Objective: To compare clinical efficacy between laparoscopic radical proximal gastrectomy with double-tract reconstruction (LPG-DTR) and laparoscopic radical total gastrectomy with Roux-en-Y reconstruction (LTG-RY) in patients with early upper gastric cancer, and to provide a reference for the selection of surgical methods in early upper gastric cancer. Methods: A retrospective cohort study method was carried out. Clinical data of 80 patients with early upper gastric cancer who underwent LPG-DTR or LTG-RY by the same surgical team at the Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to January 2021 were retrospectively analyzed. Patients were divided into the DTR group (32 cases) and R-Y group (48 cases) according to surgical procedures and digestive tract reconstruction methods. Surgical and pathological characteristics, postoperative complications (short-term complications within 30 days after surgery and long-term complications after postoperative 30 days), survival time and nutritinal status were compared between the two groups. For nutritional status, reduction rate was used to represent the changes in total protein, albumin, total cholesterol, body mass, hemoglobin and vitamin B12 levels at postoperative 1-year and 2-year. Non-normally distributed continuous data were presented as median (interquartile range), and the Mann-Whitney U test was used for comparison between groups. The χ(2) test or Fisher's exact test was used for comparison of data between groups. The Mann-Whitney U test was used to compare the ranked data between groups. The survival rate was calculated by Kaplan-Meier method categorical, and compared by using the log-rank test. Results: There were no statistically significant differences in baseline data betweeen the two groups, except that patients in the R-Y group were oldere and had larger tumor. Patients of both groups successfully completed the operation without conversion to laparotomy, combined organ resection, or perioperative death. There were no significant differences in the distance from proximal resection margin to superior margin of tumor, postoperative hospital stay, time to flatus and food-taking, hospitalization cost, short- and long-term complications between the two groups (all P>0.05). Compared with the R-Y group, the DTR group had shorter distal margins [(3.2±0.5) cm vs. (11.7±2.0) cm, t=-23.033, P<0.001], longer surgery time [232.5 (63.7) minutes vs. 185.0 (63.0) minutes, Z=-3.238, P=0.001], longer anastomosis time [62.5 (17.5) minutes vs. 40.0 (10.0) minutes, Z=-6.321, P<0.001], less intraoperative blood loss [(138.1±51.6) ml vs. (184.3±62.1) ml, t=-3.477, P=0.001], with significant differences (all P<0.05). The median follow-up of the whole group was 18 months, and the 2-year cancer-specific survival rate was 97.5%, with 100% in the DTR group and 95.8% in the R-Y group (P=0.373). Compared with R-Y group at postoperative 1 year, the reduction rate of weight, hemoglobin and vitamin B12 were lower in DTR group with significant differences (all P<0.05); at postoperative 2-year, the reduction rate of vitamin B12 was still lower with significant differences (P<0.001), but the reduction rates of total protein, albumin, total cholesterol, body weight and hemoglobin were similar between the two groups (all P>0.05). Conclusions: LPG-DTR is safe and feasible in the treatment of early upper gastric cancer. The short-term postoperative nutritional status and long-term vitamin B12 levels of patients undergoing LPG-DTR are superior to those undergoing LTG-RY.
Albumins ; Anastomosis, Roux-en-Y/adverse effects* ; Cholesterol ; Gastrectomy/methods* ; Hemoglobins ; Humans ; Laparoscopy/methods* ; Postoperative Complications/etiology* ; Retrospective Studies ; Stomach Neoplasms/pathology* ; Treatment Outcome ; Vitamin B 12

OBJECTIVE: To investigate the clinical characteristics and treatment of pneumocystis carinii pneumonia (PCP) in children with acute lymphoblastic leukemia (ALL), in order to improve the early diagnosis and effective treatment. METHODS: Clinical data of five children with ALL developing PCP in the post-chemotherapy granulocyte deficiency phase were analyzed retrospectively. The clinical manifestations, laboratory tests, imaging findings, treatment methods and effect were summarized. RESULTS: The male-to-female ratio of the five children was 1∶4, and the median age was 5.5 (2.9-8) years old. All patients developed PCP during granulocyte deficiency phase after induction remission chemotherapy. The clinical manifestations were generally non-specific, including high fever, tachypnea, dyspnea, non-severe cough, and rare rales in two lungs (wet rales in two patients). Laboratory tests showed elevated C-reactive protein (CRP), serum procalcitonin (PCT), (1,3)-β-D-glucan (BDG), lactate dehydrogenase (LDH) and inflammatory factors including IL-2R, IL-6 and IL-8. Chest CT showed diffuse bilateral infiltrates with patchy hyperdense shadows. Pneumocystis carinii(PC) was detected in bronchoalveolar lavage fluid (BALF) or induced sputum by high-throughput sequencing in all patients. When PCP was suspected, chemotherapy was discontinued immediately, treatment of trimethoprim-sulfame thoxazole (TMP-SMX) combined with caspofungin against PC was started, and adjunctive methylprednisolone was used. Meanwhile, granulocyte-stimulating factor and gammaglobulin were given as the supportive treatment. All patients were transferred to PICU receiving mechanical ventilation due to respiratory distress during treatment. Four children were cured and one died. CONCLUSION PCP should be highly suspected in ALL children with high fever, dyspnea, increased LDH and BDG, and diffuse patchy hyperdense shadow or solid changes in lung CT. The pathogen detection of respiratory specimens should be improved as soon as possible. TMP/SMZ is the first-line drug against PCP, and the combination of Caspofungin and TMP/SMZ treatment for NH-PCP may have a better efficacy. Patients with moderate and severe NH-PCP may benefit from glucocorticoid.
Caspofungin/therapeutic use* ; Child ; Child, Preschool ; Dyspnea ; Female ; Humans ; Male ; Pneumonia, Pneumocystis/therapy* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Respiratory Sounds ; Retrospective Studies

Objective:Our study aims to determine histological regression and clinical improvement after long-term antiviral therapy in hepatitis B virus-related cirrhosis patients.Methods:Treatment-na?ve chronic hepatitis B patients with histologically or clinically diagnosed liver cirrhosis were enrolled. Liver biopsies were performed after 5 years entecavir-based antiviral treatment. Patients were followed up every 6 months. Cirrhosis regression was evaluated based on Metavir system and P-I-R score. Clinical improvement was evaluated before and after the long-term treatment. Kruskal Wallis test and Wilcoxon signed-rank test were used for continuous variables, Fisher's exact test was used for categorical variables and multivariate analysis was performed using logistic regression analysis.Results:Totals of 73 patients with HBV-related liver cirrhosis were enrolled. Among them, 30 (41.1%) patients were biopsy proved liver cirrhosis and the remaining 43 (58.9%) cirrhotic patients were diagnosed by clinical features. Based on Metavir system and P-I-R score, 72.6% (53/73) patients attained histological regression. Furthermore, 30.1% (22/73) were defined as significant regression (Metavir decrease ≥2 stage), 42.5% (31/73) were mild regression (Metavir decrease 1 stage or predominantly regressive by P-I-R system if still cirrhosis after treatment) and 27.4% (20/73) were the non-regression. Compared to levels of clinical characteristics at baseline, HBV DNA, ALT, AST, liver stiffness(decreased from 12.7 to 6.4 kPa in significant regression, from 18.1 to 7.3 kPa in mild regression and from 21.4 to 11.2 kPa in non-regression)and Ishak-HAI score significantly decreased after 5 years of anti-HBV treatment, while serum levels of platelets and albumin improved remarkably ( P<0.05). In multivariate analysis, only the pre-treatment liver stiffness level was associated with significant regression ( OR=0.887, 95% CI: 0.802-0.981, P=0.020). Conclusions:After long-term antiviral therapy, patients with HBV-related cirrhosis are easily to attain improvements in clinical parameters, while a certain percentage of these patients still cannot achieve histological reversal.

Prostate cancer (PCa) is a maligmancy with high morbidity and mortality. Bone metastasis is the main cause of short survival time and difficulties in the treatment and prevention of PCa. Previous findings of our team showed 155 bone-specific genes highly expressed in bone metastatic PC3 cells, which is considered to be the key to their adaptation to the bone micro-environment, proliferation and formation of metastatic tumor, and extensively exists in cancer metastasis in multiple systems. This review summarizes the published literature on the highly expressed bone-specific genes, focusing on the roles and values of these genes in the metastasis, progression, clinical diagnosis, treatment and prognosis of PCa, offering a prospect of the direction and targets in the studies of PCa bone metastasis so as to enrich the bone metastatic theories and clinical treatment principles of this disease in the future.
Humans ; Male ; PC-3 Cells ; Prostatic Neoplasms/genetics* ; Tumor Microenvironment

Blakeslea trispora is a natural source of carotenoids, including β-carotene and lycopene, which have industrial applications. Therefore, classical selective breeding techniques have been applied to generate strains with increased productivity, and microencapsulated β-carotene preparation has been used in food industry (Li et al., 2019). In B. trispora, lycopene is synthesized via the mevalonate pathway (Venkateshwaran et al., 2015). Lycopene cyclase, which is one of the key enzymes in this pathway, is a bifunctional enzyme that can catalyze the cyclization of lycopene to produce β-carotene and exhibit phytoene synthase activity (He et al., 2017).
Citric Acid Cycle ; Fermentation ; Gas Chromatography-Mass Spectrometry/methods* ; Lycopene/metabolism* ; Mucorales/metabolism* ; Nicotine/pharmacology* ; beta Carotene/biosynthesis*

OBJECTIVE: LASS2/TMSG1 gene is a novel tumor metastasis suppressor gene cloned from human prostate cancer cell line PC-3M in 1999 by Department of Pathology,Peking University of Basic Medical Sciences. It was found out that protein encoded by LASS2/TMSG1 could interact with the c subunit of vacuolar-ATPase (ATP6V0C). In this study, we explored the effect of LASS2/TMSG1 and its mutants on proliferation, migration and invasion of human prostate cancer cells and its molecular mechanism. METHODS: We constructed four LASS2/TMSG1 mutants and stably transfected the variants to human prostate cancer cell line PC-3M-1E8 cell with high metastatic potential. The stable transfectants were identified by qPCR and Western blot through analyzing the expression of LASS2/TMSG1 and ATP6V0C, the cell biology functions of LASS2/TMSG1 and its four mutants were studied using growth curve,MTT assay, soft agar colony formation assay, wound migration assay, Matrigel invasion study and flow cytometry. Furthermore, immunofluorescence was used to analysis the interaction of LASS2/ TMSG1 mutants and ATP6V0C. RESULTS: LASS2/TMSG1 mRNA and protein in LASS2/TMSG1 group and Mut1-Mut4 groups were higher than that in Vector group; Western blot showed that ATP6V0C protein in LASS2/TMSG1 wild group was lower than that in Vector group, but ATP6V0C protein in LASS2/TMSG1 S248A group was obviously higher than that in Vector group. MTT test and growth curve assay showed growth ability in LASS2/TMSG1 S248A group was increasing compared with other groups from day 5. Soft Agar colony formation experiment showed anchor independent growth ability in LASS2/TMSG1 S248A group was higher than those in the other groups (P<0.05), Cell migrations (from 35.3%±3.2% to 70.3%±3%) in LASS2/TMSG1 S248A group was increasing compared with LASS2/TMSG1 wild group (P<0.01), and more cells passed through Matrigel in LASS2/TMSG1 S248A group compared with LASS2/TMSG1 wild group (from 50±3.2 to 203±6.5, P<0.01), the apoptosis rate in LASS2/TMSG1 S248A group was obviously higher than that in LASS2/TMSG1 wild group (from 7% to 15.1%, P<0.05), and the G0/G1 ratio in LASS2/TMSG1 S248A group was obviously higher than that in LASS2/TMSG1 wild group (from 51.0% to 85.4%). Furthermore, double immunofluorescent staining observed the colocalization between ATP6V0C and LASS2/TMSG1 protein and its mutations, the expression of ATP6V0C in LASS2/TMSG1 S248A group increased significantly compared with the other groups. CONCLUSION LASS2/TMSG1 S248A promotes proliferation, migration and invasion of prostate cancer cells through increasing ATP6V0C expression, suggesting that aa248-250 is an important function site for LASS2/TMSG1 in invasion suppression of prostate cancer cells.
Beijing ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Humans ; Male ; Membrane Proteins/genetics* ; Mutation ; Neoplasm Invasiveness ; Prostatic Neoplasms/genetics* ; Sphingosine N-Acyltransferase/genetics* ; Transfection ; Tumor Suppressor Proteins/genetics* ; Vacuolar Proton-Translocating ATPases

Objective To investigate the vascularization ability of mesenchymal stem cells(MSCs)and explore its influencing factors in aplastic anemia(AA) patients. Methods MSCs were isolated from the bone marrow of AA patients(AA MSCs) and normal controls(N MSCs) were cultured and then evaluated by flow cytometry and immunofluorescene staining technique.The expression level of vascular cell adhesion molecule-1(CD106) was detected by gene sequencing,and the content and fluorescene intensity of CD106MSCs was determined by fluorescence-activated cell sorting.The content of CD105CD106MSCs in fresh AA bone marrow was measured,followed by the determination of the capability of endothelial differentiation from AA MSCs and N MSCs with immunofluorescene analysis;finally,the capability of CD31cell differentiation from CD106-blocking N MSCs and its tubular structures formation in matrigel were tested.Results The expression of CD106 in AA patients was defective(decreased by 12.13 times when compared with N MSCs) and the concentration and fluorescene degree of CD106MSCs was also decreased in AA patients [(28.03±17.71)% vs.(59.61±12.26)%,P=0.000].The content of CD105CD106MSCs decreased significantly in the fresh bone marrow [(0.33±0.10)% vs.(2.98±0.46)%,P=0.0005].Besides, the capability of CD31cell differentiation from AA MSCs was significantly delayed [(13.67±1.50)% vs.(43.24±0.96)%,P=0.0004].Also,the capability of CD31cell differentiation and tubular structures formation of CD106-blocking N MSCs was also obviously decreased [(26.00±2.65)% vs.(91.78±2.44)%,P=0.000;(13.81±1.98)mm vs.(68.12±6.78)mm,P=0.0015].Conclusion The deficient or decreased expression of CD106MSCs accelerate the bone marrow vascularization failure in AA patients.

OBJECTIVETo establish the acute graft-versus-host disease(GVHD) mouse model based on haplo identical hematopoietic stem cell transplantation (HSCT) and to further investigate the pathogenesis of GVHD.

METHODSRecipient mice ([C57BL/6×CBA/Ca]F1(H-2)) received lethal irradiation (11 Gy) of γ ray (Cs), followed by transplantation with donor-derived [C57BL/6(H-2)] T cell-depleted bone marrow cells (TD-BM) with or without donor-derived T cells. Recipients were randomly divided into 4 groups, including irradiation group, TD-BM group, TD-BM+T cell group 1 and TD-BM+T cell group 2. Survival rate and weight change were detected after HSCT. Pathological scoring were performed on the collected organs from recipients on day 14. Moreover, bone marrow chimerism was detected on days 14 and 18 after HSCT. Additionally, differentiation of donor-derived T cells towards Th1 cells in vivo was analyzed by flow cytometry. Furthermore, proliferation of donor-derived T cells in vivo was tested using CFSE.

RESULTSThe average survival in TD-BM, irradiation, TD-BM+T cell group 1 and TD-BM+T cell groups 2 were 60, 13.29±5.50, 33±2.3 and 29.14±1.77 days, respectively. On day 14 after transplantation, recipients of TD-BM + T cell group 1 displayed significantly more severe pathology in liver, colon, lung and skin. On days 14 and 28 after HSCT, bone marrow chimerism in recipients of both TD-BM group and TD-BM+ T cell groups 1 was over 94%. On day 14 after HSCT, serum cytokines IFN-γ, TNF-α and IL-1 levels in TD-BM+T cell group 1 were significantly higher than those in TD-BM group. Percentage of H-2bH-2kCD4IFN-γin spleen cells of recipients in TD-BM+T cell group 1 was higher than that of TD-BM group, with (0.5240±0.08447)% vs (7.912±0.6087)% (P<0.05). On days 14 after HSCT, donor-derived T cells displayed obvious proliferation in vivo.

CONCLUSIONC57BL/6(H-2)→［C57BL/6×CBA/Ca］F1(H-2) HSCT model can be used as a aGVHD model of haploidentical HSCT. Additionally, Th1 may play an important role in the pathogenesis of aGVHD resulting from haplo-identical HSCT.

OBJECTIVETo explore the clinical characteristic, therapeutic efficacy and prognosis of patients with hepatitis-associated aplasitc anemia (HAAA).

METHODSthe clinical data and labrotatory examination results of 30 cases of HAAA were analyzed retrospectively, the 6-month response ratio and overall survival (OS) were assessed.

RESULTSHAAA most commonly occured in males, with the occurence rate of males and females was 4:1, the median onset age was 16 (4-43) years old, HAAA oriented focus on sever aplastic anemia (SAA)(4 cases,13%) and very sever aplastic anemia (VSAA)(22 cases,73%). Aplastic anemia (AA) could be seen on occurence of hepatitis (accompanied aplastic anemia) (7 cases,23%), or after the onset of hepatits (delayed aplastic anemia) (23 cases,77%), but more often occured in the latter. Statistical analysis showed that when compared with the patients of delayed aplastic anemia, patients accompanied aplastic anemia possesses lower levels of glutamic-pyruvic transaminase(ALT), aspertate aminotransferase (AST) and total bilirubin (TBIL)(P=0.042,0.012,0.001), and possessed a more obvious lymphoid cell disorder when AA occured, with more lower peripheral blood CD19B cells proportion (P=0.046) and more obvious imbalance of CD4/CD8ratio, but the difference was no statistical significant (P=0538). Factors affecting the 6-month respose were the severity of AA (P=0.044), the peak level of bilirubin of hepatitis (P=0.006) and the propotion of mature monocyte in bone marrow (P=0.034). The long-term follow-up showed that the 2-year OS of HAAA was 64.3±9.2%, the 6-month curative efficacy significantly affect the prognosis (P<0.001).

CONCLUSIONHAAA more often occur in young male, HAAA is mainly SAA and VSAA and mostly non-A-C hepatitis associated aplastic anemia, patients usually have a high incidence of early infection. Patients acompanied with aplastic anemia possess more obvious immunological derangement; the treatment efficacy for HAAA is poor, patients who haven't obtained 6-month response indicate a sinister prognosis, allogeneic hematopoietic stem cell transplantion is a better choice for these patients.

BACKGROUNDDebate on treatment for young patients with coronary artery disease still exists. This study aimed to investigate the intermediate- and long-term outcomes between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in patients aged 18-45 years with diabetes mellitus (DM).

METHODSBetween January 2006 and March 2016, a total of 2018 DM patients aged 18-45 years including 517 cases of CABG and 1501 cases of PCI were enrolled in the study. Using propensity score matching (PSM), 406 patients were matched from each group. The intermediate- and long-term data were collected. The primary end point of this study was long-term death. The secondary end points included long-term major adverse cardiovascular and cerebrovascular events (MACCEs), stroke, angina, myocardial infarction (MI), and repeat revascularization.

RESULTSBefore PSM, the in-hospital mortality was 1.2% in the CABG group and 0.1% in the PCI group, with statistically significant difference (P < 0.0001). The 10-year follow-up outcomes including long-term survival rate and freedom from MACCEs were better in the CABG group than those in the PCI group (97.3% vs. 94.5%, P = 0.0072; 93.2% vs. 86.3%, P < 0.0001), but CABG group was associated with lower freedom from stoke compared to PCI group (94.2% vs. 97.5%, P = 0.0059). After propensity score-matched analysis, these findings at 10-year follow-up were also confirmed. Freedom from MACCEs was higher in CABG group compared to PCI group, but no significant difference was observed (93.1% vs. 89.2%, P = 0.0720). The freedom from recurrent MI was significantly higher in CABG patients compared with PCI patients (95.6% vs. 92.5%, P = 0.0260). Furthermore, CABG was associated with a higher rate of long-term survival rate than PCI (97.5% vs. 94.6%, P = 0.0403). There was no significant difference in the freedom from stroke between CABG and PCI groups (95.3% vs. 97.3%, P = 0.9385). The hospital cost was greater for CABG (13,936 ± 4480 US dollars vs. 10,926 ± 7376 US dollars, P < 0.0001).

CONCLUSIONSIn DM patients aged 18-45 years, the cumulative survival rate, and freedom from MI and repeat revascularization for CABG were superior to those of PCI. However, a better trend to avoid stroke was observed with PCI.