeculae of the knee joint decreased significantly(P<0.05).Conclusion The rat model established in this study is consistent with the clinical characteristics of integrated traditional Chinese and Western medicine in patients with comorbidities of hypertension and KOA with liver and kidney deficiency pattern.This rat model can characterize the typical symptoms of liver and kidney deficiency pattern.It has typical pathological changes in knee cartilage and subchondral bone tissues and can maintain a stable range of high systolic and diastolic blood pressure.It also explore the scientific connotation of simultaneous treatment of different diseases in traditional Chinese medicine,revealing the therapeutic mechanism and developing new drugs.

Objective: To investigate the effects and underlying mechanisms of aspirin on endoplasmic reticulum stress in podocytes induced by hyperlipemia. Methods: Cultured podocytes were divided into four groups: control group, aspirin (100 μg/ml) group, oxidized low density lipoprotein (ox-LDL, 100 μg/ml) group, aspirin+ox-LDL group. The expression of protein kinase R-1ike endoplasmic reticulum kinase (PERK), eukaryotic translation initiation factor 2α (eIF2α), activating transcription factor-4 (ATF4) and CAAT/enhancer binding protein homologous protein (CHOP) at 6 h, 12 h, 24 h, 48 h were evaluated by real-time PCR. The related proteins of p-PERK and p-eIF2α at 24 h and ATF4 at 12 h were evaluated by Western blotting, respectively. Results: The expressions of PERK, eIF2α peaked at 24 h, while ATF4 and CHOP peaked at 12 h in ox-LDL group and aspirin+ox-LDL group. Compared with control group, the expressions of PERK, eIF2α, ATF4 and CHOP were significantly higher in ox-LDL group at each times (all P<0.05). Compared with ox-LDL group, the expressions of the above indicators were significantly lower in aspirin+ox-LDL group at each times (all P<0.05). At 24 h, compared with control group, the expressions of p-PERK and p-eIF2α were significantly higher in ox-LDL group (both P<0.05). Compared with ox-LDL group, the expressions of p-PERK and p-eIF2α were significantly lower in aspirin+ox-LDL group (both P<0.05). At 12 h, the expression of ATF4 protein in each group was similar to that of mRNA. There were no significant difference in the expressions of all indicators between aspirin group and control group. Conclusions Hyperlipidemia may cause endoplasmic reticulum stress in podocytes by inducing phosphorylation of PERK and eIF2α, activating ATF4 transcription and inducing high expression of CHOP. Aspirin may partially block the PERK pathway, which may have protective effects for podocytes.

ObjectiveTo identify the pharmacodynamic material basis of Ruyi Zhenbaowan in relieving neuropathic pain by integrating the calculation of biological network proximity and pharmacokinetic characterization. MethodThe interaction network of "drug candidate target-related gene of disease" was constructed by Cytoscape 3.8.2， and the average shortest path value of each drug putative target acting on neuropathic pain-related genes in this network was calculated by Pesca 3.8.0 tool so as to evaluate the network proximity between them， and screen prescription candidate targets with strong intervention efficiency and their corresponding potential effect components. After that， plasma and cerebrospinal fluid samples were collected from rats after administration of Ruyi Zhenbaowan at set time points， and the contents of potential effect components in samples was quantified by ultra performance liquid chromatography-quadrupole-ion trap mass spectrometry（UPLC-Q-TRAP/MS）， and drug concentration-time curves were plotted， then the pharmacokinetic parameters were calculated by DAS 2.1.1. ResultBy evaluating the network proximity between candidate targets and neuropathic pain-related genes in the interaction network， a total of 40 putative targets of Ruyi Zhenbaowan with strong intervention effects on neuropathic pain-related genes， such as estrogen receptor 1（ESR1）， cyclic adenosine monophosphate（cAMP）-dependent protein kinase catalytic subunit alpha（PRKACA） and protein kinase B1 （Akt1）， and 10 corresponding potential effect components， such as glycyrrhizic acid and betulinic acid， were obtained. Pharmacokinetic characterization showed that among the 10 potential effect components， gallic acid， apigenin-7-O-glucuronide， glycyrrhizic acid and apigenin were well absorbed and metabolized in plasma and cerebrospinal fluid， with long onset time and good bioavailability. ConclusionFrom the perspective of efficacy-target-constituent-pharmacokinetic， this study analyzes the main effective materials of Ruyi Zhenbaowan， such as glycyrrhizic acid， gallic acid， apigenin-7-O-glucuronide and apigenin， which have a high exposure in plasma or cerebrospinal fluid and have a strong intervention effect on neuropathic pain. The related results provide reliable experimental evidences for clarifying the material basis and developing quality standards of Ruyi Zhenbaowan.

ObjectiveTo systematically and objectively characterize the pharmacological effects of Fufang Biejia Ruangan pills （FBRP） in the intervention of alcoholic liver disease （ALD） using acute and chronic ALD mouse models and to elucidate its molecular mechanisms. MethodFifty SPF-grade male BALB/c mice were randomly divided into the normal group， model group， and FBRP low-， medium-， and high-dose groups （9.6， 19.2， 38.4 mg·kg^-1）. Except for the normal group， the remaining groups were given 56° white wine by gavage to establish the acute ALD model， with samples collected after 4 weeks. Thirty SPF-grade male C57BL/6N mice were randomly divided into the normal group， model group， and FBRP medium-dose group （19.2 mg·kg^-1）. The chronic ALD mouse model was established using the Lieber-DeCarli method over a 10-week period. Inflammatory markers in liver tissues were assessed using hematoxylin-eosin （HE）， Sirius Red， oil red O staining， and enzyme-linked immunosorbent assay （ELISA）. Intoxication behaviors of each group were objectively evaluated through sobering-up time， net-catching， and pole-climbing tests. Further bioinformatics analyses based on clinical transcriptomic data were conducted to identify key targets and molecular mechanisms of FBRP in alleviating ALD through liver-brain dialogue， with experimental validation by ELISA， Western blot， and immunohistochemical staining. ResultCompared with the normal group, the levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） in liver tissues of mice in the acute and chronic ALD model groups were significantly increased （P<0.05）. Compared with the model group， the levels of AST and ALT in liver tissue of mice in FBRP groups were significantly decreased （P<0.05）. Compared with the normal group， the time of grasping the net and climbing the pole in the acute ALD model group was significantly decreased within 4 weeks （P<0.01）. Compared with the model group， the grasping and climbing time of FBRP high dose groups increased significantly within 4 weeks （P<0.05）. Compared with the normal group， the expression of high mobility group protein B1 （HMGB1） protein in liver tissue and prefrontal lobe tissue of mice in the chronic ALD model group was significantly increased （P<0.01）. Compared with the model group， the expression of HMGB1 protein in FBRP medium dose group was significantly decreased （P<0.05，P<0.01）. Compared with the normal group， the expression of brain-derived neurotrophic factor （BDNF） protein and the release of γ-aminobutyric acid （GABA） in the prefrontal cortex of the model group were significantly decreased （P<0.01）. Compared with the model group, the expression of BDNF protein and the release of GABA in the FBRP medium dose group were significantly increased （P<0.05）. ConclusionThis study revealed that FBRP improved key pathological changes in ALD by modulating liver-brain dialogue mediated by the HMGB1-BDNF axis. These findings provide experimental evidence for the clinical use of FBRP in treating ALD and offer new insights for the development of ALD therapeutic agents.