OBJECTIVE: To retrospectively analyze the characteristics and influencing factors of COVID-19 infection in patients with multiple myeloma (MM) who underwent autologous hematopoietic stem cell transplantation (AHSCT). METHODS: The clinical data of MM patients who underwent AHSCT in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from May 26, 2021 to December 26, 2022 were collected. The onset of COVID-19 infection, corresponding symptoms and laboratory tests were followed up in outpatient or by the means of telephone contact and online questionnaires. Related analysis was then performed. RESULTS: This study included 96 patients, and 72 cases among them were infected with COVID-19 while 24 cases were uninfected. Logistic regression analysis showed that vaccination did not significantly reduce the risk of COVID-19 infection, but patients who received two doses of the vaccine had a lower risk of developing moderate and severe disease than those who did not receive or received one dose (OR =0.06, P =0.029). Patients who received daratumumab before had a higher risk of COVID-19 infection (OR =5.78, P =0.039), while those with a history of immunomodulatory drugs (IMiDs) had the opposite effect (OR =0.31, P =0.028). The use of both drugs did not affect the severity of COVID-19 infection. CONCLUSION For MM patients undergoing AHSCT as first-line chemotherapy, COVID-19 vaccination does not significantly reduce the infection rate, but it plays a role in preventing moderate and severe cases. The application of antineoplastic drugs with different mechanisms has a certain impact on the susceptibility to the COVID-19, which should be considered comprehensively when creating treatment plans.
Humans ; Multiple Myeloma/complications* ; COVID-19/epidemiology* ; Hematopoietic Stem Cell Transplantation ; Transplantation, Autologous ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Male ; Female ; Middle Aged ; SARS-CoV-2 ; Adult ; Antibodies, Monoclonal

Physcion (PHY) is an anthraquinone compound derived from traditional Chinese medicine such as Rhei Radix et Rhizoma. The aim of this study is to investigate the improvement of PHY on non-alcoholic fatty liver disease (NAFLD) and its underlying mechanism. NAFLD was induced in mice by feeding with the methionine- and choline-deficient diet (MCD) for 6 weeks. This experiment was approved by the Experimental Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval number: PZSHUTCM190705019). The results displayed that PHY (5 and 20 mg·kg^-1) reversed liver damage, reduced hepatic lipid accumulation and decreased the elevated NAFLD activity score (NAS) in MCD-fed NAFLD mice. Results from Western blot and enzyme activity demonstrated that PHY could enhance the protein expression and enzyme activity of carnitine palmitoyltransferase 1A (CPT1A) in the liver and L-02 cells, but it did not affect Cpt1a mRNA expression. Immunofluorescence results indicated that PHY (10 and 25 μmol·L^-1) could reduce the mitochondrial injury induced by non-esterified fatty acids (NEFA) in L-02 cells. Results from seahorse assay showed that PHY could enhance mitochondrial basic respiration, maximal respiration, ATP synthesis and reserve respiration in L-02 cells treated with NEFA, but had no effect on mitochondrial proton leakage. In summary, PHY reversed mitochondrial damage and enhanced fatty acid β-oxidation, thereby reducing hepatic steatosis and improving NAFLD.

Objective To investigate the prevalence of tick-borne rickettsial infections in selected areas of Liupanshui City, Guizhou Province, 2023, so as to provide insights into the management of tick-borne rickettsioses in the city. Methods Ticks were captured from the body surface of bovines and sheep in Gaoxing Village, Dashan Township, Liupanshui City, Guizhou Province during the period between April and June, 2023, and tick species were identified using morphological and molecular biological techniques. In addition, tick-borne Rickettsia was identified using a nested PCR assay, including spotted fever group rickettsiae (SFGR), Coxiella spp., Anaplasma spp., Ehrlichia spp., and Orientia spp., and positive amplified fragments were sequenced and aligned with known sequences accessed in the GenBank database. Results A total of 200 ticks were collected and all tick species were identified as Rhipicephalus microplus. Nestle PCR assay combined with sequencing identified ticks carrying Candidatus Rickettsia jingxinensis (40.50%), Coxiella burnetii (1.50%), and Coxiella-like endosymbionts (27.00%), and Anaplasma spp., Ehrlichia spp. or Orientsia spp. was not detected. Conclusions R. microplus carried Candidatus R. jingxinensis, C. burnetii, and Coxiella-like endosymbionts in selected areas of Liupanshui City, Guizhou Province. Intensified monitoring of tickborne rickettsial infections is needed in livestock and humans to reduce the damages caused by rickettsioses.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To investigate the regulatory effect of miR-132-3p on calmodulin-binding transcription activator 1(CAMTA1)and Schwann cell activity in rats with facial nerve injury(FNI)treated with I-125 seeds.Methods Rat Schwann cells were irradiated with I-125 seeds and transfected with miR-132-3p mimic,miR-132-3p inhibitor or sh-CAMTA1.The expressions of S100B and β-tubulin Ⅲ in the cells were detected with immunofluorescence assay,and the expressions of miR-132-3p and CAMTA1 protein were determined using RT-qPCR and Western blotting,respectively.EdU staining and Transwell assay were used to evaluate the changes in cell proliferation and migration ability.In a rat model of FNI,I-125 seeds were implanted into the facial tissues near the facial nerve 2 weeks before modeling,and miR-132-3p mimic was injected subcutaneously in the face after modeling.The pathologies of the facial nerve was assessed by HE,LFB and immunofluorescence staining.The targeting relationship between miR-132-3p and CAMTA1 was verified using StarBase v2.0 database and dual-luciferase reporter assay.Results Rat Schwann cells showed high expressions of S100B and β-tubulin Ⅲ.I-125 seeds radiation significantly decreased miR-132-3p expression and repressed proliferation and migration of the cells(P<0.001).Overexpression of miR-132-3p or CAMTA1 knockdown obviously enhanced proliferation and migration of the Schwann cells,while miR-132-3p knockdown produced the opposite effect.MiR-132-3p negatively regulated CAMTA1 expression.In the rat models of FNI,miR-132-3p injection significantly inhibited CAMTA1 expression and attenuated I-125 seeds-induced exacerbation of FNI.Conclusion Overexpression of miR-132-3p suppresses CAMTA1 expression and promotes Schwann cell proliferation and migration to alleviate I-125 seeds-induced exacerbation of FNI in rats.

Objective To provide a longitudinal evaluation tool based on the frequency of aggressive be-havior for the aggression assessment of schizophrenia patients.Methods The Life History of Aggression was translated and revised to form the Life History of Aggression-Chinese Version(LHA-CV)based on 369 patients diagnosed with schizophrenia in the Chengdu community and compulsory medical insti-tution.The reliability of LHA-CV was analyzed by means of split-half reliability,test-retest reliability and inter-evaluator consistency.The validity was analyzed by item analysis,construct validity and crite-rion validity.Results Item analysis found that LHA-CV had good homogeneity and discriminant validity.Exploratory factor analysis found that the Kaiser-Meyer-Olkin(KMO)test value was 0.80,and the Bartlett's sphericity test χ2=1203.46(P<0.05),and it revealed four factors including non-physical ag-gression,physical aggression,self-directed aggression and antisocial behavior/consequences.The factor loadings for all 11 items were greater than 0.40.Confirmatory factor analysis was performed on the factor model,Chi-square degree of freedom(χ2/df)was 3.61,root mean square error of approxima-tion(RMSEA)was 0.07,goodness-of-fit index(GFI)was 0.92,comparative fit index(CFI)was 0.90,incremental fit index(IFI)was 0.90,and the discriminant validity of each factor was good.The criterion validity test showed the total score of LHA-CV was positively correlated with the aggressive behavior level of MacArthur Community Violence Instrument,the total score of Buss-Perry Aggression Scale,and the score of Antisocial Personality Disorder Subscale of Personality Diagnostic Question-naire-4th Edition Plus(PDQ-4+_ASPD,P<0.05).The Cronbach's α coefficient of non-physical aggres-sion,physical aggression,self-directed aggression,antisocial behavior/consequences and LHA-CV total score were 0.82,0.73,0.74,0.56 and 0.79,respectively.The test-retest reliability,Spearman-Brown split-half reliability and intra-class correlation coefficient of LHA-CV total score were 0.82(P<0.05),0.66 and 0.99,respectively.Conclusion LHA-CV has good reliability and validity,and can be used as an evaluation tool for longitudinally assessing aggressive behavior in schizophrenia patients.

Objective:This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients.Methods:Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy.Results:A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions:Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

Objective To study the pharmacokinetic characteristics of lamotrigine tablets in Chinese healthy subjects under fasting and fed conditions,and to evaluate the bioequivalence and safety profiles between the domestic test preparation and the original reference preparation.Methods Twenty-four Chinese healthy male and female subjects were enrolled under fasting and fed conditions,18 male and 6 female subjects under fasting conditions,17 male and 7 female subjects under fed conditions.A random,open,single-dose,two preparations,two sequences and double-crossover design was used.Plasma samples were collected over a 72-hour period after give the test or reference preparations 50 mg under fasting and fed conditions.The concentration of lamotrigine in plasma was detected by liquid chromatography-tandem mass spectrometry,and the main pharmacokinetic parameters were calculated to evaluate the bioequivalence by WinNonLin 8.1 program.Results The main pharmacokinetic parameters of single-dose the tested and reference preparations were as follows:The fasting condition Cmax were(910.93±248.02)and(855.87±214.36)ng·mL-1;tmax were 0.50(0.25,4.00)and 1.00(0.25,3.50)h;t1/2 were(36.1±9.2)and(36.0±8.2)h;AUC0_72h were(27 402.40±4 752.00)and(26 933.90±4 085.80)h·ng·mL-1.The fed condition Cmax were(701.62±120.67)and(718.95±94.81)ng·mL-1;tmax were 4.00(1.00,5.00)and 4.00(0.50,5.00)h;t1/2 were(44.2±12.4)and(44.0±12.0)h;AUC0-72h were(30 253.20±7 018.00)and(30 324.60±6 147.70)h·ng·mL-1.The 90％confidence intervals of the geometric mean ratios of Cmax and AUC0-72 hfor the test preparation and reference preparation were all between 80.00％and 125.00％under fasting and fed conditions.Conclusion Two kinds of lamotrigine tablets are bioequivalent,and have similar safety in Chinese healthy male and female subjects under fasting and fed conditions.

Objective To explore the mechanism of action of lamotrigine in the treatment of major depressive disorder(MDD).Methods Information on the drug targets of lamotrigine and the therapeutic targets of MDD were collected for intersection target gene analysis and protein-protein interaction screening.Various biological pathways related to lamotrigine in treatment of MDD were determined through gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis.The screened core targets were preliminarily validated using molecular docking technology.Further validation of Mendelian randomization was conducted using genome-wide association analysis data from gamma-aminobutyric acid recep tor-associated protein-like 1(GABARAPL1)and MDD in the OpenGWAS database.Results The biological pathways related to lamotrigine in treatment of MDD were identified,which included gamma-aminobutyric acid(GABA)ergic synapses,nicotine addiction,glutamatergic synapses,endogenous cannabinoid signaling.Molecular docking showed that the docking energy of lamotrigine with GABRA1,GABRB2,GABRA6,GABRD,GABRG2,GABRG1,GABRA5,GABRA4,GABRB3,and GABRA2 receptors was-5.8 kCal·mol-1.Among them,the GABRB3 receptor showed the strongest docking energy with lamotrigine,which was-9.5 kCal·mol-1.In the genome-wide association analysis data of GABARAPL1,303 single nucleotide polymorphisms were associated with GABARAPL1(P＜5 × 106).15 single nucleotide polymorphisms were screened and retained for Mendelian randomization analysis,and the results showed that GABA receptors may be an important therapeutic target for MDD.Conclusion The treatment of MDD with lamotrigine may be achieved by acting on GABA receptors,which provided a research basis for the clinical application of lamotrigine in treating MDD.

Objective To investigate the regulatory effect of miR-132-3p on calmodulin-binding transcription activator 1(CAMTA1)and Schwann cell activity in rats with facial nerve injury(FNI)treated with I-125 seeds.Methods Rat Schwann cells were irradiated with I-125 seeds and transfected with miR-132-3p mimic,miR-132-3p inhibitor or sh-CAMTA1.The expressions of S100B and β-tubulin Ⅲ in the cells were detected with immunofluorescence assay,and the expressions of miR-132-3p and CAMTA1 protein were determined using RT-qPCR and Western blotting,respectively.EdU staining and Transwell assay were used to evaluate the changes in cell proliferation and migration ability.In a rat model of FNI,I-125 seeds were implanted into the facial tissues near the facial nerve 2 weeks before modeling,and miR-132-3p mimic was injected subcutaneously in the face after modeling.The pathologies of the facial nerve was assessed by HE,LFB and immunofluorescence staining.The targeting relationship between miR-132-3p and CAMTA1 was verified using StarBase v2.0 database and dual-luciferase reporter assay.Results Rat Schwann cells showed high expressions of S100B and β-tubulin Ⅲ.I-125 seeds radiation significantly decreased miR-132-3p expression and repressed proliferation and migration of the cells(P<0.001).Overexpression of miR-132-3p or CAMTA1 knockdown obviously enhanced proliferation and migration of the Schwann cells,while miR-132-3p knockdown produced the opposite effect.MiR-132-3p negatively regulated CAMTA1 expression.In the rat models of FNI,miR-132-3p injection significantly inhibited CAMTA1 expression and attenuated I-125 seeds-induced exacerbation of FNI.Conclusion Overexpression of miR-132-3p suppresses CAMTA1 expression and promotes Schwann cell proliferation and migration to alleviate I-125 seeds-induced exacerbation of FNI in rats.