Camrelizumab plus famitinib in previously chemo-immunotherapy treated patients with advanced NSCLC: results from an open-label multicenter phase 2 basket study.

BACKGROUND: The combination of immune checkpoint inhibitors and antiangiogenic agents has been effective in treating multiple cancers. This was further explored in an open-label, multicenter phase 2 basket study (NCT04346381), which evaluated the antitumor activity and safety of camrelizumab (an anti-PD-1 antibody) plus famitinib (a receptor tyrosine kinase inhibitor) in patients with advanced solid tumors. We herein report the findings from the cohort of advanced NSCLC patients who progressed after treatment with platinum-doublet chemotherapy and immunotherapy. METHODS: Eligible patients were enrolled and treated with camrelizumab (200 mg once every 3 weeks via intravenous infusion) and oral famitinib (20 mg once daily). The primary endpoint was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Forty patients were enrolled in this cohort, with a median follow-up duration of 11.5 months. Three patients (7.5%) achieved a partial response, and 29 patients (72.5%) achieved stable disease. The ORR and DCR with this combination regimen were 7.5% (95% CI, 1.6-20.4) and 80.0% (95% CI, 64.4-90.9), respectively. The median DoR was 12.1 months (95% CI, 10.3-not reached). The median PFS was 5.4 months (95% CI, 4.1-7.5), and the median OS was 12.1 months (95% CI, 9.1-16.7). The estimated 12-month OS rate was 51.5% (95% CI, 34.9-65.9). The most frequent grade 3 or higher treatment-related adverse events occurring in more than 5% of patients included hypertension (27.5%), palmar-plantar erythrodysesthesia syndrome (10%), decreased neutrophil count (10%), and proteinuria (7.5%). CONCLUSION: Camrelizumab plus famitinib demonstrated favorable benefits in PFS and OS, along with manageable safety profiles, in patients with advanced NSCLC who progressed after platinum-doublet chemotherapy and immunotherapy. This finding warrants further exploration.

Enhanced biomass production and wastewater treatment in attached co-culture of Chlorella pyrenoidosa with nitrogen-fixing bacteria Azotobacter beijerinckii.

Algae-bacteria symbiosis can promote the growth of microalgae and improve the efficiency of wastewater treatment. Attached culture is an efficient culture technique for microalgae, with benefits of high yield, low water consumption and easy harvesting. However, the promoting effects of bacteria on microalgae in attached culture are still unclear. In this study, different forms of a nitrogen-fixing bacteria, Azotobacter beijerinckii (including bacteria supernatant, live bacteria, and broken bacteria), were co-cultured with Chlorella pyrenoidosa in an attached culture system using wastewater as the culture medium. The results showed that the broken A. beijerinckii form had the best growth promotion effect on C. pyrenoidosa. Compared with the pure algae culture, the biomass of C. pyrenoidosa increased by 71.8% and the protein increased by 28.2%. The live bacteria form had the best effect on improving the efficiency of wastewater treatment by C. pyrenoidosa, with the COD, PO43- and NH4+-N removal rates increased by 20.8%, 18.5% and 8.9%, respectively, in comparison with the pure algae culture. The attached co-culture mode promoted the growth of C. pyrenodisa better than the suspended co-culture mode. This research offers a new way for improving microalgae biomass and wastewater treatment by attached algae-bacteria symbiont.

Epidermal growth factor receptor gene mutations in patients with lung adenocarcinoma differ by frequency and type between Uighur and Han ethnic groups in Xinjiang Autonomous Region.

BACKGROUND: This study was designed to investigate epidermal growth factor receptor (EGFR) mutation types affecting lung cancer treatment in patients in Xinjiang, China. We detected and analyzed differences in the EGFR mutation points of Uighur and Han patients with lung adenocarcinoma. We examined 181 specimens of lung adenocarcinoma tissue embedded with paraffin (76 Uighur and 105 Han patients) for mutations in the EGFR gene in exon 18-21 by the amplification refractory mutation system (ARMS) method. We used the chi-square statistical method to analyze the relationship between mutations and patients' clinical parameters. RESULTS: EGFR somatic mutations were detected in 59 of 181 cases (32.6%). The mutation rate was higher in Han patients (45.7%) than in Uighur patients (15.8%) (P < 0.001). The main mutation types were the exon 19 deletion and the L858R point mutation in exon 21. In Han patients we found 21 (44.7%) cases of exon 19 deletion, 24 (51.1%) cases of L858R in exon 21, 1 case (2.1%) with mutations in both exon 19 and exon 21, and 1 case (2.1%) with T790 mutation in exon 20. In Uighur patients we found 8 (66.7%) cases of exon 19 deletion and 4 (33.3%) cases of L858R in exon 21. CONCLUSIONS: In comparing these groups, the exon 19 deletion was more common than L858R in exon 21 in Uighur patients. In Han patients, EGFR-sensitive mutations occurred in female, never-smoking patients with well-differentiated tumors; but for Uighur patients only smoking history showed an obvious correlation.

METTL3-dependent N6-methyladenosine modification is involved in berberine-mediated neuroprotection in ischemic stroke by enhancing the stability of NEAT1 in astrocytes.

Ischemic stroke (IS) is one of the principal causes of disability and death worldwide. Berberine (BBR), derived from the traditional Chinese herbal medicine Huang Lian, has been reported to inhibit the progression of stroke, but the specific mechanism whereby BBR modulates the progression of ischemic stroke remains unclear. N6-methyladenosine (m6A) modification is the most typical epigenetic modification of mRNA post-transcriptional modifications, among which METTL3 is the most common methylation transferase. During the study, the middle cerebral artery occlusion/reperfusion (MCAO/R) was established in mice, and the mice primary astrocytes and neurons induced by oxygen-glucose deprivation/reoxygenation (OGD/R) was simulated in vitro. Level of LncNEAT1, miR-377-3p was detected via RT-qPCR. The levels of Nampt and METTL3 were measured by Western blot. CCK8 and LDH assay was performed to detect cell viability. Here, we found that berberine alleviates MCAO/R-induced ischemic injury and up-regulates the expression of Nampt in astrocytes, miR-377-3p inhibits the expression of Nampt in astrocytes after OGD/R, thus promoting neuronal injury. NEAT1 binds to miR-377-3p in OGD/R astrocytes and plays a neuronal protective role as a ceRNA. METTL3 can enhance NEAT1 stability in OGD/R astrocytes by modulating m6A modification of NEAT1. Taken together, our results demonstrate that berberine exerts neuroprotective effects via the m6A methyltransferase METTL3, which regulates the NEAT1/miR-377-3p/Nampt axis in mouse astrocytes to ameliorate cerebral ischemia/reperfusion (I/R) injury.

First-line treatment with camrelizumab plus famitinib in advanced or metastatic NSCLC patients with PD-L1 TPS ≥1%: results from a multicenter, open-label, phase 2 trial.

BACKGROUND: The combination of immune-checkpoint inhibitors and antiangiogenic agents can synergistically modulate the tumor microenvironment and represents a promising treatment option. Here, we evaluated the efficacy and safety of camrelizumab plus famitinib (a receptor tyrosine kinase inhibitor) as a first-line treatment for advanced or metastatic NSCLC patients with a programmed death ligand-1 (PD-L1) tumor proportion score (TPS) of ≥1%, in an open-label, multicenter, phase 2 basket trial. METHODS: Eligible patients received camrelizumab (200 mg once every 3 weeks via intravenous infusion) plus oral famitinib at an initial dose of 20 mg once daily. The primary endpoint was the objective response rate (ORR), as assessed by the investigator per Response Evaluation Criteria in Solid Tumors V.1.1. Key secondary endpoints included disease control rate (DCR), duration of respons, progression-free survival (PFS), overall survival (OS), 12-month OS rate, and safety profile. RESULTS: Of the enrolled 41 patients, 21 (51.2%) had a PD-L1 TPS of 1-49%. As of the cut-off date on June 22, 2022, the combination regimen of camrelizumab and famitinib achieved an ORR of 53.7% (95% CI 37.4% to 69.3%) and a DCR of 92.7% (95% CI 80.1% to 98.5%). The median PFS was 16.6 months (95% CI 8.3 to not reached), and OS data were not yet mature, with an estimated 12-month OS rate of 76.8% (95% CI 60.0% to 87.3%). The most common treatment-related adverse events of grade 3 or higher included hypertension (22.0%), increased alanine aminotransferase (12.2%), decreased neutrophil count (9.8%), proteinuria (7.3%), decrease platelet count (7.3%), and hypokalemia (7.3%). One (2.4%) patient died from grade 5 hemoptysis, which was considered possibly related to the study treatment by the investigator. CONCLUSION: Camrelizumab plus famitinib demonstrated promising antitumor activity in advanced or metastatic NSCLC patients and had an acceptable safety profile. These findings suggest that this combination regimen could be an alternative therapeutic option and warrant further investigation. TRIAL REGISTRATION NUMBER: NCT04346381.

A case report of autoimmune glial fibrillary acidic protein astrocytopathy presenting as an isolated spinal cord lesion.

INTRODUCTION: Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a group of neurological syndromes involving the meninges, brain, spinal cord, and optic nerves and is characterized by sensitivity to steroid therapy. Due to the diverse clinical presentation and lack of uniform diagnostic criteria, GFAP-A can easily be overlooked or diagnosed as another disease. It is even rarer when presenting as an isolated spinal cord lesion. CASE REPORT: We report the case of a 70-year-old man with initial symptoms of numbness and weakness in both lower limbs, followed by difficulty in urination and defecation, and progression of numbness upward to the hands. Magnetic resonance imaging (MRI) showed a lesion in the spinal cord from cervical level 2 to thoracic 7 in a T2-weighted image. T1-weighted image showed a punctate, lamellar strengthening lesion with significant spinal strengthening. GFAP immunoglobulin G (IgG) was detected in the cerebrospinal fluid and blood. After treatment with intravenous gamma globulin (IVIG), the patient symptoms improved and spinal cord enhancement was reduced. CONCLUSION: Long segment cases with punctate and patchy enhancement of the spinal cord are difficult to distinguish from CLAPPERS, so GFAP-A antibody detection is very important. This atypical case also increases neurologists' understanding of GFAP-A.

Improved effects of combined application of nitrogen-fixing bacteria Azotobacter beijerinckii and microalgae Chlorella pyrenoidosa on wheat growth and saline-alkali soil quality.

Soil salinization seriously affects crop yield and soil productivity. The application of bacteria and microalgae has been considered as a promising strategy to alleviate soil salinization. However, the effect of bacteria-microalgae symbiosis on saline-alkali land is still unclear. This study evaluated the effects of Azotobacter beijerinckii, Chlorella pyrenoidosa, and their combined application on the wheat growth and saline-alkali soil improvement. The results showed that, among all the treatments, A. beijerinckii + live C. pyrenoidosa combined inoculation group (BA) had the best effect on increasing wheat plant biomass, improving salt tolerance, and improving soil fertility. The dry weight of wheat plant in the BA group increased by 66.7%, 17.4%, and 35.0%, respectively, compared with the control group (CK), A. beijerinckii inoculation group (B), and live C. pyrenoidosa inoculation group (A). The total nitrogen content of wheat plant in the BA group increased by 69.5%, 76.7%, and 71.1%, compared with the CK, B, and A group. The proline content of wheat plant in the BA group was 100% higher than that in the CK group. The N/P ratio and K/Na ratio of wheat plant increased by 157% and 12.9% in the BA group compared with the CK group, respectively, which was more conducive to alleviating nitrogen limitation and salt stress. The A. beijerinckii + live C. pyrenoidosa inoculation treatment better reduced soil pH and improved the availability of phosphorus in soil. This study illustrated the comprehensive application prospects of bacteria-microalgae interactions on wheat growth promotion and soil improvement in saline-alkali land, and provided a new effective strategy for improving saline-alkali soil quality and increasing crop productivity.

Prevotella histicola Transplantation Ameliorates Cognitive Impairment and Decreases Oxidative Stress in Vascular Dementia Rats.

Vascular dementia is a type of dementia from brain damage caused by cerebrovascular lesions and vascular risk factors. Prevotella histicola is a species of Prevotella, belonging to the category of obligate anaerobe. The purpose of our work was to study the protection of Prevotella histicola on cognitive function in rats subjected to vascular dementia (VaD) and investigate underlying molecular mechanisms. The rats were randomly divided into three groups: control group, 2VO group and 2VO + Prevotella histicola group. The VaD rats (the 2VO group and 2VO + Prevotella histicola group) were generated by bilateral common carotid artery occlusion (2VO). Rats in the 2VO+ Prevotella histicola group were administered with Prevotella histicola twice daily. In comparison with the rats in the 2VO group, rats in the 2VO + Prevotella histicola group presented an enhanced cognitive ability, increased synapse-associated protein expression, a downregulation of proinflammatory factors and an upregulation of neurotrophic factors. The relevant mechanism of the protective effect of Prevotella histicola may be associated with the inhibition of glial cell-associated inflammation by regulating phosphorylation of CaMKII. In conclusion, Prevotella histicola attenuates neurological impairments via regulating synapse-associated protein expression and the liberation of inflammatory elements in vascular dementia rats. The findings above might benefit the development of Prevotella histicola transplantation as a promising treatment of VaD.

TMAO Promotes NLRP3 Inflammasome Activation of Microglia Aggravating Neurological Injury in Ischemic Stroke Through FTO/IGF2BP2.

Objective: Stroke is a kind of cerebrovascular disease with high mortality. TMAO has been shown to aggravate stroke outcomes, but its mechanism remains unclear. Materials and Methods: Mice were fed with 0.12% TMAO for 16 weeks. Then, mice were made into MCAO/R models. Neurological score, infarct volume, neuronal damage and markers associated with inflammation were assessed. Since microglia played a crucial role in ischemic stroke, microglia of MCAO/R mice were isolated for high-throughput sequencing to identify the most differentially expressed gene following TMAO treatment. Afterward, the downstream pathways of TMAO were investigated using primary microglia. Results: TMAO promoted the release of inflammatory cytokines in the brain of MCAO/R mice and promoted the activation of OGD/R microglial inflammasome, thereby exacerbating ischemic stroke outcomes. FTO/IGF2BP2 inhibited NLRP3 inflammasome activation in OGD/R microglia by downregulating the m6A level of NLRP3. TMAO can inhibit the expression of FTO and IGF2BP2, thus promoting the activation of NLRP3 inflammasome in OGD/R microglia. In conclusion, these results demonstrated that TMAO promotes NLRP3 inflammasome activation of microglia aggravating neurological injury in ischemic stroke through FTO/IGF2BP2. Conclusion: Our results demonstrated that TMAO promotes NLRP3 inflammasome activation of microglia aggravating neurological injury in ischemic stroke through FTO/IGF2BP2. These findings explained the molecular mechanism of TMAO aggravating ischemic stroke in detail and provided molecular mechanism for clinical treatment.

Berberine Mediates the Production of Butyrate to Ameliorate Cerebral Ischemia via the Gut Microbiota in Mice.

Ischemic stroke (IS) is a vascular disease group concomitant with high morbidity and mortality. Berberine is a bioactive substance and it has been known to improve stroke, but its mechanism is yet to be proven. Mice were fed with BBR for 14 days. Then, the mice were made into MCAO/R models. Neurological score, infarct volume, neuronal damage and markers associated with inflammation were detected. We tested the changes in intestinal flora in model mice after BBR administration using 16SrRNA sequencing. Chromatography-mass spectrometry was used to detect butyrate chemically. Tissue immunofluorescence was used to detect the changes in the microglia and astroglia in the mice brains. Our findings suggest that berberine improves stroke outcomes by modulating the gut microbiota. Specifically, after MCAO/R mice were given berberine, the beneficial bacteria producing butyric acid increased significantly, and the mice also had significantly higher levels of butyric acid. The administration of butyric acid and an inhibitor of butyric acid synthesis, heptanoyl-CoA, showed that butyric acid improved the stroke outcomes in the model mice. In addition, butyric acid could inhibit the activation of the microglia and astrocytes in the brains of model mice, thereby inhibiting the generation of pro-inflammatory factors IL-6, IL-1ß and TNF-α as well as improving stroke outcomes. Our results suggest that berberine may improve stroke outcomes by modulating the gut flora to increase the abundance of butyric acid. These findings elucidate the mechanisms by which berberine improves stroke outcomes and provide some basis for clinical treatment.

Improvement of phosphate solubilizing bacteria Paenibacillus xylanexedens on the growth of Chlorella pyrenoidosa and wastewater treatment in attached cultivation.

A symbiotic system of algae-bacteria, and attached cultivation, are two ways to increase microalgae biomass, and beneficially effect wastewater treatment. However, the possible advantages of the algae-bacteria co-culture in attached cultivation, are still unclear. This paper investigates the effects of different morphologies of a phosphate solubilizing bacteria-Paenibacillus xylanexedens (bacteria supernatant, bacteria, broken bacteria), on the growth of microalgae-Chlorella pyrenoidosa and wastewater treatment in an attached co-culture system. The results show that the broken bacteria had the most significant effect, with the biomass and protein content of Chlorella pyrenoidosa increasing by 125.67% and 25.04%; and the removal rate of COD, NH4+-N and PO43- in wastewater increasing by 23.57%, 146.15% and 9.96% respectively. This indicates that the intracellular material of the Paenibacillus xylanexedens was more effective in promoting the biomass growth of Chlorella pyrenoidosa and the removal rates of COD, NH4+-N and PO43-, compared to the algae growing without the bacteria. The algae-bacteria symbiotic attached mode was superior to the suspended mode, in terms of both Chlorella pyrenoidosa biomass enhancement and effective wastewater treatment. The addition of different morphologies of Paenibacillus xylanexedens significantly enlarged the difference between the two culture modes. This study provides a new method for coupled algae-bacteria co-cultures for wastewater treatment, based on the symbiotic effect.

Efficacy and safety of heat-sensitive moxibustion in the treatment of neurogenic bladder after spinal cord injury: A protocol for systematic review and meta-analysis.

BACKGROUND: Spinal cord injury (SCI) is one of the most disabling and destructive neurological diseases. Neurogenic bladder dysfunction (NBD) is one of the serious complications after SCI, 80% of patients after SCI will have neurogenic bladder symptoms. NBD after SCI may lead to urinary retention, urinary incontinence, and urinary tract infection. In severe cases, it can lead to renal failure or even death. NBD after SCI not only seriously affects the patient's quality of life but also physical and mental health. NBD after SCI is a social and medical problem. In recent years, more and more clinical studies prove that heat-sensitive can improve the clinical symptoms of NBD after SCI. Therefore, this article conducts a systematic evaluation and meta-analysis on the efficacy and safety of heat-sensitive moxibustion in treating NBD after SCI. METHODS: Search 8 electronic databases including PubMed, Embase, Web of Science, The Cochrane Library, Clinical Trials, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and China Biomedical Literature Database. We will search above electronic databases from the inception to May 2021, without any language restriction. Clinical randomized controlled trials containing heat-sensitive moxibustion for NBD after SCI and eligible interventions(s) and outcome(s) were included, with no limitation of language and publication status. Two researchers will independently conduct literature search, screening, information extraction, quality assessment, and data analysis. Review Manager 5.3 software will be used for statistical analysis. RESULTS: The findings will be submitted to a peer-reviewed publication. CONCLUSION: This systematic review and meta-analysis will provide a standard clinical decision-making guideline for heat-sensitive moxibustion treatment of NBD after SCI. INPLASY REGISTRATION NUMBER: INPLASY202150071.

Effect of extracorporeal shock wave therapy for rotator cuff tendonitis: A protocol for systematic review and meta-analysis.

BACKGROUND: Rotator cuff tendinitis is a highly prevalent cause of shoulder pain and leads to decreased patient quality of life. Extracorporeal shock wave therapy (ESWT) and ultrasound-guided needling are considered beneficial for rotator cuff tendinitis. A systematic review and meta-analysis comparing ESWT with sham-ESWT or ultrasound-guided needling in the management of pain and calcification is lacking. METHODS: We will search the following up database from its inception to August 2020 without language restriction: PubMed, Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure, China Biomedical Literature Database, Chinese Science Journal Database, and WangFang database. All randomized controlled trials compared the effect of ESWT and sham-ESWT or ultrasound-guided needling of rotator cuff tendinitis will be included in pain and calcification. Two researchers will operate literature retrieval, screening, information extraction, quality assessment, and data analysis independently. The analysis will be conducted using Review Manager 5.3 Software. RESULTS: The findings will be submitted to a peer-reviewed publication. CONCLUSION: This systematic review and meta-analysis will provide high-quality evidence for the treatment of patients with rotator cuff tendinitis. INPLASY REGISTRATION NUMBER: INPLASY202080028.

Inhibition of DNA­PK by gefitinib causes synergism between gefitinib and cisplatin in NSCLC.

Lung cancer has the highest incidence and mortality rates among the malignant tumor types worldwide. Platinum­based chemotherapy is the main treatment for advanced non­small­cell lung cancer (NSCLC), and epidermal growth factor receptor­tyrosine kinase inhibitors (EGFR­TKIs) have greatly improved the survival of patients with EGFR­sensitive mutations. However, there is no standard therapy for treating patients who are EGFR­TKI resistant. Combining EGFR­TKIs and platinum­based chemotherapy is the most popular strategy in the clinical practice. However, the synergistic mechanism between EGFR­TKIs and platinum remains unknown. Therefore, the aim of the present study was to determine the synergistic mechanism of gefitinib (an EGFR­TKI) and cisplatin (a main platinum­based drug). MTT assay, apoptosis analysis, tumorsphere formation and an orthotropic xenograft mouse model were used to examine the combination effects of gefitinib and cisplatin on NSCLC. Co­immunoprecipitation and immunofluorescence were used to identify the underlying mechanism. It was found that gefitinib could selectively inhibit EGFR from entering the nucleus, decrease DNA­PK activity and enhance the cytotoxicity of cisplatin on NSCLC. Collectively, the results suggested that inhibition of DNA­dependent protein kinase by gefitinib may be due to the synergistic mechanism between gefitinib and cisplatin. Thus, the present study provides a novel insight into potential biomarkers for the selection of combination therapy of gefitinib and cisplatin.

PARK2 Suppresses Proliferation and Tumorigenicity in Non-small Cell Lung Cancer.

Aims: PARK2 mutation is originally associated with the progression of Parkinson's disease. In recent years, PARK2 has been reported as a tumor suppressor gene in various cancers, including lung cancer. However, the biological functions and potential molecular mechanisms of PARK2 in non-small cell lung cancer (NSCLC) are still unclear. Methods: The level of PARK2 expression in 32 tissue samples of NSCLC and matched non-tumor lung tissues was detected by Western blot, and 64 specimens of NSCLC tissues were detected by immunohistochemistry. H1299 and H460 cell lines were used to PARK2 overexpression models, and H460 cell line was also used to PARK2 knockdown model. Using cell viability, colony formation, cell cycle, apoptosis, migration, and invasion assay, the biological functions of PARK2 were evaluated and the potential molecular mechanism of PARK2 was investigated in vitro. Meanwhile, 22 nude mice were employed for in vivo studies. Results: Western blot analysis revealed a decrease of PARK2 protein expression in human NSCLC samples. Immunohistochemistry also identified a vastly reduced expression of PARK2 in NSCLC (72%) and low PARK2 expression was significantly associated with tumor histological grade, lymph node metastasis and advanced TNM stage. Overexpression of PARK2 suppressed cell proliferation, colony formation, migration, and invasion, arrested cell cycle progression in the G1 phase, and induced apoptosis in human non-small cell lines H1299 and H460 in vitro. Meanwhile, knockdown of PARK2 had the opposite biological functions. In addition, PARK2 significantly decreased the tumor volumes in subcutaneous xenograft model and reduced the incidence of metastatic tumors in the transfer model. Exploration of the molecular mechanism of PARK2 in NSCLC showed that PARK2 negatively regulated the EGFR/AKT/mTOR signaling pathway. Conclusions: PARK2 was an important tumor suppressor in NSCLC, which might inhibit cancer growth and metastases through the down regulation of the EGFR/AKT/mTOR signaling pathway.

PARK2 inhibits osteosarcoma cell growth through the JAK2/STAT3/VEGF signaling pathway.

Osteosarcoma (OS) is the most common primary malignant bone tumor mainly occurring in children and adolescents. In past decades, studies revealed that PARK2 was a vital tumor suppressor gene in many malignant solid tumors. However, the role of PARK2 in OS remains largely unclear. Therefore, we assessed PARK2 expression in OS tissue and adjacent non-tumor tissues by immunohistochemical (IHC) analysis, and evaluated PARK2 mRNA expression in OS cell lines by real-time PCR analysis. The HOS and U2OS cell lines were employed to establish a PARK2 overexpression model. Using this model, we investigated the potential role of PARK2 in OS and explored the underlying molecular mechanisms. Our study showed PARK2 was downregulated in OS tissue and cell lines, which was significantly associated with higher tumor stage (P < 0.05). Overexpression of PARK2 arrested the cell cycle, inhibited cell proliferation, migration, and invasion, induced cell apoptosis, and reduced tube formation in vitro. Moreover, overexpression of PARK2 significantly suppressed tumor growth and angiogenesis in vivo. Additionally, PARK2 negatively regulated OS development through the JAK2/STAT3/VEGF pathway. Our findings demonstrate that PARK2 is a tumor suppressor gene that may negatively affect OS growth and angiogenesis via partly inhibiting the JAK2/STAT3/VEGF signaling pathway.

Meta-analysis of Soy Consumption and Gastrointestinal Cancer Risk.

Soy consumption has received considerable attention for its potential role in reducing cancer incidence and mortality. However, its effects on gastrointestinal (GI) cancer are controversial. Therefore, we performed a meta-analysis to evaluate the association between soy consumption and gastrointestinal cancer risk by searching for prospective studies in PubMed, Web of Science, EMBASE and the reference lists of the included articles. The study-specific odds ratio (OR), relative risk (RR) or hazard ratio (HR) estimates and 95% confidence intervals (CIs) were pooled using either a fixed-effect or random-effect model. Twenty-two independent prospective studies were eligible for our meta-analysis, including 21 cohort studies and one nested case-control study. Soy product consumption was inversely associated with the incidence of overall GI cancer (0.857; 95% CI: 0.766, 0.959) and the gastric cancer subgroup (0.847; 95% CI: 0.722, 0.994) but not the colorectal cancer subgroup. After stratifying the results according to gender, an inverse association was observed between soy product intake and the incidence of GI cancer for females (0.711; 95% CI: 0.506, 0.999) but not for males.

Occupational ultraviolet exposure and risk of non-Hodgkin's lymphomas: a meta-analysis.

Non-Hodgkin lymphoma is a heterogeneous group of lympho-proliferative disorders. We performed a meta-analysis to summarize the available evidence from case-control studies and cohort study on the inconsistent association between occupational sun exposure and the risk of non-Hodgkin lymphoma. We searched PubMed, ISI web of science, the Cochrane Library, EMBASE and reference lists for relevant articles. Study specific odds ratios or relative risk and 95% confidence intervals were pooled by using fixed-effects or random-effects models. Ten case-control studies and one cohort study were included in the meta-analysis. Overall, the pooled odds ratios for occupational ultraviolet exposure and non-Hodgkin lymphoma risk was 1.15(95% confidence intervals: 0.99, 1.32; I2 = 44.4%). Occupational sun exposure was positively associated with the risk of NHL 1.14 (95% confidence intervals: 1.05, 1.23; I2=25.4% p for heterogeneity =0.202) in Caucasian population. Common subtypes of non-Hodgkin lymphoma and ultraviolet exposure had the negative results. The pooled odds ratios was 1.16, (95%confidence intervals: 0.90, 1.50) for T-cell non-Hodgkin lymphoma; 0.79, (95%confidence intervals: 0.61, 1.02) for B-cell non-Hodgkin lymphoma; 1.13, (95%confidence intervals: 0.96, 1.34) for chronic lymphocytic leukemia; 1.25, (95%confidence intervals: 0.95, 1.64) for males; 1.49, (95%confidence intervals: 0.99, 2.25) for females. Data suggested that occupational ultraviolet exposure was a risk factor for non-Hodgkin lymphoma in Caucasian population. While, there had no relationship between occupational ultraviolet exposure and risk of non-Hodgkin lymphoma in general population as well as non-Hodgkin lymphoma common subtypes. Besides, gender specific occupational sun exposure also indicated no association on risk of non-Hodgkin lymphoma.