Hormesis effect has been observed in the secondary metabolite synthesis of microorganisms induced by rare earth elements. However, the underlying molecular mechanism remains unclear. To analyze the molecular mechanism of the regulatory effect of Rhodotorula mucilaginosa in the presence of lanthanum chloride, different concentrations of lanthanum chloride were added to the fermentation medium of Rhodotorula mucilaginosa, and the carotenoid content was subsequently measured. It was found that the concentrations of La³⁺ exerting the promotional and inhibitory effects were 0-100 mg/L and 100-400 mg/L, respectively. Furthermore, the expression of 33 genes and the synthesis of 55 metabolites were observed to be up-regulated, while the expression of 85 genes and the synthesis of 123 metabolites were found to be down-regulated at the concentration range of the promotional effect. Notably, the expression of carotenoid synthesis-related genes except AL1 was up-regulated. Additionally, the content of β-carotene, lycopene, and astaxanthin demonstrated increases of 10.74%, 5.02%, and 3.22%, respectively. The expression of 5 genes and the synthesis of 91 metabolites were up-regulated, while the expression of 35 genes and the synthesis of 138 metabolites were down-regulated at the concentration range of the inhibitory effect. Meanwhile, the content of β-carotene, lycopene, and astaxanthin decreased by 21.73%, 34.81%, and 35.51%, respectively. In summary, appropriate concentrations of rare earth ions can regulate the synthesis of secondary metabolites by modulating the activities of various enzymes involved in metabolic pathways, thereby exerting the hormesis effect. The findings of this study not only contribute to our comprehension for the mechanism of rare earth elements in organisms but also offer a promising avenue for the utilization of rare earth elements in diverse fields, including agriculture, pharmaceuticals, and healthcare.
Lanthanum/pharmacology* ; Rhodotorula/genetics* ; Carotenoids/metabolism* ; Hormesis/drug effects* ; Fermentation ; Multiomics

Objective:Exploring the efficacy and safety of bridging blinatumomab (BiTE) in combination with chimeric antigen receptor T (CAR-T) cell therapy for the treatment of adult patients with acute B-cell lymphoblastic leukemia (B-ALL) .Methods:Clinical data from 36 adult B-ALL patients treated at the First Affiliated Hospital of Suzhou University from August 2018 to May 2023 were retrospectively analyzed. A total of 36 cases were included: 18 men and 18 women. The median age was 43.5 years (21-72 years). Moreover, 21 cases of Philadelphia chromosome-positive acute lymphoblastic leukemia were reported, and 16 of these cases were relapsed or refractory. Eighteen patients underwent blinatumomab bridging followed by CAR-T cell therapy, and 18 patients received CAR-T cell therapy. This study analyzed the efficacy and safety of treatment in two groups of patients.Results:In the BiTE bridge-to-CAR-T group, 16 patients achieved complete remission (CR) after BiTE immunotherapy, with a CR rate of 88.9%. One month after bridging CAR-T therapy, bone marrow examination showed a CR rate of 100.0%, and the minimal residual disease (MRD) negativity rate was higher than the nonbridging therapy group (94.4% vs. 61.1%, Fisher, P=0.041). The incidence of cytokine release syndrome and other adverse reactions in the BiTE bridge-to-CAR-T group was lower than that in the nonbridging therapy group (11.1% vs. 50.0%, Fisher, P=0.027). The follow-up reveals that 13 patients continued to maintain MRD negativity, and five patients experienced relapse 8.40 months (2.57-10.20 months) after treatment. Two of five patients with relapse achieved CR after receiving the second CAR-T cell therapy. In the nonbridging therapy group, 10 patients maintained continuous MRD negativity, 7 experienced relapse, and 6 died. The 1 year overall survival rate in the BiTE bridge-to-CAR-T group was higher than that in the nonbridging therapy group, with a statistically significant difference at the 0.1 level (88.9%±10.5% vs. 66.7%±10.9%, P=0.091) . Conclusion:BiTE bridging CAR-T cell therapy demonstrates excellent efficacy in adult B-ALL treatment, with a low recent recurrence rate and ongoing assessment of long-term efficacy during follow-up.

OBJECTIVE To establish a determination method for the related substances of LPM3480392, a novel Gi protein-biased opioid receptor(MOR) agonist. METHODS The separation was carried out with Waters Symmetry Shield RP18 (150 mm×4.6 mm, 3.5 μm) by gradient elution method, using a mixture of 0.002 5 mol·L–1 sodium 1-octanesulfonate monohydrate in 0.01 mol·L–1 potassium dihydrogen phosphate-water solution(containing 0.1% triethylamine, adjusted pH to 2.50 with phosphate acid) and acetonitrile as the mobile phase at a flow rate of 1.0 mL·min–1 and the UV detection wavelength was set at 210 nm. RESULTS The chromatographic peaks of LPM3480392 and impurity A, impurity B, impurity C, impurity E and impurity F could be completely separated, the linear relationship of LPM3480392 was good in 0.064 9−5.191 2 μg·mL–1, while impurity A, impurity B, impurity C, impurity E and impurity F showed good linear relationship within 0.066 6−7.610 4 μg·mL–1, 0.166 0−3.794 0 μg·mL–1, 0.209 2−4.463 2 μg·mL–1, 0.167 9−7.672 6 μg·mL–1 and 0.016 4−7.505 7 μg·mL–1, respectively. The recovery rate was within 93.0%−103.2%. CONCLUSION The method is suitable for the determination of related substances in LPM3480392, and can provide valuable reference for the follow-up research and development of LPM3480392.

Objective To examine the reliability and validity of the Suicidal Behaviors Questionnaire-Revised(SBQ-R)among Chinese undergraduates and to find out cut-off score for screening the risk of suicide in clinical undergraduates.Methods A total of 488 Chinese undergraduates participated in this study.Of them,366 participants were asked to complete the Chinese version of SBQ-R,Psychache Scale,and Satisfaction with Life Scale.And 45 undergraduates were re-tested after four weeks;122 undergraduates were tested by using the Suicidality Module Section of the Mini International Neuropsychiatric Interview and the Chinese version of SBQ-R.Results ① The results showed that The Chinese version of SBQ-R had one factor with good fit indices.② The internal consistency reliability,split-half reliability,and one-month retest reliability of the total questionnaire were 0.76,0.79,and 0.93,respectively.③ The total score of the SBQ-R in Chinese was positively correlated with psychache but negatively correlated with satisfaction of life,indicating that the scale has good criterion-related validity.④ Receiver operating characteristics(ROC)curve evaluation suggested that the cut-off score was 9 in terms of identifying the clinical undergraduates at high risk of suicide.Conclusion SBQ-R is a reliable,valid,and practical instrument to measure the risk of suicide among Chinese undergraduates.SBQ-R＞9 is the best cut-off value for screening for high suicide risk in China.

The recently updated "Guidelines for the Prevention and Treatment of Chronic Hepatitis B" in China have brought about significant changes. The new treatment indications almost mandate the implementation of a Treat-all strategy for the chronically HBV-infected population in China. While simultaneous negativity for hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA has long been an accepted criterion for treatment discontinuation, there has been controversies over the initiation of treatment criteria starting with HBsAg and HBV DNA positivity. Despite the inconsistent treatment criteria, the academic community has started supporting treat-all strategies in recent years due to the decreasing cost of treatment, prolonged management duration, and growing evidence of poor outcomes in untreated populations. Therefore, this update to the Chinese HBV guidelines represents a new direction that suggests "The greatest truths are the simplest." However, in the process of rolling out the Treat-all strategy, we must remain cautious of possible issues arising from the new strategy. Among them, the problem of partial response or low-level viremia following treatment may become more prominent due to the inclusion of a significant number of patients with normal or low levels of alanine transaminase. As existing evidence suggests that low-level viremia increases the risk of HCC in patients, it is essential to monitor and explore optimal therapeutic options for these patients.

Objectives:To investigate the prevalence,clinical characteristics and risk factors of coronavirus disease-2019(COVID-19)in patients with pulmonary hypertension(PH). Methods:A questionnaire survey was conducted from December 30,2022 to January 6,2023 through the WeChat official account of the PH Patients Mutual Aid Organization.PH patients aged≥18 years from 26 province(municipality/autonomous region)were recruited to fill in the electronic survey questionnaire. Results:A total of 293 valid questionnaires were collected from PH patients.The mean age of patients was(40.6±12.7)years,and 226 patients(77.1%)of them were female.The vaccination rate was 59.7%(175/293),117 patients(39.9%)received three or more doses of vaccine,145 patients(49.5%)received inactivated vaccine.242 patients(82.6%)had COVID-19.The most common symptoms during infection were fever(85.5%),cough(77.7%),and fatigue(66.5%).10.7%of the patients had severe or critical COVID-19.Age(OR =1.057,95%CI:1.027-1.087,P<0.001)and comorbid pulmonary disease(OR=3.341,95%CI:1.215-9.184,P=0.019)were associated with severe or critical COVID-19.After adjusting for confounding factors,age was an independent risk factor for severe or critical COVID-19(OR=1.049,95%CI:1.019-1.080,P=0.001).Severe or critical COVID-19 was an independent risk factor for worsening heart failure in PH patients during COVID-19 pandemic(OR=10.522,95%CI:4.311-25.682,P<0.001). Conclusions:The immunization coverage of PH patients is insufficient.PH patients have a higher risk of developing severe or critical COVID-19 than general population.Ageing is an independent risk factor for severe or critical COVID-19,and the risk of worsening heart failure in PH patients with severe or critical COVID-19 is significantly increased during COVID-19 pandemic.

BACKGROUND: Pathological cardiac hypertrophy is one of the main activators of heart failure. Currently, no drug can completely reverse or inhibit the development of pathological cardiac hypertrophy. To this end, we proposed a silicate ion therapy based on extract derived from calcium silicate (CS) bioceramics for the treatment of angiotensin II (Ang II) induced cardiac hypertrophy. METHODS: In this study, the Ang II induced cardiac hypertrophy mouse model was established, and the silicate ion extract was injected to mice intravenously. The cardiac function was evaluated by using a high-resolution Vevo 3100 small animal ultrasound imaging system. Wheat germ Agglutinin, Fluo4-AM staining and immunofluorescent staining was conducted to assess the cardiac hypertrophy, intracellular calcium and angiogenesis of heart tissue, respectively. RESULTS: The in vitro results showed that silicate ions could inhibit the cell size of cardiomyocytes, reduce cardiac hypertrophic gene expression, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and b-myosin heavy chain (b-MHC), decrease the content of intracellular calcium induced by Ang II. In vivo experiments in mice confirmed that intravenous injection of silicate ions could remarkably inhibit the cardiac hypertrophy and promote the formation of capillaries, further alleviating Ang II-induced cardiac function disorder. CONCLUSION This study demonstrated that the released silicate ions from CS possessed potential value as a novel therapeutic strategy of pathological cardiac hypertrophy, which provided a new insight for clinical trials.

Objective To prepare a sustained-release membrane with longer adhesion time and dissolution time, and compare it with the commercially available oral ulcer membrane. Method Adhesion strength, adhesion time, swelling coefficient, dissolution time, etc. were used as the inspection indicators, and a combination of single factor inspection and analytic hierarchy process were used to screen the membrane -forming materials. The dispersion method of clotrimazole, ornidazole and borneol were investigated to prevent the drug from seed out. The method of combining orthogonal experiment and analytic hierarchy process were used to optimize the dosage of CMC-Na, PVA-1788 and glycerin; and the commercial products were compared. Results Through single-factor investigation and orthogonal experiment, the optimal ratio of excipients was selected as CMC-Na∶PVA-1788∶glycerol (3∶1∶0.08). The water-insoluble component clotrimazole, ornidazole and borneol were treated by precipitation in liquid with good effect. The best method was used to prepare the membrane. The adhesion strength was 102 g. The adhesion time was 55 min. The swelling coefficient was 1 939.52. The average dissolution time was 110 min. The appearance was white and the surface was free of bubbles, soft and elastic. The membrane forming time at 60 ℃ was 300 min and the demolding effect was better which could be completely peeled off with moderate thickness. Conclusion The oral ulcer membrane developed in this method has good appearance, comfortable use, strong adhesion, long adhesion time and dissolution time, and could stay on the ulcer surface for a long time to form physical isolation, and slowly release the drug during the dissolution process, which could play the role of long-term pain relief, antibacterial, anti-inflammatory and promote healing effects on oral ulcers.

Objective:To understand the source and related factors among heterosexual casual partners among male college students for providing AIDS prevention strategies in this population.Methods:Stratified cluster sampling method was used to conduct a questionnaire survey among 31 674 college students in 13 colleges in Zhejiang Province, from October to November, 2018. A total of 2 665 male college students who reported having had heterosexual casual behavior and the source of their sexual partners were recruited. Data on demographic characteristics, knowledge of HIV/AIDS prevention, sexual behavior, and having received AIDS-related interventions were collected. The multivariable logistics regression model was used to analyze the related factors of the source of casual heterosexual behavior partners among male college students.Results:A total of 423 male college students having casual heterosexual sex were investigated, accounting for 15.9% (423/2 665) of the male college students who self-reported having sexual behaviors and informed their sexual partners. Among them, 39.4% (147/373), 37.5% (140/373), and 23.1% (86/373) of participants had 1, 2-4, and 5 or more heterosexual casual sexual partners, respectively. 40.1% (167/416) of participants used condoms consistently with casual partners. 143 (33.8%) participants with social individual's partners were an average age of (20.27±1.40) years old. Multivariate logistic regression analysis showed that: when compared with one person, common acquaintances, and no heterosexual casual partners in the previous year, the factors that related to the source of heterosexual casual partners of male college students appeared as follows: the number of heterosexual casual sexual partners ≥5 (a OR=3.00, 95% CI:1.53-5.89), seeking the casual sexual partners through entertainment venues (a OR=3.04,95% CI:1.64-5.64), male college students having sex with a regular partner in the last one year (a OR=0.41, 95% CI:0.25-0.68). Conclusions:Some of the male college students had heterosexual casual sexual behaviors, with the related factors as having five or more heterosexual casual sexual partners, seeking casual sex partners through entertainment venues, and low condom use. Self-protection awareness and ability should be emphasized to advocate safe sex to reduce the risk of AIDS transmission among college students.

In this article, methods of measuring and evaluating treatment adherence, based on whether they are objective and subjective, are reviewed upon literature examination, and the advantages and disadvantages of each method for different population segments are also discussed.It is intended to provide medical professionals and researchers with a general framework about adherence assessment methods.During treatment and research, medical professionals and researchers should select the most appropriate methods for their purposes and provide effective and personalized evaluation methods to ultimately evaluate and improve patients' medication adherence.