Objective:To investigate the clinicopathological features and differential diagnosis of eosinophilic vacuolated tumor (EVT).Methods:Seven cases of EVT with characteristic morphology and unequivocal diagnosis from the Affiliated Hospital of Qingdao University (6 cases), Qingdao, China and the 971 Hospital of PLA Navy (1 case), Qingdao, China between January 2010 and December 2021 were subject to morphological and immunohistochemical analyses. Additionally, whole exome sequencing (WES) was performed in two cases. Twenty-two cases of renal oncocytoma (RO) and 17 cases of eosinophilic chromophobe renal cell carcinoma (eChRCC) diagnosed at the same time were used as controls.Results:Four males and three females with a mean age of 42 years (range: 29-61 years) were included in the study. The tumors were nodular and well-circumscribed, with sizes ranging from 1.5 to 4.5 cm. On cross-section, they appeared gray-red or gray-white, solid, and soft. Tumor cells were arranged in nests, solid sheets, and acinar or small vesicular structures. These cells exhibited eosinophilic cytoplasm with large, prominent clear vacuoles and round nuclei with prominent nucleoli. Perinuclear halos were focally present in four cases, while small tumor cells with sparse cytoplasm and hyperchromatic nuclei were seen in one case. No necrosis or mitosis was noted. Edematous stroma was detected in three cases. All tumors were positive for CD117 and Cathepsin K, but negative for vimentin and CK7. CK20 was positive in scattered individual cells, and Ki-67 positivity ranged from 1% to 4%. Point mutations in MTOR were identified in both patients who were subject to the molecular analysis. Statistical differences in the expression of Cathepsin K, CD10, S-100A1, and Cyclin D1 between EVT and RO ( P<0.05) were significant, so were the differences in the expression of Cathepsin K, CD10, CK7 and claudin 7 between EVT and eChRCC ( P<0.001). Seven patients were followed up for 4 to 96 months (mean, 50 months), with no recurrences or metastases. Conclusions:EVT is a rare renal tumor that shares morphological and immunophenotypic features with RO and eChRCC, and it is closely linked to the TSC/MTOR pathway. The presence of large prominent transparent vacuoles in eosinophilic cytoplasm along with conspicuous nucleoli is its key morphological characteristics. The use of combined immunohistochemical stains greatly aids in its diagnosis. Typically, the tumor exhibits indolent biological behaviors with a favorable prognosis.

Purpose: Bone metastasis (BM) adversely affects the prognosis of gastric cancer (GC). We investigated molecular features and immune microenvironment that characterize GC with BM compared to GC without BM. Materials and Methods: Targeted DNA and whole transcriptome sequencing were performed using formalin-fixed paraffin-embedded primary tumor tissues (gastrectomy specimens) of 50 GC cases with distant metastases (14 with BM and 36 without BM). In addition, immunohistochemistry (IHC) for mucin-12 and multiplex IHC for immune cell markers were performed. Results: Most GC cases with BM had a histologic type of poorly cohesive carcinoma and showed worse overall survival (OS) than GC without BM (p < 0.05). GC with BM tended to have higher mutation rates in TP53, KDR, APC, KDM5A, and RHOA than GC without BM. Chief cell-enriched genes (PGA3, PGC, and LIPF), MUC12, MFSD4A, TSPAN7, and TRIM50 were upregulated in GC with BM compared to GC without BM, which was correlated with poor OS (p < 0.05). However, the expression of SERPINA6, SLC30A2, PMAIP1, and ITIH2 were downregulated in GC with BM. GC with BM was associated with PIK3/AKT/mTOR pathway activation, whereas GC without BM showed the opposite effect. The densities of helper, cytotoxic, and regulatory T cells did not differ between the two groups, whereas the densities of macrophages were lower in GC with BM (p < 0.05). Conclusion GC with BM had different gene mutation and expression profiles than GC without BM, and had more genetic alterations associated with a poor prognosis.

ObjectiveTo explore the effect of Anmeidan on the sleep quality and serum levels of brain-derived neurotrophic factor （BDNF）， glial fibrillary acidic protein （GFAP）， and irisin in the patients with chronic insomnia. MethodA multicenter， randomized， double-blind， placebo-controlled clinical study was carried out， including 480 patients with chronic insomnia （deficiency syndrome） in Wuhan （Hubei）， Guangzhou （Guangdong）， and Lanzhou （Gansu）. They were randomized into an observation group and a control group at a ratio of 1∶1. The observation group was orally administered with Anmeidan granules at a dose of 11 g， 3 times per day， and the control group with Anmeidan simulant at a dose of 11 g， 3 times per day， Both groups of patients received sleep education after enrollment. After 4 weeks of medication， the Athens insomnia scale （AIS） scores， Spiegel scale scores， and serum levels of BDNF， GFAP， and irisin were compared between the two groups as well as between before and after treatment. ResultA total of 480 adult patients with chronic insomnia were enrolled in this study， with 64 patients falled off. Finally， the 415 patients were included in the analysis， including 213 patients in the observation group and 202 patients in the control group. There was no difference in age or sex between the two groups of patients. Compared with before treatment， the treatment in both groups decreased the AIS and Spiegel scores （P<0.01）. After treatment， the observation group had lower AIS and Spiegel scores than the control group （P<0.01）. The treatment in the observation group slightly lowered the level of BDNF， elevated the level of irisin （P<0.05）， and lowered the level of GFAP （P<0.05） in the serum. After treatment， the observation group showed higher level of irisin （P<0.05） and lower levels of BDNF and GFAP in the serum than the control group. ConclusionAnmeidan may improve the sleep quality of patients with chronic insomnia by elevating the irisin level and lowering the GFAP level in the serum.

Objective:To analyze the apply effect of radiofrequency ablation assisted associating liver partition and portal vein ligation for staged hepatectomy (RALPPS) in liver cancer patients with insufficient future liver remnant (FLR).Methods:The data of 29 patients who underwent RALPPS in the First Affiliated Hospital of the Army Military Medical University from June 2014 to July 2020 were analyzed, including 25 males and 4 females, aged (46.6±9.9) years. The patients were divided into the second stage group (completed the second stage operation, n=18) and the first stage group (completed only the first stage operation, n=11) according to whether they had successfully completed the second stage operation. FLR, percentage of FLR in standard liver volume (percentage of FLR), growth rate of FLR, liver function after operation, operation time and radiofrequency ablation time of first stage operation, surgical complications were compared between the two groups. Results:The percentage of FLR before the first stage operation was (30.0±7.0)% in 29 patients, and the second stage operation was completed in 18 patients (62.1%). After the first stage operation, the aspartate aminotransferase and alanine aminotransferase in the second stage group were 519.0 (362.9, 696.0) U/L and 391.8 (297.2, 591.1) U/L, which were better than those of the first stage group 931.0 (711.7, 1131.9) U/L and 851.3 (426.6, 888.0) U/L (both P<0.05). There was no significant difference between the two groups in FLR and percentage of FLR before the first stage operation, duration time, amount of bleeding and time of radiofrequency ablation of the first stage operation (all P>0.05). In the second stage group, the interval between two operations was (21.6±6.7) days, the FLR before the second stage operation was (623.2±101.8) cm 3, the FLR percentage was (49.0±7.0)%, and the FLR growth rate was (19.0±5.0)%. In the first stage group, there were 11 patients (100.0%) who developed complication after first stage operation, induding 7 patients (63.6%) with complication above Clavien-Dindo grade Ⅲb. In the second stage group, 18 patients (100.0%) developed complication after the first stage operation. There were no complication above grade Ⅲb. The causes of 11 patients who did not completed secondary surgery included poor liver function and insufficient FLR in 4 patients, tumor progression in 6 patients, and death in 1 patient. Conclusion:RALPPS is a therapeutic option for liver cancer patients with insufficient FLR, and the therapeutic effect is reasonable.

Objective Clinical research is a critical procedure for the development of medicine.Reliability of the clinical research finding is determined by the quality of study design and analysis courses.It will also further impact the guideline development and clinical practice.This study was focus on the evaluation of clinical research quality during its whole process.Methods Subjects of this study were the clinical summary reports from a government funded project which were submitted in 2016.Standardized data collecting form had been used to capture the key features regarding to the quality of study design and data analysis.After the review of data accuracy,descriptive analysis had been carried to interpret the observed findings both for design and analysis aspects.Results There were 67 project summary reports included in our analysis.The top three investigated therapeutic areas were oncology,cardiovascular/cerebrovascular diseases and orthopedics (19.4 ％,11.9 ％ and 11.9 ％).Most of studies fulfilled the evaluation criteria according to their original plan.94 ％ studies were strictly compliance with the original protocol with no interim amendment.Meanwhile,the report on sample size determination and appropriate use of multi-variable analysis should be improved.Conclusions Usually,clinical research program can fulfill the evaluate goal according to funding requirements.But the methodology quality should be paid more attention.It is highly suggested to cooperate with the professional statistical team and do continuous improvement effort to enhance the validity of study findings.

Objective To compare the value of ultrasound-guided fine-needle aspiration (FNA) and core needle biopsy (CNB) in diagnosing benign and malignant cervical lymph nodes.Methods A retrospective analysis was performed on 88 patients who received biopsy for cervical lymph node enlargement from January 2015 to May 2017.FNA (n =39) or CNB (n =49) were performed respectively to compare the sensitivity,specificity and accuracy of the two methods in diagnosing benign and malignant cervical lymph node enlargement.Results 84.6％ (33/39) of FNA cases were successfully collected,and 98％ (48/49) of FNA cases were successfully collected for definite pathological diagnosis (P =0.000).The sensitivity,specificity and accuracy of FNA and CNB in diagnosing malignant cervical lymph nodes were 90.9％ and 97.2％,94.1％ and 100％,92.3％ and 98％,respectively.Compared with FNA,there were statistically significant differences in sensitivity,specificity and accuracy in differentiating benign and malignant lymphatic lesions in cervical enlargement (P ＜0.01).The sensitivity and specificity of FNA and CNB in diagnosing cervical lymph node metastatic carcinoma were 100％ and 100％,95.2％ and 100％.Compared with FNA,there was no statistically significant difference in the sensitivity to the diagnosis of cervical lymph node metastatic carcinoma (P =0.102).Conclusions CNB is superior to FNA in sensitivity,specificity and accuracy in diagnosing cervical lymphadenopathy.However,when metastatic cancer was diagnosed,FNA was not significantly different from CNB in sensitivity (P =0.102),and FNA was recommended as the first choice.

Objective To study the feasibility and safety of simultaneous super-selective hepatic arterial and portal vein embolization for staged hepatectomy (ASAPS) in the treatment of patients with hepatocellular carcinoma (HCC) and cirrhosis.Methods The clinical data of 8 patients with HCC who underwent ASAPS at the First Affiliated Hospital of the Army Medical University from December 2016 to January 2018 were retrospectively analyzed.All the patients,including 7 males and 1 female with an average age of 44.3± 9.2,were diagnosed to have cirrhosis with insufficient volume of future liver remnant (FLR).Portal vein embolization (PVE) and super-selective hepatic arterial embolization (SHAE) were performed simultaneously.The patients were then closely monitored for the volumes of FLR.Once the FLR achieved the target volume,a second staged resectional surgery would be performed.The postoperative major complications,laboratory tests and patient long-term survival were studied.Results The ratio of FLR to the average standard liver volume (SLV) increased from (28.5±5) ％ to (49.6±7.3) ％ following the first-stage procedure.All the patients underwent liver resection successfully.The average second-stage operation time was 342.6±92.8 min,and the intraoperative blood loss was 743.8±432.1 ml.Both the postoperative serum alanine amin otransferase (ALT) and aspartate aminotransferase (AST) levels were elevated remarkably and then droppedto the near normal levels.All the patients were discharged home without any severe complications.Among them,3 patients relapsed early in the postoperative period,5 survived without recurrence,and 3 survived for over 1 year.Conclusions The first-stage surgery of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) using ASAPS was minimally invasive.The volume growth rate of the FLR after ASAPS was comparable to that of the conventional first stage of ALPPS.In conclusion,ASAPS is a promising alternative to the traditional ALPPS as the first-line treatment of patients with insufficient FLR.

In order to enhance the anticoagulant properties of decellularized biological materials as scaffolds for tissue engineering research via heparinized process, the decellularized porcine liver scaffolds were respectively immobilized with heparin through layer-by-layer self-assembly technique (LBL), multi-point attachment (MPA) or end-point attachment (EPA). The effects of heparinization and anticoagulant ability were tested. The results showed that the three different scaffolds had different contents of heparin. All the three kinds of heparinized scaffolds gained better performance of anticoagulant than that of the control scaffold. The thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (APTT) of EPA scaffold group were longest in all the groups, and all the three times exceeded the measurement limit of the instrument. In addition, EPA scaffolds group showed the shortest prepared time, the slowest speed for heparin release and the longest recalcification time among all the groups. The decellularized biological materials for tissue engineering acquire the best effect of anticoagulant ability in vitro via EPA heparinized technique.
Animals ; Anticoagulants ; chemistry ; Biocompatible Materials ; chemistry ; Heparin ; chemistry ; Liver ; Swine ; Tissue Engineering ; Tissue Scaffolds

Objective To investigate the effect of the application of tranexamic acid in unilateral total knee arthroplasty (TKA)with different methods .Methods Totally 120 cases of primary unilateral TKA patients admitted from June 2013 to May 2012 were studied ,including 33 males and 97 females ,with the average age of (65 ± 9) years (31 to 81 years) .Patients were divided into intravenous tranexamic acid group (group V ) ,topical tranexamic acid group (group T ) and irrigation using tranexamic acid group (group I) ,and control group (group C) .There were 30 cases in each group .Four groups of patients had no differences in age ,gender ,body mass index and disease diagnosis ,operative time ,preoperative hemoglobin ,preoperative hematocrit differences sta‐tistically(P>0 .05) .Postoperative blood loss and blood transfusion were observed .Groups were compared using one‐way ANOVA analysis .Results The total blood loss of group V was (368 ± 95)mL ,total blood loss of group T was (407 ± 118)mL ,both were less than the control group (509 ± 96)mL ,the difference was statistically significant (P<0 .05) .The differences between the blood loss of group I (491 ± 122) mL and the control group was not statistically significant (P=0 .924) .Group V showed the least a‐mount of hidden blood loss .Group T showed the least amount of visible blood loss .There were not deep vein thrombosis ,infections and other complications in any groups .Conclusion Intravenous and topical application of tranexamic acid can significantly reduce postoperative blood loss in TKA .Irrigation with tranexamic acid can not reduce the blood loss effectively .

Objective To study the effect of α-lipoic acid on the retinal expression level of VEGF and diabetic retinopathy in rats with diabetes mellitus and mechanism.Methods Totally 72 Wistar rats were divided into 4 groups:12 (control group)in group A,24 in modeling group(group B),24 in group treated withα-LA(group C)and 12 in high-glucose(group D).Group B to group D were given 60 mg/kg STZ through intraperitoneal injection,rats in group C were given 100 mg/kg α-LA and rats in group D were given 5.0% glucose-solution.The body mass,FPG,FINS,HOMA-IR,expression level of VEGF,activity of SOD,GSH and IL-6 of 4 groups were compared by statistics.Results After 72 h,the FPG of group A was(4.57 ±0.1 5 )mmol/L,that of group B was (21.72±4.28)mmol/L,that of group C was(21.54±4.96)mmol/L and that of group D was(21.83±4.77)mmol/L,the difference had statistical significance (P <0.05).The body mass of group A was(210.5±5.2)g,that of group B was(21 1.2 ±5.7)g,that of group C was(209.8±5.8)g and that of group D was(208.7±3.4)g,the difference had no statistical significance (P >0.05).The body mass,FPG,FINS,HOMA-IR,expression level of VEGF,activity of SOD,GSH and IL-6 among 4 groups at 4 w,8 w and 12 w had statistical difference (P <0.05).After 12 w,the difference of GR stage among group B to group D had statistical significance (P <0.05).Conclusion α-LA can inhibit the expression of VEGF in rats with diabetes mellitus,which is related to its ability to re-duce the oxidative stress and inflammation reaction,as well as to alleviate the insulin resistance.