Objective The aim of this study was to evaluate the efficacy and side effects of sacubitril/valsartan in the treatment of patients with chronic kidney disease(CKD)at stage 5 with resistant hypertension,and to explore the cardiovascular benefits and security of medical in the patients.Methods Patients with CKD5 resistant hypertension diagnosed and treated in the First Affiliated Hospital of Guangxi Medical University from September 2020 to March 2022 were selected and divided into the observation group(treated with routine treatment of kidney disease at end-stage and sacubitril/valsartan)and control group(include droutine treatment of renal disease at end-stage and ACEI or ARB drugs)according to treatment strategy.The patients in both two groups were treated with adequate dialysis treatment and conventional drug treatment of renal disease at end-stage.The patients were followed up for at least 3 months,the clinical efficacy of three months after treated with sacubitril/valsartan was observed,and the efficacy indicators and security indicators and adverse cardiovascular events were observed,the occurrence of adverse effects during the period of drug use were compared with the control group.Results A total of 110 patients were included in this study and there were 55 cases in each group.There were no significant differences in gender,age,age of dialysis,etiology,dialysis mode and blood pressure between the two groups(P>0.05).The Systolic blood pressure(SBP),diastolic blood pressure(DBP),b-type urinary natriuretic peptide precursor(Pro-BNP)and cardiac function grade in the observation group after treatment was significantly decreased compared with before treatment.The left ventricular ejection fraction(LVEF)and the ratio of LVEF<50%in the observation group was significantly reduced after treatment(P<0.05).SBP,DBP and Pro-BNP decreased 3 months after treatment compared with the baseline before treatment,and improved significantly in the first month after treatment(P<0.05).The decrease of DBP and BNP before and after treatment was significantly different between the two groups,and the decrease of DBP and BNP was more significant in the observation group(P<0.05).The difference of LVEF and left ventricular end diastolic diameter(LVEDD)between the two groups before and after treatment was statistically significant,and the improvement was more obvious in the observation group(P<0.05).There were no significant differences in the safety indicators of serum potassium,estimated glomerular filtration rate(eGFR)and liver function between two groups before and after treatment(P>0.05).In terms of adverse reactions,only 1 case in the control group developed hyperkalemia within 3 months of follow-up,and no hypotension or other adverse reactions occurred in the two groups.Conclusions The treatment of patients with CKD stage 5 hypertension with sacubitril/valsartan has obvious cardiovascular benefits.Sacubitril/Valsartan has efficacy in lowering blood pressure,improving cardiac function and reducing volume load,with less adverse events and higher safety than control group.

BACKGROUND:Currently,there have been a variety of conservative and surgical treatment plans for spontaneous osteonecrosis of the knee,achieving excellent results.However,a broad consensus on indication and guide of surgical treatment has not been announced.In clinical practice,there is still a misunderstanding that unicondylar replacement or total knee arthroplasty should be performed upon the discovery of spontaneous osteonecrosis of the knee,while an urgent need for universal access to the concept of stepwise therapy. OBJECTIVE:To summarize and find the factors leading to the poor effect of conservative treatment in spontaneous osteonecrosis of the knee,which occurred on the medial femoral condyle,from the literature and clinical cases,at the same time,combined with the Koshino stage,to propose the strategy of stepwise spontaneous osteonecrosis of the knee treatment on the medial femoral condyle. METHODS:A systematic search of the literature database was conducted to summarize the factors leading to poor outcomes of conservative treatment in spontaneous osteonecrosis of the medial femoral condyle.Meanwhile,according to the Clinical&Health Records for analytics&Sharing system,the cases receiving conservative and surgical treatment in spontaneous osteonecrosis of the medial femoral condyle in the Department of Orthopedics of Guangdong Provincial Hospital of Chinese Medicine from January 2017 to January 2023 were analyzed retrospectively,then the causes of success and failure in typical cases were summarized and analyzed. RESULTS AND CONCLUSION:(1)Early diagnosis and treatment of spontaneous osteonecrosis of the knee were very important for prognosis.For sudden knee pain in some patients,if no obvious abnormality was found in the X-ray examination,and the symptoms persisted and could not be relieved for more than 1 week,an MRI examination was recommended to detect early spontaneous osteonecrosis of the knee.(2)The X-ray images of Koshino stage 1 and stage 2 of spontaneous osteonecrosis of the medial femoral condyle were difficult to be distinguished,which needed to be probed by MRI.MRI images of Koshino stage 1 were mainly characterized by bone marrow edema,and an osteonecrosis area with a clear boundary was not formed,while MR images of Koshino stage 2 showed a necrotic area with a clear boundary.(3)Five factors leading to the poor effect of conservative treatment on spontaneous osteonecrosis of the medial femoral condyle were summarized:a.The necrotic area was＞5 cm2;b.The necrotic area accounted for more than 40%of the condyle;c.relative compression percentage of medial meniscus≥33%(with or without medial meniscus injury and subchondral bone marrow edema);d.MRI depth of necrotic area(anterior-posterior diameter of sagittal necrotic area)＞20 mm;e.varus deformity of lower limb＞6°.(4)Conservative treatment of spontaneous osteonecrosis of the knee in Koshino stage 1 was good.For spontaneous osteonecrosis of the knee in Koshino stage 2,conservative treatment was preferred or combined with drilling decompression.If there was no relief or improvement of symptoms or in MRI after 3 months,while the patient had any of the previous five factors,then knee preservation surgery should be considered.For spontaneous osteonecrosis of the knee in Koshino stage 3 and stage 4,knee preservation surgery should be selected based on the previous five factors,including age,gender and activity level of the patient.Total knee arthroplasty was used for spontaneous osteonecrosis in Koshino stage 4,which was associated with symptomatic patellofemoral arthritis,valgus alignment,or necrotic area,which greatly affected the stability of unicondyle prosthesis.

The extremely low bioavailability of oral paclitaxel (PTX) mainly due to the complicated gastrointestinal environment, the obstruction of intestinal mucus layer and epithelium barrier. Thus, it is of great significance to construct a coordinative delivery system which can overcome multiple intestinal physicochemical obstacles simultaneously. In this work, a high-density PEGylation-based glycocholic acid-decorated micelles (PTX@GNPs) was constructed by a novel polymer, 9-Fluorenylmethoxycarbonyl-polyethylene glycocholic acid (Fmoc-PEG-GCA). The Fmoc motif in this polymer could encapsulate PTX via π‒π stacking to form the core of micelles, and the low molecular weight and non-long hydrophobic chain of Fmoc ensures the high-density of PEG. Based on this versatile and flexible carriers, PTX@GNPs possess mucus trapping escape ability due to the flexible PEG, and excellent intestine epithelium targeting attributed to the high affinity of GCA with apical sodium-dependent bile acid transporter. The in vitro and in vivo results showed that this oral micelle could enhance oral bioavailability of PTX, and exhibited similar antitumor efficacy to Taxol injection via intravenous route. In addition, oral PTX@GNPs administered with lower dosage within shorter interval could increase in vivo retention time of PTX, which supposed to remodel immune microenvironment and enhance oral chemotherapy efficacy by synergistic effect.

Objective To observe the consistency of the effect directions of electroacupuncture(EA)at the"Ciliao"(BL32)and EA on the auricular concha(AC)in regulating intragastric pressure(IGP)and heart rate variability(HRV),and to observe whether the combined EA of"Ciliao"(BL32)and AC has a synergistic effect.Methods SD male rats were divided into EA-AC group,EA-BL32 group and EA-"AC+BL32"group,with 8 rats in each group.And the IGP and HRV were measured before and during EA(30 Hz,2 mA,pluse width 0.2 ms±30%,continuous wave)for 2 min in each group.Results ①Changes in IGP compared with before EA:the IGP in EA-AC group significantly increased especially during the 30th to 60th(P<0.05)and 60th to 90th second of EA(P<0.05);The IGP in EA-BL32 group significantly increased especially during the 60th to 90th second of EA(P<0.05);The IGP in EA-"AC+BL32"group significantly increased especially during the 60th to 90th(P<0.01)and 90th to 120th second of EA(P<0.05).The change rate of IGP of EA-"AC+BL32"group was significantly higher than that of the EA-AC group especially during the 60th to 90th(P<0.01)and 90th to 120th second of EA(P<0.01),and EA-BL32 group especially during the 60th to 90th(P<0.05)and 90th to 120th second of EA(P<0.05).②Changes in HRV compared with before EA:the high frequency(HF)significantly increased(P<0.01,P<0.05,P<0.01,P<0.05),low frequency(LF)significantly increased(P<0.01,P<0.01,P<0.05,P<0.05),and very low frequency(VLF)significantly increased(P<0.05,P<0.05,P<0.05,P<0.05)throughout the EA in EA-AC group;The HF significantly increased(P<0.05,P<0.05,P<0.05,P<0.05),LF significantly increased(P<0.05,P<0.05,P<0.05,P<0.05),and VLF significantly increased(P<0.05,P<0.05,P<0.05,P<0.05)throughout the EA in EA-BL32 group;The HF significantly increased(P<0.05,P<0.05,P<0.05,P<0.05),LF significantly increased(P<0.001,P<0.05,P<0.01,P<0.01),and VLF significantly increased(P<0.05,P<0.01,P<0.05,P<0.05)throughout the EA in EA-"AC+BL32"group.The LF/HF in EA-AC group significantly decreased especially during the 0 to 30th(P<0.01),30th to 60th(P<0.05)and 60th to 90th second of EA(P<0.05);The LF/HF in EA-BL32 group significantly decreased especially during the 0 to 30th second of EA(P<0.05);The LF/HF in EA-"AC+BL32"group significantly decreased especially during the 30th to 60th(P<0.05),60th to 90th(P<0.01)and 90th to 120th second of EA(P<0.01).The change rate of LF/HF of EA-"AC+BL32"group was significantly lower than that of the EA-AC group especially during the 90th to 120th second of EA(P<0.05),and EA-BL32 group especially during the 60th to 90th(P<0.05)and 90th to 120th second of EA(P<0.05).Conclusion The effect direction of EA at"Ciliao"(BL32)and EA on the AC in regulating the vagus nerve is basically the same,and the combined EA of"Ciliao"(BL32)and AC can produce a synergistic effect.

Objective:To explore the relationship between low serum albumin levels and its duration on first episode of peritonitis in peritoneal dialysis (PD) patients.Methods:PD patients who were regularly followed up in the Pearl River Delta region from September 1, 2000 to July 6, 2021 in Shunde Hospital of Southern Medical University, Nanfang Hospital of Southern Medical University, and Foshan First People′s Hospital were retrospectively selected. The patients were divided into low serum albumin group (LSA group, mean albumin<35 g/L), moderate serum albumin group (MSA group, 35 g/L≤mean albumin<40 g/L) and high serum albumin group (HSA group, mean albumin≥40 g/L) according to the mean albumin of the patients, and the differences among the three groups were compared. The Kaplan-Meier survival analysis method was used to compare the risk of peritonitis events in different mean albumin groups and different durations of hypoalbuminemia. The multivariate Cox regression model was used to analyze the relationship between serum albumin levels and duration of hypoalbuminemia and new-onset peritonitis.Results:A total of 1 853 PD patients were included in this study, aged (49.72±15.34) years, and 1 036(55.9%) males. There were 551 patients (29.7%) in the LSA group, 920 patients (49.7%) in the MSA group, and 382 patients (20.6%) in the HSA group. The median follow-up was 37 (15, 66) months and there were 508 patients (27.4%) with new-onset peritonitis during the follow-up. Compared with the LSA group, the incidence of new peritonitis in the MSA group and HSA group was lower ( χ2=14.053, P<0.001; χ2=21.857, P<0.001), but there was no significant difference in the incidence of new peritonitis between the HSA group and MSA group. The Kaplan-Meier survival analysis showed that the cumulative incidence of peritonitis in the LSA group was significantly higher than that in the MSA group and HSA group (Log-rank χ2=22.128, P<0.001). Compared with PD patients with normal serum albumin, the patients with longer duration of hypoalbuminemia tended to have a higher incidence of new peritonitis. Multivariate Cox regression analysis showed that the mean albumin<35 g/L (LSA group/MSA group, HR=1.495, 95% CI 1.198-1.866, P<0.001; LSA group/HSA group, HR=1.459, 95% CI 1.104-1.928, P=0.008) was an independent risk factor of new-onset peritonitis in PD patients and the prolongation of duration of hypoalbuminemia had a significantly higher risk of new-onset peritonitis ( HR=1.013, 95% CI 1.003-1.024, P=0.014). Conclusion:The mean albumin<35 g/L and prolong duration of hypoalbuminemia are independent risk factors of PD-related peritonitis in PD patients.

Objective:To establish a method of measuring the contents of gallic acid, brevifolin, corilagin, geraniin, ellagic acid and rutin in Phyllanthus urinaria L. simultaneously with fingerprint study for analysis. Methods:Phyllanthus urinaria L. was extracted by ultrasound with 50% methanol. Chromatographic separation was performed on a Phenonmenex Luna C18 (4.6 mm×250 mm, 5 μm). The mobile phase consisted of acetonitrile (A) and 0.1% phosphoric acid aqueous solution (B) with gradient elution. The flow rate was 1.0 ml/min. The column temperature was 25 ℃, and the injection volume was 10 μl. The detection wavelength was 270 nm. HPLC fingerprints of Phyllanthus urinaria L. from different habitats was established. PCA and OPLS-DA were used to analyze the differences in chemical components of different habitats. Results:Gallic acid, brevifolin, corilagin, geraniin, ellagic acid and rutin showed good linearity at 0.042 8-0.641 6, 0.033 4-0.501 4, 0.142 2-2.133 1, 0.383 1-5.746 5, 0.063 1-0.946 2 and 0.019 2-0.287 8 μg, respectively. The average recovery rate of them was 103.65%, 96.39%, 101.85%, 95.04%, 98.79% and 98.33%, respectively. The HPLC fingerprints of different habitats contained 14 characteristic common peaks, and six compounds characteristic peaks were identified. PCA analysis showed that the chemical components of Phyllanthus urinaria L. from different habitats were different. Geraniin, ellagic acid and corilagin were screened by OPLS-DA. Conclusions:The method is efficient, accurate and sensitive, which can be used to measure the six components in Phyllanthus urinaria L.. The established HPLC fingerprint of different habitats combined with the measrurement method of six components can be used for the quality control and evaluation of Phyllanthus urinaria L..

OBJECTIVE：To ex plore the protective effects of Longbie capsule contained serum （called“LBJN”for short ）on the apoptosis of chondrocytes induced by YAP inhibitor verteporfin and its mechanism. METHODS ：Primary human knee osteoarthritis（OA）chondrocytes were extracted by two-step enzymatic digestion ，and then identif ied by toluidine blue staining and type Ⅱ collagen immunofluorescence staining. The effects of 2，5 μmol/L verteporfin alone or combined with 5％LBJN on cell apoptosis were detected by flow cytometry. Solvent control （0.1％ DMSO）and 5％ LBJN were set. Western blot assay was adopted to detect the expression of apoptosis related proteins （YAP，Bcl-2，cleaved-caspase-3） after treated with 0.1％DMSO（solvent control ），2 μmol/L verteporfin，2 μmol/L verteporfin+5％LBJN 和 0（blank control ），2.5％ LBJN and 5％ LBJN for 48 h. The expression of autophagy related proteins （mTOR，Beclin-1，LC3A/B） after treated with 0 （blank control ），2.5％，5％ LBJN for 48 h were det ected by Western blot assay. RESULTS ：The isolated cells accorded with the characteristics of chondrocytes. Compared with 0.1％DMSO， the apoptosis rates of cells were increased significantly after treated with 2，5 μmol/L verteporfin（P＜0.05），and the effects of the two concentrations were similar （P＞0.05）. Compared with verteporfin alone ，2，5 μmol/L verteporfin combined with 5％LBJN could significantly decrease the apoptotic rate of cells （P＜0.05）. Compared with 0.1％DMSO，the protein expression of YAP and Bcl-2 were decreased significantly after treated with 2 μ mol/L verteporfin （P＜0.05）， while the protein expression of cleaved-caspase-3 were increased significantly （P＜0.05）. Compared with 2 μmol/L verteporfin，protein expression of YAP and Bcl-2 were increased significantly after treated with 2 μmol/L verteporfin+5％LBJN（P＜0.05），while the protein expression of cleaved-caspase-3 were decreased significantly （P＜0.05）. Compared with blank control ，the protein expression of YAP ，Bcl-2 and Beclin-1 were increased significantly after treated with 2.5％，5％LBJN（P＜0.05），while protein expression of cleaved-caspase- 3 and mTOR were decreased significantly （P＜0.05）. CONCLUSIONS ：LBJN can block the apoptosis of chondrocytes induced by YAP inhibitor verteporfin ，and its mechanism may be related to regulating the expression of apoptosis related proteins and enhancing autophagy of chondrocytes.

At present, the main treatment strategy for acute ischemic stroke is to recanalize the occluded blood vessels through drug or endovascular interventional therapy, and to save the ischemic penumbra is the key of the treatment, but due to the factors such as time window and indications, some patients cannot benefit from them. NeuroFlo technology can redistribute blood flow in body, increase intracranial blood supply, promote the establishment of collateral circulation around infarctions, effectively save ischemic penumbra, and ultimately improve the long-term prognosis of patients.

OBJECTIVE： To study the effects of ligustrazine on miR-20b/VEGF and BMP2/Smad1 pathways in subchondral bone of knee osteoarthritis （KOA） model rats， and to investigate the mechanism of ligustrazine for KOA prevention and treatment. METHODS： Totally 18 healthy male SD rats were randomly divided into normal control group， model group and ligustrazine group， with 6 rats in each group. The rats in the latter two groups were used to establish KOA model by intra-articular injection of 4％ papain solution. From the 2nd day after the last injection， ligustrazine group was given intragastrical administration of Ligustrazine suspension （100 mg/kg） 2 mL； normal control group and model group were given intragastrical administration of isometrical normal saline， once a day， for consecutive 6 weeks. After the last after medication， the situation of bilateral knee articular cartilage of rats were observed after exposure. The knee joints of rats were sectioned and stained with HE. The pathological change of articular cartilage were observed by microscope and scored by modified Mankin’s score. mRNA expression of VEGF， BMP2 and Smad1， and the expression of miR-20b were detected by RT-PCR； the protein expression of VEGF， BMP2 and Smad1 were detected by Western blot assay. RESULTS： Model group and ligustrazine group suffered from cartilage injury of knee joint at varying degrees. Compared with normal control group， Mankin’s scores of knee joint and cartilage tissue were increased significantly in model group （P＜0.01）； mRNA and protein expression of BMP and Smad1， the expression of miR-20b in subchondral bone of model group were decreased significantly， while mRNA and protein expression of VEGF were increased significantly （P＜0.01）. Compared with model group， Mankin’s score of cartilage tissue were decreased significantly in ligustrazine group （P＜0.01）； mRNA and protein expression of BMP and Smad1， the expression of miR-20b in subchondral bone were increased significantly， while mRNA and protein expression of VEGF were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： Ligustrazine can repair damaged articular cartilage in KOA model rats， the mechanism of which may be associated with inhibiting the protein expression of VEGF and activating BMP-2/Smad1 signaling pathway via up-regulating the expression of miR-20b， and promoting the degradation of VEGF mRNA in subchondral bone.

Objective: To observe ascitic interleukin-7 expression level in cirrhotic patients complicated with spontaneous bacterial peritonitis, and to detect the effect of recombinant human IL-7 on CD4⁺ and CD8⁺T lymphocyte function. Methods: A total of 84 patients with liver cirrhosis who were hospitalized from August 2017 to April 2018 were selected. Among them, 51 cases were complicated with cirrhosis and untainted ascites, and 33 cases were cirrhosis complicated with spontaneous bacterial peritonitis. Peripheral blood and ascites were collected routinely. The levels of IL-7 in peripheral blood and ascites were measured by enzyme-linked immunosorbent assay. CD4⁺T cells and CD8⁺T cells were purified from ascites, and were stimulated with recombinant IL-7. Cellular proliferation, key transcription factors for mRNA, and cytokines production by CD4⁺T cells in response to IL-7 stimulation was measured. mRNA expression corresponding to perforin, granzyme B, and granulysin as well as cytokines production by CD8⁺T cells was also measured in response to IL-7 stimulation. Cytolytic and non-cytolytic activity of CD8⁺T cells in response to IL-7 stimulation was also investigated in both direct and indirect contact co-culture system. Measurement data of the normal distribution were compared between the two groups by Student’s t-test and the data before and after stimulation were compared by paired t-test. Measurements that did not conform to normal distribution were compared between the two groups using Mann-Whitney U test, and data before and after stimulation were compared using Wilcoxon paired test. Results: There was no significant statistical difference in serum IL-7 levels between the two groups [(5 001 ± 1 458) pg/ml vs. (4 768 ± 1 128) pg/ml, P = 0.41]. The level of ascitic IL-7 in cirrhotic patients complicated with SBP was significantly lower than cirrhosis patients with untainted ascites [(966.4 + 155.8) pg/ml vs. (792.1 + 126.4) pg/ml, P < 0.01]. Recombinant IL-7 stimulation promoted the proliferation of CD4⁺ and CD8⁺T cells from ascites in patients with liver cirrhosis complicated by SBP. T-bet mRNA relative expression and IFN-γ secretion in CD4⁺T cells was also elevated in response to IL-7 stimulation in vitro. Moreover, IL-7 stimulation also increased the mRNA expressions of perforin, granzyme B, and granulysin as well as productions of IFN-γ and TNF-α by CD8⁺T cells. Recombinant IL-7 stimulation elevated cytolytic and non-cytolytic activity of CD8⁺T cells from ascites in patients with liver cirrohosis complicated by SBP, which manifested as increased target cell death and IFN-γ production in both direct and indirect contact co-culture system. Conclusion Ascitic IL-7 promotes T lymphocyte function in patients with liver cirrhosis complicated with SBP.