OBJECTIVE To investigate the regulatory effect of autophagy on the resistance of human liver cancer cell Huh7 to lenvatinib. METHODS Using human liver cancer cell Huh7 as subject， the lenvatinib-resist cell model （Huh7-LR） was generated by the low-dose gradient method combined with long-term administration. The sensitivity of parental cell Huh7 and drug-resistant cell Huh7-LR to lenvatinib was detected by using CCK-8 assay and flow cytometry. Western blot assay and GFP-mCherry-LC3 plasmid transfection were performed to detect the expression levels of autophagic protein Beclin-1， autophagic adapter protein sequestosome 1 （p62）， microtubule-associated protein 1 light chain 3 （LC3） and autophagic level. Furthermore， an autophagy activation model was constructed by cell starvation， the protein expression of p62 and autophagy level were detected by using Western blot assay and GFP-mCherry-LC3 plasmid transfection， and the effect of autophagy activation on the sensitivity of Huh7-LR cells to lenvatinib was detected by flow cytometry. RESULTS Compared with parental cells， the drug resistance index of Huh7-LR cells was 6.2； protein expression of p62 was increased significantly， while apoptotic rate， protein expression of Beclin-1 and LC3Ⅱ/ LC3Ⅰ ratio were all reduced significantly （P＜0.05 or P＜0.01）； the level of autophagy was decreased to some extent. Autophagy activation could significantly increase the protein expression of p62 in Huh7-LR cells （P＜0.05） and autophagy level， and significantly increase its apoptotic rate （P＜0.05）. CONCLUSIONS Autophagy is involved in lenvatinib resistance， and activating autophagy can reverse the resistance of liver cancer cells to lenvatinib to some extent.

As prominent immune cells in the central nervous system, microglia constantly monitor the environment and provide neuronal protection, which are important functions for maintaining brain homeostasis. In the diseased brain, microglia are crucial mediators of neuroinflammation that regulates a broad spectrum of cellular responses. In this review, we summarize current knowledge on the multifunctional contributions of microglia to homeostasis and their involvement in neurodegeneration. We further provide a comprehensive overview of therapeutic interventions targeting microglia in neurodegenerative diseases. Notably, we propose microglial depletion and subsequent repopulation as promising replacement therapy. Although microglial replacement therapy is still in its infancy, it will likely be a trend in the development of treatments for neurodegenerative diseases due to its versatility and selectivity.
Humans ; Microglia/physiology* ; Central Nervous System ; Neurodegenerative Diseases/therapy* ; Brain/physiology* ; Homeostasis

Objective:To examine the surgical treatment of Stanford type A aortic dissection (type A dissection) after thoracic endovascular aortic repair (TEVAR).Methods:The data of 58 patients with reoccurrence of type A dissection after TEVAR admitted into the Department of Cardiovascular Surgery, Henan Chest Hospital from February 2012 to January 2020 were analyzed retrospectively. There were 40 males and 18 females, aged (57.0±6.7) years (range: 31 to 71 years). The time between recurrence of type A dissection and TEVAR ( M( Q R)) was 37 days (72.8 months) (range: 1 h to 14 years). Forty-eight cases underwent emergency operation, 9 cases underwent sub-emergency operation, and 1 case died of dissection rupture on the way to the operating room. All 57 patients underwent radical treatment. Fifty-four cases underwent the frozen elephant trunk technique under deep hypothermia circulatory arrest and selective cerebral perfusion, and 3 cases (>65 years old) underwent arch debranch anastomosis+ascending aorta replacement+descending arch covered stent implantation under mild hypothermia. Results:The operation time was (445±32) minutes (range: 382 to 485 minutes), the aortic crossclamp time was (103±19) minutes (range: 89 to 133 minutes), the cardiopulmonary bypass time was (189±27) minutes (range: 162 to 221 minutes), and the intraoperative blood loss was (665±343) ml (range: 450 to 1 750 ml). Postoperative ICU stay time was 5 (6) days (range: 2 to 27 days), and postoperative hospital stay was 14.0 (4.5) days (range: 2 to 36 days). Three cases died, including 2 cases with severe brain complications and 1 case with systemic multiple organ failure caused by severe liver insufficiency and gastrointestinal hemorrhage. Postoperative follow-up was 0.5 to 7.0 years, which showed that 1 case had left coronary artery anastomotic stoma fistula 3 months after operation and underwent reoperation, 2 cases underwent thoracoabdominal aortic replacement again, and the rest of patients had no anastomotic stoma fistula and incomplete stent distortion and expansion on CT angiography. Four cases died during follow-up, and 1 case died of sudden cerebral infarction 2 years after operation.Conclusion:The recurrent type A dissection after TEVAR is mostly related to stent graft, and the patients can undergo operation actively with good prognosis.

Objective:To examine the surgical treatment of Stanford type A aortic dissection (type A dissection) after thoracic endovascular aortic repair (TEVAR).Methods:The data of 58 patients with reoccurrence of type A dissection after TEVAR admitted into the Department of Cardiovascular Surgery, Henan Chest Hospital from February 2012 to January 2020 were analyzed retrospectively. There were 40 males and 18 females, aged (57.0±6.7) years (range: 31 to 71 years). The time between recurrence of type A dissection and TEVAR ( M( Q R)) was 37 days (72.8 months) (range: 1 h to 14 years). Forty-eight cases underwent emergency operation, 9 cases underwent sub-emergency operation, and 1 case died of dissection rupture on the way to the operating room. All 57 patients underwent radical treatment. Fifty-four cases underwent the frozen elephant trunk technique under deep hypothermia circulatory arrest and selective cerebral perfusion, and 3 cases (>65 years old) underwent arch debranch anastomosis+ascending aorta replacement+descending arch covered stent implantation under mild hypothermia. Results:The operation time was (445±32) minutes (range: 382 to 485 minutes), the aortic crossclamp time was (103±19) minutes (range: 89 to 133 minutes), the cardiopulmonary bypass time was (189±27) minutes (range: 162 to 221 minutes), and the intraoperative blood loss was (665±343) ml (range: 450 to 1 750 ml). Postoperative ICU stay time was 5 (6) days (range: 2 to 27 days), and postoperative hospital stay was 14.0 (4.5) days (range: 2 to 36 days). Three cases died, including 2 cases with severe brain complications and 1 case with systemic multiple organ failure caused by severe liver insufficiency and gastrointestinal hemorrhage. Postoperative follow-up was 0.5 to 7.0 years, which showed that 1 case had left coronary artery anastomotic stoma fistula 3 months after operation and underwent reoperation, 2 cases underwent thoracoabdominal aortic replacement again, and the rest of patients had no anastomotic stoma fistula and incomplete stent distortion and expansion on CT angiography. Four cases died during follow-up, and 1 case died of sudden cerebral infarction 2 years after operation.Conclusion:The recurrent type A dissection after TEVAR is mostly related to stent graft, and the patients can undergo operation actively with good prognosis.

OBJECTIVETo compare the clinical therapeutic effects and safety on menopausal symptoms between manual acupuncture (MA) and electroacupuncture (EA).

METHODSFifty patients were randomized into an MA group (25 cases) and an EA group (25 cases). In the MA group, the regular needling technique and pseudo-EA were used at Guanyuan (CV 4), Zigong (EX-CA 1), Tianshu (ST 25) and Sanyinjiao (SP 6). In the EA group, the acupoints were the same as the MA group and stimulated with EA and pseudo-MA (no manipulation applied in treatment), with disperse-dense wave, 10 Hz/50 Hz, 0.5 to 1.0 mA. In the two groups, the needles were retained for 30 min. The treatment was given once every two days, three times a week, totally for 8 consecutive weeks. The results of the menopause rating scale (MRS), the menopause-specific quality of life (MENQOL), the self-rating anxiety scale (SAS) and the self-rating depression scale (SDS), follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E) as well as adverse reactions were evaluated before treatment, in 4 and 8 weeks of treatment separately.

RESULTSCompared with those before treatment, the scores of MRS, MENQOL, SAS and SDS were all reduced in the 4 and 8 weeks of treatment in the two groups (all<0.05). The results in 8 weeks of treatment were lower than those in 4 weeks of treatment in the two groups (all<0.05). The differen-ces were not significant statistically between the two groups (all>0.05). Compared with those before treatment, the levels of FSH and LH reduced and Eincreased after treatment in the two groups, without significant differences (all>0.05). The differences were not significant statistically between the two groups (all>0.05). The severe adverse reactions were not found in the treatment of the two groups.

CONCLUSIONSBoth manual acupuncture and electroacupuncture relieve the symptoms of depression and anxiety in menopausal syndrome,improve the living quality and do not induce apparent changes in serological sex hormones in the patients.

This paper was aimed to study the effect of Qing-Chang Wen-Zhong (QCWZ) decoction on interferon gamma induced protein 10 (IP10) in colon tissues of rats with ulcerative colitis (UC).The UC model was induced using 4.5％ DSS added to distilled water for 7 days.At the same time,low-,medium-and high-dose of QCWZ decoction and mesalazine was given by gavage route daily.Then,the rats were killed and the colon tissues were taken.Expression level of interleukin-1 alpha (IL-1α),IL-1β,IL-6,tumor necrosis factor alpha (TNF-α) and interferon gamma (INF-γ) in colon were detected by Elisa assay.The expression and distribution of IP10 protein were detected by immunohistochemistry (IHC).The results showed that compared with the normal group,inflammatory factors (IL-1α,IL-1β,IL-6,TNF-α,INF-γ) and IP10 expression level in DSS-induced UC rats were significantly increased.After 7 days of intervention,inflammatory factors (IL-1α,IL-1β,IL-6,TNF-α,INF-γ) and IP10 decreased significantly (p＜0.01,p＜0.05).It was concluded that QCWZ decoction may down-regulate the expression of IP 10 and inflammatory factors (IL-1α,IL-1β,IL-6,TNF-α,INF-γ),and then inhibit intestinal inflammation and repair intestinal mucosal damage,so as to achieve the purpose of UC treatment.

OBJECTIVETo correlate the clinical characteristics with mutations of the STK11 and FHIT genes in 16 patients with Peutz-Jeghers syndrome (PJS).

METHODSPotential mutations in the coding regions and flanking sequences of the STK11 and FHIT genes were detected with PCR and Sanger sequencing.

RESULTSOf the 16 patients with PJS, 8 had novel mutations in the coding region of the STK11 gene, 1 had a previously reported mutation. 1 carried a mutation in the exon 10 of the FHIT gene, which is a non-coding region. None of the mutations was detected in the immediate family members. None of the patients with STK11 gene mutations had mutation in the FHIT gene. The mutation rate of the STK11 gene among patients with PJS was 56.25%.

CONCLUSIONMutations of the STK11 gene are the major cause of PJS. Few such patients had mutations of the FHIT gene. Mutations of the FHIT gene may play a part in the pathogenesis of PJS.

Acid Anhydride Hydrolases ; genetics ; Adolescent ; Adult ; Base Sequence ; Child ; DNA Mutational Analysis ; Exons ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation ; Neoplasm Proteins ; genetics ; Pedigree ; Peutz-Jeghers Syndrome ; genetics ; Protein-Serine-Threonine Kinases ; genetics ; Young Adult

Objective To investigate the relationship between serum pregnancy associated plasma protein A (PAAA‐A) ex‐pression and gene polymorphism with the severity of coronary lesions in the patients with coronary heart disease (CHD) .Methods Ninety‐eight patients with CHD in the Nanyang Municipal Central Hospital were selected as the observation group and divided into single vessel lesion group and multiple vessel lesion group according to coronary angiographic results .Ninety‐eight individuals un‐dergoing healthy physical examination were selected as the control group .The venous blood was collected at the visiting hospital in the observation group and at the physical examination in the control group for detecting the serum PAPP‐A protein level by ELISA .PAPP‐A gene and IVS6+ 95 polymorphism were analyzed by adopting polymerase chain reaction restriction fragment length polymorphism(PCR‐RELP) .Results Compared with the control group ,peripheral blood PAPP‐A protein level in the obser‐vation group was significantly increased(P<0 .05) ,moreover the PAPP‐A protein level in the multiple vessel lesion group was sig‐nificantly higher than that of the single vessel lesion group (P<0 .05) .The peripheral blood PAPP‐A level was positively correlated with the severity of CHD .Three genotypes existed in PAPP‐A gene IVS6+95 locus ,including CG heterozygous ,homozygous CC and GG homozygous type .The CC homozygous allele frequency in the patients with multiple vessel lesion was higher than that in the patients with single vessel lesion (P<0 .05) .Conclusion The PAPP‐A protein level and IVS6+95 polymorphism have a close relation with the severity of coronary lesions in patients with CHD .CC genotype may be one of genetic susceptibility gene markers in the patients with CHD .

OBJECTIVETo investigate the preventive effects of garlic oil (GO) on benzene-induced hematotoxicity in mice.

METHODSSpecific pathogen-free male Kunming mice were randomly divided into 5 groups, i.e., control group, model group, and low-, middle-, and high-dose GO groups (n = 20 in each group). Mice in GO groups were orally given GO at 20, 40, or 80 mg/kg BW, while mice in the other two groups received an equal volume of corn oil. Two hours later, mice in model group and GO groups were orally given benzene (20%, v/v, dissolved in corn oil, 10 ml/kg BW) for 21 days consecutively. On the 22nd day, blood was collected from the orbital sinus, to determine the counts of red blood cells (RBC), white blood cells (WBC), and platelets (PLT) and hemoglobin level using an automatic blood cell counter. The mice were sacrificed thereafter. The spleen was excised and weighed for calculation of the spleen index (spleen weight/body weight×100%).

RESULTSThe counts of WBC, RBC, and PLT and Hb level in the model group were reduced by 40%, 18%, 28%, and 23.6%, respectively, as compared with those in the control group (P < 0.01). Compared with those in the model group, WBC and PLT counts in the high-dose GO group increased by 95% and 66%, respectively (P < 0.01), wherein lymphocytes and monocytes increased by 142% and 100%, respectively (P < 0.01); the RBC count and Hb level in the low-dose GO group increased by 15% and 16%, respectively (P < 0.05). GO significantly suppressed benzene-induced decreases in spleen weight and spleen index.

CONCLUSIONGO is capable of suppressing benzene-induced hematotoxicity in mice. One possible mechanism may be promotion of hematopoiesis in the spleen.

Allyl Compounds ; pharmacology ; Animals ; Benzene ; poisoning ; Blood Cell Count ; Disease Models, Animal ; Garlic ; chemistry ; Male ; Mice ; Plant Oils ; pharmacology ; Sulfides ; pharmacology