AIM To investigate the variation rules of main secondary metabolites in Hedysari Radix before and after rubbing strip.METHODS UPLC-MS/MS was adopted in the content determination of formononetin,ononin,calycosin,calycosin-7-glucoside,medicarpin,genistein,luteolin,liquiritigenin,isoliquiritigenin,vanillic acid,ferulic acid,γ-aminobutyric acid,adenosine and betaine,after which cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were used for chemical pattern recognition to explore differential components.RESULTS After rubbing strip,formononetin,calycosin,liquiritigenin and γ-aminobutynic acid demonstrated increased contents,along with decreased contents of ononin,calycosin-7-glucoside and vanillic acid.The samples with and without rubbing strip were clustered into two types,calycosin-7-glucoside,formononetin,γ-aminobutynic acid,vanillic acid,calycosin-7-glucoside and formononetin were differential components.CONCLUSION This experiment clarifies the differences of chemical constituents in Hedysari Radix before and after rubbing strip,which can provide a reference for the research on rubbing strip mechanism of other medicinal materials.

Ameloblastoma is a benign tumor characterized by locally invasive phenotypes,leading to facial bone destruction and a high recurrence rate.However,the mechanisms governing tumor initiation and recurrence are poorly understood.Here,we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution.Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response(IR),bone remodeling(BR),tooth development(TD),epithelial development(ED),and cell cycle(CC)signatures.Of note,we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence,which was dominated by the EZH2-mediated program.Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids.These data described the tumor subpopulation and clarified the identity,function,and regulatory mechanism of CC ameloblastoma cells,providing a potential therapeutic target for ameloblastoma.

Chronic atrophic gastritis(CAG)is a common intractable gastric disease in clinic,which belongs to the gastric precancerous lesions.Professor LIU Feng-Bin and his team have performed the exploration and practice in the field of CAG for more than 30 years,and they proposed that the evolution of the traditional Chinse medicine(TCM)pathogenesis of inflammation-to-tumor transition(ITT)in CAG was characterized by spleen deficiency being the root cause,qi stagnation,blood stasis and dampness retention being the branch cause,and stasis and toxin being the aggravating factors.Deificiency of the spleen and stomach is the initial factor of CAG,which influences the whole process of the disease.Qi stagnation,blood stasis and dampness retention are the triggering and aggravating factors for the ITT in CAG.The formation of blood stasis and toxin is the key to the progression and transition of CAG.Treatment of ITT in CAG should be based on the results of syndrome differentiation and gastroscopic findings by staging therapy.Before treatment,disease dianosis and syndrome differentiation should be made,and macro and micro syndrome differentiation should be carried out for assistance.Therapy of strengthening the spleen and supporting healthy qi should be implemented throughout the whole process of the disease.The early stage of CAG has the features of gastric mucosa with mild to moderate atrophy and with or without mild intestinal epithelial hyperplasia,the pathogenesis of early CAG is characterized by weakness of the spleen and stomach and is accompanied with the pathological factors of qi stagnation,damp-retention and blood stasis,and the basic treatment should adopt the therapies of strengthening the spleen and clearing heat,regulating qi and activating blood stasis.The advanced stage of CAG has the features of severe atrophic gastric mucosa with or without moderate to severe intestinal epithelial and/or mild to moderate intraepithelial neoplasia,the pathogenesis is characterized by weakness of the spleen and stomach,phlegm blended with blood stasis,and stasis-toxin in the gastric collaterals,and the basic treatment should adopt the therapies of supporting healthy qi and dissipating masses,and unblocking the collaterals and removing toxin,so as to construct an intact line to blocking the ITT in CAG with traditional Chinese medicine.

Objective To explore the efficacy and safety of modified meibomian gland massage combined with ultrasonic atomization and drug therapy for dry eye in high-altitude military personnel.Methods A total of 180 patients(360 eyes)with dry eye who were diagnosed and treated by the medical team of General Hospital of Central Theater Command of Chinese PLA from July to October 2022 in Linzhi,Tibet(average altitude of 3100 meters)were selected as the research subjects.Patients were divided into four block groups based on the course of the disease:＜1 month,1-3 months,3-6 months,and≥6 months,and each block group was randomly assigned to control group,traditional group and modified group by random number table method,with 60 cases in each group.Control group received routine treatment(artificial tear drops and atomization fumigation);on the basis of routine treatment,traditional group underwent traditional meibomian gland massage,and modified group underwent modified meibomian gland massage.After 3 months of treatment,the scores of symptoms and signs,total effective rate,duration of treatment and incidence of adverse events were compared among the 3 groups.Results In the intra-group comparison before and after treatment,except for control group's symptom scores difference which was not statistically significant(P＞0.05),all other scores decreased significantly(P＜0.05).In the inter-group comparison after treatment,the scores of both traditional group and modified group were significantly better than those of control group(P＜0.05),but no significant difference was observed in symptom and sign scores between traditional and modified groups(P＞0.05).Compared with control group,the total effective rates of traditional group and modified group both significantly increased(P＜0.01),but there was no significant difference in total effective rate between traditional and modified groups(P＞0.05).The treatment time in modified group was significantly longer than that in control group(P＜0.05),but significantly shorter than that in traditional group(P＜0.05).The incidence of adverse events was significantly lower in modified group than that in traditional group(P＜0.001).Conclusion In high-altitude areas,modified meibomian gland massage combined with ultrasonic atomization and local drug therapy for dry eye is safe and effective,non-invasiveness and easy to perform,and suitable for promoting and application in military field training.

Interleukin-1 receptor associated kinase 4 (IRAK-4), acting as a serine threonine kinase, is considered as a key signal node for the transduction of IL-1R family and TLRs signal pathway. Studies have found that IRAK-4 has a hand in many signal pathways, involving the inflammatory response of human joints, intestines, liver and nervous system, as well as other autoimmune diseases. It is also one of the causes of drug resistance of some cancer cells. Therefore, IRAK-4 tends to be an effective therapeutic target for inflammatory diseases and cancer. The prospects for the development of drugs in this pathway is to develop novel IRAK-4 small molecule inhibitors and investigate their safety and effectiveness, enrich the clinical treatment of inflammatory and cancer diseases finally. This paper classified and summarized the latest research progress on small molecule inhibitors of IRAK-4 signaling pathway according to structures of the compounds, in order to provide assistances and references for the research and development of related drugs.

INTRODUCTION: Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity. METHOD: Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases. RESULTS: A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection. CONCLUSION This study demonstrates the benefit of early administration of the third dose among cancer patients.
Humans ; SARS-CoV-2 ; COVID-19/prevention & control* ; Treatment Outcome ; Neoplasms/drug therapy* ; Hematologic Neoplasms ; Vaccination ; RNA, Messenger ; Antibodies, Viral ; Immunogenicity, Vaccine

Objective: To investigate the clinical effects of one-stage revision combined with intra-articular infusion of vancomycin in the treatment of chronic prosthetic joint infection (PJI) caused by Enterococcal. Methods: From May 2013 to June 2020,the clinical data of 9 patients (2 males and 7 females) with chronic Enterococcal PJI treated with one-stage revision using intra-articular infusion of vancomycin at Department of Orthopaedics,First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed,including 8 hips and 1 knee.A total of 9 patients with age of (63.9±11.7)years (range:43 to 76 years) were included, and the body mass index was (23.6±4.3)kg/m² (range:18 to 30 kg/m²).There were 6 cases with antibiotic history and 5 cases with sinus tract.The joint fluid,infected tissue around the prosthesis and ultrasonic shock fluid of the prosthesis were collected during operation for microbial culture identification and drug sensitivity test.After thorough debridement of the infected site and removal of the infected prosthesis,a new prosthesis was implanted,then the drainage tube in the operation area was placed.After surgery,vancomycin(1.0 g,q12 h) was combined with intra-articular vancomycin(0.5 g,qd) in monomicrobial PJI,and vancomycin(1.0 g,q12 h) was combined with intra-articular vancomycin (0.5 g,qd) and imipenem/meropenem (0.5 g,qd),and the interval between the two drugs was 12 hours in polymicrobial PJI.Hip and knee functions were evaluated by Harris Hip Score or Knee Society Score(KSS),respectively.The comparison of hip function scores before and after operation was performed by paired t-test. Results: All patients were followed up for (60±39)months(range:24 to 110 months).Two cases were infected with Enterococcus faecium and 7 cases were infected with Enterococcus faecalis.There were 7 cases of monomicrobial infection and 2 cases of polymicrobial infection.Erythromycin(5/9),tetracycline(4/9),ciprofloxacin and β-lactam antibiotics(3/9) were the top three antibiotics in Enterococci resistance rate.The sensitive antibiotics for Enterococcal were vancomycin,linezolid and tigecycline.The average duration of intravenous antibiotics was (14±1)days (range:13 to 17 days),and the average duration of antibiotics in articular cavity was (15±2)days(range:11 to 20 days).Mean duration of oral antibiotic use after discharge was (2±1)months(range:1 to 3 months).One case of polymicrobial PJI treatment failed,with a failure rate of 1/9.At last follow-up,the Harris score of patients with hip PJI increased from (43±6)points to (84±6)points(t=-11.899, P<0.01). KSS score of knee function was improved from 33 point pre-operatively to 85 point post-operatively;overall function score was improved from 35 point pre-operatively to 80 point post-operatively.During the treatment,no formation of sinus tract of the hip joint caused by a catheter,skin necrosis at the knee puncture site or leakage of joint fluid;no complications such as deep vein thrombosis and pulmonary embolism occurred. Conclusions: One-stage revision combined with intra-articular infusion of vancomycin can achieve acceptable infection control rate and joint function in patients with chronic Enterococcus PJI.However,the treatment of polymicrobial PJI still needs to be further verified.
Female ; Male ; Humans ; Vancomycin/therapeutic use* ; Retrospective Studies ; Anti-Bacterial Agents/therapeutic use* ; Enterococcus ; Prostheses and Implants ; Inflammation

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male ; Humans ; Prostate-Specific Antigen ; Treatment Outcome ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies

Aim To explore the effect of salidroside on the learning and memory ability of mice under high altitude hypoxia. Methods Forty-eight C57BL/6J male mice were randomly divided into plain control group, plateau model group and salidroside group according to their body weight, with 16 mice in each group. The animals in each group were given prophylactic doses for three days and then rushed to a plateau with an altitude of 4 010 m. After one day of hypoxia exposure, Morris water maze was performed to test the learning and memory ability of mice; malondialdehyde(MDA), hydrogen peroxide(H

OBJECTIVE: To investigate the predictive value of blood cell ratios and inflammatory markers for adverse prognosis in patients with primary Sjögren's syndrome (PSS) combined with coronavirus disease 2019 (COVID-19). METHODS: We retrospectively collected clinical data from 80 patients with PSS and COVID-19 who visited the Rheumatology and Immunology Department of the First Affiliated Hospital of Nanchang University from December 2022 to February 2023. Inclusion criteria were (1) meeting the American College of Rheumatology (ACR) classification criteria for Sjögren's syndrome; (2) confirmed diagnosis of COVID-19 by real-time reverse transcription polymerase chain reaction or antigen testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); (3) availability of necessary clinical data; (4) age > 18 years. According to the clinical classification criteria of the "Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (trial the 10th Revised Edition)", the patients were divided into the mild and severe groups. Disease activity in primary Sjögren' s syndrome was assessed using the European League Against Rheumatism (EULAR) Sjögren' s syndrome disease activity index (ESSDAI). Platelet-lymphocyte ratio (PLR), C-reactive protein-lymphocyte ratio (CLR), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and other laboratory data were compared between the two groups within 24-72 hours post-infection. RESULTS: The mild group consisted of 66 cases with an average age of (51. 52±13. 16) years, and the severe group consisted of 14 cases with an average age of (52.64±10.20) years. Disease activity, CRP, platelets, PLR, and CLR were significantly higher in the severe group compared with the mild group (P < 0.05). Univariate analysis using age, disease activity, CRP, platelets, PLR, and CLR as independent variables indicated that disease activity, CRP, PLR, and CLR were correlated with the severity of COVID-19 (P < 0.05). Multivariate logistic regression analysis further confirmed that PLR (OR=1.016, P < 0.05) and CLR (OR=1.504, P < 0.05) were independent risk factors for the severity of COVID-19 in the critically ill patients. Receiver operator characteristic (ROC) curve analysis showed that the area under the curve (AUC) for PLR and CLR was 0.708 (95%CI: 0.588-0.828) and 0.725 (95%CI: 0.578-0.871), respectively. The sensitivity for PLR and CLR was 0.429 and 0.803, respectively, while the highest specificity was 0.714 and 0.758, respectively. The optimal cutoff values for PLR and CLR were 166.214 and 0.870, respectively. CONCLUSION PLR and CLR, particularly the latter, may serve as simple and effective indicators for predicting the prognosis of patients with PSS and COVID-19.
Humans ; Adult ; Middle Aged ; Sjogren's Syndrome/diagnosis* ; Retrospective Studies ; C-Reactive Protein ; COVID-19 ; SARS-CoV-2