Effectiveness Differences of Ranibizumab and Aflibercept Action in the Treatment of Diabetic Retinopathy.

Objective: To compare the difference in the effectiveness of ranibizumab (LU) and aflibercept (AF) in the treatment of diabetic retinopathy (DR). Methods: Ninety-four patients with DR admitted to Sunshine Union Hospital from August 2020 to February 2022 were selected for the study and were divided into LU group (n = 47) and AF group (n = 47) according to the random number table method. Both groups underwent 25G vitrectomy in our hospital, with LU injected into the vitreous before surgery in the LU group and AF in the AF group. Vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in the pre-and post-injection atrial water were compared between the two groups, and the operative time, intraoperative bleeding, and the occurrence of medically induced fissures were recorded in both groups. In addition, the expression of best corrected visual acuity (BCVA), Central Macular Thickness (CMT), and inflammatory factors were compared before and after surgery. Finally, patients were counted for adverse reactions and prognosis of DR recurrence during treatment. Results: After injection, VEGF decreased and PEDF increased in both groups (P < .001). There were no differences in operative time (P = .604), intraoperative bleeding rate (P = .694), the incidence of medically induced fissure (P = .557), BCVA [P = .665 (T0), P > .999 (T1), P = .727 (T2)], and CMT [P = .688 (T0), P = .065 (T1), P = .148 (T2)] between the two groups, while IL-6, IL-8, and MMP-9 were lower in the AF group than in the LU group at 2 months after surgery (P < .001). Finally, there was no difference between both groups in terms of adverse effects and prognosis of DR recurrence rate (P = 1.000, .478). Conclusion: Both vitreous cavity injections of LU and AF can effectively reduce the expression of vascular-related factors in the atrial fluid of DR patients, but AF has a more significant inhibitory effect on the level of inflammatory factors in patients in the short term after treatment.

AREDS2 Supplementation in Patients with Wet Age-Related Macular Degeneration.

BACKGROUND: In recent years, major progress has been made in treating the wet form of age-related macular degeneration (AMD) with anti-vascular endothelial growth factors, which reportedly stabilize and improve vision. OBJECTIVES: To examine the effect of dietary supplementation, as recommended by the Age-Related Eye Disease Study 2 (AREDS2), on the number of anti-vascular endothelial growth factor injections administered to patients with wet AMD. METHODS: A retrospective study was conducted with 57 participants (27 participants in the study group and 30 in the control group) receiving injections of anti-vascular endothelial growth factors. The study group received dietary supplements for at least one year before the treatment was initiated, while the control group did not. Primary outcome was the number of injections a patient received over a 3-year period. Secondary outcomes were central macular thickness and visual acuity. RESULTS: The average number of injections per patient after 3 years was 21.89 ± 7.85 in the study group and 26.00 ± 5.62 in the control group (P = 0.083). Final visual acuities were 0.45 ± 0.45 and 0.8 ± 0.73 (P = 0.09), and final central macular thicknesses were 288.26 ± 55.38 and 313.12 ± 107.36 (P = 0.38) in the study and control groups, respectively. CONCLUSIONS: The average number of injections after 3 years was lower in the study group, but this difference did not reach statistical significance. No statistically significant difference was found in final visual acuity or central macular thickness between the groups.

Anti-angiogenic and anti-proliferative activity of ziziphus leaf extract as a novel potential therapeutic agent for reducing hepatic injury in experimental hamster schistosomiasis.

BACKGROUND: Schistosomiasis is one of the most prevalent helminthic infections worldwide. Praziquantel (PZQ) resistance poses a possible danger to the disease's ability to be controlled. Little is known about the role of Ziziphus spina-christi leaf extract (ZLE) in the treatment of hepatic schistosomiasis. However, no study has explored ZLE's anti-angiogenic and anti-proliferative activity as a possible mechanism for reducing hepatic injury in this context. Therefore, this study aimed to evaluate the therapeutic potential of ZLE as an anti-angiogenic, and anti-proliferative agent in hamsters infected with S. mansoni. METHODS: Fifty hamsters were used and divided into 5 groups (10 hamsters each); noninfected untreated (controls), noninfected treated with ZLE, infected untreated, infected treated with PZQ- and infected treated with ZLE. Anti-angiogenic and anti-fibrotic effects of the drugs were assessed pathologically through the immunohistochemical expression of VEGF, Ki-67, and TGF ß1 in liver sections. Some oxidative stress parameters were measured in hepatic homogenates (NO, GSH, GST, and SOD), and serum liver enzymes were also assessed. RESULTS: A significant decrease in worm burden, granuloma size, granuloma area, and numbers in the ZLE- and PZQ-treated groups compared to the infected untreated group, and the decrease in granulomas number and tissue egg load was significantly lower in PZQ treated group compared to ZLE treated group (p<0.05). ZLE exhibited significant anti-angiogenic and anti-fibrotic effects on granulomas, illustrated by significantly lower expression of VEGF and TGF-ß1 than infected untreated and PZQ-treated groups. ZLE exhibits antiproliferative activity evidenced by a significant reduction of positive Ki-67 hepatocytes percentage compared to the infected untreated group. Moreover, ZLE exhibits potent antioxidant effects evidenced by a significantly lowered NO and conservation of hepatic GSH, GST, and SOD in hepatic homogenates compared to infected untreated and PZQ-treated groups (p<0.05). CONCLUSION: Our results point to ZLE as a promising hepatoprotective therapeutic tool in the treatment of schistosome hepatic fibrosis as it has anti-angiogenic, anti-proliferative, anti-fibrotic, and antioxidant effects in hamsters infected with S. mansoni, providing scientific support for its use in conventional medicine.

Lenvatinib in the treatment of unresectable hepatocellular carcinoma: a systematic review of economic evaluations.

PURPOSE: This aim of this study was to conduct a systematic review of economic evaluations comparing lenvatinib to other vascular endothelial growth factor (VEGF) inhibitors and other treatment options in the management of unresectable hepatocellular carcinoma (uHCC). METHODS: A comprehensive literature search was conducted using highly sensitive search syntax. The titles and abstracts of all records were studied and screened to identify eligible economic evaluations. To enable comparison across different countries, the results of economic evaluations make it possible to compare, the costs and ICER of all studies were converted into 2022 US dollars, and a 3% annual increase for inflation was applied. The quality of the studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. This study is conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: Lenvatinib was found to be cost-effective (ICER = dominant) compared to most drugs in the included studies, except in studies where it was compared with donafenib or when the price of sorafenib was significantly discounted (e.g., with a 90% discount, the value of ICER was + 104,669 USD). CONCLUSION: Lenvatinib was generally cost-effective in most studies, but not compared to donafenib or sorafenib (if the price sorafenib was significantly discounted).

Effects of NBP injection on the inflammatory response, oxidative stress response and vascular endothelial function in patients with ACI: A systematic review and meta-analysis.

BACKGROUND: Acute cerebral infarction (ACI) is a common medical emergency. This study is the first systematic review of the use of Dl-3-n-butylphthalide (NBP) injection in the treatment of ACI. The purpose of this study was to systematically evaluate the effects of NBP injection on the inflammatory response, oxidative stress response and vascular endothelial function in patients with acute ACI. The objective is to provide reference for clinical application. METHODS: From the establishment of the database until August 2022, we systematically searched EMbase, PubMed, Cochrane Library, Web of Science, CNKI, VIP, and Wanfang Database. RCTs and retrospective studies were included in this study, and the results that qualified for inclusion were screened by 2 researchers and cross-checked. After the relevant data were extracted, a meta-analysis was performed using RevMan5.3 software. RESULTS: A total of 3307 patients with ACI from 34 studies were analyzed. The meta-analysis showed that the C-reactive protein levels in the NBP combined group were effectively reduced compared with those in the control group (MD = -3.75, 95% confidence intervals [95% CI] [-4.95, -2.56], P < .00001). Based on comparison with the control group, it is evident that combination treatment with NBP is more effective than control group in reducing the oxidative stress response of ACI (MD[superoxide dismutase levels] = 22.16, 95% CI [14.20,30.11], P < .00001; MD[malondialdehyde levels] = -1.97, 95% CI [-2.62, -1.32], P < .00001). Comparison with the control group shows that combination treatment with NBP is more effective in improving vascular endothelial function in ACI patients (MD[vascular endothelial growth factor levels] = 71.44, 95% CI [41.22, 101.66], P < .00001; MD[endothelin-1 levels] = -11.47, 95% CI [-17.39, -5.55], P = .0001; MD[nitric oxide levels] = 9.54, 95% CI [8.39, 10.68], P < .00001) than control group. The NBP combined group also showed a greater reduction in cerebral infarct volume (CIV) and cerebral infarct size (CIS) of ACI (MD[CIV] = -1.52, 95% CI [-2.23, -0.81], P < .0001; MD[CIS] = -2.79, 95% CI [-3.65, -1.94], P < .00001). The NBP combined group did not show an increase in the incidence of adverse reactions compared with the control group (odds ratio = 1.06, 95% CI [0.73, 1.53], P = .77). CONCLUSION: In summary, the use of NBP in combination with control group for ACI can reduce the degree of nerve damage, reduce inflammation and oxidative stress, improve vascular endothelial function, and reduce CIS and CIV in ACI patients, without increasing the incidence of clinical adverse events.

Simultaneous Administration of Bevacizumab with Bee-Pollen Extract-Loaded Hybrid Protein Hydrogel NPs Is a Promising Targeted Strategy against Cancer Cells.

Bevacizumab (Bev) a humanized monoclonal antibody that fights vascular endothelial growth factor A (VEGF-A). It was the first specifically considered angiogenesis inhibitor and it has now become the normative first-line therapy for advanced non-small-cell lung cancer (NSCLC). In the current study, polyphenolic compounds were isolated from bee pollen (PCIBP) and encapsulated (EPCIBP) inside moieties of hybrid peptide-protein hydrogel nanoparticles in which bovine serum albumin (BSA) was combined with protamine-free sulfate and targeted with folic acid (FA). The apoptotic effects of PCIBP and its encapsulation (EPCIBP) were further investigated using A549 and MCF-7 cell lines, providing significant upregulation of Bax and caspase 3 genes and downregulation of Bcl2, HRAS, and MAPK as well. This effect was synergistically improved in combination with Bev. Our findings may contribute to the use of EPCIBP simultaneously with chemotherapy to strengthen the effectiveness and minimize the required dose.

Indonesian consensus on systemic therapies for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a deadly cancer with a rising incidence in the last 20 years. Most patients are diagnosed late when curative treatment is no longer feasible. With the background of chronic liver disease in most patients, the management of HCC becomes more complicated, in which well-preserved liver function is a prerequisite for locoregional or systemic therapies. In 2008, sorafenib became the first systemic agent proven to provide survival benefit for patients with advanced-stage HCC. For nearly a decade, no treatment has succeeded in providing better results than sorafenib. However, numerous advances in systemic therapies have emerged in the last 5 years to fulfill the unmet needs of effective therapeutic options. Several agents have been approved for clinical use after positive results in phase III clinical trials, including lenvatinib, regorafenib, cabozantinib, ramucirumab, and lastly immune checkpoint inhibitor atezolizumab in combination with bevacizumab, a monoclonal antibody targeting the vascular endothelial growth factor. With various options available, knowledge on the clinical evidence of each drug, their safety profile, as well as the patient characteristics and preferences become mandatory in clinical decision making. The objective of this consensus is to help clinicians, health-care workers, and policy makers in providing best clinical care for HCC patients.

A Randomized Double-blind Clinical Trial of Weierkang Pills for the Treatment of Chronic Atrophic Gastritis.

BACKGROUND AND GOALS: There are currently no standard treatments for chronic atrophic gastritis and traditional Chinese medicine may be effective. This study aims to investigate the efficacy and safety of Weierkang pills in treating chronic atrophic gastritis. MATERIALS AND METHODS: There were 108 patients in our study. They were randomly assigned to 2 groups. In group A, patients received Weierkang pills and patients in group B received folic acid combined with teprenone. Symptoms, endoscopic scores, and biopsy specimens were compared at baseline and 3 months after treatment. Meanwhile, the expressions of vascular endothelial growth factor and trefoil factor 3 (TFF3) in biopsy specimens were also compared. RESULTS: Our study showed that the total effective rates of atrophy/intestinal metaplasia in group A reached the same level as group B (51.7% vs. 40.0%, P =0.419). Weierkang significantly improved the total effective rate of atrophy/intestinal metaplasia in gastric angle compared with group B (64.7% vs. 33.3%, P =0.024). Weierkang can significantly lower the total Kyoto risk score (2.6±1.1 vs. 3.3±1.0, P =0.002) and atrophy score (1.4±0.6 vs. 1.8±0.5, P =0.001) after treatment. In addition, Weierkang improves symptoms (1.3±1.3 vs. 2.3±1.8, P =0.003) and epigastric pain (0.2±0.4 vs. 0.5±0.6, P =0.041). The expression of TFF3 in gastric mucosa decreased significantly after treatment with Weierkang ( P =0.002). CONCLUSIONS: Weierkang can improve the endoscopic appearance and pathologic changes of chronic atrophic gastritis patients. Symptoms also improved. TFF3 may be involved the pathophysiology mechanism.

A Review of Current and Emerging Therapies for Advanced Hepatocellular Carcinoma.

Hepatocellular carcinoma remains a leading cause of cancer-related deaths worldwide. Liver disease including cirrhosis and viral hepatitis remains among the leading causes of hepatocellular carcinoma and despite increased screening, many patients are diagnosed in the advanced stages precluding them from locoregional therapy. Therapeutic agents for advanced hepatocellular carcinoma were limited to Sorafenib for several years; however, with the emergence of molecular targeted therapies including tyrosine kinase inhibitors and vascular endothelial growth factor inhibitors, in addition to immunotherapies, the way hepatocellular carcinoma is treated has changed significantly. In this review, we summarize the key clinical trials that lead to the approval of these agents for systemic treatment of hepatocellular carcinoma and discuss the preferred sequence of treatment options as well as prospective studies for management of hepatocellular carcinoma.

Understanding patient preferences in anti-VEGF treatment options for age-related macular degeneration.

PURPOSE: (1) To investigate the relative importance of convenience (consultation frequency and injection frequency) against treatment outcomes (visual and anatomical outcomes) and out-of-pocket medical costs via a discrete choice experiment (DCE), and (2) to investigate how patient characteristics affect patient treatment preferences. METHODS: Eligibility criteria were: (1) receiving a neovascular age-related macular degeneration (nAMD) diagnosis; (2) receiving anti-VEGF treatment; (3) being ≥21 years old, and (4) being able to speak and understand English/Mandarin. Patients were presented with eight choice tasks and asked to choose between their current treatment and two hypothetical treatments that varied by six attributes: number of clinic visits in a year, number of injections in a year, vision quality, control of swelling in retina, drug labelling and out-of-pocket cost. RESULTS: This analysis involved 180 patients. Based on latent class logistic regressions, vision quality was the most important attribute (34%) followed by cost (24%). The frequency of total clinic visits (15%) was the third most-important attribute, closely followed by labelling (12%) and control of retina swelling (11%). Injection frequency was the least important attribute (4%). CONCLUSIONS: Vision quality was the most important attribute followed by the out-of-pocket costs. Given the same outcomes, patients preferred treatment regimens which require fewer total clinic visits. In comparison, injection frequency alone did not influence patient preferences. With increasing treatment options for nAMD, understanding patients' preferences can help clinicians in selecting agents and treatment regimen most preferred for each patient, which may lead to improved long-term adherence and outcomes.

Orchestrated Action of AMPK Activation and Combined VEGF/PD-1 Blockade with Lipid Metabolic Tunning as Multi-Target Therapeutics against Ovarian Cancers.

Ovarian cancer is one of the most lethal gynecological malignancies worldwide, and chemoresistance is a critical obstacle in the clinical management of the disease. Recent studies have suggested that exploiting cancer cell metabolism by applying AMP-activated protein kinase (AMPK)-activating agents and distinctive adjuvant targeted therapies can be a plausible alternative approach in cancer treatment. Therefore, the perspectives about the combination of AMPK activators together with VEGF/PD-1 blockade as a dual-targeted therapy against ovarian cancer were discussed herein. Additionally, ferroptosis, a non-apoptotic regulated cell death triggered by the availability of redox-active iron, have been proposed to be governed by multiple layers of metabolic signalings and can be synergized with immunotherapies. To this end, ferroptosis initiating therapies (FITs) and metabolic rewiring and immunotherapeutic approaches may have substantial clinical potential in combating ovarian cancer development and progression. It is hoped that the viewpoints deliberated in this review would accelerate the translation of remedial concepts into clinical trials and improve the effectiveness of ovarian cancer treatment.

Clinical Effect of Bushen Huoxue Method Combined with Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis and Its Effect on IL-1, IL-6, VEGF, and PGE-2.

Objective: To observe the clinical efficacy of the Bushen Huoxue method combined with platelet-rich plasma (PRP) in the treatment of knee osteoarthritis (KOA) and its effect on serum and joint fluid interleukin-1 (IL-1), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE-2). Methods: A total of 64 cases of KOA diagnosed and treated from January 2020 to January 2021 were randomly divided into research group and control group, with 32 cases in each group. The control group was treated with PRP, and the research group took the prescription of the Bushen Huoxue method on the basis of the control group. The clinical efficacy was assessed according to the criteria in "the diagnosis and Treatment of osteoarthritis," osteoarthritis index score and pain visual analogue score (VAS). Serum and articular fluid VAS, IL-1, IL-6, VEGF, and PGE-2 levels were detected by the enzyme-linked immunosorbent assay (ELISA). Results: The clinical effective rate of the research group was 93.8%, which was significantly higher than that of the control group (90.6%). There was no significant difference in the scores of osteoarthritis index between the two groups before treatment, but the scores of both groups decreased after treatment and was lower in the research group than those in the control group. VAS was significantly decreased in two groups after treatment and it was lower in the research group than that in the control group. After treatment, the levels of IL-1, IL-6, and PGE-2 in serum and articular fluid all indexes were decreased, and the levels in the research group were lower than those in the control group. Conclusions: PRP joint cavity injection combined with oral administration of Bushen Huoxue prescription, and PRP joint cavity injection alone can improve the efficacy of KOA, relieve knee pain, and promote the recovery of knee function. The mechanism may be related to the reduction of IL-1, IL-6, VEGF levels, and PGE-2 levels in the serum and joint fluid. However, the efficacy of combination therapy was superior to PRP alone.

Efficacy of Buqi Huoxue Decoction Combined with Cardiac Rehabilitation Nursing after Coronary Intervention in Patients with Acute ST-Segment Elevation Myocardial Infarction and Its Influence on Prognosis.

Objective: To investigate the efficacy of the application of Buqi Huoxue Decoction combined with cardiac rehabilitation nursing for patients with acute ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) and its influence on the prognosis. Methods: 120 STEMI patients undergoing PCI were randomly divided into control group, cardiac care group, traditional Chinese medicine and western medicine group (TCM + WM group), and comprehensive treatment group. The control group was treated with a conventional antiplatelet therapy. On the basis of the control group, the cardiac care group was combined with cardiac care treatment. The TCM + WM group was combined with Buqi Huoxue Decoction, and the comprehensive treatment group was combined with cardiac rehabilitation care and Buqi Huoxue Decoction. The total clinical effective rate, readmission rate, and adverse reaction rate of the four groups were measured. Moreover, the myocardial injury markers (creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), and α-Hydroxybutyrate dehydrogenase (α-HBDH)), vascular endothelial function indexes (endothelin (ET-1) and vascular endothelial growth factor (VEGF)), cardiac function indexes (left ventricular ejection fraction (LVEF), left ventricle shortening rate (LFS), left ventricular end diastolic diameter (LVEDd), and left ventricular end systolic diameter (LVESd)), and QOL quality of life score (appetite, spirit, sleep, fatigue, and daily life) were measured. Results: The total effective rate of comprehensive treatment group was obviously increased versus to the control group and cardiac care group. The CK-MB, cTnI, α-HBDH, ET-1, LVEDd, and LVESd levels and SAS and SDS scores in the four groups were decreased, and VEGF, LVEF, and FS levels and QOL quality of life scores were increased after treatment. Moreover, the comprehensive treatment group has more significant changes than the other three groups. The readmission rate in comprehensive treatment group was significantly lower than the other three groups, and the difference in the incidence of adverse reactions in the four groups was not statistically significant. Conclusion: Buqi Huoxue Decoction combined with cardiac rehabilitation after PCI has a significant clinical effect on STEMI patients with PCI postoperative treatment, which can effectively reduce myocardial injury, improve the patient's cardiac function and vascular endothelial function, and improve the patient's quality of life, which can better improve the prognosis of patients.

[Special tumor entities in the head and neck region : Nasopharyngeal carcinoma, salivary gland, and thyroid cancer]. / Spezielle Tumorentitäten im Kopf-Hals-Bereich : Nasopharynxkarzinom, Speicheldrüsenkarzinom und Schilddrüsenkarzinom.

BACKGROUND: In recent years the number of studies on special tumor entities in the head and neck region has increased. During the 2021 meetings of the American Society of Clinical Oncology (ASMO) and the European Society for Medical Oncology (ESMO), several studies were presented which predict changes in clinical treatment algorithms for nasopharyngeal carcinoma, salivary gland, and thyroid cancer. OBJECTIVE: Future treatment alterations in specific head and neck tumor entities were evaluated after screening clinical studies presented at the 2021 ASCO and ESMO meetings. MATERIALS AND METHODS: A systematic analysis of the phase II and III clinical trials for nasopharyngeal carcinoma, salivary gland, and thyroid cancer treatment presented at ASCO and ESMO 2021 was performed. Taking into account current treatment standards, the results are structured in terms of their potential clinical significance. RESULTS AND CONCLUSION: In curative treatment of advanced nasopharyngeal carcinoma, adjuvant therapy with capecitabine after primary chemoradiation should be discussed as a new standard. In the palliative treatment of nasopharyngeal carcinoma, an increasing role of immunotherapy can be predicted. Recurrent or metastatic salivary gland cancer can often be treated very effectively with targeted substances if molecular target lesions are present. Immunotherapies currently play a subordinate role; they only seem to be effective in a few patients with salivary gland cancer, who cannot currently be reliably identified using predictive markers. Patients with radioiodine-refractory differentiated thyroid cancer benefit from treatment with the multi-tyrosine kinase inhibitor cabozantinib after failure of vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) therapy.

Potential Therapeutic Strategies to Combat HCC.

Hepatocellular carcinoma (HCC) is a complex, life-threatening and most common neoplasm in the world. HCC tumors are genetically and phenotypically heterogeneous, and involve various molecular mechanisms and stimulation of several signaling pathways, such as Vascular Endothelial Growth Factor, Epidermal Growth Factor Receptors (EGFR), Insulin growth factor, Ras/extracellular signal-stimulated kinase, the mammalian goal of rapamycin (mTOR), c-mesenchymal- epithelial transition factor-1 (c-Met), Hedgehog, Wnt and apoptotic signaling. Lately, in patients, multi-kinase cascade blockers, such as sorafenib, selumetinib and regorafenib, have increased the survival rate of progressive HCC. This development presents a step forward towards the therapy of liver cancer infection and attests that molecular systemic rehabilitation can be useful in HCC treatment. The development of these systemic therapeutic agents has further expanded the research area for surplus molecular mediators to auxiliary increase the cure rate of patients. This article reviews the complete focus on cascades, current enduring clinical tests by means of HCC therapeutic mediators, and imminent prospects in the cure of HCC.

Significant vision improvement and successful prevention of recurrence by electroacupuncture in hemiretinal vein occlusion combined with macular edema: A case report.

RATIONALE: Retinal vein occlusion (RVO) is the second commonest retinal vascular pathology, with macular edema (ME) as one of its major complications, which could finally cause vision loss. Anti-vascular endothelial growth factor (anti-VEGF therapy), as the standard therapy, has an unsustainable effect and needs repeated injections, which associates with frequent adverse events and significant economic burden. We reported a patient who had developed RVO and ME, and finally recovered after electroacupuncture treatment. PATIENT CONCERNS: A 56-year-old woman complained a decrease of visual acuity in the right eye for 1 year. She received injection of 0.5 mg Conbercept, one of the anti-VEGF therapies, in the vitreous cavity 6 times in 1 year, and finally turned to acupuncture for help out of short-term effectiveness after each injection and high expenditure (CNY 40,800). No other severe medical history was reported. DIAGNOSIS: Under comprehensive consideration of clinical manifestations and the results of fluorescein fundus angiography and optical coherence tomography, the patient was diagnosed with hemi-RVO and ME. INTERVENTIONS: The patient received electroacupuncture 3 sessions per week throughout 8 months (93 sessions in total). OUTCOMES: The visual acuity of the patient was improved from 0.6 to 0.9 after the 8-month electroacupuncture treatment and remained stable during the 24-month follow-up; the central retinal thickness remained stable between 350 and 414 throughout the treatment and follow-up periods. Patients regarded the vision-related quality of life as satisfactory. The total expenditure of electroacupuncture treatment was CNY 6045. The patient did not receive any Conbercept injection over the whole period of 32 months. No relevant adverse events occurred. LESSONS: Electroacupuncture might be effective in alleviating the symptoms of hemi-RVO-associated ME, with a potential of long-lasting effect. The frequency of anti-VEGF therapy could be reduced to the most extent, and the possibility of recurrence could be reduced as well, resulting good economic benefits.

Epidural Stimulation Combined with Triple Gene Therapy for Spinal Cord Injury Treatment.

The translation of new therapies for spinal cord injury to clinical trials can be facilitated with large animal models close in morpho-physiological scale to humans. Here, we report functional restoration and morphological reorganization after spinal contusion in pigs, following a combined treatment of locomotor training facilitated with epidural electrical stimulation (EES) and cell-mediated triple gene therapy with umbilical cord blood mononuclear cells overexpressing recombinant vascular endothelial growth factor, glial-derived neurotrophic factor, and neural cell adhesion molecule. Preliminary results obtained on a small sample of pigs 2 months after spinal contusion revealed the difference in post-traumatic spinal cord outcomes in control and treated animals. In treated pigs, motor performance was enabled by EES and the corresponding morpho-functional changes in hind limb skeletal muscles were accompanied by the reorganization of the glial cell, the reaction of stress cell, and synaptic proteins. Our data demonstrate effects of combined EES-facilitated motor training and cell-mediated triple gene therapy after spinal contusion in large animals, informing a background for further animal studies and clinical translation.

Recent advances in tumor microenvironment associated therapeutic strategies and evaluation models.

As per a report of the world health organization, an estimated 9.6 million people died due to cancer in 2018, globally. Most of the cancer death attributed to the lack of early detection and effective treatment. In the case of solid tumors, various factors such as leaky vasculature, angiogenesis, interstitial fluid pressure and lymphatic drainage are important in cancer chemotherapy. The poor penetration and retention of the drug/drug delivery system in tumor tissue are most critical issues in the way of effective treatment. In this scenario, the challenges are to design the specific nano-therapeutics with the potential to penetrate inside the adverse condition of tumor microenvironment (TME) including high interstitial pressure region and abnormal vasculature. The modification of nanocarriers surfaces with enzymes, peptides, pH-responsive moieties, antibodies etc. could be a promising strategy to improve the nanocarriers penetration inside the solid tumor. The priming with the drug before the administration of nanotherapeutics may also represents an efficient approach for solid tumor treatment. Further, the growth factors including fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and their pathways could offer potential targeting opportunities for anticancer treatment. Recently, there is a surge in various approaches and formulation design directed towards abnormal TME for more effective cancer therapy. In this review, various factors related to the poor penetration, retention and specific delivery of chemotherapeutics inside tumor cells/tissues are discussed. The emerging formulations strategies directed to the TME and various methodologies for evaluation of their efficacy are also included in this review.

Allotransplantation of adult spinal cord tissues after complete transected spinal cord injury: Long-term survival and functional recovery in canines.

Spinal cord injury (SCI), especially complete transected SCI, leads to loss of cells and extracellular matrix and functional impairments. In a previous study, we transplanted adult spinal cord tissues (aSCTs) to replace lost tissues and facilitate recovery in a rat SCI model. However, rodents display considerable differences from human patients in the scale, anatomy and functions of spinal cord systems, and responses after injury. Thus, use of a large animal SCI model is required to examine the repair efficiency of potential therapeutic approaches. In this study, we transplanted allogenic aSCTs from adult dogs to the lesion area of canines after complete transection of the thoracic spinal cord, and investigated the long-term cell survival and functional recovery. To enhance repair efficiency, a growth factor cocktail was added during aSCT transplantation, providing a favorable microenvironment. The results showed that transplantation of aSCTs, in particular with the addition of growth factors, significantly improves locomotor function restoration and increases the number of neurofilament-, microtubule-associated protein 2-, 5-hydroxytryptamine-, choline acetyltransferase- and tyrosine hydroxylase-positive neurons in the lesion area at 6 months post-surgery. In addition, we demonstrated that donor neurons in aSCTs can survive for a long period after transplantation. This study showed for the first time that transplanting aSCTs combined with growth factor supplementation facilitates reconstruction of injured spinal cords, and consequently promotes long lasting motor function recovery in a large animal complete transected SCI model, and therefore could be considered as a possible therapeutic strategy in humans.

Adjuvant Therapy in High-Risk Renal Cell Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating risk-benefit for adjuvant postoperative treatments in high-risk renal cell carcinoma by assessing reported disease-free survival (DFS), overall survival (OS), toxicity, and quality of life. METHODS: A literature search was performed in PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials to identify relevant RCTs (from database inception through May 15, 2018). The results of the ATLAS trial were published while writing this manuscript, and the manuscript was updated accordingly. A generic variance-weighted random effects model was used to derive estimates for efficacy and common adverse effects. Heterogeneity was assessed using the Cochran Q statistic and was quantified using the I2 test. RESULTS: Adjuvant therapy with tyrosine kinase inhibitors compared with placebo was observed to have a DFS hazard ratio [HR] of 0.92 (95% CI, 0.83-1.01) and an OS HR of 1.01 (95% CI, 0.89-1.15) (4 RCTs; 4417 patients). Analysis of DFS for sunitinib compared with placebo (n=1909) in the adjuvant setting detected an HR of 0.90 (95% CI, 0.67-1.19). Increased risk of grade 3 or 4 adverse events (relative risk [RR]=2.6; 95% CI, 2.28-2.97), diarrhea (RR=9.89; 95% CI, 4.22-23.14), fatigue (RR=3.11; 95% CI, 1.86-5.18), hypertension (RR=3.63; 95% CI, 2.99-4.41), and palmar/plantar dysesthesia (RR=2.70; 95% CI, 2.47-2.96) was observed. CONCLUSION: Adjuvant vascular endothelial growth factor tyrosine kinase inhibitors in high-risk renal cell carcinoma did not improve OS or DFS, and there was a significant increased risk of toxicity in greater than half of the patients, leading to a decline in quality of life.