Background::Hepatic ischemia-reperfusion injury (HIRI) remains a common complication during liver transplantation (LT) in patients. As a key downstream effector of the Hippo pathway, Yes-associated protein (YAP) has been reported to be involved in various physiological and pathological processes. However, it remains elusive whether and how YAP may control autophagy activation during ischemia-reperfusion.Methods::Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy activation. Both an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of regulation. Results::Autophagy was activated in the post-perfusion liver grafts during LT in patients, and the expression of YAP positively correlated with the autophagic level of hepatocytes. Liver-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI ( P <0.05). YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models ( P <0.05). Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with 3-methyladenine. In addition, inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species ( P <0.05). Moreover, the regulation of autophagy by YAP during HIRI was mediated by AP1 (c-Jun) N-terminal kinase (JNK) signaling through binding to the transcriptional enhanced associate domain (TEAD). Conclusions::YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of hepatocytes. Targeting Hippo (YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.

Objective:To analyze the risk factors of hypoparathyroidism after thyroid cancer surgery.Methods:The clinical data of 430 patients who underwent total thyroidectomy and central lymph node dissection due to thyroid cancer from Jan. 2021 to Dec. 2021 in the First Ward of Head and Neck Surgery of Sichuan Cancer Hospital were collected. They were divided into two groups according to their parathyroid hormone levels at day 1 and 6 months after surgery: temporary hypoparathyroidism group ( n = 174) and permanent hypoparathyroidism group ( n = 11). and patients with normal parathyroid function were selected as control group (256 cases on postoperative day 1 and 419 cases on postoperative month 6). Gender, age, body mass index, tumor diameter, invasion, central lymph node dissection, parathyroid transplantation, Hashimoto’s thyroiditis, and lymph node dissection in lateral neck region were monitored. The suspicious risk factors of hypoparathyroidism were evaluated by χ2 test and multivariate logistic regression analysis. Results:Univariate analysis showed that women (86.21% vs 77.34%, χ2 = 5.73, P = 0.022) and parathyroid autotransplantation (44.83% vs 28.91%, χ2 = 11.49, P = 0.001) were associated with postoperative transient hypoparathyroidism. The posterior capsule of tumor invasion (81.82% vs 45.11%, χ2 = 5.81, P = 0.016) was associated with postoperative hypoparathyroidism.Multivariate analysis showed that the independent risk factors of transient hypoparathyroidism were female ( P=0.028, OR=1.870), the largest diameter of tumor ( P=0.043, OR=1.595), extravasation of tumor ( P=0.018, OR=1.587), and parathyroid transplantation ( P=0.001, OR=1.966). The independent risk factor of permanent parathyroidism was the posterior capsule of tumor invasion ( P=0.046, OR=4.658) . Conclusions:Female, the largest tumor diameter, tumor invasion and parathyroid transplantation are independent risk factors for transient hypoparathyroidism after total thyroidectomy. The posterior capsule of tumor invasion is an independent risk factor for permanent hypoparathyroidism after total thyroidectomy.

Objective:To summarize the situation of dead newborns and their parents after parents gave up treatment, and analyze the reasons and emotional needs of parents who gave up treatment, so as to provide reference for reducing neonatal mortality and negative emotions of parents.Methods:A retrospective study was conducted to collect the data of neonates and mothers who died after giving up treatment reported in Hunan Children′s Hospital from January 2019 to December 2021. The general information, perinatal risk factors, and the incidence of in-hospital diseases were analyzed. Then, semi-structured interviews were conducted with parents of newborns who died after giving up treatment from February to December 2021. Understand why parents give up treatment and their emotional needs.Results:A total of 172 newborns died after giving up were included in the analysis, including 103 males (59.88%) and 74 premature infants (43.02%); Umbilical cord, placenta and amniotic fluid abnormalities were 21 cases (12.21%), 39 cases (22.67%) and 25 cases (14.53%), respectively. Birth asphyxia was 31 cases (18.02%), including severe asphyxia in 18 cases (10.46%); There were 21 (12.21%), 35 (20.35%) and 30 (17.44%) cases of maternal infection in the third trimester, hypertension in pregnancy and diabetes in pregnancy, respectively. The top three causes of death were septicemia (18.02%), congenital malformation (16.86%) and severe pneumonia (10.47%). The main reason why parents give up treatment was that the child′s disease was critical and irreversible, and parents had strong emotional needs for hospice care in their hearts.Conclusions:There are many high risk factors of perinatal death of newborns after giving up treatment. Sepsis is the primary cause of death, and strengthening perinatal health care is fundamental. Parents have a strong demand for hospice care, so it is of practical significance to implement family-centered hospice care model for such special newborns.

Objective To investigate the role and mechanism of circular RNA SNRK (circSNRK) in ischemia-reperfusion injury (IRI). Methods A hypoxia-reoxygenation (IRI) cell model was established. The expression level of circSNRK after IRI treatment and the effect of overexpression of circSNRK on cell proliferation and apoptosis were detected. The targets of circSNRK were identified. HK2 cells were divided into the blank group (Mock group), IRI group, control plasmid+IRI group (IRI+NC group), human circSNRK overexpression+IRI group (IRI+circSNRK group), human circSNRK overexpression+IRI+protein kinase B (Akt) inhibitor group (IRI+circSNRK+MK2206 group) and control plasmid group (NC group). Cell proliferation and apoptosis were detected in the Mock, IRI, IRI+NC and IRI+circSNRK groups. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the target of circSNRK were carried out. The expression levels of CDKN1A, Akt, B-cell lymphoma (Bcl)-2, cysteinyl aspartate specific proteinase (Caspase)-9 messenger RNA (mRNA), and those of p21, Bcl-2, Caspase-9, Akt and p-Akt proteins were detected in the Mock, IRI, IRI+NC and IRI+circSNRK groups, respectively. Cell proliferation and apoptosis were determined in the NC, IRI+NC, IRI+circSNRK and IRI+circSNRK+MK2206 groups. Results Compared with the Mock group, the expression level of circSNRK was lower, and cell proliferation capability of HK2 cells was decreased and cell apoptosis was increased in the IRI group. In the IRI+circSNRK group, cell proliferation capability was higher, whereas cell apoptosis was lower than those in the IRI+NC group. circSNRK could act on 648 targets through 51 microRNAs (miRNAs). GO enrichment analysis revealed that the targets of circSNRK were mainly enriched in biological processes (such as cell process and biological regulation), cell components (such as cell parts, cells and extracellular parts), and molecular functions (such as binding, binding proteins and enzymes). KEGG enrichment analysis showed that the targets of circSNRK were mainly enriched in cancer signaling pathway, phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway, miRNA in cancer and other related signaling pathways. Compared with the Mock group, the relative expression levels of CDKN1A and Caspase-9 mRNA were higher, the expression level of miR-99a-5p RNA was higher and the relative expression levels of Akt and Bcl-2 mRNA were lower in the IRI group. Compared with the IRI+NC group, the relative expression levels of CDKN1A and Caspase-9 mRNA were lower, those of Akt and Bcl-2 mRNA were higher, and the expression level of miR-99a-5p RNA was lower in the IRI+circSNRK group, and the differences were statistically significant (all P < 0.05). Compared with the Mock group, the expression levels of p21 and Caspase-9 proteins were higher, while those of p-Akt, Akt and Bcl-2 proteins were lower in the IRI group. Compared with the IRI+NC group, the expression levels of p21 and Caspase-9 proteins were lower, whereas those of p-Akt, Akt and Bcl-2 proteins were higher in the IRI+circSNRK group. The miR-99a-5p binding sites were observed in circSNRK and Akt. Compared with the NC group, cell proliferation capability was declined in the IRI+NC group. Compared with the IRI+NC group, cell proliferation capability was elevated in the IRI+circSNRK group. Compared with the IRI+circSNRK group, cell proliferation capability was declined in the IRI+circSNRK+MK2206 group (all P < 0.05). The cell apoptosis level in the IRI+NC group was higher than that in the NC group. The cell apoptosis level in the IRI+circSNRK group was lower compared with that in the IRI+NC group. The cell apoptosis level in the IRI+circSNRK+MK2206 group was higher than that in the IRI+circSNRK group. Conclusions Under IRI conditions, circSNRK may affect the proliferation and apoptosis of HK2 cells probably via the Akt signaling pathway.

Objective:To investigate the clinical characteristics, treatment and prognosis of primary vitreoretinal lymphoma (PVRL) diagnosed and treated in our hospital during the past 10 years.Methods:A retrospective clinical study. From 2011 to 2021, 126 eyes of 67 patients with PVRL who were diagnosed and treated in Department of Ophthalmology, Eye-ENT Hospital, Fudan University were included in the study. Among them, there were 23 males (34.3%, 23/67) and 44 females (65.7%, 44/67); the average age was 57.1 years. There were 59 cases with both eyes (88.1%, 59/67) and 8 cases with one eye (11.9%, 8/67). At the initial eye diagnosis, 22 cases had a clear history of primary central nervous system lymphoma (PCNSL); 5 cases were found to have intracranial lesions by head imaging examination; 40 cases had no central nervous system involvement. Twenty cases were treated with glucocorticoids due to misdiagnosed uveitis. All patients received intravitreal injection of methotrexate (IVM) treatment. The treatment regimen was twice a week in the induction period for 2 weeks, once a week in the consolidation period for 1 month, and once a month in the maintenance period. Patients with PCNSL or both eyes received concurrent systemic chemotherapy (chemotherapy), and some in combination with radiation therapy to the brain (radiotherapy). The mean follow-up time was 39.3 months. The clinical manifestations, treatment and prognosis of the patients were retrospectively analyzed. The visual acuity before and after treatment was compared by t test. Results:Among the 22 cases with a clear history of PCNSL at the initial eye diagnosis, the average time from intracranial diagnosis to eye diagnosis was 22.9 months. Among the 40 cases without central nervous system involvement at first, 14 cases (20.9%, 14/67) developed central nervous system lesions during follow-up period. The mean time from ocular diagnosis to intracranial diagnosis was 9.9 months. Among the 126 eyes, 42 eyes (33.3%, 42/126) had anterior segment inflammation. vitreous inflammation type, retinal type, and vitreous retinal type were 58 (46.0%, 58/126), 7 (5.6%, 7/126), and 61 (48.4%, 61/126) eyes, and 9 of them (7.1%, 9/126) had optic nerve involvement at the same time. Patients received an average of 12 IVM treatments. IVM combined with systemic chemotherapy in 59 cases (88.1%, 59/67), of which 16 cases were combined with brain radiotherapy. All patients achieved complete remission after completing the treatment cycle (100.0%, 67/67). After treatment, 21 eyes (16.7%, 21/126) had ocular recurrence; 22 (32.8%, 22/67) had intracranial recurrence; 8 cases (11.9%, 8/67) died. The mean progression-free survival of patients was 23.7 months; the mean survival time was 43.6 months; the 5-year overall survival rate was 72.5%.Conclusions:The manifestations of PVRL are complex and diverse, and most of them are accompanied by involvement of the central nervous system. It can be divided into vitreitis type, retinal type and vitreoretinal type, and the optic nerve can be involved at the same time; IVM combined with systemic treatment can completely relieve the disease.

Objective To evaluate the clinical efficacy of percutaneous transluminal angioplasty (PTA) combined with stent implantation in the treatment of transplant renal artery stenosis (TRAS) after renal transplantation. Methods Clinical data of 21 patients with TRAS after renal transplantation undergoing PTA combined with stent implantation were retrospectively analyzed. The incidence of TRAS in renal transplant recipients was summarized. The changes of relevant indexes in patients with TRAS were statistically compared before and after interventional treatment. Clinical prognosis of patients with TRAS was evaluated. Results The incidence of TRAS in renal transplant recipients was 4.1%(21/507). TRAS was diagnosed at postoperative 5 (4, 7) months, and 67% (14/21) of patients developed TRAS within postoperative 6 months. Compared with the values before interventional therapy, the serum creatinine level, systolic and diastolic blood pressure and peak flow velocity of transplant renal artery of patients with TRAS were significantly decreased, and the estimated glomerular filtration rate (eGFR) and interlobar arterial resistance index were significantly increased at 1 week and 1 month after interventional therapy (all P < 0.05). During postoperative follow-up after PTA combined with stent implantation, 1 patient suffered re-stenosis of the transplant renal artery, which was improved after simple balloon dilatation. One patient developed pseudoaneurysm formation at the puncture site of the right femoral artery. One patient presented with renal atrophy and loss of function due to atresia of the transplant renal artery. All the remaining 18 patients were well recovered after surgery. Conclusions PTA combined with stent implantation is the optimal treatment of TRAS after renal transplantation, which can significantly improve the function of transplant kidney and considerably prolong the survival time of transplant kidney.

Esophageal cancer is one of the most common malignant tumors of upper digestive tract.Squamous cell carcinoma dominates in China and other parts of Asia,while adenocarcinoma dominates in Europe and the United States.Therefore,there are great differences in the pathogenesis of its biological characteristics and the selection of relevant treatment methods.Currently,surgery is still the preferred method for patients with esophageal cancer.But for patients locally advanced or distant metastases who are inoperable and for patients who are operable but do not want surgery,concurrent chemotherapy with radiotherapy is considered the standard noninvasive treatment.

Objective To evaluate the effect of dexmedetomidine on gastric mucosal injury induced by intestinal ischemia-reperfusion (I/R) in rats.Methods Thirty-six healthy male Sprague-Dawley rats,aged 4-5 months,weighing 200-250 g,were randomly divided into 4 groups (n =9 each) using a random number table:sham operation group (group S),intestinal I/R group (group I/R),low-dose dexmedetomidine group (group LD),and high-dose dexmedetomidine group (group HD).Intestinal I/R was produced by occlusion of the superior mesenteric artery for 1 h followed by 2 h reperfusion in anesthetized rats.Dexmedetomidine 2.5 and 5.0 μg · kg-1 · h-1 were infused via the caudal vein for 1 h starting from 1 h before ischemia in LD and HD groups,respectively.The rats were sacrificed at 2 h of reperfusion,and the gastric mucosa was obtained for examination of the pathological changes (with light microscope) and for determination of the expression of serine/threonine kinase (Akt),phosphorylated Akt (p-Akt),activated caspase-3 and caspase-3 (by Western blot).The ratio of p-Akt to Akt (p-Akt/Akt)was calculated to reflect the phosphorylation of Akt.The ratio of activated caspase-3 to easpase-3 (activated caspase-3/caspase-3) was calculated to reflect the activation of caspase-3.Results Compared with group S,the expression of Akt was significantly up-regulated,the expression of p-Akt was significantly downregulated,the phosphorylation of Akt was significantly decreased,and the activation of caspase-3 was significantly increased in group I/R,and the expression of p-Akt was significantly up-regulated,and the phosphorylation of Akt and activation of caspase-3 were significantly increased in LD and HD groups (P＜0.05).Compared with group I/R,the expression of Akt was significantly down-regulated,the expression of p-Akt was significantly up-regulated,the phosphorylation of Akt was significantly increased,and the activation of caspase-3 was significantly decreased in LD and HD groups (P＜0.05).The degree of gastric mucosal injury was significantly lower in LD and HD groups than in group I/R,and there was no significant difference in the degree of gastric mucosal injury between group LD and group HD.Conclusion Dexmedetomidine can attenuate gastric mucosal injury induced by intestinal I/R,and the mechanism may be related to activation of PI3K/Akt signaling pathways and inhibition of cell apoptosis in rats.

OBJECTIVETo explore the impacts on the life quality and the effect mechanism in the patients of allergic rhinitis (AR) treated with warm acupuncture in winter and summer.

METHODSTwo hundred and forty patients of AR were randomized into a summer and winter acupuncture group, a non-summer and winter acupuncture group and a western medication group, 80 cases in each one. In the two acupuncture groups, Dazhui (GV 14), Fengmen (BL 12), Feishu (BL 13), Pishu (BL 20) and Shenshu (BL 23) were selected. In the summer and winter acupuncture group, the warm acupuncture started at the first day of the three periods of hot season and the first day of the third nine-day period after the winter solstice. The treatment was given once every two days, continuously for 15 times. Totally, 30 treatments were required a year. In the non-summer and winter acupuncture group, the warm acupuncture was applied out of the three periods of the hot season and the third nine-day period after the winter solstice. The treatment was given once every two days and 30 treatments for a year. In the western medication group, cetirizine was taken orally, continuously for 30 days as one session. In the three groups, the treatment for 1 year was taken as one session. The second session started in the next year. Totally, 2 sessions were required. The score of rhinoconjunctivitis quality of life questionnaire (RQLQ) and the level of serum immunoglobulin E (IgE) were compared in the patients' of each group before treatment and in 1 and 2 sessions of treatment.

RESULTSAfter treatment, the scores of 7 domains, named activities, common complaints, practical problems, sleep, ocular symptoms, nasal symptoms and emotions were all improved as compared with those before treatment, in the patients of the three groups (all P < 0.05). After 2 sessions treatment, the results in the summer and winter acupuncture group were better than those in the other two groups (all P < 0.05), and the results in the non-summer and winter acupuncture group were better than those in the western medication group (all P < 0.05). After treatment, serum IgE level was lower averagely than that before treatment in the three groups (all P < 0.05). After 2 sessions treatment, the result in the summer and winter acupuncture group was lower than that in the other two groups (both P < 0.05), and the result in the non-summer and winter acupuncture group was lower than that in the western medication group (P < 0.05). After treatment, the total effective rate was 92.3% (72/78) in the summer and winter acupuncture group, better than 80.5% (62/77) in the non-summer and winter acupuncture group and 69.7% (53/76) in the western medication group (both P < 0.05).

CONCLUSIONThe warm acupuncture in both summer and winter achieves the definite efficacy on AR and the effect mechanism is relevant with reducing serum IgE level.

Acupuncture Points ; Acupuncture Therapy ; instrumentation ; methods ; Adolescent ; Adult ; Female ; Humans ; Male ; Middle Aged ; Quality of Life ; Rhinitis, Allergic ; therapy ; Seasons ; Treatment Outcome ; Young Adult

Objective To study the value of the liver and spleen interventional therapy in primary carcinoma of the liver with hyperspleenism. Methods The treatment was given to 25 patients. Using the method of Seldinger,the 5FRH into artery hepatica propria to infuse 2/3 of the overall dose of chemotherapy medicine and embolism was inserted into the liver segment. Then 1/3 of it was infused into artery lienalis and gelatin sponge was infused into artery lienalis Rr. lienales. Combined regimens were used in chemotherapy: 5-Fu 750mg, EADM 40mg, MMC 10mmg,and 10 of the 25 added DDP 40mg. LUF and gelatin sponge were used for embolisation. Results Of the 25 patients,the WBC and PLT increased in 25 patients 4 weeks after the operation. The difference was significant. The survival rate at 6 and 12 months was 100% and 60% respectively,with 1 case of CR,8 cases of PR and 6 cases of SD. Patients had fever after the treatment but few with abnormal liver function tests. Conclusion Liver and spleen interventional therapy may relieve hyperspleenism and suggests that the treatment of primary carcinoma of the liver is effective.