Objective To explore the impact of the sialic acid binding lectin-E(Siglec-E)on the inhibitory properties of parthenolide(PTL)against lipopolysaccharide(LPS)-induced M1 polarization of microglia(BV2).Methods ①Single cell sequencing data of Siglece related mouse brain tissue was obtained from Gene Expression Omnibus(GEO)database and divided into the WT group(n=3)and the Siglece-/-group(n=4).The microglia cells were screened,and the enrichment analysis was performed to analyze related differential genes and pathways.BV2 cells were constructed by the shRNA interference technique and were divided into NC-shRNA and Siglece-shRNA to detect the expression level of Siglec-E(Siglece).② NC-shRNA and Siglece-shRNA cells were respectively divided into the Control group,LPS group,PTL group and PTL+LPS group(n=3).The mRNA levels of markers of M1 polarization in microglia,iNOS,IL-1 β and IL-6,were detected by RT-qPCR.Siglecefl/fl and Cx3cr1cre mice were mated to obtain microglia-specific Siglece deletion(Siglecefl/fl×Cx3cr1cre)mice,and LPS-induced neuroinflammation model was established.③ Nine WT and Siglecefl/fl×Cx3cr1cre male mice were assigned to the Control group,LPS group and PTL+LPS group(n=3).RT-qPCR,immunofluorescence assay and Western blotting were used to verify the knock-out effect and polarization-related pathways,and to investigate the mechanism of Siglec-E affecting PTL inhibition of M1 polarization of microglia.Results Compared with the NC-shRNA group,the expression of Siglec-E in the Siglece-shRNA group was significantly decreased(P<0.01),indicating that the Siglec-E knock-down cell model was successfully established.With the stimulation of LPS,mRNA levels ofiNOS,IL-1 β and IL-6 were significantly up-regulated compared with the Control group both in shRNA cells and Siglece-shRNA cells(P<0.01).With the influence of PTL and LPS,the markers of M1 polarization in NC-shRNA cells mentioned before were significantly decreased(P<0.05),while for Siglice-shRNA cells,there were no significant changes in the markers of M1 polarization.PTL inhibited the phosphorylation of JNK and IκB protein(P<0.01)and the nuclear translocation of NF-κB in BV2 cells,down-regulated Siglec-E,and weakened the inhibitory effect.Compared with mice in the WT group,the expression of Siglec-E in microglia of Siglecefl/fl×Cx3cr1cre mice was decreased significantly(P<0.01),and the inhibitory effect of PTL on the phosphorylation of NF-κB in microglia of Siglecefl/fl×Cx3cr1cre mice was also decreased.Conclusion The absence of Siglec-E in microglia attenuates the inhibition of M1 polarization by the MAPK/NF-κB pathway targeted by PTL.

Recently,the substance P(SP)/neurokinin-1 receptor(NK-1R)system has been found to be involved in various human pathophysiological disorders including the symptoms of coronavirus disease 2019(COVID-19).Besides,studies in the oncological field have demonstrated an intricate correlation between the upregulation of NK-1R and the activation of SP/NK-1R system with the progression of multiple carcinoma types and poor clinical prognosis.These findings indicate that the modulation of SP/NK-1R system with NK-1R antagonists can be a potential broad-spectrum antitumor strategy.This review updates the latest potential and applications of NK-1R antagonists in the treatment of human diseases and cancers,as well as the underlying mechanisms.Furthermore,the strategies to improve the bioavailability and efficacy of NK-1R antagonist drugs are summarized,such as solid dispersion systems,nanonization,and nanoencapsulation.As a radiopharmaceutical therapeutic,the NK-1R antagonist aprepitant was originally developed as radioligand receptor to target NK-1R-overexpressing tumors.However,combining NK-1R antagonists with other drugs can produce a synergistic effect,thereby enhancing the therapeutic effect,alleviating the symptoms,and improving patients'quality of life in several diseases and cancers.

Background::Alterations in macular thickness and vascular density before clinically visible diabetic retinopathy (DR) remain inconclusive. This study aimed to determine whether retinal manifestations in abnormal glucose metabolism (AGM) patients differ from those in the healthy individuals.Methods::PubMed, Embase, and Web of Science were searched between 2000 and 2021. The eligibility criteria were AGM patients without DR. Primary and secondary outcomes measured by optical coherence tomography (OCT) and OCT angiography (OCTA) were analyzed and expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs). A random-effects model was used in the data synthesis. The potential publication bias for the variables was evaluated using Egger’s test.Results::A total of 86 observational studies involving 13,773 participants and 15,416 eyes were included. OCT revealed that compared to healthy controls, the total macular thickness of AGM patients was thinner, including the thickness of fovea (–0.24, 95% CI [–0.39, –0.08]; P = 0.002, I2 = 87.7%), all regions of parafovea (–0.32, 95% CI [–0.54, –0.11]; P = 0.003; I2 = 71.7%) and the four quadrants of perifovea; the thickness of peripapillary retinal nerve fiber layer (pRNFL), macular retinal nerve fiber layer (mRNFL), and ganglion cell layer (GCL) also decreased. OCTA indicated that the superficial and deep vascular density decreased, the foveal avascular zone (FAZ) area enlarged, and the acircularity index (AI) reduced in AGM individuals. Conclusions::Retinal thinning and microvascular lesions have occurred before the advent of clinically detectable DR; OCT and OCTA may have the potential to detect these preclinical changes.Registration::PROSPERO; http://www.crd.york.ac.uk/prospero/; No. CRD42021269885.

Objective To investigate the impact of the timing of continuous renal replacement therapy (CRRT) on the efficacy and prognosis of patients with septic shock undergoing bundle therapy. Methods A total of 84 patients with septic shock who underwent bundle therapy were enrolled, receiving bundle therapy. Based on the timing of CRRT, the patients were divided into early CRRT group and late CRRT group, with 42 patients in each group. Clinical data (heart rate, time to normalization of body temperature, ICU length of stay) and infection status[C-reactive protein (CRP), procalcitonin (PCT)]and immune function (CD4⁺, CD8⁺, CD14⁺), as well as the Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) scores before and after treatment were compared between the two groups. The 28-day survival of patients in both groups was also followed up. Results The heart rate in the early CRRT group was lower than that in the late CRRT group, and the time to normalization of body temperature and ICU length of stay were shorter in the early CRRT group compared with the late CRRT group (P < 0.05). After treatment, the levels of CRP and PCT in both groups were lower than those before treatment, and their levels in the early CRRT group were lower than those in the late CRRT group (P < 0.05). After treatment, the levels of CD8⁺ in both groups were lower than those before treatment, and the early CRRT group had lower level than that in the late CRRT group (P < 0.05); after treatment, the levels of CD4⁺ and CD14⁺ in both groups were higher than those before treatment, and their levels in the early CRRT group were higher than those in the late CRRT group (P < 0.05). After treatment, the APACHE Ⅱ scores of both groups were lower than those before treatment, and the early CRRT group had lower APACHE Ⅱ score than that in the late CRRT group (P < 0.05). The follow-up results showed that the 28-day cumulative survival rate was 83.33%(35/42) in the early CRRT group, which was higher than 64.29%(27/42) in the late CRRT group (P < 0.05). Conclusion For patients with septic shock undergoing bundle therapy, early application of CRRT is superior to late application in clinical efficacy, and contributes to improving the prognosis of patients.

ObjectiveTo explore the medication characteristics and clinical efficacy of the Tenghuang Jiangu tablets in the treatment of knee osteoarthritis （KOA） in the remission stage in the real world，providing references for rational clinical use of this prescription. MethodBased on the "registration system of KOA treated with Tenghuang Jiangu tablets"，2 439 KOA cases in the remission stage were analyzed by SPSS 25.0，IBM SPSS Modeler18.0，and Apriori algorithm. To be specific，the age，body mass index （BMI），and course of treatment were described in the form of x̄±s. The information on gender，K-L grade，daily dose，and frequency of drug use was described by frequency analysis. The number of cases，course of treatment，daily dose，and drug use frequency of the single-use group and the combined-use group were described by frequency analysis，and the combination of drugs was described by frequency analysis and Apriori algorithm. Mann-Whitney U test was employed to compare the scores of Visual Analogue Scale （VAS），Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC），pain，stiffness，and joint function between the single-use group and the combined-use group. ResultThe results of clinical treatment showed that 2 439 patients with KOA in the remission stage were treated with Tenghuang Jiangu tablets，with 1 432 （58.71%） in the single-use group and 1 007 （41.29%） in the combined-use group. The average daily dose of Tenghuang Jiangu tablets was （3.90±1.44） g，and the majority of the patients were at grade Ⅱ （54.47%）. The daily average daily dose of Tenghuang Jiangu tablets in the single-use group was （3.64±1.35） g，which was lower than that in the combined-use group ［（4.26±1.48） g，P<0.05］. In the combined use，the top three western medicines were glucosamine （270 times，14.68%），sodium hyaluronate （126 times，6.85%），and imrecoxib （116 times，6.31%），and the top three Chinese medicines were Huoxuezhitong capsules/tablets/ointments （31 times，1.69%），Biqi capsules （25 times，1.36%），and Maizhiling （23 times，1.25%）. As for the overall clinical efficacy，the VAS score was （5.13±0.93） score before treatment and （2.22±1.18） score after treatment （P<0.05），with an overall average decrease of （2.91±1.14） score， and the average decrease in the single-use group was （2.76±1.43） score， which was lower than that in the combined-use group ［（3.12±1.36） score，（P<0.01）］. The WOMAC score was （31.05±11.84） score before treatment and （13.55±9.91） score after treatment （P<0.05）. The overall average decrease was （17.50±11.79） score， and the average decrease in the single-use group and combined-use group was （16.39±11.14） score and （19.08±12.50） score，respectively （P<0.01）. The patients with KOA>grade Ⅱ accounted for 91.34%（1 308/1 432） and 93.55%（942/1 007） in the single-use group and combined-use group，respectively （χ²=80.026，P<0.05）. A total of 43.37%（621/1 432） of the patients in the single-use group had other complications，lower than that in the combined-use group ［54.92%（553/1 432），（χ²=20.087，P<0.01）］. ConclusionMore than half of the patients with KOA in the remission stage are treated with Tenghuang Jiangu tablets alone，and the combination therapy is mainly applied in patients with severe conditions or other complications. In relieving knee joint pain and improving joint stiffness and joint function，both the Tenghuang Jiangu tablets alone and the combination therapy are effective.

ObjectiveTo investigate the clinical efficacy of Tenghuang Jiangu tablets （THJGT） combined with oral non-steroidal anti-inflammatory drugs （NSAIDs） in the treatment of osteoarthritis of the knee and its applicable stage based on real-world data， and provide a basis for the rational clinical use of THJGT. MethodA total of 218 cases treated with THJGT combined with oral NSAIDs included in the "THJGT for knee osteoarthritis case registry" from September 2019 to January 2021 were selected as the observation group， and 126 cases treated with oral NSAIDs alone as the control group （CG）. The data of gender， age， body mass index， Kellgren-Lawrence grading scale （K-L scale） score， visual analogue score （VAS score）， Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC） score， swelling grade， joint fear of cold score， back pain and weakness score， and occurrence of adverse events/reactions of the patients in both groups were used for the evaluation of efficacy with full analysis set. The propensity score matching method was used to exclude the influence of confounding factors between groups， and the sub-data sets were established， with which the repeated measures analysis of variance （ANOVA） was carried out to evaluate the efficacy. Visit points were at registration， 4 weeks and 8 weeks after registration. The data were statistically analyzed in Excel 2019 and SPSS 23.0. ResultThe proportion of females in the observation group was 66.06% （144/218）， which was higher than that （58.73%， 74/126） in the control group （χ²=1.846）. The average age in the observation group was （61.12±7.01） years， which was higher than that ［（59.38±5.99） years］ in the control group （W=19 918.50， P<0.05）. The remission rate in the observation group was 98.17% （214/218）. In the observation group， the proportions of the patients at K-L grades Ⅱ and Ⅲ were 64.22% （144/218） and 25.23% （55/218）， respectively. The effect analysis of the whole data set for enrollment and treatment for 8 weeks showed that the VAS score of the experimental group decreased by （3.27±1.24） points on average， which was better than that of the control group [（2.75±1.20）， W=34 179.00， P<0.05]. The average WOMAC score decreased （23.43±11.46） points， which was better than that of the control group [（16.71±8.86）， W=32 387.00， P<0.05]. The average swelling grade decreased （0.63±0.64）， which was better than the control group [（0.33±0.59）， W=33 847.50， P<0.05]. The average score of joint chills decreased （1.90±1.84）， points， which was better than that of control group [（1.40±1.28）， W=35 165.00， P<0.05]. The average lumbar acid fatigue score decreased by （2.02±1.64） points, which was better than that of the control group [（1.10±1.28）， W=32 986.50， P<0.05]. Efficacy analysis of subdata sets for enrollment， 4 weeks of medication and 8 weeks of medication showed that VAS scores of both groups showed a downward trend after treatment， and the improvement of experimental group was more significant than that of control group at 4 weeks， with statistical significance （P<0.05）. After treatment， the total WOMAC score of both groups showed a downward trend， and the improvement of experimental groups was more significant at 4 weeks and 8 weeks （P<0.05）. After treatment， swelling， cold fear grade and lumbar acid fatigue score of both groups showed a decreasing trend,， and the improvement of experimental group was more significant at 8 weeks （P<0.05）. The therapeutic effect analysis of patients in the attack stage and remission stage of the experimental group showed that the total WOMAC score of the two groups showed a downward trend after treatment， and the trend was basically the same， and there was no statistical difference between the two groups at enrollment， 4 weeks after treatment， and 8 weeks after treatment （t=1.675， t=2.068， t=2.364）. The total WOMAC score of the patients in remission stage in the experimental group with K-L grading between grade 0 and grade Ⅲ had statistical significance at 4 weeks after treatment compared with the time of entry （P<0.05， P<0.01）. Group of adverse event rate was 4.13% （9/218）， lower than the control group 10.32% （13/126） （χ²= 5.109， P<0.05）. ConclusionThe population receiving THJGT combined with oral NSAIDs is mostly female， old， in remission， and with K-L grades Ⅱ and Ⅲ. THJGT can enhance the anti-inflammatory and analgesic effects of oral NSAIDs and keep the drug effect in improving joint function and alleviating fear of cold， swelling， and back pain and weakness. The drug combination can be applied to patients in both attack and remission， and the clinical application should take patient's disease stage and degree of osteoarthritis into account. Furthermore， the combination has the potential to reduce the incidence of adverse events caused by NSAIDs.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

BACKGROUND: Recombinant human thrombopoietin (rh-TPO) and eltrombopag are two distinct TPO receptor agonists (TPO-RAs) with different mechanisms. During the pandemic, when immunosuppressive medications are controversial, switching to another TPO-RA may be worth exploring in patients who do not benefit from their first TPO-RA. We investigated the outcomes of switching from rh-TPO to eltrombopag or vice versa in immune thrombocytopenia (ITP) patients. METHODS: This prospective, open-label, observational investigation included 96 adult ITP patients who needed to switch between rh-TPO and eltrombopag between January 2020 and January 2021 at Peking University People's Hospital in China. The study evaluated response rates and platelet counts at different time points after the switch, bleeding events, time to response, duration of response, and adverse events. RESULTS: At 6 weeks after switching, response was observed in 21/49 patients (43%) who switched for inefficacy and 34/47 patients (72%) who switched for non-efficacy-related issues. In the inefficacy group, 9/27 patients (33%) responded to eltrombopag, and 12/22 patients (55%) responded to rh-TPO. In the non-efficacy-related group, 21/26 (81%) and 13/21 (62%) patients in the eltrombopag and rh-TPO groups maintained their response rates at 6 weeks after switching, respectively. Response at 6 months was achieved in 24/49 patients (49%) switching for inefficacy and 37/47 patients (79%) switching for non-efficacy issues. In the inefficacy group, 13/27 patients (48%) responded to eltrombopag, and 11/22 patients (50%) responded to rh-TPO. In the non-efficacy-related group, 22/26 patients (85%) and 15/21 patients (71%) in the eltrombopag and rh-TPO groups maintained their response rates at 6 months after switching, respectively. Both eltrombopag and rh-TPO were well tolerated. CONCLUSIONS: Our study confirmed the safety and effectiveness of switching between rh-TPO and eltrombopag for ITP patients who had no response to or experienced adverse events with their first TPO-RA. When the switch was motivated by other reasons, including patient preference and platelet count fluctuations, the probability of response was high. REGISTRATION ClinicalTrials.gov, NCT04214951.
Adult ; Humans ; Purpura, Thrombocytopenic, Idiopathic ; Thrombopoietin/adverse effects* ; Prospective Studies ; Recombinant Fusion Proteins ; Receptors, Fc/therapeutic use* ; Receptors, Thrombopoietin/therapeutic use* ; Thrombocytopenia/chemically induced* ; Benzoates/adverse effects* ; Hydrazines/adverse effects*

Objective:To investigate the effects of sorafenib on hypoxia inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) levels and recurrence in patients with intrahepatic cholangiocarcinoma with microvascular invasion.Methods:Ninety-two patients with intrahepatic cholangiocarcinoma who received treatment in Yiwu Central Hospital between November 2013 and November 2019 were included in this study. They were randomly assigned to undergo either conventional basic treatment (control group, n = 46) or conventional basic treatment and sorafenib treatment (study group, n = 46). Clinical efficacy, the incidence of adverse reactions and recurrence rate were compared between the two groups. Before and after treatment, HIF-1, alpha fetoprotein (AFP) and VEGF levels were also compared between the two groups. Results:After treatment, total effective rate in the study group was significantly higher than that in the control group [63.04% (29 /46) vs. 28.26% (13/46), χ2 = 11.215, P < 0.05]. After treatment, HIF-1, AFP and VEGF levels in each group were significantly lower than those before treatment (all P > 0.05). After treatment, HIF-1 [(165.23 ± 39.67) pg/mL], AFP [(109.16 ± 67.31) ng/mL] and VEGF [(297.28 ± 42.41) pg/mL] levels in the study group were significantly lower than those in the control group [(205.56 ± 40.23) pg/mL, (235.17 ± 106.41) ng/mL, (365.16 ± 40.91) pg/mL, t = 4.841, 6.788, 7.813, all P < 0.05]. There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Six-month follow-up revealed that the incidence of recurrence in the study group was significantly lower than that in the control group ( χ2 = 4.792, P < 0.05). Conclusion:Sorafenib can reduce the HIF-1, AFP and VEGF levels in patients with intrahepatic cholangiocarcinoma with microvascular invasion, improve the clinical efficacy, decrease the incidence of recurrence, but cannot increase the incidence of adverse reactions.

Objective: To learn the willingness and influencing factors of influenza vaccination among the community managed diabetic patients in Keqiao District, Shaoxing, so as to provide the basis for influenza vaccination promotion. Methods: A self-compiled questionnaire survey was conducted from October to December 2017 among all the managed diabetic patients in Keqiao District. The contents of questionnaire included the basic information of the respondents, awareness of influenza vaccine, vaccination status and vaccination intention. Logistic regression model was used to analyze the influencing factors for the willingness of influenza vaccination. Results: A total of 15 060 questionnaires were sent out and 13 781 valid ones were retrieved, the response rate was 91.51%. There were 3 888 patients with the awareness of influenza vaccine, accounting for 28.21%; 4 259 patients with the willingness to be vaccinated, accounting for 30.90%; 630 previously-vaccinated patients, accounting for 4.57%. The patients who were female (OR=1.157, 95%CI: 1.064-1.258) , were married (OR=1.242, 95%CI:1.107-1.393), were with other chronic diseases (OR=1.199, 95%CI: 1.103-1.303) , believed diabetic patients were more susceptible to influenza (OR=1.251, 95%CI: 1.102-1.419) , believed influenza aggravate diabetes status (OR=1.640, 95%CI: 1.445-1.860) , believed that the vaccination effectively prevent influenza (OR=3.129, 95%CI: 2.866-3.416) , knew about influenza vaccine (OR=1.111, 95%CI: 1.105-1.216) and ever received influenza vaccination (OR=1.316, 95%CI: 1.103-1.570) were more willing to be vaccinated. Conclusions The willingness of influenza vaccination among the community managed diabetic patients in Keqiao District is low. The patients＇gender, married status, other chronic diseases, awareness of influenza vaccine and the history of vaccination can affect the willingness of influenza vaccination.