Huopo Xialingtang is a famous classical formula for treating dampness and warmth， which is included in the Catalogue of Ancient Famous Classical Formulas（The First Batch）. In this paper， bibliometric methods was used to collect the literature related to Huopo Xialingtang， and 16 items of related literature were retrieved， involving five medical books， which were used to textual research on the origin， name， composition， drug dosage， preparation method， processing and main treatment symptoms of this formula. The results indicated that Huopo Xialingtang was originated from Yiyuan written by Shi Funan in the Qing dynasty， and and was later named and extended by He Lianchen. The composition of the proposed formula was consistent with the record of Yiyuan， and the origin of each Chinese materia medica was basically clear. Houpo was the dried bark and root bark of Magnolia officinalis， Zexie was the dried tubers of Alisma orientale， Kuxingren was the dried mature seeds of Prunus armeniaca， Doukou was the dried mature fruits of Amomum kravanh， the origin of Tuhuoxiang was consistent with the 2018 edition of Shanghai Standards of Processing Chinese Crud Drugs， and the origins of the remaining Chinese medicines were consistent with the 2020 edition of Chinese Pharmacopoeia. The converted dose of each Chinese medicine was 7.46 g for Agastache rugosa， 3.73 g for Magnoliae Officinalis Cortex， 8.39 g for Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine， 11.19 g for Poria， 11.19 g for Armeniacae Semen Amarum， 14.92 g for Coicis Semen， 2.61 g for Amomi Fructus Rotundus， 5.60 g for Polyporus， 5.60 g for Alismatis Rhizoma， 14.92 g for Tetrapanacis Medulla. Huopo Xialingtang was initially used for the treatment of dampness and warmth at the beginning of the disease， and was later expanded to treat dampness obstruction， dampness-warming dysentery and so on， but always with the dampness-heat in the lungs and spleen as the pathogenesis. In modern times， the clinical application is more extensive， used in digestive， respiratory， endocrine， nervous system and other types of diseases， especially for chronic gastritis， stomach pain and fever. By combing the ancient literature of Huopo Xialingtang， we verified the origin of the formula and determined the key information of the prescription， which can provide literature reference for the clinical application and drug development of this formula.

Objective To investigate the global burden of visceral leishmaniasis (VL) from 1990 to 2021 and predict the trends in the burden of VL from 2022 to 2035, so as to provide insights into global VL prevention and control. Methods The global age-standardized incidence, prevalence, mortality and disability-adjusted life years (DALYs) rates of VL and their 95% uncertainty intervals (UI) were captured from the Global Burden of Disease Study 2021 (GBD 2021) data resources. The trends in the global burden of VL were evaluated with average annual percent change (AAPC) and 95% confidence interval (CI) from 1990 to 2021, and gender-, age-, country-, geographical area- and socio-demographic index (SDI)-stratified burdens of VL were analyzed. The trends in the global burden of VL were projected with a Bayesian age-period-cohort (BAPC) model from 2022 to 2035, and the associations of age-standardized incidence, prevalence, mortality, and DALYs rates of VL with SDI levels were examined with a smoothing spline model. Results The global age-standardized incidence [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)], prevalence [AAPC = -0.06%, 95% CI: (-0.06%, -0.06%)], mortality [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)] and DALYs rates of VL [AAPC = -2.38%, 95% CI: (-2.44%, -2.33%)] all appeared a tendency towards a decline from 1990 to 2021, and the highest age-standardized incidence [2.55/10⁵, 95% UI: (1.49/10⁵, 4.07/10⁵)], prevalence [0.64/10⁵, 95% UI: (0.37/10⁵, 1.02/10⁵)], mortality [0.51/10⁵, 95% UI: (0, 1.80/10⁵)] and DALYs rates of VL [33.81/10⁵, 95% UI: (0.06/10⁵, 124.09/10⁵)] were seen in tropical Latin America in 2021. The global age-standardized incidence and prevalence of VL were both higher among men [0.57/10⁵, 95% UI: (0.45/10⁵, 0.72/10⁵); 0.14/10⁵, 95% UI: (0.11/10⁵, 0.18/10⁵)] than among women [0.27/10⁵, 95% UI: (0.21/10⁵, 0.33/10⁵); 0.06/10⁵, 95% UI: (0.05/10⁵, 0.08/10⁵)], and the highest mortality of VL was found among children under 5 years of age [0.24/10⁵, 95% UI: (0.08/10⁵, 0.66/10⁵)]. The age-standardized incidence (r = -0.483, P < 0.001), prevalence (r = -0.483, P < 0.001), mortality (r = -0.511, P < 0.001) and DALYs rates of VL (r = -0.514, P < 0.001) correlated negatively with SDI levels from 1990 to 2021. In addition, the global burden of VL was projected with the BAPC model to appear a tendency towards a decline from 2022 to 2035, and the age-standardized incidence, prevalence, mortality and DALYs rates were projected to be reduced to 0.11/10⁵, 0.03/10⁵, 0.02/10⁵ and 1.44/10⁵ in 2035, respectively. Conclusions Although the global burden of VL appeared an overall tendency towards a decline from 1990 to 2021, the burden of VL showed a tendency towards a rise in Central Asia and western sub-Saharan African areas. The age-standardized incidence and prevalence rates of VL were relatively higher among men, and the age-standardized mortality of VL was relatively higher among children under 5 years of age. The global burden of VL was projected to continue to decline from 2022 to 2035.

Objective To study the cellular senescence and molecular mechanism of olaparib in MCF-7 breast cancer cells.Methods The effects of olaparib on the proliferation and migration of MCF-7 cells were detected dynamically by real-time cell analysis(RTCA)technology.The effects of olaparib on the Senescence was detected by using the senescence-associated β-galactosidase(SA-β-gal).Quantitative polymerase chain reaction was used to analyze the effects of olaparib on the expression levels of genes encoding the senescence-associated factors p16,p21,C/EBP homologous protein,interleukin(IL)-6,IL-8,plasminogen activator inhibitor 1,phosphatase and tensin homolog deleted on chromosome 10,p27,retinoblastoma gene,Ki67,and E2F1.The effects of olaparib on the expression levels of the senescence-associated proteins p21,γH2AX,pRB,cyclin D1,insulin-like growth factor binding protein 3,and Ki67 were analyzed by Western Blot.Results Olaparib inhibited the proliferation and migration and induced the senescence of MCF-7 cells.Long-term(96 h)treatment with olaparib significantly up-regulated the gene expression levels of p16,p21,p27,C/EBP homologous protein,IL-6,IL-8,plasminogen activator inhibitor 1,phosphatase and tensin homolog deleted on chromosome 10,and retinoblastoma protein(P＜0.01)and significantly down-regulated the gene expression levels of Ki67 and E2F1(P＜0.01)in MCF-7 cells.Olaparib significantly increased protein expression levels of p21,γH2AX,and insulin-like growth factor binding protein 3 in MCF-7 cells(P＜0.01,P＜0.01,P＜0.05)and significantly decreased cyclin D1,pRB,and Ki67 levels(P＜0.05,P＜0.01,P＜0.05).Conclusions Olaparib can inhibit proliferation and migration and induce senescence in MCF-7 breast cancer cells.

Objective:To study the clinical features, treatment and prognosis of multiple myeloma (MM)complicated with extramedullary disease (EMD).Methods:A total of 65 patiens admitted to the Characteristic Medical Center and Tianjing First Central Hospital from January 2014 to May 2020 were analyzed retrospectively as the study subjects. The age ranged from 22 to 79 years, with a median age of 56(22,79) years, and the ratio of female to male was 27/38. They were respectively treated by chemotherapy, radiotherapy or autologous hematopoietic stem cell transplantation (AHSCT). Fluorescence in situ hybridization (FISH) was used in all 65 patients to detect t(4;14), t(14;16), 1q21, del(17p). The measurement data of non-normal distribution were expressed in M (Q1,Q3), and the survival curve was constructed by Kaplan-Meier method.Result:The increase of β2- microglobulin and lactate dehydrogenase, multiple osteolytic lesions were found in all patients. The most common rate of chromosomal abnormalities were10.8% for t(4;14), 16.9% for t(14;16), 18.5% for 1q21, 21.5% for del(17p). Both 1q21 and del(17p) were co-existed in 7.7% of patients. The effective rate of 65 patients treated with V-DRPACE regimen was 89.2%(58/65). Thirty-two patients who were in partial remission were treated with radiotherapy. The complete remission rate of radiotherapy was 18.8%(6/32). Twenty patients eligible for transplantation underwent AHSCT and 13 patients achieved complete remission. At the end of follow-up, the median overall survival(OS) of 65 patients was 44.8 months, and progression-free survival (PFS) was11 months.Conclusion:MM with EMD usually involve multiple sites, prone to multiple osteolytic lesions, increased β2- microglobulin and lactate dehydrogenase. The rate of cytogenetic abnormalities in such patients is significantly increased. The V-DRPACE regimen is effective in treating MM patients with extramedullary lesions and can benefit from AHSCT.

Purpose: Male overweight and obesity could affect sperm quality and reproductive health. However, the impact of body mass index (BMI) on assisted reproductive technology (ART) outcomes in oligospermia and/or asthenospermia patients is yet lacking. This study aims to assess the impact of paternal BMI on ART and neonatal outcomes among oligozoospermia and/or asthenospermia patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Materials and Methods: In this study, 2,075 couples undergoing their first fresh embryo transfer between January 2015 and June 2022 were recruited. Following the World Health Organization’s (WHO’s) categories, couples were stratified into three cohorts based on paternal BMI: normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), and obese (≥30.0 kg/m2). Modified Poisson regression models were used to assess the associations of paternal BMI with fertilization, in vitro embryonic development, and pregnancy outcomes. Logistic regression models were performed to investigate the associations of paternal BMI with pregnancy loss and neonatal outcomes. Furthermore, stratified analyses were performed based on fertilization methods, male infertility cause, and maternal BMI. Results: Higher paternal BMI is associated with a lower likelihood of achieving normal fertilized (p-trend=0.002), Day 3 transferable (p-trend=0.007), and high-quality embryos (p-trend=0.046) in IVF cycles, rather than in ICSI cycles. Paternal BMI of oligospermia or asthenospermia was negatively correlated with day 3 transferable (p-trend=0.013 and 0.030) and high-quality embryos (p-trend=0.024 and 0.027). Moreover, for neonatal outcomes, paternal BMI was positively associated with macrosomia (p-trend=0.019), large for gestational age (LGA) (p-trend=0.031), and very LGA (p-trend=0.045). Conclusions Our data suggested that higher paternal BMI was associated with fetal overgrowth, reduced fertilization, and embryonic development potential. Among males with oligospermia and/or asthenospermia, the impact of overweight and obesity on the choice of fertilization method and the long-term effects on their offspring need to be further investigated.

Adult ; Atherosclerosis ; Cardiovascular Diseases ; China ; Habits ; Humans ; Lipids

Objective:To investigate the effect of ionizing radiation on the ferroptosis of skin cells and the potential therapeutic strategy of ferroptosis inhibitor Ferrostatin-1 (Fer-1) on irradiated skin cells.Methods:HaCaT cells were pre-treated with Fer-1 before X-ray irradiation. After irradiation, CCK-8 assay and LDH release assay were used to detect cell viability and cell death, flow cytometry was used to detect the lipid peroxidation levels, crystal violet staining assay was used to detect colony forming ability, and the expressions of ferroptosis related proteins ACSL4 and GPX4 were detected by Western blot.Results:The cell viability of HaCaT cells was significantly decreased ( t=5.63, 8.74, P<0.05) and the release of LDH was significantly increased ( t=3.98, 5.08, 9.27, P<0.05) after different doses of X-ray irradiation. The cell viability was improved ( t=5.79, P<0.05) and the release of LDH was reduced ( t=12.36, 11.96, 18.13, 9.96, P<0.05) after the pre-treatment with Fer-1. The lipid peroxidation levels of HaCaT cells were significantly increased ( t=9.59, P<0.05) and the clonogenic survival ability were reduced ( t=4.26, P<0.05) after 10 Gy X-ray irradiation, while Fer-1 pre-treatment reduced ( t=6.48, 17.04, P<0.05) the increase of lipid peroxidation level induced by X-ray irradiation and also effectively restore ( t=3.96, P<0.05) the clonogenic survival ability. The expressions of ACSL4 and GPX4 were decreased after 10 Gy X-ray irradiation, while they recovered to normal level ( t=5.23, 7.16, 4.78, 8.29, 6.43, P<0.05) after the pre-treatment with Fer-1. Conclusions:Ferroptosis inhibitor Fer-1 alleviates the progress of radiation-induced skin injury by inhibiting ferroptosis after ionizing radiation at the cellular level, which provides a potential strategy for the protection of radiation injury.

This study aimed to investigate whether β-elemene could improve the dysfunction of vascular endothelial cells induced by low shear force (LSS), and the proliferation and migration of vascular smooth muscle cells induced by oxidized low-density lipoprotein (ox-LDL). Parallel plate flow chambers and ox-LDL were used to establish vascular endothelial cells (ECs) dysfunction model and vascular smooth muscle cell (VSMCs) proliferation and migration model, respectively, and the effects of β-elemene on ECs dysfunction and VSMCs proliferation and migration were examined. The activity of ROS in ECs was measured by DHE and the activity of NO in ECs was tested by DAF-FM DA. The protein phosphorylation of Akt and ERK in ECs were detected by Western blot. The proliferation of VSMCs was measured by MTT. The migration of VSMCs was examined by cell scratch test and Transwell assay. The gene expression of MMP-2 and MMP-9 in VSMCs was measured by RT-qPCR. In ECs, β-elemene could significantly reduce the LSS-induced increase in ROS, significantly increase the LSS-induced decrease in NO, decrease the phosphorylation of ERK, and increase the phosphorylation of Akt. In VSMCs, β-elemene could significantly reduce the proliferation and migration of VSMCs induced by ox-LDL, and reduce the gene expression of MMP-2 and MMP-9. To conclude, β-elemene can improve the LSS-induced ECs dysfunction and ox-LDL-induced VSMCs proliferation and migration.

Objective: To determine whether T1 mapping could monitor the dynamic changes of injury in myocardial infarction (MI) and be histologically validated. Materials and Methods: In 22 pigs, MI was induced by ligating the left anterior descending artery and they underwent serial cardiovascular magnetic resonance examinations with modified Look-Locker inversion T1 mapping and extracellular volume (ECV) computation in acute (within 24 hours, n = 22), subacute (7 days, n = 13), and chronic (3 months, n = 7) phases of MI. Masson’s trichrome staining was performed for histological ECV calculation. Myocardial native T1 and ECV were obtained by region of interest measurement in infarcted, peri-infarct, and remote myocardium. Results: Native T1 and ECV in peri-infarct myocardium differed from remote myocardium in acute (1181 ± 62 ms vs. 1113 ± 64 ms, p = 0.002; 24 ± 4% vs. 19 ± 4%, p = 0.031) and subacute phases (1264 ± 41 ms vs. 1171 ± 56 ms, p < 0.001; 27 ± 4% vs. 22 ± 2%, p = 0.009) but not in chronic phase (1157 ± 57 ms vs. 1120 ± 54 ms, p = 0.934; 23 ± 2% vs. 20 ± 1%, p = 0.109). From acute to chronic MI, infarcted native T1 peaked in subacute phase (1275 ± 63 ms vs. 1637 ± 123 ms vs. 1471 ± 98 ms, p < 0.001), while ECV progressively increased with time (35 ± 7% vs. 46 ± 6% vs. 52 ± 4%,p < 0.001). Native T1 correlated well with histological findings (R2 = 0.65 to 0.89, all p < 0.001) so did ECV (R2 = 0.73 to 0.94, all p < 0.001). Conclusion T1 mapping allows the quantitative assessment of injury in MI and the noninvasive monitoring of tissue injury evolution, which correlates well with histological findings.

Objective: To determine whether T1 mapping could monitor the dynamic changes of injury in myocardial infarction (MI) and be histologically validated. Materials and Methods: In 22 pigs, MI was induced by ligating the left anterior descending artery and they underwent serial cardiovascular magnetic resonance examinations with modified Look-Locker inversion T1 mapping and extracellular volume (ECV) computation in acute (within 24 hours, n = 22), subacute (7 days, n = 13), and chronic (3 months, n = 7) phases of MI. Masson’s trichrome staining was performed for histological ECV calculation. Myocardial native T1 and ECV were obtained by region of interest measurement in infarcted, peri-infarct, and remote myocardium. Results: Native T1 and ECV in peri-infarct myocardium differed from remote myocardium in acute (1181 ± 62 ms vs. 1113 ± 64 ms, p = 0.002; 24 ± 4% vs. 19 ± 4%, p = 0.031) and subacute phases (1264 ± 41 ms vs. 1171 ± 56 ms, p < 0.001; 27 ± 4% vs. 22 ± 2%, p = 0.009) but not in chronic phase (1157 ± 57 ms vs. 1120 ± 54 ms, p = 0.934; 23 ± 2% vs. 20 ± 1%, p = 0.109). From acute to chronic MI, infarcted native T1 peaked in subacute phase (1275 ± 63 ms vs. 1637 ± 123 ms vs. 1471 ± 98 ms, p < 0.001), while ECV progressively increased with time (35 ± 7% vs. 46 ± 6% vs. 52 ± 4%,p < 0.001). Native T1 correlated well with histological findings (R2 = 0.65 to 0.89, all p < 0.001) so did ECV (R2 = 0.73 to 0.94, all p < 0.001). Conclusion T1 mapping allows the quantitative assessment of injury in MI and the noninvasive monitoring of tissue injury evolution, which correlates well with histological findings.