Background/Aims: Steatotic liver disease (SLD) is a common manifestation in chronic hepatitis C (CHC). Metabolic alterations in CHC are associated with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to elucidate whether hepatitis C virus (HCV) eradication mitigates MASLD occurrence or resolution. Methods: We enrolled 5,840 CHC patients whose HCV was eradicated by direct-acting antivirals in a nationwide HCV registry. MASLD and the associated cardiometabolic risk factors (CMRFs) were evaluated at baseline and 6 months after HCV cure. Results: There were 2,147 (36.8%) patients with SLD, and 1,986 (34.0%) of them met the MASLD criteria before treatment. After treatment, HbA1c (6.0% vs. 5.9%, p<0.001) and BMI (24.8 kg/m2 vs. 24.7 kg/m2, p<0.001) decreased, whereas HDL-C (49.1 mg/dL vs. 51.9 mg/dL, p<0.001) and triglycerides (102.8 mg/dL vs. 111.9 mg/dL, p<0.001) increased significantly. The proportion of patients with SLD was 37.5% after HCV eradication, which did not change significantly compared with the pretreatment status. The percentage of the patients who had post-treatment MASLD was 34.8%, which did not differ significantly from the pretreatment status (p=0.17). Body mass index (BMI) (odds ratio [OR] 0.89; 95% confidence intervals [CI] 0.85–0.92; p<0.001) was the only factor associated with MASLD resolution. In contrast, unfavorable CMRFs, including BMI (OR 1.10; 95% CI 1.06–1.14; p<0.001) and HbA1c (OR 1.19; 95% CI 1.04–1.35; p=0.01), were independently associated with MASLD development after HCV cure. Conclusions HCV eradication mitigates MASLD in CHC patients. CMRF surveillance is mandatory for CHC patients with metabolic alterations, which are altered after HCV eradication and predict the evolution of MASLD.

Objective: To explore the possible neuroprotective activities of Humulus japonicus extract against Parkinson's disease (PD) in a cellular model. Methods: PD was modeled in PC12 cells using 6-hydroxydopamine (6-OHDA). The cell activity, intracellular levels of reactive oxygen species (ROS), anti-oxidative and anti-apoptotic effects, and other related indicators and related signaling pathways were evaluated to elucidate the neuroprotective effects of Humulus japonicus extract. Results: Humulus japonicus extract exhibited anti-oxidative and anti-apoptotic effects in 6-OHDA-stimulated PC12 cells. It also reduced oxidative stress-induced ROS accumulation; upregulated antioxidant enzymes, such as glutathione, catalase, heme oxidase-1, and 8-oxguanine glycosylase 1; promoted cell survival by decreasing BAX and increasing Bcl-2 and sirtuin 1 expression via the MAPK and/or Nrf2 signaling pathways. Conclusions: Humulus japonicus extract has antioxidative and anti-apoptotic effects and could be developed as a promising candidate for preventing and treating oxidative stress-related neurodegenerative diseases.

Background/Aims: Direct‐acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population. Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan. Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10). Conclusions HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.

Major depressive disorder is a complex neuropsychiatric disorder with few treatment options. Non-targeted antidepressants have low efficacy and can induce series of side effects. While a neuropeptide, melanin-concentrating hormone (MCH), is known to exhibit regulator of affective state, no study to date has assessed the anti-depressive effects of MCH in a stress-induced depression model. This study aimed to evaluate the pharmacological effects of intranasal administration of MCH on depression-related behavior in stressed rats and mice. Using a number of behavioral tests, we found that MCH treatment significantly decreased anxiety- and depressive-like behaviors induced by stress. Notably, the effects of MCH were equivalent to those of fluoxetine. MCH treatment also restored the activity of the mammalian target of rapamycin (mTOR) signaling pathway and normalized the levels of synaptic proteins, including postsynaptic density 95, glutamate receptor 1, and synapsin 1, which were all downregulated by stress. Interestingly, the protective effects of MCH were blocked by the mTOR inhibitor, rapamycin. These results suggest that MCH exhibits antidepressant properties by modulating the mTOR pathway. Altogether, this study provides an insight into the molecular mechanisms involved in the antidepressant-like effects of MCH, thereby paving the way for the future clinical application of MCH.

BACKGROUND: Insulin like growth factor 2 (IGF2) is an important embryonic mitosis growth promoting factor, whichplays a critical role in the process of maintaining normal cell growth. The gene expression of IGF2 is under epigeneticregulation in the way of genomic imprinting. Imprinting loss of IGF2 is likely to be associated with the abnormaldevelopment of the individual and tumorigenesis.OBJECTIVE: To investigate the effect of imprinting loss of IGF2 gene on the differentiation of mouse embryonic stemcells into islet-like cells.METHODS: Two kinds of mouse embryonic stem cells (SF1-G and SF1-1) were induced to differentiate into islet-likecells in vitro. The expression of Insulin gene was detected by real-time PCR and cell immunofluorescence. Theexpression of IGF2 was detected by the polymerase chain reaction-restriction fragment length polymorphism in the cellsbefore and after induced differentiation. The level of insulin released at terminal differentiation stage was tested by insulinrelease assay in vitro.RESULTS AND CONCLUSION: (1) There was no change in the imprinting state of the two kinds of mouse embryonicstem cells with normal and imprinted IGF-2 gene before and after differentiation. (2) In the induced cells, the expressionlevel of insulin in the SF1-1 group was higher than that in the SF1-G group, although there was no significant differencein the insulin release between the two kinds of cells. (3)The imprinting loss of IGF-2 gene may be related to theup-regulation of insulin mRNA expression in terminal cells during induced differentiation.

BACKGROUND:Increasing autologous stem cellmobilization is conceived to achieve effectively repair of cardiac ischemic injury. Therefore, it is important to seek a specific and effective mobilization agent. OBJECTIVE:To observe the effects of hypoxia-inducible factor-1α(HIF-1α) on bone marrow mesenchymal stem cellmobilization in myocardial infarction. METHODS:Left anterior descending artery was ligated to establish a rat model of acute myocardial infarction in 90 outbreeding Sprague-Dawley rats, and then the models were randomly divided into three groups. In HIF-1α-antisense oligonucleotide (ASODN) group, HIF-1α-ASODN was infused into the tail vein to restrain the expression of HIF-1αin infarcted ischemic tissue. In HIF-1α-missense oligonucleotide (MSODN) group or control group, an equal volume of HIF-1α-MSODN or saline was injected. RESULTS AND CONCLUSION:After 30 hours and 7 days of modeling, the number of bone marrow mesenchymal stem cells and expression of vascular endothelial growth factor in the peripheral blood of the control group were similar to the HIF-1α-MSODN group, but significantly higher than the HIF-1α-ASODN group. After 7 days of modeling, the expressions of HIF-1αprotein, vascular endothelial growth factor protein and mRNA in the ischemic myocardial tissues of the control group were similar to the HIF-1α-MSODN group, but significantly higher than the HIF-1α-ASODN group. After 7, 14 and 28 days of modeling, the capil ary density in the ischemic myocardial tissues of the control group was similar to the HIF-1α-MSODN group, but significantly higher than the HIF-1α-ASODN group. These findings indicate that after acute myocardial infarction, high expression of HIF-1αexhibits a causal relationship with mobilization of bone marrow mesenchymal stem cells, initiating a series of self-healing process of myocardial tissues.

AIDS is a serious threat to the human health. Although highly active anti-retroviral therapy (HAART) has obviously prohibited the progress of AIDS, a yearly increasing problems of human immunodeficiency virus (HIV) drug resistance have arousing more attention, affecting the clinical efficacy of HAART, and even resulting in treatment failure. We are lack of exchangeable medicines, while the therapeutic course of AIDS treatment is longer. It is not feasible to monitor and detect the drug resistance of medicine takers by taking the exchangeable medicines as the outcome. Better indications have been obtained by combining the experiences for Chinese medicine and pharmacy (CMP) intervention and CMP's intervening HIV drug resistance by clinical trails. Based on retrospective studies on the HIV biological features, reasons for HIV drug resistance, the occurrence, the predisposing population, and the mutation sites, the authors addressed it is a good opportunity for CMP in intervening HIV drug resistance at present situation in China. Meanwhile, the authors also raised too much difficulties and challenges. We hope CMP's intervention can minimize and delay the generation of drug resistance to the utmost, solve key problems in HIV/AIDS prevention and control in China.
Anti-HIV Agents ; pharmacology ; Drug Resistance, Viral ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; HIV ; drug effects ; Humans

Objective To study the expression changes of placental insulin-like growth factor Ⅰ and Ⅱ (IGF-Ⅰ and IGF-Ⅰ) between pregnancies following the in vitro fertilization and embryo transfer (IVF-ET) and those conceived spontaneously.Methods The placenta were collected from 49 cases of pregnancies after IVF-ET(case group) and 49 cases of pregnancies who were normal (control group).The expressions of IGF-Ⅰ and IGF-Ⅱ mRNA in placenta were detected by reverse transcription-polymeras chain reaction (RT-PCR).The levels of IGF-Ⅰ and IGF-Ⅱ protein were determined by immunohistochemistry.Results The mRNA levels of the placental IGF-Ⅰ and IGF Ⅱ were 0.30 ±0.13 and 0.28 ±0.04 in the IVF-ET group,and 0.65 ±0.10 and 0.91 ±0.26 in the control group.The protein levels of the placental IGF-Ⅰ and IGF-Ⅱ were 0.26 ±0.04 and 0.29 ± 0.05 in the IVF-ET group,and 0.32 ± 0.07 and 0.34 ± 0.04 in the control group.The mRNA and protein expressions of IGF-Ⅰ and IGF-Ⅱ in human placenta were significantly decreased in IVF-ET group compared to control group (P ＜ 0.05).The incidence rate of low birth weight infant in IVF-ET group was significantly higher than control(P ＞ 0.05).Conclusions Expressions of placental IGF-Ⅰ and IGF-Ⅱ in the IVF-ET group did not affect fetal growth and development.

OBJECTIVETo summarize and discuss the lapsus and the treatment of the lumbar intervertebral disc herniation using percutaneous endoscopic lumbar discectomy (PELD).

METHODSBetween July 2002 and October 2010, 689 patients with lumbar intervertebral disc herniation treated by PELD were analyzed, including 448 males, and 241 females. Single lumbar intervertebral disc herniation were 669 cases. double lumbar intervertebral disc herniation were 19; three lumbar intervertebral disc herniation were 1. Central type in 66, side central type in 365, lateral type in 242, extreme lateral type in 10, sequestered type in 6. These cases with complications in operation and postoperation were studied retrospectively.

RESULTSThere were nucleus pulposus omissions in 5 patients and 2 patients underwent open resection of nucleus pulposus during operation immediately and the second operation was needed in 3 cases, 1 case with transforaminal lumbar interbody fusion (TLIF) and the others with open resection of nucleus pulposus. Two patients had nerve root injury, but all completely recovered in 3 - 6 months after operation. Spinal dura mater disruption was in 2 patients, recovered after suturing of skin wound. All 689 patients were followed up for 6 - 96 months, mean follow-up time was 33 months. Postoperative spondylodiscitis was in 7 patients, recovery after expectant treatment in 1, percutaneous puncture irrigation and drainage for continued use of local antibiotics in 4, posterior infective lumbar discectomy in 2. Postoperative relapse was in 6 patients, operated secondly by PELD in 4 and by TLIF in 2, recovery after the second operation. Nerve root induced hyperalgesia and burning-like nerve root pain was seen in 19 patients, the symptom was improved by analgesic drug, neurotrophy drug and physiotherapy. The effect of single segment PELD was not good in 10 patients with spinal stenosis, who underwent multiple segment TLIF later.

CONCLUSIONSThe complications during operation usually are nucleus pulposus omissions, nerve root injury, spinal dura mater disruption. Accordingly the complications after operation include spondylodiscitis, recurrence, nerve root induced hyperalgesia or burning-like nerve root pain. Strict indication, aseptic technique, skilled operation and proper rehabilitation exercise are effective ways to reduce complications.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Diskectomy, Percutaneous ; adverse effects ; methods ; Endoscopy ; Female ; Follow-Up Studies ; Humans ; Intervertebral Disc Displacement ; surgery ; Intraoperative Complications ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; Postoperative Complications ; Retrospective Studies ; Treatment Outcome ; Young Adult

BACKGROUNDIt is well known that dehydration can impair bodily functions. To evaluate the impact of hydration status under ambient environmental temperature on the immune system, 25 male collegiate wrestlers were recruited to undergo an experimental dehydration program.

METHODSThirteen subjects had controlled diets with individual energy requirements to prevent body mass loss and restricted water intake to cause 4.52% dehydration; they formed the dehydrated group (DE). These subjects developed a urine specific gravity of about 1.030 in 84 hours. Twelve other subjects had no water restriction and maintained their total body weight comprised the euhydrated group (EU). Peripheral blood monocytes (PBMNC) were isolated after dehydration to perform immune response testing by being incubated with a polysaccharide fraction from fu-ling, Poria cocos (polysaccharide fraction from Poria cocos, PCPS, 1 - 30 £g/L), to prepare a conditioned medium termed conditioned medium of PBMNC stimulated by PCPS (PCPS-MNC-CM). More PCPS (25 µg/L) was needed in the DE group to prepare the PCPS-MNC-CM, which was assayed with a growth inhibitory curve for treated U973 cells.

RESULTSThe treated U937 cells, incubated together with PCPS-MNC-CM from the DE group, exhibited a much lower nitroblue tetrazolium (NBT) positive value of (63.7 ± 4.7)%. The concentration of interferon-gamma (IFN-γ), interleukin (IL)-1β and tumor necrosis factor (TNF)-α in PCPS-MNC-CM from subjects after dehydration was much lower than in the CM from the EU group.

CONCLUSIONThe immune response to PCPS in the DE group was lower than in normally hydrated subjects.

Adolescent ; Adult ; Dehydration ; physiopathology ; Drugs, Chinese Herbal ; chemistry ; Fever ; Humans ; Immunologic Factors ; Interferon-gamma ; metabolism ; Interleukin-1beta ; metabolism ; Leukocytes, Mononuclear ; drug effects ; metabolism ; Male ; Polysaccharides ; chemistry ; immunology ; Tumor Necrosis Factor-alpha ; metabolism ; U937 Cells ; Universities ; Wolfiporia ; Wrestling ; Young Adult