[Expression and clinical significance of plasma exosomal miR-34-5p and miR-142-3p in systemic sclerosis].

OBJECTIVE: To detect the expression of plasma exosomal microRNA (miRNA) in systemic sclerosis (SSc), and to investigate its clinical significance. METHODS: A total of 20 patients who were initially diagnosed with SSc and did not receive medication in Department of Rheumatology and Immunology of Meizhou People' s Hospital from January 2020 to January 2022 were recruited, as well as 15 healthy individuals whose gender and age matched with those of the SSc patients. Plasma exosomes were isolated using ultracentrifugation method. The expression levels of exosomal miR-34-5p, miR-92-3p and miR-142-3p were detected by quantative real-time polymerase chain reaction (qRT-PCR). Correlations between the expression levels of exosomal miRNAs and clinical characteristic were analyzed by Spearman's rank correlation coefficient test. RESULTS: The mean age of 20 patients with SSc was (52.6±12.6) years, including 7 males and 13 females. Among the 20 SSc patients, 13 cases were diagnosed as limited cutaneous systemic sclerosis (lcSSc) and 7 cases were diagnosed as diffuse cutaneous systemic sclerosis (dcSSc) according to the extent of skin involvement. According to the findings of high resolution chest CT, 7 of 20 SSc patients were diagnosed with interstitial lung disease (ILD) and 13 SSc patients were diagnosed with non-ILD. The expression levels of exosomal miR-34-5p, miR-92-3p and miR-142-3p were significantly elevated in the SSc patients compared with those in the healthy controls group (P=0.003, P=0.000 1, and P=0.016, respectively). Compared with the SSc patients without ILD, the expression levels of miR-34-5p and miR-142-3p were significantly lower in the SSc patients with ILD (P=0.037 and P=0.015, respectively). The expression levels of exosomal miR-34-5p and miR-142-3p showed negative correlation with ILD (r=-0.48, P=0.031 and r=-0.55, P=0.011, respectively), and arthritis (r=-0.46, P=0.040 and r=-0.48, P=0.032, respectively). The expression levels of exosomal miR-142-3p showed a negative correlation with erythrocyte sedimentation rate (ESR) (r=-0.55, P=0.012). CONCLUSION: Plasma exosomal miR-34-5p, miR-92-3p and miR-142-3p were dysregulated in SSc. The dyregulation of exosomal miR-34-5p and miR-142-3p showed correlation with SSc associated ILD (SSc-ILD).

Identifying priority protection areas of key food resources of the giant panda.

Animals that live in seasonal environments adjust their reproduction cycle to optimize seasonal forage quality. Giant pandas ( Ailuropoda melanoleuca) are seasonal altitudinal migrants that feed on bamboo shoots and leaves with different nutritional quality. However, the importance of bamboo shoots to giant pandas, especially small and isolated populations, is not fully appreciated. Here, we explored whether mating time of giant pandas is shaped by bamboo shoot phenology. We also assessed the intensity of ongoing bamboo shoot harvesting by local communities in 42 giant panda reserves based on questionnaire surveys. Varying intensity and protection levels of bamboo shoot harvesting were found. From these data, we developed a priority ranking scheme of protection areas for this key food resource. Our study showed that pandas time their mating behavior to coincide with bamboo shoot phenology due to the high nutritional demands associated with mating and pregnancy. We also found that bamboo shoots were not well protected in many places. Liangshan, Daxiangling, and Xiaoxiangling, containing the most isolated panda populations, were identified as the areas with the most urgent need of protection. Furthermore, equal attention should be paid to the QiongL-B population, as this region holds considerable potential to serve as a corridor between the Minshan and Qionglai populations. To address the challenges posed by bamboo shoot harvesting, we recommend establishing more practical bamboo shoot management policies, increasing public awareness of bamboo shoot protection, and providing alternative sources of income for local communities.

Prognostic value of TIMM50 expression in colorectal cancer.

Introduction: Translocase of the inner mitochondrial membrane 50 (TIMM50) is universally considered to play a key role in several malignancies. However, its role in predicting colorectal cancer (CRC) patient prognosis remains unclear. Material and methods: A total of 192 CRC patients (123 men and 69 women) who underwent radical resection participated in this study. The patients were followed up every 3 months after surgery for 5 years. TIMM50 expression in tumour tissues was measured by quantitative real-time PCR, Western blotting and immunohistochemistry. TIMM50 expression was studied to assess correlations with clinicopathological factors and survival time. Results: TIMM50 expression increased significantly in CRC tumour tissues. Moreover, high TIMM50 expression was related to pathologic stage (p = 0.043), N stage (p = 0.048) and distant metastasis (p = 0.015), but TIMM50 expression was not related to other clinical factors. A Kaplan-Meier survival analysis indicated that patients with low TIMM50 expression had a longer overall survival than those with high TIMM50 expression (p = 0.002). Furthermore, distant metastasis and high TIMM50 expression were confirmed as independent prognostic factors for the overall survival of CRC patients in a multivariate analysis (p = 0.003). Conclusions: TIMM50 may be a key factor for monitoring CRC and a new prognosis indicator for CRC patients.

[META analysis of mobile bearing and fixed bearing unicondyle replacement for medial knee osteoarthritis].

OBJECTIVE: To evaluate of the clinical effects of mobile-bearing(MB) and fixed-bearing(FB) unicompartmental knee arthroplasty(UKA) in the treatment of knee osteoarthritis by Meta-analysis. METHODS: The literature on FB UKA and MB UKA in the treatment of knee osteoarthritis in PubMed, CNKI, Wanfang, Cochrane and EMBASE database were searched by computer from January 2000 to April 2020. According to the inclusion and exclusion criteria, two authors were selected independently and the selected literature was evaluated for quality.After literature data were extracted, Review Manager 5.3 software was used to analyze knee function score, postoperative activity, revision rate, polyethylene wear rate, pad dislocation, aseptic loosening, postoperative pain, knee arthritis progression, mechanical shaft alignment of lower limbs, and imaging clarity line respectively. RESULTS: A total of 13 literatures were included in this meta-analysis, including 2 randomized controlled studies and 11 cohort studies. A total of 1 871 patients were included, including 913 in FB UKA group and 958 in MB UKA group. Meta analysis results showed that:postoperative knee joint function score[MD=-0.84, 95%CI(-1.46, -0.21), P=0.008] and postoperative knee joint range of motion [MD=-1.51, 95%CI(-2.84, -0.18), P=0.03] in FB UKA group were better than those in MB UKA group. Compared with FB UKA group, MB UKA group had a higher lower limb mechanical axis alignment rate[OR=2.08, 95%CI(1.27, 3.39), P=0.003], and the wear rate of polyethylene [OR=0.11, 95%CI(0.01, 0.91), P=0.04] was lower. There were no differences between two groups in the renovation rate [OR=1.16, 95%CI(0.75, 1.80), P=0.50), liner dislocation rate[OR=3.78, 95%CI(0.93, 15.29), P=0.06], aseptic loosening [OR=2.11, 95%CI(0.81, 5.51), P=0.13], postoperative pain[OR=1.13, 95%CI(0.37, 3.43), P=0.83], osteoarthritis progression[OR=1.28, 95%CI(0.67, 2.47), P=0.46)and imaging radiolucent line[OR=1.62, 95%CI(0.09, 30.22), P=0.75]. CONCLUSION: FB UKA has a higher postoperative functional score and range of motion.MB UKA has more advantages in the correction of lower limb mechanical axis, and the wear rate of polyethylene is also lower. There was no significant difference between the two groups in revision rate, dislocation of the liner, aseptic loosening, postoperative pain, progression of osteoarthritis, and postoperative translucency.

[Arthroscopic surgery combined with platelet-rich plasma for meniscus injury:a Meta analysis].

OBJECTIVE: To evaluate clinical efficacy of arthroscopic with platelet-rich plasma (PRP) in treating meniscus injury. METHODS: From January 2015 to December 2019, clinical control study on repair meniscus injury by arthroscopic with PRP between arthroscopic were searched by PubMed, Science Direct, Cochrane library, Chinese Journal Full-text Database, Wanfang and VIP database. Literature screening, data extraction and quality evaluation according to inclusion and exclusion criteria. Visual analogue scale(VAS) of knee joint and Lysholm score at 1, 6 and 12 months after opertaion between two groups were compared, and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) at 3, 6 and 12 months after opertaion between twogroups were also compared. RESULTS: Totally 9 literatures and 329 patients with meniscal injuries were screened, include 146 patients treated by arthroscopic with PRP and 183 patients treated by arthroscopic. There were no statistical differences in VAS between two groups at 1, 6 and 12 months after opertaion. There were differences in Lysholm score at 1 and 6 months after operation between two groups [MD=3.85, 95%CI (1.25, 6.44), P<0.05], [MD=2.88, 95%CI (0.13, 5.63), P<0.05];while there was no difference at 12 months[MD=5.88, 95%CI(-8.72, 20.48), P=0.43]. There were differneces in WOMAC score at 3 and 6 months after operation between two groups[MD=-8.07, 95%CI(-11.17, -4.89), P<0.000 01], [MD=-7.96, 95%CI(-11.44, -4.48), P<0.000 01];and no difference at 12 months after operation[MD=-6.61, 95%CI (-16.64, 3.41), P>0.05]. CONCLUSION: Arthroscopic with PRP for repair meniscus injury has short term efficacy of knee function and delay arthritis, while has similar effect in long term clinical efficacy and relieve pain.

[Outcomes of quadriceps tendon autograft versus bone-patellar tendon-bone autograft for anterior cruciate ligament reconstruction:a Meta-analysis].

OBJECTIVE: To evaluate clinical effect of quadriceps tendon autograft and bone-patellar tendon-bone autograft on anterior cruciate ligament reconstruction by Meta-analysis. METHODS: From the time of building databases to May 2019, literatures on case control study on quadriceps tendon and bone-patellar tendon-bone autograft on anterior cruciate ligament reconstruction were searched form PubMed, EMbase, the Cochrane library, Wanfang and CNKI database. Literature screening, quality evaluation and data extraction were carried out according to include and exclude standard. Difference of forward displacement between the affected and health knee, Lachman test, axial shift test, Lysholm score, international knee documentation committee (IKDC) objective grade, anterior knee joint pain and transplant failure rate were analyzed by Meta analysis. RESULTS: Totally 6 literatures were included, including 915 patients with anterior cruciate ligament reconstruction, 495 patients with quadriceps tendon autograft and 420 patients with bone patellar tendon bone autograft. There were no statistical differences in anterior displacement of tibia was less than 3 mm[OR=1.53, 95%CI(0.68, 3.44), P=0.31], 3 to 5 mm [OR=0.64, 95%CI(0.31, 1.35), P=0.24], greater than 5 mm[OR=1.18, 95%CI(0.33, 4.22), P=0.80], negative rate of Lachman test[OR=0.88, 95%CI(0.38, 2.02), P=0.76], negative rate of axial shift test[OR=0.63, 95%CI(0.24, 1.68), P=0.36] between two groups. There were no differences in Lyshlom score[MD=-0.56, 95%CI(-2.00, 0.89), P=0.45], IKDC objective grade A and B[OR=0.87, 95%CI (0.47, 1.60), P=0.66], and transplant failure rate [OR=0.76, 95%CI (0.28, 2.02), P= 0.58]. In reducing anterior knee pain, quadriceps tendon autograft was better than that of bone patellar tendon bone autograft [OR=0.16, 95%CI (0.09, 0.29), P<0.000 01]. CONCLUSION: Quadriceps tendon autograft and bone patellar tendon bone autograft on anterior cruciate ligament reconstruction has equal clinical and functional outcomes, transplant failure rate, quadriceps tendon autograft could reduce anterior knee pain. For patients with anterior cruciate ligament reconstruction, quadriceps tendon autograft could be seen as suitable alternative bone graft substitutes for anterior cruciate ligament reconstruction.

miR-194 Inhibits the Proliferation of SW620 Colon Cancer Stem Cells Through Downregulation of SSH2 Expression.

PURPOSE: Colorectal cancer (CRC) stem cells are tumorigenic, capable of self-renewal, and resistant to therapy. Although the expression pattern and functions of micro RNA (miR)-194 in CRC cells have been widely investigated, little is known about its role in CRC stem cells. Therefore, the aim of this study was to investigate the potential role of miR-194 in CRC stem cells. MATERIALS AND METHODS: CRC stem cells were isolated from the SW620 colon cancer cell line using microbeads. The expression levels of miR-194 and slingshot 2 (SSH2) in CRC stem cells were detected by RT-PCR and Western blot. A luciferase reporter assay was performed to confirm that miR-194 directly targets SSH2. Proliferation of CRC stem cells was examined by colony formation and MTT assays. Apoptosis in CRC stem cells was detected by cell cycle and apoptosis assays. The role of miR-194 in tumor growth was determined in vivo. RESULTS: Cells positive for CD44 and CD133 accounted for approximately 88.7% of the isolated population after microbead isolation. We reveal for the first time that miR-194 expression is decreased in CRC stem cells. Specifically, miR-194 is involved in inhibiting the proliferation of CRC stem cells and promoting CRC stem cell apoptosis by directly targeting SSH2. Furthermore, overexpression of miR-194 resulted in blocking the G1/S transition, the induction of cellular apoptotic process, thereby suppressing the malignant behaviors of CRC stem cells. CONCLUSION: This study represents a novel characterization of miR-194 function in CRC stem cells, which may aid in the development of promising therapeutic strategies targeting CRC.

The Role Of Hepatic Stellate Cells In Promoting Liver Metastasis Of Colorectal Carcinoma.

PURPOSE: Colorectal cancer (CRC) is the most common malignancy in the gastrointestinal tract. The liver is the most common location of CRC metastases, which are the main causes of CRC-related death. However, the mechanisms underlying metastasis of CRC to the liver have not been characterized, resulting in therapeutic challenges. METHODS: The effects of hepatic stellate cells (HSCs) on T cells were evaluated using in vitro mixed lymphocyte reactions (MLRs) and cytokine production assays. HSC-induced CT26 cell migration and proliferation were evaluated in vitro and in vivo. RESULTS: HSCs induced T cell hypo-responsiveness, promoted T cell apoptosis, and induced regulatory T cell expansion in vitro. IL-2 and IL-4 were significantly lower in MLRs incubated with HSCs. Supernatants of MLRs with HSCs promoted CT26 cell proliferation and migration. Furthermore, the presence of HSCs increased the number of liver metastases and promoted proliferation of liver metastatic tumor cells in vivo. CONCLUSION: HSCs may contribute to an immunosuppressive liver microenvironment, resulting in a favorable environment for the colonization of CRC cells in the liver. These findings highlight a potential strategy for treatment of CRC liver metastases.

Adenovirus-mediated transduction with Histone Deacetylase 4 ameliorates disease progression in an osteoarthritis rat model.

BACKGROUND: Downregulation of histone deacetylase-4 (HDAC4) contributes to cartilage degeneration in osteoarthritis (OA) because it promotes upregulation of runt-related transcription factor-2 (Runx-2) and osteoarthritis-related genes. The effect of HDAC4 upregulation on cartilage damage in OA remains unknown. METHODS: Rat chondrocytes were infected with Ad-GFP or Ad-HDAC4-GFP for 48 h, stimulated with interleukin-1ß (IL-1ß, 10 ng/mL) for 24 h, and then harvested for RT-qPCR. Male Sprague-Dawley rats in 3 groups were given anterior cruciate ligament transection (ACLT) or sham operation, and knee injections with different adenovirus (Ad) vectors at 48 h after surgery and every 3 weeks thereafter: ACLT+Ad-GFP (n = 17); ACLT+Ad-HDAC4-GFP (n = 20); and sham+Ad-GFP (n = 15). Three ACLT-Ad-HDAC4-GFP rats were sacrificed at different times to examine the expression of HDAC4. Two ACLT-Ad-GFP rats and two ACLT-Ad-HDAC4-GFP rats were euthanized at week-2; articular cartilage was harvested and expression of HDAC4 was determined by RT-qPCR. All other rats were euthanized at week-8. Cartilage damage and OA progression was assessed using radiography, fluorescence molecular tomography (FMT), histology, immunohistochemistry (IHC), ELISA, and RT-qPCR. RESULTS: Overexpression of HDAC4 in chondrocytes stimulated by IL-1ß reduced the levels of Runx-2, MMP-13, and Collagen X, but increased the levels of Collagen II and Aggrecan. Upregulation of HDAC4 reduced osteophyte formation and cartilage damage, and increased articular cartilage anabolism. CONCLUSION: HDAC4 attenuated articular cartilage damage by repression of Runx-2, MMP-13, and collagen X and induction of collagen II and ACAN in this rat model of OA. Upregulation of HDAC4 may provide chondroprotection in OA patients.

Intraoperative monitoring of pelvic autonomic nerves during laparoscopic low anterior resection of rectal cancer.

BACKGROUND: Some patients with low rectal cancer experience anorectal and urogenital dysfunctions after surgery, which can influence the long-term quality of life. In this study, we aimed to protect nerve function in such scenarios by performing intraoperative monitoring of pelvic autonomic nerves (IMPAN). PATIENTS AND METHODS: We retrospectively investigated a series of 87 patients undergoing laparoscopic low anterior resection of rectal cancer. Nerve-sparing was evaluated both visually and electrophysiologically. IMPAN was performed by stimulating the pelvic autonomic nerves under processed electromyography of the internal anal sphincter. Urination, defecation, sexual function, and the quality of life were evaluated using validated and standardized questionnaires preoperatively and at follow-up, 12 months after surgery. RESULTS: Among a total of 87 patients (53 male and 34 female patients), IMPAN with simultaneous electromyography of the internal anal sphincter was performed in 58 (66.7%) patients. Bilateral positive IMPAN results for both measurements, indicating successfully confirmed pelvic autonomic nerve preservation, were obtained in 45 (51.7%) patients. No significant difference was found in terms of urogenital and anorectal functions between preoperative and postoperative patients with bilateral positive IMPAN (P>0.05). Compared to preoperative patients with IMPAN (unilateral) or without IMPAN, these patients exhibited higher International Prostate Symptom Score, a lower International Index of Erectile Function-5, and a lower Female Sexual Function Index score at 12 months postoperatively (P<0.05). CONCLUSION: IMPAN is an appropriate method with which to laparoscopically protect nerve function.

Application of cryoablation to treat peritoneal carcinomatosis from gastric cancer in a rabbit model.

OBJECTIVES: Peritoneal carcinomatosis is one of the causes of death in patients with advanced gastric cancer. We assumed that cryoablation could be applied as adjuvant therapy to control peritoneal carcinomatosis from gastric cancer. METHODS: We investigated the feasibility of cryoablation technique in rabbit model using a novel cryoablation balloon probe. The cryozones were harvested 7 days after cryoablation for histological evaluation. The levels of cytokines in the peripheral blood of rabbits were also detected. RESULTS: The results demonstrated that cryoablation could be applied in a rabbit model of peritoneal carcinomatosis from gastric cancer. Seven days after cryoablation, necrotic tumor cells could be seen the cryozones. Higher level of IFN-γ was observed. The level of IL-10 was decreased after treatment. CONCLUSIONS: The findings provided the experimental basis for the future application of cryoablation in patients.

A long noncoding RNA MAP3K1-2 promotes proliferation and invasion in gastric cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) have been implicated in several human cancers. The expression profile and underlying mechanism of the lncRNA MAP3K1-2 in gastric cancer (GC) are poorly understood. METHODS: Sixty-one patients with GC were recruited from Shanghai Baoshan Luo Dian Hospital (Shanghai, China). Tumor tissues and paired normal tissues (5 cm adjacent to the tumor) were obtained. Expression of lncRNA MAP3K1-2 in GC cell lines was examined using quantitative real-time polymerase chain reaction. Protein expression was detected using Western blot. Cell cycle analysis was assessed using flow cytometry. Cell proliferation was assessed using soft agar assays, and cell invasion was assessed using Transwell assays. RESULTS: The expression level of lncRNA MAP3K1-2 was upregulated in GC cells and markedly higher in poorly differentiated cell lines. Silencing treatment of lncRNA MAP3K1-2 significantly inhibited cell proliferation and invasion in GC. In addition, knockdown of lncRNA MAP3K1-2 significantly inhibited the function of important genes in the MAPK signaling pathway. Higher expression of lncRNA MAP3K1-2 was often associated with poorer prognosis in patients with GC. CONCLUSIONS: lncRNA MAP3K1-2 is a critical effector in GC tumorigenesis and progression, representing novel therapeutic targets. High lncRNA MAP3K1-2 expression may serve as a novel independent prognostic marker for predicting the outcome of GC.

Advantages of Early Preventive Ileostomy Closure after Total Mesorectal Excision Surgery for Rectal Cancer: An Institutional Retrospective Study of 123 Consecutive Patients.

BACKGROUND/AIM: Preventive ileostomy is frequently constructed to minimizethe consequences of anastomotic leakage after resection of rectal cancer. There is no consensus regarding the best timing for temporary stoma closure after proctectomy for rectal cancer. This retrospective study sought to determine whether the timing of stoma closure influenced postoperative outcomes. METHODS: Subjects were 123 patients with rectal cancer undergoing laparoscopic or open total mesorectal excision surgery with preventive ileostomy from 2012 to 2015. They were divided into 2 groups according the timing of stoma closure: the standard group who had closure within 90 (60-120) days (n = 78) and the late group who had closure after 180 (150-210) days (n = 45). RESULTS: There was no significant difference in operative time, operative blood loss or postoperative complications between the 2 groups. Timing of postoperative fasting and length of hospital stay was similar in both groups. Adjuvant chemotherapy was not a risk factor for postoperative complications after stoma closure. CONCLUSIONS: There was no significant difference between different timings of temporary stoma closure in relation to postoperative complications. Delayed stoma closure showed no benefit in prevention of morbidity. Early closure is safe and can provide better quality of life for patients.

Clinical safety and outcomes of laparoscopic surgery versus open surgery for palliative resection of primary tumors in patients with stage IV colorectal cancer: a meta-analysis.

BACKGROUND: This study was performed to compare the clinical safety and outcomes of laparoscopic versus open surgery for primary tumors in patients with stage IV colorectal cancer. METHODS: Pertinent studies were selected from the MEDLINE, EMBASE, and Cochrane Library databases; references from published articles; and reviews. Both prospective and retrospective studies were included for the meta-analysis. Clinical outcomes included safety, complications, mortality, and survival. RESULTS: Six trials involving 1802 patients were included. The operative time was longer for laparoscopic than for open surgery (mean difference (MD) = 44.20, 95 % confidence interval (CI) 17.31-71.09, Z = 3.22, P = 0.001). Laparoscopic surgery was also associated with fewer postoperative complications (odds ratio 0.53, 95 % CI 0.37-0.78, Z = 3.29, P = 0.001) and less operative blood loss (MD = -65.40, 95 % CI -102.37 to -28.42, Z = 3.47, P = 0.0005). Median survival ranged from 11.4 to 30.1 months. The total hospital stay was 1.68 days shorter for laparoscopic than for open surgery (95 % CI -1.83 to -1.53, Z = 21.64, P < 0.00001). CONCLUSION: Laparoscopic surgery for palliative resection of stage IV colorectal cancer is associated with better perioperative outcomes than open surgery.

Prognostic factors and multidisciplinary treatment modalities for brain metastases from colorectal cancer: analysis of 93 patients.

BACKGROUND: The purpose of this study was to review patient characteristics and evaluate the potential factors affecting prognosis in cases of brain metastasis (BM) from colorectal cancer (CRC). METHODS: We retrospectively reviewed 93 cases of BM from CRC in our hospital. Patient demographics, neurologic symptoms, and location and number of BMs were recorded. Factors analyzed included: age; sex; Karnofsky performance score; number of BMs; presence of extracranial metastases; dimensions; location of tumors; treatment modalities. RESULTS: The overall 1- and 2-year survival rates were 27.7 and 9.9%. On multivariate analysis, the number of BMs, extracranial metastases and the initial treatment modalities were found to be independent prognostic factors for overall survival. Patients treated with surgical resection followed by WBRT or SRS had an improved prognosis relative to those treated with surgery alone (P=0.02 and P=0.02, respectively). No significance difference in survival rate was found between patients treated with SRS alone or SRS plus WBRT (P=0.11). CONCLUSIONS: Surgical resection of BMs from CRC in selected patients may help prolong survival. Additional radiotherapy following surgery is valuable in improving prognosis. Extracranial metastasis, multiple BM lesions and initial non operation can be considered as independent factors associated with poor prognosis.

Comparison of clinical safety and outcomes of early versus delayed laparoscopic cholecystectomy for acute cholecystitis: a meta-analysis.

OBJECTIVE: To compare the clinical safety and outcomes of early laparoscopic cholecystectomy versus delayed laparoscopic cholecystectomy for acute cholecystitis. METHODS: Pertinent studies were selected from the Medline, EMBASE, and Cochrane library databases, references from published articles, and reviews. Seven randomized controlled trials (early laparoscopic cholecystectomy versus delayed laparoscopic cholecystectomy) were selected. Conventional meta-analysis according to Cochrane Collaboration was used for the pooling of the results. RESULTS: Seven trials with 1106 patients were included. There was no significant difference between the two groups in terms of bile duct injury (Peto odds ratio 0.49 (95% confidence interval 0.05 to 4.72); P = 0.54) or conversion to open cholecystectomy (risk ratio 0.91 (95% confidence interval 0.69 to 1.20); P = 0.50). The total hospital stay was shorter by 4 days for early laparoscopic cholecystectomy (mean difference -4.12 (95% confidence interval -5.22 to -3.03) days; P < 0.00001). CONCLUSION: Early laparoscopic cholecystectomy during acute cholecystitis is safe and shortens the total hospital stay.

Clinical application of adoptive T cell therapy in solid tumors.

As an emerging therapeutic approach, adoptive T cell therapy shown promise in advanced solid malignancies. The results obtained in patients with metastatic melanoma and kidney cancer are encouraging because of the visible clinical benefits and limited adverse effects. Recently, the genetically-modified T cells expressing specific T cell receptors or chimeric antigen receptors are just now entering the clinical arena and show great potential for high avidity to tumor-associated antigens and long-lasting anti-tumor responses. However, continued investigations are necessary to improve the cell product quality so as to decrease adverse effects and clinical costs, and make adoptive T cell therapy a tool of choice for solid malignancies.

Expression of C4.4A is a potential independent prognostic factor for patients with gastric cancer.

C4.4A, a metastasis-associated gene, encodes a glycolipid-anchored membrane protein which is overexpressed in several human malignancies. However, there are few data available on C4.4A expression and its relationship with progression in gastric cancer. Our study was designed to explore the expression of C4.4A in gastric cancer and to correlate it with clinical outcome. C4.4A expression was studied by quantitative real-time RT-PCR and immunohistochemistry for assessment of correlations with clinicopathological factors. C4.4A mRNA expression was significantly up-regulated in gastric cancer as compared with noncancerous tissue (p<0.05)., being observed in 107 (88.4%) of the 121 gastric cancer cases by immunohistochemistry. We found that the expression of C4.4A mRNA was correlated with size of the tumor, depth of invasion, lymph node metastasis, distant metastasis and TNM stage. Moreover, patients with overexpression of C4.4A has a significantly worse survival (p<0.05). Further multivariable analysis indicated that the expression of C4.4A was an independent prognostic indicator for gastric cancer (p<0.05). In conclusion, overexpression of C4.4A correlates with metastatic potential of gastric cancer and C4.4A could be a novel independent prognostic marker for predicting outcome.

Recipient dendritic cells modified by RNA interference targeting CD80 and CD86 elicit T cell hyporesponsiveness via enhanced T cell apoptosis.

BACKGROUND: Despite extensive research, the mechanism of immature dendritic cells (DCs) induced immune hyporesponsiveness remains incompletely understood. METHODS: Recipient DCs from C3H mouse bone marrow cells were incubated with donor antigen from splenic lymphocytes of C57BL/6 mouse; these DCs were transfected with CD80/86 specific siRNA using lentiviral vectors. Flow cytometry was used to evaluate expression of CD80/86 on the antigen-pulsed recipient DCs. Immune regulatory activity was examined by mixed lymphocyte reaction, in which irradiated DCs were cultured with C3H spleen T cells. After the reaction, interleukin (IL)-2, IL-4, IL-10, and interferon (INF)-γ levels of mixed lymphocyte reaction culture supernatant were measured by enzyme-linked immunosorbent assay. The apoptotic T lymphocytes were identified by Annexin V and CD3 staining. RESULTS: There was a significant inhibition of CD80/86 expression in DCs transfected with CD80/86 lentiviral vectors compared with the control groups (P < 0.05), indicating the specificity of RNA interference. Enzyme-linked immunosorbent assay results showed a significant reduction of INF-γ, IL-2 and IL-10 in the CD80/86 lentivirus transfected group compared to the control groups (P < 0.05). There was no significant difference in IL-4 levels between the groups (P > 0.05). We also showed that CD80/86 low DCs loaded with alloantigen (1) stimulated low T cell proliferative responses via the indirect recognition pathway and (2) enhanced apoptotic activity (P < 0.05) in co-cultured T cells. CONCLUSIONS: Lentiviral vector transfection can effectively and specifically knock down target genes in DCs. The CD80/86 low DCs may show tolerogenic activity via induction of T-cell apoptosis, thereby modulating the activity of recipient-derived DCs. The use of this approach may potentially be clinically applicable.