Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective:To analyze the efficacy and safety of daratumumab plus dexamethasone in the treatment of renal injury patients with light chain amyloidosis, and to provide clinical reference.Methods:It was a single center retrospective observational study. The clinical data before and after daratumumab treatment of renal injury patients with light chain amyloidosis treated with daratumumab plus dexamethasone from December 2021 to August 2022 were retrospectively collected. The hematologic response, kidney response, prognosis, and adverse events were analyzed. The treatment regimen was 16 mg/kg intravenous infusion of daratumumab on day 1 + 20 mg intravenous push of dexamethasone on day 1-2, once every 2 weeks. The follow-up was up to February 28, 2023.Results:The study included 18 patients, with age of (58.4±7.7) years old, and a male to female ratio of 11∶7. Eleven patients were newly diagnosed and 7 patients were retreated. There were 7, 5, 5 and 1 patients, respectively at the stage Ⅰ, Ⅱ, Ⅲ and Ⅳ of light chain amyloidosis according to 2012 Mayo stage criteria. The median course of disease before onset was 2.5 (1.0, 8.0) months and the follow-up time was (8.7±2.8) months. The patients received (10±3) times of treatment. The overall hematologic response rates were 9/13, 11/13 and 13/13 at 1 month, 3 months, and 6 months respectively after treatment, meanwhile 8/13, 10/13 and 12/13 achieved at least very good partial response at 1 month, 3 months, and 6 months respectively (the other 5 patients did not undergo detailed evaluation due to baseline difference of serum free κ and λ light chain <20 mg/L). The median duration of hematologic response was 16 (13, 40) days. At 3 months, 6 months and the end of follow-up, 10, 13 and 13 of 18 patients respectively achieved renal response, and the median duration of response was 66 (26, 182) days. During follow-up, the median difference of serum free κ and λ light chain decreased by 93% (72%, 97%). Until the last follow-up, one patient died of organ hemorrhage. Other infusion reactions, leukopenia, neutropenia and infection all improved after symptomatic treatments.Conclusion:Daratumumab plus dexamethasone treatment is effective for light chain amyloidosis nephropathy in inducing hematologic remission and kidney remission, with good safety.

Tumor-associated macrophages(TAMs)are the predominant cell group in the tumor microenvironment(TME)and are the most important regulatory cells of immune system suppression and tumor cell proliferation in TIME.Src homology-2 domain-containing protein tyrosine phosphatase 2(SHP-2)is a non-receptor protein tyrosine phosphatase that plays an important role in the transmission of signals from the cell surface to the nucleus.SHP-2 is a key intracellular regulatory factor mediating cell proliferation and differentiation and is involved in a variety of growth factor and cytokine signaling pathways linking the cell surface to the nucleus.Recent studies have shown that SHP-2 is a key enzyme in determining the function of TAMs,but because of its variable function,it plays different or even opposite roles in different solid TMEs.This paper reviews the function of SHP-2 in TAMs and related solid tumors to provide a comprehensive reference for tumor immunity and targeted therapy research.

Objective To analyze the sensitivity of ARHGAP8 in predicting the efficacy of neoadjuvant chemotherapy in the patients with locally advanced mid-low colorectal cancer and provide accurate evidence for the treatment of advanced colorectal cancer.Methods The differentially expressed gene ARHGAP8 was screened out by bioinformatics analysis.Cancer tissue and rectal tissue of 68 patients with primary rectal cancer were select-ed.The rectal cancer tissue samples and the rectal tissue samples were collected for clinical validation of ARH-GAP8 expression by quantitative real-time PCR,Western blotting,and immunohistochemistry.The clinical and pathological features such as gender,age,tumor stage,differentiation degree,and pathological type of the pa-tients were collected for functional validation.Forty-four patients with locally advanced mid-low rectal cancer who received neoadjuvant chemotherapy were selected for immunohistochemical examination of ARHGAP8 expres-sion.The expression level of ARHGAP8 was compared between before and after chemotherapy and among different efficacy groups.Results The bioinformatics analysis revealed differences in the expression level of ARHGAP8 between the cancer tissue and rectal tissue(P＜0.001).The expression level of ARHGAP8 was correlated with tumor stage(P=0.024),lymph node metastasis(P=0.007),and age(P=0.005).Quantitative real-time PCR results showed that the mRNA level of ARHGAP8 in the cancer tissue was higher than that in the rectal tis-sue(P＜0.001).Western blotting and immunohistochemistry results demonstrated that the protein level of ARH-GAP8 in the cancer tissue was higher than that in the rectal tissue(P=0.011).The expression of ARHGAP8 was correlated with tumor size(P=0.010)and pathological stage(P=0.005),while it showed no significant association with tumor differentiation degree,lymph node metastasis,liver metastasis,Ki-67,or microsatellite instability expression level.The 44 patients receiving neoadjuvant chemotherapy included 13,8,8,and 15 pa-tients of tumor regression grades 0,1,2,and 3,respectively.Among them,65.91％(29/44)patients showed responses to the treatment.After neoadjuvant chemotherapy,the expression of ARHGAP8 in the cancer tissue was down-regulated in the patients who responded to the chemotherapy(P＜0.001).The response rate in the patients with low protein level of ARHGAP8 was 92.86％,which was higher than that(53.33％)in the patients with high pro-tein level of ARHGAP8(P=0.033).Conclusions ARHGAP8 is highly expressed in the rectal cancer tissue.The pa-tients with locally advanced mid-low rectal cancer and low ARHGAP8 expression are more sensitive to neoadjuvant chemotherapy with the XELOX protocol.ARHGAP8 can serve as a potential biomarker for the occurrence and develop-ment of rectal cancer and an important index for evaluating the efficacy of neoadjuvant chemotherapy with the XELOX protocol in the patients with locally advanced mid-low rectal cancer.

CD200 and its receptor CD200R constitute an endogenous inhibitory signal. The binding of CD200 and CD200R can regulate the immune response to pathogenic stimuli, which has received much attention in recent years. It has been found that CD200-CD200R is involved in the regulation of many kinds of pathological inflammation, including autoimmune diseases, cardiac cerebrovascular disease, infection and tumor. This paper reviews the protein structure, distribution, expression, biological function of CD200-CD200R and the correlation with diseases, and analyses the current status and development ideas of CD200-CD200R as drug targets. It aims to provide theoretical support for new drug research and development based on this target.

Objective To explore and compare the clinical efficacy of orthopedic robot assisted femoral neck system(FNS)and traditional manual FNS in the treatment of femoral neck fractures in middle-aged and young people.Methods The clinical data of 62 consecutive patients with femoral neck fracture and age less than 65 years old admitted to the Intelligent Or-thopaedic Department of Beijing Jishuitan Hospital from June 2021 to June 2022 were retrospectively analyzed.According to whether orthopedic robot-assisted surgery the patients were divided into two groups:30 patients aged 34 to 56 years old were treated with orthopedic robot assisted FNS internal fixation after closed or limited open reduction(experimental group);32 pa-tients aged 33 to 54 years old underwent FNS internal fixation after closed or limited open reduction(control group).The age,gender,time from injury to admission,average hospital stay,surgical duration,intraoperative bleeding volume,and intraopera-tive fluoroscopy frequency of two groups of patients were analyzed and compared.The hip joint function in both groups of pa-tients was evaluated using the Harris hip joint scoring standard at 6 months after surgery.Results All 62 patients with femoral neck fractures successfully completed the surgery.There was no significant difference(P＞0.05)between the experimental group and the control group in terms of baseline data such as age,gender,time from injury to admission,time from admission to surgery and the intraoperative bleeding.The surgical duration of the experimental group was significantly shorter than that of the control group[42.1(28.5,50.7)min vs.53.4(36.9,62.5)min,Z=-2.338,P=0.019].The intraoperative X-ray fluoroscopy frequency of the experimental group was significantly lower than that of the control group[8.0(6.0,11.0)times vs.15.0(13.0,17.0)times,Z=-5.960,P＜0.001].In terms of postoperative hip joint function,there was no significant difference in Harris score between the two groups of patients at 6-month follow-up(P＞0.05).Conclusion Compared with manual operation of FNS,orthopedic robot assisted FNS in the treatment of femoral neck fractures can help shorten surgical time,reduce intraop-erative fluoroscopy frequency,and have similar therapeutic effects on long-term hip joint function recovery.

Objective To study the relationship between the changes of sagittal spinopelvic parameters and facet joint-derived low back pain in patients with hip osteoarthritis after hip arthroplasty.Methods The clinical data of 30 patients with facet joint-derived low back pain induced by hip osteoarthritis who underwent unilateral hip arthroplasty(observation group)from June 2019 to November 2020 in our hospital were retrospectively analyzed,and 50 healthy subjects who underwent lumbar X-ray examination in the physical examination center of our hospital at the same time were randomly selected as the control group.The sagittal spinopelvic parameters were measured based on the X-ray,including pelvic incidence(PI),pelvic tilt(PT),sacral slope(SS),lumbar lordosis(LL),sacrum pubic incidence(SPI)and sacrum pubic posterior angle(SPPA).The correlation between the changes of sagittal spinopelvic parameters and facet joint-derived low back pain was analyzed by multiple linear regression,and its diagnostic efficacy to facet joint-derived low back pain was analyzed by receiver operating characteristic(ROC)curve.Results The PI,LL,SPI or SPA before and 1 year after surgery of the observation group had no significant difference combined with those of the control group(P>0.05).The PT before surgery of the observation group was smaller than that of the control group(P<0.05),and the SS before surgery was larger than that of the control group(P<0.05).Multiple linear regression analysis showed that PT and SS before surgery were correlated with facet joint-derived low back pain(P<0.05).The sensitivity of PT and SS before surgery in diagnosing facet joint-derived low back pain were 50.00%and 73.30%,with the specificity of 88.00%and 78.00%,respectively.ROC curve analysis showed that the area under the curve of PT and SS before surgery in diagnosing facet joint-derived low back pain were 0.708(95%CI:0.595 to 0.822)and 0.775(95%CI:0.673 to 0.877),respectively.Conclusion Patients with hip osteoarthritis pain have significantly larger SS and significantly smaller PT.Hip arthroplasty can alleviate the symptoms of low back pain without affecting the sagittal spinopelvic balance;the PT and SS before surgery are correlated with the facet joint-derived low back pain,and they are of high value in the diagnosing facet joint-derived low back pain.

The distribution of Ixodes and Ana plasma carried by Ixodes ticks in Anhui Province was clarified as reference for prevention and control of anaplasmosis.In total,630 hard ticks were collected from Jinzhai County,Hanshan County,Jing-de County and Chaohu City in Anhui Province from April to August 2023.Ticks were identified by morphological analysis and 16S rRNA sequencing.Nested PCR with Anaplasma species-specific primers were used to detect 16S rRNA of Anaplasma spe-cies carried by ticks.A phylogenetic tree was constructed using MEGA11.0 software.Of the identified ticks,18.8％(18/96)were Rhipicephalus microplus and 81.2％(78/96)were Haemaphysalis longicorni in Jinzhai County of Anhui Province,all were H.longicorni in Hanshan County and Chaohu City,while the main species in Jingde County was R.microplus.The posi-tive rate of Anaplasma carried by H.longicornis was 30.9％(102/330),which included A.bovis at 1.8％(6/330),A.phagocytophilum at 21.8％(72/330)and uncultured Anaplasma species at 7.3％(24/330).R.microplus was positively cor-related to A.bovis(13.6％,18/132).The uncultured Anaplasma species was mainly detected in host-free ticks.A.phagocy-tophilum was detected in 24.4％of parasitic ticks and 15.8％of host-free ticks.The positive rates of host-free and parasitic ticks were 19.9％and 17.8％,respectively.These results show that H.longicornis and R.microplus were the dominant ticks in several counties of Anhui Province.H.longicornis and R.microplus as well as free and parasitic ticks all carried Anaplas-ma.

Genicular nerve block is usually used for the treatment of chronic pain of knee osteoar-thritis,which can effectively relieve knee pain and preservemotor function.With the rapid development of ultrasound technology,ultrasound-guided genicular nerve block can improve the accuracy of nerve block and reduce block-related complications.This article reviews the research progress of ultrasound-guided genicular nerve block in three aspects:anatomy,operation methods and clinical application.