Association between alcohol consumption and the risk of ovarian cancer: a meta-analysis of prospective observational studies.

BACKGROUND: Alcohol consumption has been inconsistently associated with the risk of ovarian cancer. The purpose of this study was to summarize the data from prospective cohort studies on the relationship between alcohol consumption and ovarian cancer using a meta-analytic approach. METHODS: We performed electronic searches of PubMed, Embase, and the Cochrane Library in May 2014 to identify studies that examined the effects of alcohol consumption on the incidence of ovarian cancer. Only prospective cohort studies that reported effect estimates about the incidence of ovarian cancer with 95% confidence intervals (CIs) of alcohol intake were included. RESULTS: Collectively, we included 13 prospective studies that reported on data from 1,996,841 individuals and included 5,857 cases of ovarian cancer. Alcohol consumption had little to no effect on ovarian cancer incidence when compared to non-drinkers (risk ratio [RR], 1.03; 95% CI, 0.96-1.10; P = 0.473). Similarly, low (RR, 0.96; 95% CI, 0.93-1.00; P = 0.059), moderate (RR, 1.08; 95% CI, 0.92-1.27; P = 0.333), and heavy (RR, 0.99; 95% CI, 0.88-1.12; P = 0.904) alcohol consumption was not associated with the risk of ovarian cancer. Furthermore, subgroup analyses suggested that low alcohol intake was associated with a reduced risk of ovarian cancer whereas heavy alcohol intake was associated with an increased risk of ovarian cancer in multiple subpopulations. CONCLUSIONS: Our study suggests that alcohol intake is not associated with an increased risk of ovarian cancer. Subgroup analyses indicated that alcohol consumption might be associated with the risk of ovarian cancer in specific population or in studies with specific characteristics.

Abnormal sialylation and fucosylation of saliva glycoproteins: Characteristics of lung cancer-specific biomarkers.

Dysregulated surface glycoproteins play an important role in tumor cell proliferation and progression. Abnormal glycosylation of these glycoproteins may activate tumor signal transduction and lead to tumor development. The tumor microenvironment alters its molecular composition, some of which regulate protein glycosylation biosynthesis. The glycosylation of saliva proteins in lung cancer patients is different from healthy controls, in which the glycans of cancer patients are highly sialylated and hyperfucosylated. Most studies have shown that O-glycans from cancer are truncated O-glycans, while N-glycans contain fucoses and sialic acids. Because glycosylation analysis is challenging, there are few reports on how glycosylation of saliva proteins is related to the occurrence or progression of lung cancer. In this review, we discussed glycoenzymes involved in protein glycosylation, their changes in tumor microenvironment, potential tumor biomarkers present in body fluids, and abnormal glycosylation of saliva or lung glycoproteins. We further explored the effect of glycosylation changes on tumor signal transduction, and emphasized the role of receptor tyrosine kinases in tumorigenesis and metastasis.

Temporomandibular joint and Giant Panda's (Ailuropoda melanoleuca) adaptation to bamboo diet.

Here, we present new evidence that evolutionary adaptation of the Ailuripodinae lineage to bamboo diet has taken place by morphological adaptations in the masticatory system. The giant panda in the wild and in captivity removes without an exception the outer skin of all bamboo shoots, rich in abrasive and toxic compounds, by the highly adapted premolars P3 and P4. The temporomandibular joint (TMJ) allows sidewise movement of the jaw and the premolars can, in a cusp-to-cusp position, remove the poorly digestible outer skin of the bamboo before crushing the bamboo with molars. Based on the evidence presented here, we suggest that adaptation of TMJ to lateral movement for enabling cusp-to-cusp contact of premolars is the crucial evolutionary factor as which we consider the key to understand the Ailuropodinae lineage adaptive pathway to utilize the bamboo resource.

Neuroprotective effect and mechanism of butylphthalide after cerebral ischemia-reperfusion injury in rats.

INTRODUCTION: To investigate the neuroprotective effect and mechanism of DL-3-n-butylphthalide (NBP) on the brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) and its downstream signalling pathway after cerebral ischemia/reperfusion injury (CIRI) in rats. MATERIAL AND METHODS: The middle cerebral artery occlusion/reperfusion (MCAO/R) model was used. Reperfusion was performed 2 h after ischemia, and 20 mg/kg of NBP was intraperitoneally injected. Neurological defect score and pathological changes were performed. Apoptotic cells were detected using in situ end-labelling with TUNEL. The expression of BDNF and TrkB proteins was measured by Western blot and immunohistochemical staining. BDNF mRNA, TrkB mRNA, protein kinase B (AKT) mRNA and caspase-3 mRNA expression were measured using real-time polymerase chain reaction (qPCR). RESULTS: After 24 h of reperfusion, the neurological defect score and the percentage of apoptotic cells in the ischemia/reperfusion group (I/R group) were higher than those in the ischemia/reperfusion + drug group (I/R + d group). The positive expressions of BDNF and TrkB mRNA and protein in the I/R + d group were obviously higher than those in the I/R group (p < 0.05). After intervention with the TrkB receptor inhibitor (K252a), the expression levels of BDNF and TrkB and AKT mRNA were significantly decreased in the ischemia/reperfusion + drug + TrkB receptor inhibitor group (I/R + d + R group) compared with the I/R + d group, however the caspase-3 mRNA expression level showed the reverse trend. The expressions of BDNF, TrkB and p-Akt proteins in the I/R + d group were remarkably higher than those in the I/R group at each time point, and reached the peak at 24 hours after reperfusion, which were earlier than that in the I/R group. CONCLUSIONS: Butylphthalide represents a neuroprotective effect after CIRI in rats and used within 24 h of early onset contributes to better prognosis. The underlying mechanism may be related to reducing the apoptosis of nerve cells through BDNF/TrkB signalling pathway.

Muscle ultrasonography in the diagnosis of amyotrophic lateral sclerosis.

Objectives: The aims of this study were to investigate the differences of fasciculations detected by muscle ultrasonography (MUS) among patients with amyotrophic lateral sclerosis (ALS), patients with ALS mimics and healthy controls, and to propose a simplified MUS fasciculation score for the diagnosis of ALS.Methods: We included 16 patients with ALS (ALS group), 10 patients with ALS mimics (disease-control group), and 10 healthy adults (healthy control group). Subjects underwent MUS in 11 muscles, including the tongue, and bilateral upper trapezius, biceps brachii, abductor pollicis brevis, rectus femoris, and tibialis anterior.Results: The number of muscles with fasciculations per person was more in the ALS group (6.44 ± 2.56) than in the disease-control group (1.20 ± 1.87, P = 0.001) and healthy control group (0.50 ± 1.08, P < 0.001). Fasciculations in 3 of 11 muscles could predict the ALS diagnosis with high sensitivity (88.2%) and specificity (94.7%).Conclusions: Fasciculations detected by MUS can be a simple and useful diagnostic tool for ALS.

A brief discussion on the Chinese translation of disease-modifying therapies / 中华神经科杂志

Ever since interferon-β was introduced into China more than 20 years ago and used in the disease-modifying therapies (DMT) of multiple sclerosis (MS) patients, the Chinese translations of DMT used in China are quite puzzling, even clinicians are also difficult to understand the meaning of DMT. The authors searched and traced the origins of current DMT translations, which may be mainly due to the fact that the word "modifying" in Chinese contains two meanings: correction and alleviation, obviously currently used names prefer to correct, while the exact meaning of DMT should be to alleviate disease. Considering that inaccurate translation is widely used in domestic academic conferences and academic journals, it is easy to cause misunderstanding and ambiguity. The authors believe that the meaning of DMT should be correctly and deeply understood in the specific context, and the original meaning of alleviating disease should be returned, which is also in line with the two endpoints of immunomodulatory therapy for MS and optic neuromyelitis spectrum disease, the primary endpoint being to reduce the annual recurrence rate of the diseases, the secondary one being to slow the progression of disease disability.

Clinical analysis of 21 cases of primary Ewing sarcoma of the thoracic wall / 中国癌症杂志

Background and Purpose:Primary Ewing sarcoma of the thoracic wall(PEST)is a rare extraosseous Ewing sarcoma that occurs in the chest wall or thoracic cavity with a short survival,poor prognosis and a high rate of recurrence.Early diagnosis and treatment are the best way to prolong survival time since the cause of PEST is not clear.This study aimed to explore the clinicopathologic characteristics,diagnosis and treatment of PEST to improve clinical understanding of this disease.Methods:A total of 21 cases with PEST were treated at The First Affiliated Hospital of Soochow University,and reviews were published from 2018 to 2023.Clinical data,pathological features,treatment and follow-up of the patients were analyzed respectively.The survival was from the start of treatment to the death of the patient or the end of the follow-up.Cumulative survival was estimated by Kaplan-Meier method.Results:A total of 21 cases with PEST(male/female ratio,13∶8;sites of left/right chest ratio,6∶15;median age,20 years;mean age,28 years;median diameter of the tumor,8.0 cm;mean diameter of the tumor,18.1 cm)met the inclusion criteria.65.2%of the patients presented with the pain in the ipsilateral thoracic and abdominal area.In 47.1%of cases,the ipsilateral ribs were invaded with pleural effusion.Pathological morphology microscopy showed most tumor cells were tightly packed or lobular distribution of small blue round cells.In immunohistochemistry,CD99 and vimentin were positive in 100%and 80%cases respectively while neurogenic markers were expressed to varying degrees.EWSR1 separated signal was found by fluorescence in situ hybridization(FISH),and the EWSR1-FLI1 fusion was detected by next-generation sequencing(NGS)in two cases at our hospital.Two cases received neoadjuvant chemotherapy,10 patients received chemotherapy and radiotherapy after operation,5 cases were treated with radiotherapy only,1 case received surgery only,and 3 cases had no surgical data.A total of 14 cases were followed up for 3-38 month while 7 cases were lost to visit.Cumulative survival correlates with age at disease.The mean survival time was 19.98 months,and the median survival time was 13.00 months.Conclusion:Young males,right chest and the mass larger than 8 cm are more often found.Most cases can be initially diagnosed using histopathology and immunohistochemical markers.FISH or NGS of the EWSR1 gene test are a highly accurate method for diagnosis.The prognosis of PEST is extremely poor,and the cumulative survival rate is negatively correlated with the age of onset.Surgery,radiotherapy and chemotherapy are the main treatments for this disease.

Transthoracic closure of ventricular septal defects guided by transesophageal echocardiography.

BACKGROUND: This study aims to investigate the effectiveness and safety of transthoracic closure of ventricular septal defects totally guided by transesophageal echocardiography. METHODS: A total of 119 patients (62 males, 57 females; mean age 2.1±5.2 years; range, 11 months to 50 years) who underwent transthoracic closure of ventricular septal defects in our center between April 2017 and November 2018 were included. All patients were evaluated in terms of the diameter and morphological features of ventricular septal defects via transesophageal echocardiography. During the procedure, transthoracic echocardiography was used as the only guiding tool for occluder implantation. RESULTS: Of the patients, 116 underwent successful transthoracic device closure procedure. Two patients were switched to surgical repair due to new-onset aortic regurgitation in one patient and severe arrhythmias after device release in the other patient. One patient underwent a second operation for occluder migration during the hospital stay. In the first attempt, 106 ventricular septal defect occluders were correctly positioned. Transthoracic echocardiography revealed the insecure position or significant residual shunting in 10 patients. The original device was replaced with an asymmetric device or a more extensive occluder, and satisfactory results were finally obtained. No complications such as new-onset aortic regurgitation, residual shunt, complete heart block, or device dislodgement occurred during follow-up. CONCLUSION: Transthoracic closure of ventricular septal defects under the total guidance of transthoracic echocardiography is a safe and effective method.

The Investigation and Analysis of the Situation of COVID-19 Vaccination and Vaccination Willingness in HIV/AIDS Population in Yunnan Province / 昆明医科大学学报

Objective To investigate the vaccination status and vaccination willingness of novel coronavirus in HIV/AIDS population in Yunnan.Methods From October 2021 to June 2022,a questionnaire survey was conducted among 2180 HIV/AIDS patients in Kunming,Qujing,Yuxi,Zhaotong,Puer,Baoshan,Lincang,Honghe,Wenshan,Xishuangbanna,Dali,Dehong and Nujiang prefectures.The questionnaire included age,sex,education,nationality,education level,vaccination,adverse reactions within 7 days after the vaccination,safety of COVID-19 vaccine,awareness of effectiveness,vaccination willingness and so on.Results Among the subjects,2109 completed 3 injections,accounting for 96.74%,and 71 were not vaccinated,accounting for 3.26% .Within 7 days of inoculation,local adverse reactions occurred in 116 cases,accounting for 5.50%,and systemic adverse reactions occurred in 56 cases,accounting for 2.66% .Injection site pain,fatigue and muscle pain accounted for the highest proportion of adverse symptoms in different sex,age and the Han nationality,while the proportion of minority adverse reactions was very low,and there was no difference among the different sex and age(P>0.05).The main reasons for the reluctance of HIV/AIDS population to be vaccinated were(recommended by doctors)that HIV/AIDS patients could not be vaccinated(67.61%)and may have serious adverse reactions after the vaccination(19.72%).The factors affecting the vaccination were found by logistic regression analysis,whether they were worried about infecting novel coronavirus(OR = 0.121,95% CI = 0.083～0.640,P<0.001)and how much they knew about COVID-19 vaccine(OR = 28.932,95% CI = 15.469～54.115,P<0.001),safety of vaccination(OR = 13.953,95% CI = 4.819～40.404,P<0.001)and belief in the preventive effect of vaccine(OR = 14.017,95% CI = 4.752～41.348,P<0.001)were significant factors affecting vaccination.Among the 13 prefectures and cities,Dehong(20),Zhaotong(21)and Lincang(14)had the largest number of unvaccinated people.Conclusion After the mass vaccination,the rate of adverse reaction in HIV/AIDS population is low,the symptoms are mild,the correct and scientific advice and guidance from doctors and the full understanding of the harmfulness of the disease,the safety,prevention and effectiveness of the vaccine are the key to complete vaccination and put an end to vaccine hesitancy.

Research progress of return to work in patients with hematological malignancies / 中国实用护理杂志

This review summarized the importance of return to work to patients with hematologic malignancies and their families, the research status at home and abroad, the factors affecting return to work and their intervention status, in order to provide reference for more current research and intervention measures in China.

Clinical-imaging features and prognoses of 8 children with acute encephalopathy combined with biphasic seizures and late reduced diffusion / 中华神经医学杂志

Objective:To summarize the clinical-imaging features and prognoses of acute encephalopathy combined with biphasic seizures and late reduced diffusion (AESD).Methods:A retrospective analysis was performed. The clinical and imaging data and follow-up results of 8 children with AESD, admitted to Departments of Neurology and Rehabilitation Medicine, Wuhan Children's Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from January 2020 to April 2022 were collected.Results:The antecedent infections in 8 children were predominantly gastrointestinal and respiratory tract infections and convulsive seizures occured within 24 h of fever. The clinical presentation was biphasic: 3 had sustained convulsive state in the first phase of the disease, and all showed cluster seizures with worsening impairment of consciousness in the second phase of the disease, including 4 with involuntary movements during recovery from the disease. Seven children required admission to Intensive Care Unit, 4 required tracheal intubation for assisted ventilation, and 1 was combined with septic shock. Brain MRI findings of 8 children were "bright tree" in the second phase of the disease, including bilateral symmetrical and bilateral asymmetrical involvements, with diffuse and focal involvements. All 8 children were treated with glucocorticoids and/or gammaglobulin, and 2 were given mild hypothermia brain protection. Follow-up was performed for more than 3 months, and brain MRI indicated cerebral atrophy, subdural effusion and cerebral malacia. All the 8 children survived with different degrees of sequelae. Two children had Extended Glasgow Outcome Scale scores of 4, 4 had scores of 5, and 2 had scores of 7.Conclusion:AESD is a special clinical-maging syndrome, characterized by biphasic seizure and "bright tree" on head MRI; the survival is high, but neurological sequelae of different degrees are easily left behind.

Therapeutic effects of Danggui Zicao ointment on diabetic pruritus caused by heat and wind in blood / 中国基层医药

Objective:To investigate the clinical efficacy of Danggui Zicao ointment on diabetic pruritus caused by heat and wind in blood. Methods:A total of 197 patients with diabetic pruritus caused by heat and wind in blood who received treatment in Jinhua Hospital of Traditional Chinese Medicine from November 2020 to March 2022 were included in this randomized controlled study. They were randomly divided into a control group ( n = 99) and an observation group ( n = 98). Based on basic hypoglycemic treatment, the control group was given oral levocetirizine hydrochloride tablets, while the observation group was externally given Danggui Zicao ointment. Both groups were treated for 4 successive weeks. Pre- and post-treatment 12-Item Pruritus Severity Scale (12-PSS) score and clinical efficacy were compared between the two groups. Results:After 4 weeks of treatment, the 12-PSS score in each group significantly decreased compared with that before treatment ( t = 18.09, 11.31, both P < 0.05). The 12-PSS score in the observation group was (7.72 ± 1.64) points, which was significantly lower than (9.35 ± 2.18) points in the control group ( t = 3.52, P < 0.05). The total effective rate in the observation group was 87.8% (86/98), which was significantly higher than 76.8% (76/98) in the control group ( χ2 = 4.06, P < 0.05). Conclusion:Danggui Zicao ointment can effectively improve the clinical symptoms of patients with diabetic pruritus caused by heat and wind in blood, improve quality of life, and deserves clinical promotion.

A pedigree study of paroxysmal exercise-induced dyskinesia with Parkinson-like symptoms associated with the expression of the PRRT2 gene in the elderly / 中华老年医学杂志

Objective:To study the clinical and genetic characteristics of familial paroxysmal exercise-induced dyskinesia with Parkinson-like manifestations in the elderly.Methods:Clinical data of 9 family members were analyzed, including 2 patients(both received treatment)consenting to appropriate therapy and prediction protocols.DNA was extracted from peripheral blood samples, and then second-generation sequencing mutation screening.Results:The tremor of two probands in the family was completely brought under control by oxcarbazepine treatment.In 5 family members, a heterozygous mutation of base G>C in exon 2 c. G366C: P.QCon122H at position 29824741 of the PRRT2 gene was found, resulting in the mutation of the amino acid at 122 from glutamine to histidine, which was predicted by SIFT and M-CAP to be harmful.Sanger sequencing of pedigree samples showed that the sisters, brothers and nephews of the proband were heterozygous and their nieces were of the wild type.Conclusions:Q122 of PRRT2 protein can cause the Parkinson-like limb tremor phenotype, and antiepileptic drugs are also effective for paroxysmal exercise-induced dyskinesia in the elderly.

Applicability of Seven Glomerular Filtration Rate Evaluation Formulas in Dose Adjustment of High Concentration of Methotrexate Chemotherapy in Children with ALL / 中国实验血液学杂志

OBJECTIVE@#To investigate the diagnostic efficacy of seven glomerular filtration rate (GFR) evaluation formulas Schwartz2009, Schwartz1976, Counahan-Barratt, Filler, CKD-EPIscysc, Cockrofi-Gault, CKD-EPIScysC-Scr in high concentration of methotrexate (HDMTX) chemotherapy dose adjusted cut-off point (GFR ≤85 ml/min) in children with acute lymphoblastic leukemia (ALL).@*METHODS@#One hundred and twenty-four children with ALL were included in the study. GFR determined by renal dynamic imaging (sGFR) was used as the standard to evaluate the accuracy, consistency of eGFR calculated by seven formulas and sGFR, and the diagnostic efficacy of each formula when the sGFR ≤85 ml/min boundary.@*RESULTS@#All of the accuracy of eGFR estimated by Schwartz2009 were greater than 70% in the 0-3, >4 and ≤6, >6 and ≤9, >9 and ≤16 years old group and male group, and the consistency exceeded the professional threshold. When the sensitivity of the ROC curve sGFR ≤85 ml/min was 100% of CKD-EPIscysc in the 0-3, >3 and ≤4 years old group, Filler in the >3 and ≤4 years old group, and Cockrofi-Gault in the >6 and ≤9 years old group, the specificity was 73.02%, 78.95%, 78.95%, 69.32%, respectively, and the AUC under the ROC curve was the largest (P<0.05).@*CONCLUSION@#Schwartz2009 formula predicts the highest accuracy of eGFR in the 7 glomerular filtration rate. CKD-EPIscysc, Filler, and Cockrofi-Gault formulas have more guiding signi-ficance for the adjustment of HDMTX chemotherapy in pre-adolescence in children with ALL when sGFR ≤85 ml/min.

Meconopsis quintuplinervia Regel Improves Cutibacterium acnes-Induced Inflammatory Responses in a Mouse Ear Edema Model and Suppresses Pro-Inflammatory Chemokine Production via the MAPK and NF-κB Pathways in RAW264.7Cells

Background@#Acne vulgaris (AV) is a common adolescent skin condition which is mainly caused by Cutibacterium acnes overcolonization and subsequent inflammation. @*Objective@#Our previous studies demonstrated that ethanol extracts of Meconopsis quintuplinervia Regel (EMQ) possess significant antimicrobial properties. However, their protective effects and potential mechanisms against AV remain unclear. @*Methods@#In the present study, the EMQ treatment potential for AV was evaluated in a C.acnes-induced mouse ear edema model, and the EMQ anti-inflammatory mechanism was evaluated in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells. @*Results@#The results showed that EMQ alleviated edema formation and inflammatory cell infiltration in an acne mouse model by suppressing inflammatory cytokines interleukin (IL)-6, IL-1β, and tumor necrosis factor α expression. Moreover, EMQ inhibited the phosphorylation of MAP kinases (MAPKs) such as p38, JNK, and ERK, the phosphorylation and degradation of IκB-α and the nuclear translocation of nuclear factor kappa B (NF-κB) p65 in LPS-induced RAW264.7 cells. @*Conclusion@#These findings suggest the potent anti-inflammatory activity of EMQ is possibly through the regulation of the MAPKs and NF-κB signaling pathways. Inhibition of C. acnes activity combined with a powerful anti-inflammatory effect of EMQ indicated its potential as a novel therapeutic option for AV.

Activation of HIF-1α/ACLY signaling axis promotes progression of clear cell renal cell carcinoma with VHL inactivation mutation / 中华病理学杂志

Objective: To explore the potential pathogenesis of clear cell renal cell carcinoma (ccRCC) based on the HIF-1α/ACLY signaling pathway, as well as to provide new ideas for the treatment of ccRCC. Methods: Seventy-eight ccRCC cases diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China were collected. The VHL mutation was examined using exon sequencing. The expression of HIF-1α/ACLY in VHL-mutated ccRCC was evaluated using immunohistochemical staining and further validated in VHL-mutated ccRCC cell lines (786-O, A498, UM-RC-2, SNU-333, and Caki-2) using Western blot. The mRNA and protein levels of ACLY were detected using real-time quantitative PCR and Western blot after overexpression or interference with HIF-1α in ccRCC cell lines. HeLa cells were treated with CoCl2 and hypoxia (1%O2) to activate HIF-1α and then subject to the detection of the ACLY mRNA and protein levels. The potential molecular mechanism of HIF-1α-induced ACLY activation was explored through JASPAR database combined with chromatin immunoprecipitation assay (ChIP) and luciferase reporter gene assay. The effect of HIF-1α/ACLY regulation axis on lipid accumulation was detected using BODIPY staining and other cell biological techniques. The expression of ACLY was compared between patients with ccRCC and those with benign lesions, and the feasibility of ACLY as a prognostic indicator for ccRCC was explored through survival analysis. Results: Exon sequencing revealed that 55 (70.5%) of the 78 ccRCC patients harbored a VHL inactivation mutation, and HIF-1α expression was associated with ACLY protein levels. The protein levels of ACLY and HIF-1α in ccRCC cell lines carrying VHL mutation were also correlated to various degrees. Overexpression of HIF-1α in A498 cells increased the mRNA and protein levels of ACLY, and knockdown of HIF-1α in Caki-2 cells inhibited the mRNA and protein levels of ACLY (P<0.001 for all). CoCl2 and hypoxia treatment significantly increased the mRNA and protein levels of ACLY by activating HIF-1α (P<0.001 for all). The quantification of transcriptional activity of luciferase reporter gene and ChIP-qPCR results suggested that HIF-1α could directly bind to ACLY promoter region to transcriptionally activate ACLY expression and increase ACLY protein level (P<0.001 for all). The results of BODIPY staining suggested that the content of free fatty acids in cell lines was associated with the levels of HIF-1α and ACLY. The depletion of HIF-1α could effectively reduce the accumulation of lipid in cells, while the overexpression of ACLY could reverse this process. At the same time, cell function experiments showed that the proliferation rate of ccRCC cells with HIF-1α knockdown was significantly decreased, and overexpression of ACLY could restore proliferation of these tumor cells (P<0.001). Survival analysis further showed that compared with the ccRCC patients with low ACLY expression, the ccRCC patients with high ACLY expression had a poorer prognosis and a shorter median survival (P<0.001). Conclusions: VHL mutation-mediated HIF-1α overexpression in ccRCC promotes lipid synthesis and tumor progression by activating ACLY. Targeting the HIF-1α/ACLY signaling axis may provide a theoretical basis for the clinical diagnosis and treatment of ccRCC.

Perivascular epithelioid cell tumor of the lung: a clinicopathological analysis of eight cases / 中华病理学杂志

Objective: To investigate the clinicopathological features of perivascular epithelioid cell tumor (PEComa) of the lung. Methods: Eight PEComa cases of the lung diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China from July 2008 to December 2021 were collected and subject to immunohistochemical staining, fluorescence in situ hybridization and next generation sequencing. The relevant literature was reviewed and the clinicopathological features were analyzed. Results: There were 5 males and 3 females, aged from 18 to 70 years (mean 39 years). There were 3 cases of the right upper lung, 3 cases of the left lower lung, 1 case of the left upper lung and 1 case of the right middle lung. Seven cases were solitary and 1 case was multifocal (4 lesions). Seven cases were benign while one was malignant. The tumors were all located in the peripheral part of the lung, with a maximum diameter of 0.2-4.0 cm. Grossly, they were oval and well circumscribed. Microscopically, the tumor cells were oval, short spindle-shaped, arranged in solid nests, acinar or hemangiopericytoma-like patterns, with clear or eosinophilic cytoplasm. The stroma was rich in blood vessels with hyalinization. Coagulated necrosis and high-grade nuclei were seen in the malignant case, and calcification was seen in 2 cases. Immunohistochemically, the tumor cells were positive for Melan A (8/8), HMB45 (7/8), CD34 (6/8), TFE3 (4/7), and SMA (3/8). All cases were negative for CKpan and S-100. TFE3 (Xp11.2) gene fusion was examined using the TFE3 break-apart fluorescence in situ hybridization in 5 cases, in which only the malignant case was positive. The next generation sequencing revealed the SFPQ-TFE3 [t(X;1)(p11.2;p34)] fusion. Follow-up of the patients ranged from 12 to 173 months while one patient was lost to the follow-up. The malignant case had tumor metastasis to the brain 4 years after the operation and then received radiotherapy. Other 6 cases had no recurrence and metastasis, and all the 7 patients survived. Conclusions: Most of the PEComas of the lung are benign. When there are malignant morphological features such as necrosis, high-grade nuclei or SFPQ-TFE3 gene fusion, close follow-up seems necessary.

Biofluid Biomarkers of Alzheimer's Disease: Progress, Problems, and Perspectives / 神经科学通报·英文版

Since the establishment of the biomarker-based A-T-N (Amyloid/Tau/Neurodegeneration) framework in Alzheimer's disease (AD), the diagnosis of AD has become more precise, and cerebrospinal fluid tests and positron emission tomography examinations based on this framework have become widely accepted. However, the A-T-N framework does not encompass the whole spectrum of AD pathologies, and problems with invasiveness and high cost limit the application of the above diagnostic methods aimed at the central nervous system. Therefore, we suggest the addition of an "X" to the A-T-N framework and a focus on peripheral biomarkers in the diagnosis of AD. In this review, we retrospectively describe the recent progress in biomarkers based on the A-T-N-X framework, analyze the problems, and present our perspectives on the diagnosis of AD.

Effects of acteoside on hypoxia/reoxygenation-induced cardiomyocyte damage by regulating the Rnd 3/NF-κB pathway / 中国药房

OBJECTIVE To explore the effects of acteoside on hypoxia/reoxygena tion（H/R）-induced cardiomyocyte damage by regulating Rho family GTPase 3（Rnd3）/nuclear factor κB（NF-κB）pathway. METHODS The H 9c2 cardiomyocyte were divided into control group （no administration ，no modeling ），H/R group （only modeling ），H/R+AS-L group ，H/R+AS-M group ， H/R+AS-H group （10，30，90 μmol/L acteoside for above 3 groups firstly ，and then modeling ），H/R+pcDNA group [transfecting pcDNA （empty vector ） firstly，and then modeling] ，H/R + pcDNA-Rnd 3 group [overexpression of Rnd 3 by transfecting pcDNA-Rnd3（Rnd3 overexpression vector ）firstly，and then modeling] ，H/R+AS-H+si-NC group [transfecting si-NC （negative control）firstly，and then giving 90 μmol/L acteoside and modeling]，H/R+AS-H+si-Rnd3 group [inhibiting overexpression of Rnd 3 by transfecting si-Rnd 3 （Rnd3 small interfering RNA ） firstly，and then giving 90 μ mol/L acteoside and modeling]. After corresponding treatment ，the apoptotic rate ，release of lactate dehydrogenase （LDH），malondialdehyde（MDA）level，the activity of superoxide dismutase （SOD），the level of tumor necrosis factor α（TNF-α），interleukin 1β（IL-1β）and interleukin- 6（IL-6）， mRNA and protein expression of Rnd 3 and NF-κB subunit p65（NF-κB p65），the expression of aspartate proteolytic enzyme 3 （Cleaved Caspase- 3）protein and Cleaved Caspase- 9 protein were detected. RESULTS Different concentrations of acteoside could reduce the apoptotic rate of H/R-induced H 9c2 cardiomyocyte，the protein expressions of Cleaved Caspase- 3 and Cleaved Caspase-9，mRNA and protein expressions of NF-κB p65，the levels of LDH release and MDA ，TNF-α，IL-1β and IL-6，while increase the activity of SOD and mRNA and protein expressions of Rnd 3（P＜0.05），in a dose-dependent manner. Overexpression of Rnd 3 could decrease the apoptotic rate of H 9c2 cardiomyocyte，protein expressions of NF-κB p65，Cleaved Caspase- 3 and Cleaved Caspase- 9， the levels of LDH release ， MDA， TNF-α，IL-1β and IL-6，while increase the protein expression of Rnd 3 and the activity of SOD （P＜0.05）. The inhibition overexpression of Rnd 3 could weaken the inhibitory effects of acteoside on H/R-induced apoptosis of H 9c2 cardiomyocyte， oxidative stress and inflammatory reaction （P＜0.05）. CONCLUSIONS Acteoside could regulate Rnd 3/NF-κ B pathway by promoting the expression of Rnd 3 and inhibiting the expression of NF-κB p65，inhibit cardiomyocyte apoptosis ，oxidative stress and inflammation reaction so as to relieve the H/R-induced cardiomyocyte damage.

Cultivation and characterization of primary human parathyroid cells from patients with severe secondary hyperparathyroidism / 南方医科大学学报

OBJECTIVE@#To establish an cell model of hyperparathyroidism by isolation, in vitro culture, and identification of parathyroid cells from patients with secondary hyperparathyroidism (SHPT).@*METHODS@#The parathyroid gland tissues obtained from 10 patients with SHPT were dissociated by collagenase digestion for primary culture of the parathyroid cells. Morphological changes and growth characteristics of the cells were assessed by microscopic imaging and cell counting. The mRNA and protein expression levels of parathyroid hormone (PTH), calcium-sensing receptor (CaSR), and glial cells missing 2 (GCM2) in the primary and passaged cells were determined by immunofluorescence, qRT-PCR, and Western blotting.@*RESULTS@#Primary cultures of parathyroid cells were successfully obtained. The cells exhibited a high expression of PTH shown by immunofluorescence assay and had a population doubling time of approximately 71.61 h. PTH secretion in the second-passage (P2) cells was significantly lower than that in the primary (P0) and first-passage (P1) cells (P < 0.001). Despite a significant downregulation of CaSR mRNA (P=0.017) and protein (P=0.006) in P1 cells as compared with P0 cells, no significant differences were found in mRNA and protein expressions of PTH or GCM2 between the two cell generations.@*CONCLUSION@#Primary cultures of parathyroid cells isolated from SHPT patients by collagenase digestion show similar biological properties to the cells in vivo.