Gene mutation profiles and clinicopathological features of patients with non-small cell lung cancer harboring KRAS G12C mutation: a single-center retrospective study / 中华病理学杂志

Objective: To accurately screen non-small cell lung cancer (NSCLC) patients with KRAS G12C mutation and to evaluate their clinicopathological features, prognostic factors and current treatment status. Methods: A total of 19 410 NSCLC cases diagnosed at the Department of Pathology of Shanghai Chest Hospital, Shanghai, China from January 2018 to September 2021 were retrospectively reviewed, and the cases with KRAS gene mutation detected by next-generation sequencing were included. The clinicopathological and genetic mutation data of these cases were collected and analyzed. Results: A total of 1 633 (8.4%) NSCLC patients carried a KRAS gene mutation, among whom G12C was the most frequent (468 cases, 28.7%) mutant subtype. The mutation was more commonly found in males (414/468, 88.5%), patients with a history of smoking (308/468, 65.8%), and patients with a pathological type of invasive adenocarcinoma (231/468, 49.4%). The most common co-mutated genes in KRAS G12C mutant NSCLC were TP53 (52.4%, 245/468), STK11 (18.6%, 87/468) and ATM (13.2%, 62/468). The proportion of PD-L1 expression (≥1%) in KRAS G12C mutant NSCLC was significantly higher than that in patients without G12C mutation [64.3% (90/140) vs. 56.1% (193/344), P=0.014]. Immune checkpoint inhibitors (ICIs) treatment significantly prolonged progression-free survival (PFS) in NSCLC patients (10.0 months vs. 5.0 months, P=0.011). However, combination of chemotherapy and ICIs with anti-angiogenesis inhibitors or multi-target inhibitors did not significantly improve PFS in patients with KRAS G12C mutant NSCLC (P>0.05). Patients with KRAS G12C mutation NSCLC treated with ICIs and KRAS G12C patients with TP53 mutation had significantly longer median PFS than those with STK11 mutation (9.0 months vs. 4.3 months, P=0.012). Conclusions: Patients with KRAS G12C mutant NSCLC have relatively higher levels of PD-L1 expression and can benefit from ICIs treatment. The feasibility of chemotherapy, ICIs therapy and their combination needs further investigation.

Pancreatic glucagonoma with metastasis followed up for 15 years: A case report / 中华内分泌代谢杂志

To explore the clinical characteristics, diagnosis, and management of pancreatic glucagonoma, a retrospective analysis of the clinical data and diagnostic algorithm of a patient with pancreatic glucagonoma was conducted, along with literature review. Pancreatic glucagonoma is a rare neuroendocrine tumor that originates from the pancreatic alpha cells. The main manifestations of glucagonoma syndrome(GS) include necrolytic migratory erythema, diabetes, anemia, and other systemic involvement. Early diagnosis of GS is challenging and crucial. Early identification and recognition of skin lesions contribute to timely diagnosis and treatment of the disease. Surgical resection is an effective treatment modality for glucagonoma.

Inhibition of glutaminolysis alleviates myocardial fibrosis induced by angiotensin II / 生理学报

The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.

Ketogenic diet improves low temperature tolerance in mice by up-regulating PPARα in the liver and brown adipose tissue / 生理学报

The aim of the present study was to investigate the effects of short-term ketogenic diet on the low temperature tolerance of mice and the involvement of peroxisome proliferator-activated receptor α (PPARα). C57BL/6J mice were divided into two groups: normal diet (WT+ND) group and ketogenic diet (WT+KD) group. After being fed with normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The changes in core temperature, blood glucose, blood pressure of mice under low temperature condition were detected, and the protein expression levels of PPARα and mitochondrial uncoupling protein 1 (UCP1) were detected by Western blot. PPARα knockout mice were divided into normal diet (PPARα-/-+ND) group and ketogenic diet (PPARα-/-+KD) group. After being fed with the normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The above indicators were also detected. The results showed that, at room temperature, the protein expression levels of PPARα and UCP1 in liver and brown adipose tissue of WT+KD group were significantly up-regulated, compared with those of WT+ND group. Under low temperature condition, compared with WT+ND, the core temperature and blood glucose of WT+KD group were increased, while mean arterial pressure was decreased; The ketogenic diet up-regulated PPARα protein expression in brown adipose tissue, as well as UCP1 protein expression in liver and brown adipose tissue of WT+KD group. Under low temperature condition, compared to WT+ND group, PPARα-/-+ND group exhibited decreased core temperature and down-regulated PPARα and UCP1 protein expression levels in liver, skeletal muscle, white and brown adipose tissue. Compared to the PPARα-/-+ND group, the PPARα-/-+KD group exhibited decreased core temperature and did not show any difference in the protein expression of UCP1 in liver, skeletal muscle, white and brown adipose tissue. These results suggest that the ketogenic diet promotes UCP1 expression by up-regulating PPARα, thus improving low temperature tolerance of mice. Therefore, short-term ketogenic diet can be used as a potential intervention to improve the low temperature tolerance.

Diagnosis and treatment strategies of 56 cases of middle ear myoclonus / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the clinical characteristics and treatment of middle ear myoclonus. Methods: Fifty-six cases of middle ear myoclonus were enrolled in Shandong Provincial ENT Hospital, Shandong University from September 2019 to August 2021, including 23 males and 33 females. The age ranged from 6 to 75 years, with a median age of 35 years; Forty-seven cases were unilateral tinnitus, nine cases were bilateral tinnitus. The time of tinnitus ranged from 20 days to 8 years. The voice characteristics, inducing factors, nature (frequency) of tinnitus, tympanic membrane conditions during tinnitus, audiological related tests, including long-term acoustic tympanogram, stapedius acoustic reflex, pure tone auditory threshold, short increment sensitivity test, alternate binaural loudness balance test, loudness discomfort threshold, vestibular function examination, facial electromyography, and imaging examination were recorded. Oral carbamazepine and/or surgical treatment were used. The patients were followed up for 6-24 months and the tinnitus changes were observed. Results: Tinnitus was diverse, including stepping on snow liking sound, rhythmic drumming, white noise, and so on. The inducing factors included external sound, body position change, touching the skin around the face and ears, speaking, chewing and blinking, etc. Forty-four cases were induced by single factor and 9 cases were induced by two or more factors. There was no definite inducing factor in 1 case. One patient had tinnitus with epilepsy. One case of traumatic facial paralysis after facial nerve decompression could induce tinnitus on the affected side when the auricle moved. Tympanic membrane flutter with the same frequency as tinnitus was found in 12 cases by otoscopy, and the waveform with the same frequency as tinnitus was found by long-term tympanogram examination. There were 7 patients with no tympanic membrane activity by otoscopy, the 7 cases also with the same frequency of tinnitus by long-term tympanogram examination, but the change rate of the waveform was faster than that of the patients with tympanic membrane flutter. All patients with tinnitus had no change in hearing. One case of tinnitus complicated with epilepsy (a 6-year-old child) was treated with antiepileptic drug (topiramate) and tinnitus subsided. One case suffered from tinnitus after facial nerve decompression for traumatic facial paralysis was not given special treatment. Fifty-four cases were treated with oral drug (carbamazepine), of which 10 cases were completely controlled and 23 cases were relieved; 21 cases were invalid. Among the 21 patients with no effect of carbamazepine treatment, 8 patients were treated by surgery, 7 patients had no tinnitus after surgery, 1 patient received three times of operation, and the third operation was followed up for 6 months, no tinnitus occurred again. The other 13 cases refused the surgical treatment due to personal reasons. Conclusions: Middle ear myoclonus tinnitus and the inducing factors manifestate diversity. Oral carbamazepine and other sedative drugs are effective for some patients, and surgical treatment is feasible for those who are ineffective for medication.

Immunotherapy Based on Tumor Microenvironment in Renal Cell Carcinoma / 中国医学科学院学报

Renal cell carcinoma (RCC) is a common lethal urological cancer,the distant metastasis of which is the leading cause of death.Although targeted agents have remarkably improved the overall prognosis of RCC patients,nearly all the patients eventually acquire therapeutic resistance.With the advent of immune checkpoint inhibitors,immunotherapy based on tumor microenvironment (TME) has shown a broad scope in clinical application.The deepening understanding of TME leads to the changes of therapeutic strategies for advanced RCC,and the combination of targeted therapy and immunotherapy is exhibiting a promising prospect.Herein,we reviewed the TME characteristics,candidate predictive biomarkers,and possible targets for future development of drugs against RCC.

Renal functional compensation after unilateral radical nephrectomy of renal cell carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To investigate factors influencing renal functional compensation(RFC) of the preserved kidney after radical nephrectomy (RN).@*METHODS@#A total of 286 patients treated with RN in Peking University People's Hospital were retrospectively analyzed. Preoperative body mass index (BMI), systolic blood pressure (SBP), history of smoking, history of chronic diseases and other basic information, as well as preoperative blood biochemistry, urine routine, imaging examination results were recorded. All the patients underwent 99mtechnetium-diethylenetriamine pentaacetic acid (99mTc-DTPA) renal scans before operation. The surgical method, pathology and blood creatinine values from 1 month to 60 months after RN were recorded. Preoperative and postoperative estimated glomerular filtration rate (eGFR) was calculated by the chronic kidney disease epidemiology collaboration (CKD-EPI) formula. Renal functional compensation was defined as percent change in eGFR of the preserved kidney after RN compared with the preoperative eGFR. Univariate and multivariate regression analyses were used to identify predictive factors of RFC.@*RESULTS@#Median age was 61 years and 65.4% of the patients were male. Early stage (T1 or T2) tumors were found in 83.6% of the cases. 18.5% of the patients had preoperative diabetes mellitus, 39.5% had hypertension, 19.2% had a history of smoking, and 27.6% were found to have renal cyst on the contralateral side. In the study, 226 cases underwent laparoscopic radical nephrectomy and 60 cases underwent open radical nephrectomy. Renal clear cell carcinoma was the most common pathological type, accounting for 88.5%. The median tumor maximum diameter was 4.5 cm (0.7-13.5 cm). Median renal function compensation was 27% one month after radical nephrectomy. Functional stability was then observed to 5 years. The results of univariate analysis showed that age, gender, preoperative blood uric acid, preoperative urine protein, contralateral renal cyst, and percentage of split renal function of contralateral kidney were correlated with RFC (P < 0.05). Among them, UA level and split renal function of contralateral kidney were strongly negatively correlated with RFC. The results of multivariate linear regression analysis showed age (P < 0.001), blood uric acid (P < 0.001), urine protein (P=0.002), preoperative eGFR (P < 0.001) and the split renal function of contralateral kidney (P < 0.001) were independent predictors of RFC.@*CONCLUSION@#The basic examinations, such as blood biochemistry, urine routine and renal scan before RN are of great significance in predicting the compen-satory ability of the preserved kidney after RN, which is supposed to be taken into consideration when making clinical decision.

Clinical analysis of non-small cell lung cancer patients with leptomeningeal metastasis / 肿瘤研究与临床

Objective:To investigate the treatment, safety and prognosis of advanced non-small cell lung cancer patients with leptomeningeal metastasis and performance status score more than 3.Methods:The clinical data of 6 NSCLC patients with leptomeningeal metastasis admitted to the People's Hospital of Wuhan University from November 2016 to September 2018 were analyzed retrospectively. The curative effect and adverse reactions were observed, and the prognosis was analyzed.Results:There were 5 females and 1 male among 6 patients. The median age was 57 years old (46-74 years old). All 6 patients were diagnosed as stage Ⅳ lung adenocarcinoma. There were 3 patients with epidermal growth factor receptor (EGFR) exon 21 mutation, 2 patients with exon 19 mutation and one with anaplastic lymphoma kinase (ALK) fusion mutation. The time window of leptomeningeal metastasis occurred after the progression of adenocarcinoma of lung: 3 cases was more than 12 months, the other 3 cases was less than 12 months, and the average was 20.3 month. Performance status score was more than 3 when leptomeningeal metastasis occurred. The brain magnetic resonance imaging of 6 patients showed linear enhancement of leptomeningeal, cancer cells were found in cerebrospinal fluid in one case, 4 cases were treated with a combination of bevacizumab and EGFR-tyrosine kinase inhibitor (EGFR-TKI), 1 case was treated with oral administration of EGFR-TKI, 1 case was treated with oral administration of EGFR-TKI combined with temozolomide. The median overall survival (mOS) was 9 months (2-13 months), and the median progression free survival was 6 months (2-11 months).Conclusion:Lung adenocarcinoma may be prone to leptomeningeal metastasis; for NSCLC patients with leptomeningeal metastasis and performance status score more than 3, a combination of EGFR-TKI and bevacizumab has good tolerance, high safety and considerable curative effect.

Effect of Tripterygium Glycosides Tablets in treating rheumatoid arthritis:a systematic review and Meta-analysis / 中国中药杂志

To evaluate the effect of Tripterygium Glycosides Tablets extract in the treatment of rheumatoid arthritis( RA). Clinical trials of treating rheumatoid arthritis with Tripterygium Glycosides Tablets published by Meta-analysis were retrieved from EMbase,PubMed,Clinical Trials,Web of Science,Cochrane Library,CNKI,Wanfang,VIP,CBM and Chi CTR,and comprehensively analyzed. A total of 3 studies were enrolled,the modified Sharp score( m TSS),tender join joint erosions( JE) and joint space narrowing( JSN) of Tripterygium Glycosides Tablets group were significant superior to those of control group,including positive drugs methotrexate( MTX) and salazopyridine( SSZ)( P<0. 01). Tripterygium Glycosides Tablets had an effect in treating RA. Due to the small sample size,this study shall be verified with high-quality,large-sample-size double-blinded RCTs.

Determination of related substances in cinnarizine by supercritical fluid chromatography / 中国药学杂志

OBJECTIVE: To develop a gradient supercritical fluid chromatography method for the separation of cinnarizine and its four related substances. METHODS: Cinnarizine and its four related substances were separated on a Torus DIOL column (3.0 mm×100 mm,1.7 μm) maintained at 40 ℃ with the mobile phase consisting of CO2 and methanol with 0.1% TFA-0.1% TEA at 1.5 mL•min-1, the detection wavelength was set at 230 nm and the back pressure was set at 1.38×107 Pa. RESULTS: Cinnarizine and its four related substances were separated in 4.5 min with satisfying resolutions. Good linear relationships were established between the peak response and the concentration in the range of 2-20 μg•mL-1 for each related substance (r>0.999 9) and the detection limits were 0.7-1.3 ng(S/N≥3). Good linear relationships were established between the peak response and the concentration in the range of 0.05-1.0 μg•mL-1 for cinnarizine (r=1.000 0). The spiked recovery of four related substances of cinnarizine was 98.0%-106.7%, and the RSD was 2.57%-4.44%(n=9). CONCLUSION: The established method can be applied in the simultaneous determination of the related substances of cinnarizine and provide reference for the quality control.

Second-trimester serum IL-1, IL-6, IL-8, TNF-a, CRH levels in prediction of preterm labor / 上海预防医学

[Objective]To determine the relationship between maternal serum IL-1, IL-6, IL-8, TNF-a and CRH levels and preterm labor in asymptomatic women at 24 to 28 weeks' gestation. [Methods] We performed a prospective cohort study from January 2015 to December 2017 for asymptomatic women at 24 to28 weeks' gestation and maternal serum. According to the pregnancy outcome, 100 cases of preterm labor were selected as experimental group and another 100 cases of term labor as control group. The levels of serum IL-1, IL-6, IL-8, TNF-a and CRH were measured by ELISA. The partial membranes of all cases were examined pathologically after labor. [Results] The levels of serum IL-1, IL-6 and IL-8 in preterm labor group were significantly higher than those in the control group (P <0.05). The levels of serum IL-6and IL-8 in preterm labor with chorioamnionitis were significantly higher than those without chorioamnionitis and term labor (P < 0.05). The level of IL-1 in preterm labor without chorioamnionitis was significantly higher than that of term labor (P<0.05). The levels of serum TNF-a and CRH had no difference between the groups (P>0.05). Receiver-operating characteristic curves demonstrated that serum IL-1, IL-6 and IL-8 predicted preterm labor. The area under the curve (AUC) of IL-1 was 0.843. The AUC of IL-6 was0.675 and IL-8 was 0.55. [Conclusion] Maternal serum IL-1, IL-6 and IL-8 in asymptomatic women at24 to 28 weeks' gestation are useful markers for prediction of preterm labor.

Analysis of follow-up results after percutaneous coronary intervention in patients with primary thrombocythemia / 中国介入心脏病学杂志

Objective To analyze the characteristics, treatment and prognosis during follow-up in patients with essential thrombocythemia(ET)after percutaneous coronary intervention(PCI). Methods A total of 9 patients with ET who had CAD and treated with PCI in our hospital from 2010-01 to 2017-07 were retrospectively studied. The basic clinical information with clinical data,data of coronary intervention,application of anti-platelet and platelet reducing drugs,and the results of long-term follow-up were recorded in all patients. Results There were 5 male and 4 female with a mean age of (60.9 ± 14.3) years The 9 patients included 3 cases of acute myocardial infaction(MI),3 cases of old MI,2 cases of unstable angina and 2 cases stable angina. Coronary angiography revealed that there were 4 cases with single vessle involved and 5 cases with two-three vessles involved. All the patients were implante with drug-eluting stents. The mean platelet counts of the patients at admission were(596±233)×109/L. In 4 patients, ET was diagnosed during current hospitalization and their mean platelet counts were(803±105)×109/L. All patients received dual anti-platelet drugs after PCI and 8 patients had hydroxyurea during follow-up. During the follow-up of (53.2±26.9) months,no cardiovascular events occurred. One case of gastrointestinal bleeding occurred during the follow-up due to gastric ulcer. Conclusions Application of platelet reducing therapy with dual anti-platelet drugs in ET patients after PCI is eff ective and safe.

Clinical value of negative pressure vacuum cushion combined with thermoplastic body membrane in radiotherapy for Wilms tumor in children / 中华放射肿瘤学杂志

Objective To investigate the clinical value of negative pressure vacuum cushion combined with thermoplastic body membrane in radiotherapy for Wilms tumor in children.Methods A total of 42 pediatric patients with Wilms tumor who received radiotherapy after surgery were enrolled in the study and were randomly divided into two groups according to the fixation positions:group A and group B.During radiotherapy, the patients in group A were fixed with negative pressure vacuum cushion, and those in group B were fixed by negative pressure vacuum cushion combined with thermoplastic body membrane.The setup errors, short-term effects, adverse reactions, and prognosis were compared between the two groups.ResultsGroup B showed significantly lower translational errors and rotational errors, as well as significantly higher rates of ≤3 mm and ≤5 mm errors, compared with the group A (P=0.04,0.04,0.04,0.03,0.00,0.04,0.04,0.00,0.04).Group B also showed significantly higher complete remission rates and response rates than group A (P=0.02,0.04).There were no significant differences in the adverse reaction rates (P=0.75) and the overall survival (OS) rates at 2 and 3 years (P=0.68,0.74) between the two groups.Group A had the MPTV values in left-right (LR) direction (x-axis), superior-inferior (SI) direction (y-axis), and anterior-posterior (AP) direction (z-axis) being 5.74 mm, 5.93 mm, and 5.94 mm, respectively, and group B had the MPTV values at LR, SI, and AP directions being 4.21 mm, 5.71 mm, and 4.61 mm, respectively.Conclusions In the radiotherapy positioning for Wilms tumor in children, fixation limbs with negative pressure vacuum cushion combined with thermoplastic body membrane effectively reduces the setup errors and improves the effect of radiotherapy, so it holds promise for clinical application.

The Value of Transvaginal Ultrasound in Clinical Surgical Treatment of Cesarean Scar Pregnancy / 华中科技大学学报（医学）（英德文版）

The clinical value of transvaginal ultrasound in clinical surgical treatment of cesarean scar pregnancy (CSP) was evaluated.The clinical data of 104 patients with CSP admitted at Tongji Hospital from 2013 to 2016 were collected and analyzed retrospectively,including the patients' age,gestational age,the size of gestational sac or uneven mass,the uterine scar thickness,β human chorionic gonadotropin (hCG) levels and so on.Of these 104 cases,30 cases were subjected to laparotomy,29 cases to laparoscopy,27 cases to hysteroscopy,16 cases to ultrasound-guided uterine curettage,and 2 cases to conservative treatment.The transvaginal ultrasound showed that uterine scar thickness and gestational sac or uneven mass size had significant difference (P＜0.05) among different surgical methods by comparatively analyzing the patients' data.It was suggested that transvaginal ultrasound may provide the valuable reference for choosing clinical surgical procedures for CSP.

Night Sleep Duration and Risk of Cognitive Impairment in a Chinese Population: A Cross-sectional Study / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Although sleep is one of the most important health-related behavioral factors, the association between night sleep duration and cognitive impairment has not been fully understood. A cross-sectional study was conducted with a random sample of 2,514 participants (⋝ 40 years of age; 46.6% women) in China to examine the association between night sleep duration and cognitive impairment.</p><p><b>METHODS</b>Night sleep duration was categorized as ⋜ 5, 6, 7, 8, or ⋝ 9 h per night. Cognitive function was measured using the Mini-Mental State Examination. A multivariate regression analysis was used to analyze the association of night sleep duration with cognitive impairment. A total of 122 participants were diagnosed with cognitive impairment.</p><p><b>RESULTS</b>A U-shaped association between night sleep duration and cognitive impairment was found. The odds ratios (95% confidence intervals) of cognitive impairment (with 7 h of daily sleep being considered as the reference) for individuals reporting ⋜ 5, 6, 8, and ⋝ 9 h were 2.14 (1.20-3.83), 1.13 (0.67-1.89), 1.51 (0.82-2.79), and 5.37 (1.62-17.80), respectively (P ⋜ 0.01).</p><p><b>CONCLUSION</b>Short or long night sleep duration was an important sleep-related factor independently associated with cognitive impairment and may be a useful marker for increased risk of cognitive impairment..</p>

Regulatory mechanism of PESV on tumor-infiltrating natural killer cells in liver orthotopic transplantation tumor / 中国免疫学杂志

Objective:To investigate the regulatory mechanism of PESV on tumor-infiltrating natural killer ( NK) cells in a mice model with H22 orthotopic transplantation tumor .Methods:Suspensions of H22 cells were injected into the lobe of liver on C 57BL/6 mice for establishing liver orthotopic transplantation tumor model ,then the mice were randomly divided into four groups:normal group , control group ,PESV low dose group ( PESV-L ) and PESV high dose group ( PESV-H ) .Mice were either sacrificed for mechanistic studies or survival followed 14 days of therapy.The volume and weight of the tumor were measured .The proportion of infiltrating NK cells was measured by flow cytometry and the expression of NK 1.1(NK) cells was investigated by immunohistochemistry method .The expression of perforin and granzyme B were further investigated by real-time PCR.Results: In contrast to control group , the tumor inhibition rate was 15.38%and 30.77% in PESV-L group and PESV-H group respectively.The survival showed that PESV-H could significantly prolong the survival time of mice ,and life extension rate was 34.06%,(P<0.05).Histological analysis revealed significant pleomorphism of the neoplastic cells and invasive extendion in control group ,while there were more necrosis and less degree of atypia in PESV-L and PESV-H.The level of tumor-infiltrating NK cell was significantly higher in PESV-H than in tumor-bearing control group [(5.91±0.49)%vs.(3.69±0.50)%,P<0.05],and NK cells were infiltrating in peritumoral lesions.The mRNA of perforin and granzyme B in PESV-H were respectively 3.62 and 5.82 times than that of control group ( P<0.05 ) .Conclusion: These findings suggest that the treatment of PESV might increase the infiltration of natural killer cells in the orthotopic transplantation tumor and contribute to NK cells migration to the tumor , which induct and maintain the activities of natural killer cells against tumor cells by expressing perforin and granzyme B in vivo .

Pterional keyhole approach in surgical treatment of ruptured anterior circulation intracranial aneurysm: a report of 313 cases / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To review the surgical modality with pterional keyhole approach in treatment of anterior circulation aneurysm.</p><p><b>METHODS</b>Three hundred and thirteen patients with ruptured anterior circulation intracranial aneurysm treated surgically with pterional keyhole approach between January 2009 and June 2014 in Department of Neurosurgery, the Second Affiliated Hospital of Zhejiang University School of Medicine, were included in the analysis. Complete occlusion rate of aneurysms and incidence of major complications including delayed cerebral ischemia and chronic hydrocephalus were documented. Surgical outcomes at 6-month follow up were assessed by modified Rankin Scale.</p><p><b>RESULTS</b>Totally 348 aneurysms were treated with pterional keyhole approach, 326 aneurysms were completely clipped, 16 aneurysms were partly clipped, and 6 aneurysms were wrapped with gauze material. Among 313 patients, 15 patients (4.79%) suffered from delayed cerebral ischemia, and 10 patients (3.19%) suffered from hydrocephalus. At the 6-month follow up, the rate of good outcome was 66.77% (209/313).</p><p><b>CONCLUSIONS</b>The pterional keyhole approach can be used to clip most of anterior circulation aneurysms, and it seems to have advantages over the traditional approaches with lower incidence of complications and similar outcomes.</p>

Visualization of endolymphatic hydrops in 3D-FLAIR MRI after intratympanic Gd-DTPA administration in Meniere's disease patients / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the feasibility of endolymphatic visualization and the diagnosis of Meniere's disease by applying intratympanic gadolinium administration through the tympanic membrance and three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging (3D-FLAIR MRI). To study the relationship between the endolymphatic hydrops visualized by MRI and audio-vestibular functional tests, such as pure tone audiometry (PTA), electrocochleography (EcoG), caloric test and vestibular evoked myogenic potential (VEMP).</p><p><b>METHODS</b>With a three Tesla magnetic resonance imaging (MRI) unit, 3D-FLAIR imaging was performed 24 hours after intratympanic gadolinium through the tympanic membrance in 32 patients with clinically diagnosed unilateral Meniere's Disease. We visualized the enhanced imaging of perilymphatic space in bilateral cochlea, vestibular and (or) canal, scoring scala tympani and scala vestibule of bilateral cochlear basal turn respectively and measuring the developing area of bilateral vestibule and the signal intensity ratio (SIR) between the vestibule and the brain stem subjectively. PTA, EcoG, caloric test and VEMP were performed. The relationship between the endolymphatic hydrops visualized by MRI and audio-vestibular functional tests were studied.</p><p><b>RESULTS</b>The gadolinium appeared in almost all parts of the perilymph in cochlea, vestibular and (or) canals in all 32 patients' inner ears, so the endolymphatic space was clearly shown on 3D-FLAIR imaging. The scala vestibuli score value between the affected side and the healthy side were statistically significant (Z = 4.309, P < 0.05) . The developing vestibular area between the affected side and the healthy side [(6.04 ± 2.89) mm(2), (8.28 ± 3.04)mm(2)] were statistically significant (t = 3.322, P < 0.05) . Abnormal vestibular evoked myogenic potentials were significantly correlated with the developing vestibular area of the affected side (F = 11.96, P < 0.05) . Abnormal electrocochleography were significantly correlated with scala vestibuli score value of cochlear basal turn in the affected side (Z = 3.17, P < 0.05) . No significant correlation was found between the scala vestibuli score value or the developing vestibular area and caloric test or PTA findings.</p><p><b>CONCLUSIONS</b>3D-FLAIR MRI with intratympanic gadolinium injection through the tympanic membrance can discriminate the border between the perilymph and the endolymph and show endolymphatic hydrops. This method may provide radiographic reference for the diagnosis of Meniere's disease. The results of VEMP and electrocochleography might have appropriate correlation with degree of vestibular and cochlear hydrops.</p>

Short-term efficacy of semicircular canal occlusion in the treatment of intractable Meniere's disease / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the short-term efficacy and safety of triple semicircular canal occlusion (TSCO) in the treatment of intractable Meniere's disease (MD), so as to provide an alternative surgical procedure for treating MD.</p><p><b>METHODS</b>Seventeen patients, who had received standardized conservative treatment for at least one year with poor effect, underwent TSCO were retrospectively analyzed. Vertigo control and auditory function were evaluated. Pure tone audiometry, caloric test, and vestibular evoked myogenic potential (VEMP) were performed for evaluation of audiological and vestibular function. Postoperative follow-up period was 6 - 13 months, with an average of ten months.</p><p><b>RESULTS</b>According to the preoperative staging of hearing, among the 17 patients, there were 2 cases in stage II (with an average hearing threshold of 25 - 40 dBHL) and 15 in stage III (41 - 70 dBHL). No vertigo was found during the follow-up period, with 100% control rate of vertigo. During the same period, we had performed endolymphatic sac decompression operation in 25 MD patients. The control rate of vertigo was 72.0%. The vertigo control rate of TSCO was significantly higher than that of endolymphatic sac decompression operation (χ(2) = 3.87, P < 0.05). Three months after surgery, 12 patients showed no significant change in comparison to primary status, 5 patients presented with an mild increase in the average hearing threshold of less than 20 dBHL, with 29.4% of hearing loss rate. Post-operatively, all patients suffered from temporary vertigo and balance disorders. Vertigo was disappeared in all patients within 3 days, while, balance disorders were disappeared in 10 patients within 1 - 2 weeks after surgery, and in another 7 patients within 2 months, with an average recovery time of 12.6 days. Three months after treatment, loss of semicircular canal function by caloric test was found in the operation side of all patients and no change in VEMP test was noted. All patients had no facial paralysis, cerebrospinal fluid leakage, and other complications.</p><p><b>CONCLUSIONS</b>TSCO, which can reduce vertiginous symptoms in patients with intractable MD, represents an effective and safe therapy for this disorder. TSCO is expected to be used as an alternative procedure for the treatment of MD in selected patients suffering from moderate to severe hearing loss.</p>

Long-term outcome analysis of patients underwent percutaneous coronary intervention with prior ischemic stroke / 中华心血管病杂志

<p><b>OBJECTIVE</b>To analyze the clinical characteristics and long-term outcomes of patients underwent percutaneous coronary intervention (PCI) with prior ischemic stroke.</p><p><b>METHODS</b>A total of 2053 patients underwent PCI in Peking union medical college hospital from January 2003 to December 2007 were included in this analysis and patients were followed up to December 2009. End-point included all-cause mortality, cardiac death, stent thrombosis, target-lesion revascularization, myocardial infarction, re-cerebral infarction. Major bleeding events were recorded during follow-up.</p><p><b>RESULTS</b>There are 1945 coronary heart disease patients were followed up and 222 patients with prior ischemic stroke. Compared patients without prior ischemic stroke, patients with prior ischemic stroke were older (P = 0.000), had higher hypertension morbidity (P = 0.000), higher diabetes mellitus morbidity (P = 0.005), higher incidence of multi-vessels disease (P = 0.000). During the follow-up of (35.0 ± 19.6) months, cardiac death rate (8.5% vs. 3.9%, P = 0.002) and re-cerebral infarction rate (5.8% vs. 1.4%, P = 0.000) were higher in patients with prior ischemic stroke than patients without prior ischemic stroke. Dual antiplatelet therapy treatment time [(13.77 ± 11.33) months vs. (13.94 ± 11.33) months, P = 0.986] and major bleeding events (5.8% vs. 3.6%, P = 0.100) were similar between the two groups and cerebral hemorrhage rate (1.8% vs. 0.5%, P = 0.028) were higher in patients with prior ischemic stroke than patients without prior ischemic stroke.</p><p><b>CONCLUSION</b>Patients with prior ischemic stroke were associated with increased rate of risk factors, multiple coronary artery disease, cardiac death and re-cerebral infarction and higher cerebral hemorrhage rate during follow-up despite similar dual-anti platelet therapy time.</p>