OBJECTIVE: Photodynamic therapy has become an important method in clinical tumor treatment. This study aimed to investigate the effects of hematoporphyrin on multiple myeloma (MM) and its potential applications. METHODS: The MM cell line RPMI 8226 was treated with hematoporphyrin derivative (HPD), and CCK-8 assay was used to determine cell viability, apoptosis was detected by flow cytometry, intracellular reactive oxygen species (ROS) levels were measured using a detection kit combined with flow cytometry, and Western blot assay was used to detect apoptosis-related proteins and key signaling pathway protein levels. RESULTS: The optimal incubation time for the maximum absorption of HPD in RPMI 8226 cells was 4 hours. HPD significantly inhibited the proliferation of RPMI 8226 cells in a dose- and illumination time-dependent manner ( r =0.981; r =0.961). Additionally, HPD induced apoptosis in RPMI 8226 cells, but had no significant inhibitory effect on peripheral blood mononuclear cells derived from healthy individuals. HPD combined with illumination treatment significantly increased the intracellular ROS level, upregulated the expression of apoptosis-related proteins such as cleaved PARP, cleaved caspase-3 and Bax, and down-regulated the expression of proteins that maintain cell survival, such as NF-κB and Akt. CONCLUSION The HPD can inhibit the proliferation and induce apoptosis of multiple myeloma cells.
Humans ; Multiple Myeloma/pathology* ; Hematoporphyrins/pharmacology* ; Apoptosis/drug effects* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Cell Proliferation/drug effects* ; Photochemotherapy ; Cell Survival/drug effects* ; Signal Transduction

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Humans ; Obesity/prevention & control* ; Healthy Lifestyle

Humans ; Obesity/prevention & control* ; Healthy Lifestyle

Background: The present study investigated the regulatory effects of N6-methyladenosine (m6A) methyltransferase like-3 (METTL3) in diabetes-induced testicular damage. Methods: In vivo diabetic mice and high glucose (HG) treated GC-1 spg cells were established. The mRNA and protein expressions were determined by real-time quantitative polymerase chain reaction, Western blot, immunofluorescence and immunohistochemistry staining. Levels of testosterone, blood glucose, cell viability, and apoptosis were detected by enzyme-linked immunosorbent assay, MTT, and flow cytometry, respectively. Molecular interactions were verified by RNA immunoprecipitation and RNA pull-down assay. Histopathological staining was performed to evaluate testicular injury. Results: METTL3 and long non-coding RNA taurine up-regulated 1 (lncRNA TUG1) were downregulated in testicular tissues of diabetic mice and HG-treated GC-1 spg cells. METTL3 overexpression could reduce the blood glucose level, oxidative stress and testicular damage but enhance testosterone secretion in diabetic mouse model and HG-stimulated GC-1 spg cells. Mechanically, METTL3-mediated m6A methylation enhanced the stability of TUG1, then stabilizing the clusterin mRNA via recruiting serine and arginine rich splicing factor 1. Moreover, inhibition of TUG1/clusterin signaling markedly reversed the protective impacts of METTL3 overexpression on HG-stimulated GC-1 spg cells. Conclusion This study demonstrated that METTL3 ameliorated diabetes-induced testicular damage by upregulating the TUG1/clusterin signaling. These data further elucidate the potential regulatory mechanisms of m6A modification on diabetes-induced testicular injury.

ObjectiveTo compare the effects of programmed intermittent epidural bolus （PIEB） and continuous epidural infusion （CEI） on enhanced recovery after cesarean section. MethodsTotally 120 women scheduled to undergo elective cesarean section under combined spinal and epidural anesthesia， aged 18-45 years， with single fetus， full-term pregnancy （≥37 weeks）， ASA grade II or III， were recruited， with 60 cases in each group. At the end of the surgery， after a similar epidural loading dose， patients were randomLy assigned to receive either PIEB （6 mL·h^-1 beginning 30 minutes after the loading dose） or CEI （6 mL·h^-1， beginning immediately after the loading dose） for the maintenance of analgesia with 0.1% ropivacaine. At 2， 6， 12， 24 and 36 h postoperatively， VAS score was used to evaluate the composite pain， and Bromage Score was used to evaluate the degree of lower extremity motor block. The time to first flatus， time to first ambulation and the satisfaction scores were also recorded. ResultsThe VAS scores at 12， 24 and 36 h postoperatively and the lower extremity motor block scores at 6， 12 and 24 h postoperatively in the PIEB group were significantly lower than those in the CEI group （P < 0.01）. The epidural analgesic dosage was less in the PIEB group than that of the CEI group （P=0.002）. The time to first flatus and time to first ambulation were significantly shorter than those in the CEI group （P < 0.05）. The satisfaction scores were significantly higher in the PIEB group than in the CEI group （P < 0.05）. There was no significant difference in the first urination time after urinary catheter removal and the length of hospital stay between the two groups （P > 0.05）. ConclusionCompared with CEI， PIEB provides better postoperative analgesia， less motor block scores， lower epidural analgesic dosage， shorter the time to first flatus and defecation and time to first ambulation， and greater patient satisfaction， which is more consistent with the ERAS concept of analgesia.

Continuous spermatogenesis depends on the self-renewal and differentiation of spermatogonial stem cells (SSCs). SSCs, the only male reproductive stem cells that transmit genetic material to subsequent generations, possess an inherent self-renewal ability, which allows the maintenance of a steady stem cell pool. SSCs eventually differentiate to produce sperm. However, in an in vitro culture system, SSCs can be induced to differentiate into various types of germ cells. Rodent SSCs are well defined, and a culture system has been successfully established for them. In contrast, available information on the biomolecular markers and a culture system for livestock SSCs is limited. This review summarizes the existing knowledge and research progress regarding mammalian SSCs to determine the mammalian spermatogenic process, the biology and niche of SSCs, the isolation and culture systems of SSCs, and the biomolecular markers and identification of SSCs. This information can be used for the effective utilization of SSCs in reproductive technologies for large livestock animals, enhancement of human male fertility, reproductive medicine, and protection of endangered species.
Adult Germline Stem Cells ; Animals ; Cell Differentiation ; Male ; Spermatogenesis ; Spermatogonia ; Stem Cells

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

OBJECTIVE: To develop a convenient method for rapid purification of fresh Pheretima proteins and assess the inhibitory effect of these proteins against pulmonary fibrosis. METHODS: The crude extract of fresh Pheretima was obtained by freeze-drying method and then purified by size exclusion chromatography. The composition of the purified proteins was analyzed by mass spectrometry. MRC-5 cells were treated with 5 ng/mL TGF-β1 alone (model group) or in combination with SB431542 (2 μmol/L) or the purified proteins (13.125 μg/mL), and the cytotoxicity of purified proteins and their inhibitory effects on cell proliferation were detected with CCK8 assay. Flow cytometry was used to detect the changes in cell apoptosis, and the cellular expressions of α-SMA, Vimentin, E-cadherin, collagen I, Smad2/3 and P-Smad2/3 were detected using RT-PCR and Western blotting. In the animal experiment, adult male C57BL/6 mice were subjected to intratracheal instillation of bleomycin followed by treatment with the purified proteins (5 mg/mL) for 21 days, after which HE and Masson staining was used to observe the pathological changes in the lung tissue of the mice. RESULTS: We successfully obtained purified proteins from fresh Pheretima protein by size exclusion chromatography. Treatment with the purified proteins significantly inhibited TGF-β1-induced proliferation of MRC-5 cells (P < 0.01), reduced the cellular expressions of α-SMA, Vimentin and collagen I (P < 0.001 or P < 0.01), increased the expression of E-cadherin (P < 0.01), and inhibited the expressions of Smad2/3 and P-Smad2/3 (P < 0.001 or P < 0.01). In male C57BL/6 mice models of bleomycin-induced pulmonary fibrosis, treatment with the purified proteins obviously reduced the number of inflammatory cells and fibrotic area in the lungs. CONCLUSION The purified proteins from fresh Pheretima obtained by size exclusion chromatography can inhibit pulmonary fibrosis in mice by regulating the TGF-β/ Smad pathway.
Animals ; Biological Products/pharmacology* ; Bleomycin/adverse effects* ; Cadherins/metabolism* ; Collagen Type I ; Lung/pathology* ; Male ; Mice ; Mice, Inbred C57BL ; Oligochaeta/chemistry* ; Pulmonary Fibrosis/drug therapy* ; Transforming Growth Factor beta1/metabolism* ; Vimentin/metabolism*