Cyclic hexadepsipeptides from the fermentation of Fusarium sp. DCJ-A and their cytotoxic activities.

Beauvercin H (1), a new cyclic hexadepsipeptide, and two known ones (2 and 3) were isolated from the EtOH extract of the solid culture of Fusarium sp. Their structures were elucidated by spectroscopic analysis, including extensive 1D and 2D NMR techniques, as well as comparison with literature values. Additionally, compounds 1-3 were tested for their cytotoxic activities. The results showed that all isolated compounds exhibited cytotoxic activities against five human cancer cell lines with IC50 values ranging from 1.379 to 13.12 µM.

Glycosides for Peripheral Neuropathic Pain: A Potential Medicinal Components.

Neuropathic pain is a refractory disease that occurs across the world and pharmacotherapy has limited efficacy and/or safety. This disease imposes a significant burden on both the somatic and mental health of patients; indeed, some patients have referred to neuropathic pain as being 'worse than death'. The pharmacological agents that are used to treat neuropathic pain at present can produce mild effects in certain patients, and induce many adverse reactions, such as sedation, dizziness, vomiting, and peripheral oedema. Therefore, there is an urgent need to discover novel drugs that are safer and more effective. Natural compounds from medical plants have become potential sources of analgesics, and evidence has shown that glycosides alleviated neuropathic pain via regulating oxidative stress, transcriptional regulation, ion channels, membrane receptors and so on. In this review, we summarize the epidemiology of neuropathic pain and the existing therapeutic drugs used for disease prevention and treatment. We also demonstrate how glycosides exhibit an antinociceptive effect on neuropathic pain in laboratory research and describe the antinociceptive mechanisms involved to facilitate the discovery of new drugs to improve the quality of life of patients experiencing neuropathic pain.

Long-Term Survival Outcomes After Liver Resection for Binodular Hepatocellular Carcinoma: A Multicenter Cohort Study.

BACKGROUND: The long-term prognosis after liver resection for multinodular (≥3 nodules) hepatocellular carcinoma (HCC) is generally considered to be unfavorable. However, the role of liver resection for binodular HCC is less investigated. SUBJECTS, MATERIALS, AND METHODS: From a multicenter database, consecutive patients who underwent curative-intent liver resection for binodular HCC and without macrovascular invasion between 2003 and 2015 were retrospectively reviewed. Patients' clinical variables as well as perioperative and long-term survival outcomes were analyzed. Univariable and multivariable analyses were performed to identify the risk factors associated with overall survival (OS) and recurrence-free survival (RFS) after curative resection. RESULTS: Of 263 enrolled patients, the perioperative 30-day mortality and morbidity rates were 1.5% and 28.5%. The 1-, 3-, and 5-year OS and RFS rates were 81.5%, 52.4%, and 39.1% and 57.1%, 35.8%, and 26.6%, respectively. Multivariable Cox-regression analyses identified preoperative alpha-fetoprotein level >400 µg/L, tumor size with a sum of two nodules >8 cm, tumor size ratio of large/small nodule >1.5 (asymmetrical proportion), unilateral hemiliver distribution of two nodules, distance of ≤3 cm between two nodules, and microvascular invasion in any nodule as independent risk factors associated with decreased OS and RFS. CONCLUSION: Liver resection was safe and feasible in patients with binodular HCC, with acceptable perioperative and long-term outcomes. Sum of two tumor sizes, size ratio and distribution, and distance between two nodules were independent risk factors associated with long-term survival outcomes after surgery. These results may guide clinicians to make individualized surgical decisions and estimate long-term prognosis for these patients. IMPLICATIONS FOR PRACTICE: Liver resection was safe and feasible in patients with binodular hepatocellular carcinoma, with acceptable perioperative and long-term outcomes. The sum of two tumor sizes, the size ratio and distribution of the two nodules, and the distance between two nodules were independent risk factors associated with long-term overall survival and recurrence-free survival after liver resection. The results of this study may guide clinicians to make individualized surgical decisions, estimate long-term prognosis, and plan recurrence surveillance and adjuvant therapy for these patients.

Echinacoside Alleviates Hypoxic-Ischemic Brain Injury in Neonatal Rat by Enhancing Antioxidant Capacity and Inhibiting Apoptosis.

Hypoxic-ischemic brain damage (HIBD) is a leading cause of death and disability in neonatal or perinatal all over the world, seriously affecting children, families and society. Unfortunately, only few satisfactory therapeutic strategies have been developed. It has been demonstrated that Echinacoside (ECH), the major active component of Cistanches Herba, exerts many beneficial effects, including antioxidative, anti-apoptosis, and neuroprotective in the traditional medical practice in China. Previous research has demonstrated that ECH plays a protective effect on ischemic brain injury. This study aimed to investigate whether ECH provides neuroprotection against HIBD in neonatal rats. We subjected 120 seven-day-old Sprague-Dawley rats to cerebral hypoxia-ischemia (HI) and randomly divided into the following groups: sham group, HI group and ECH (40, 80 and 160 mg/kg, intraperitoneal) post-administration group. After 48 h of HI, 2,3,5-Triphenyltetrazolium chloride, Hematoxylin-Eosin and Nissl staining were conducted to evaluate the extent of brain damage. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities, total antioxidant capacity (T-AOC), and malondialdehyde (MDA) production were assessed to determine the antioxidant capacity of ECH. TUNEL staining and Western blot analysis was performed to respectively estimate the extent of brain cell apoptosis and the expression level of the apoptosis-related proteins caspase-3, Bax, and Bcl-2. Results showed that ECH remarkably reduced the brain infarct volume and ameliorated the histopathological damage to neurons. ECH post-administration helped recovering the antioxidant enzyme activities and decreasing the MDA production. Furthermore, ECH treatment suppressed neuronal apoptosis in the rats with HIBD was by reduced TUNEL-positive neurons, the caspase-3 levels and increased the Bcl-2/Bax ratio. These results suggested that ECH treatment was beneficial to reducing neuronal damage by attenuating oxidative stress and apoptosis in the brain under HIBD.

Neuroprotection of Cytisine Against Cerebral Ischemia-Reperfusion Injury in Mice by Regulating NR2B-ERK/CREB Signal Pathway.

The aim of the study was to elucidate the therapeutic effects of Cytisine (CYT) on cerebral ischemia-reperfusion injury in mice. Male ICR mice were pretreated with reagents (drug), and then subjected to 2 h focal cerebral ischemia and 24 h reperfusion. Morphologically, the histopathological impairment were estimated by the TTC, HE and TUNEL staining. The expression of GluN2B-containing NMDA receptor, phosphorylation of extracellular regulated protein kinases, total ERK, phosphorylation of cAMP-response element binding protein and total CREB were determined by immunofluorescence and Western blot assay, respectively. The mRNA expression of NR2B, ERK and CREB were quantified by the real-time RT-PCR. CYT significantly diminished the infarct size and neuronal apoptosis. Additionally, it ameliorated histopathological lesion dramatically. CYT promoted the phosphorylation of ERK, CREB and their mRNA expression. In contrast, the expression of NR2B was suppressed in concomitant with the down-regulation of genes. The overall results thus far suggest that CYT confers the neuroprotection against cerebral I/R injury by regulating the NR2B-ERK/CREB signal pathway.

Betaine Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats via Inhibiting Inflammatory Response.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, leading to right ventricular failure and death. Recent studies have suggested that chronic inflammatory processes are involved in the pathogenesis of PAH. Several studies have demonstrated that betaine possesses outstanding anti-inflammatory effects. However, whether betaine exerts protective effects on PAH by inhibiting inflammatory responses in the lungs needs to be explored. To test our hypothesis, we aimed to investigate the effects of betaine on monocrotaline-induced PAH in rats and attempted to further clarify the possible mechanisms. METHODS: PAH was induced by monocrotaline (50 mg/kg) and oral administration of betaine (100, 200, and 400 mg/kg/day). The mean pulmonary arterial pressure, right ventricular systolic pressure, and right ventricle hypertrophy index were used to evaluate the development of PAH. Hematoxylin and eosin staining and Masson staining were performed to measure the extents of vascular remodeling and proliferation in fibrous tissue. Monocyte chemoattractant protein-1 (MCP-1) and endothelin-1 (ET-1) were also detected by immunohistochemical staining. Nuclear factor-κB (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin-1ß (IL-1ß) were assessed by Western blot. RESULTS: This study showed that betaine improved the abnormalities in right ventricular systolic pressure, mean pulmonary arterial pressure, right ventricle hypertrophy index, and pulmonary arterial remodeling induced by monocrotaline compared with the PAH group. The levels of MCP-1 and ET-1 also decreased. Western blot indicated that the protein expression levels of NF-κB, TNF-α, and IL-1ß significantly decreased (p < 0.01). CONCLUSION: Our study demonstrated that betaine attenuated PAH through its anti-inflammatory effects. Hence, the present data may offer novel targets and promising pharmacological perspectives for treating monocrotaline-induced PAH.

Influence of cirrhosis on long-term prognosis after surgery in patients with combined hepatocellular-cholangiocarcinoma.

BACKGROUND: Little is known about the prognostic impact of cirrhosis on long-term survival of patients with combined hepatocellular-cholangiocarcinoma (cHCC-CC) after hepatic resection. The aim of this study was to elucidate the long-term outcome of hepatectomy in cHCC-CC patients with cirrhosis. METHODS: A total of 144 patients who underwent curative hepatectomy for cHCC-CC were divided into two groups: cirrhotic group (n = 91) and noncirrhotic group (n = 53). Long-term postoperative outcomes were compared between the two groups. RESULTS: Patients with cirrhosis had worse preoperative liver function, higher frequency of HBV infection, and smaller tumor size in comparison to those without cirrhosis. The 5-year overall survival rate in cirrhotic group was significantly lower than that in non-cirrhotic group (34.5% versus 54.1%, P = 0.032). The cancer recurrence-related death rate was similar between the two groups (46.2% versus 39.6%, P = 0.446), while the hepatic insufficiency-related death rate was higher in cirrhotic group (12.1% versus 1.9%, P = 0.033). Multivariate analysis indicated that cirrhosis was an independent prognostic factor of poor overall survival (hazard ratio 2.072, 95% confidence interval 1.041-4.123; P = 0.038). CONCLUSIONS: The presence of cirrhosis is significantly associated with poor prognosis in cHCC-CC patietns after surgical resection, possibly due to decreased liver function.

Large-size nanosheets of 9,10-bis(phenylethynyl)anthracene with high photoresponse and light emission anisotropy.

Large-size single crystalline nanosheets of 9,10-bis(phenylethynyl)-anthracene were prepared by a facile solution process and were fully characterized. The prototype photodetector was then fabricated on the basis of a single nanosheet and exhibited superior performance with the largest photoresponse ratio up to ca. 10(5). Moreover, the nanosheets show obvious light emission anisotropy.

Correction: Large-size nanosheets of 9,10-bis(phenylethynyl)anthracene with high photoresponse and light emission anisotropy.

Correction for 'Large-size nanosheets of 9,10-bis(phenylethynyl)anthracene with high photoresponse and light emission anisotropy' by Juan-Ye Wang et al., Phys. Chem. Chem. Phys., 2016, DOI: 10.1039/c5cp05507e.

Postoperative complications affect early recurrence of hepatocellular carcinoma after curative resection.

BACKGROUND: Postoperative recurrence remains the major cause of death after curative resection for hepatocellular carcinoma (HCC). This study was conducted to evaluate the impact of postoperative complications on HCC recurrence after curative resection. METHODS: The postoperative outcomes of 274 HCC patients who underwent curative resection were analysed retrospectively. RESULTS: Of the 247 HCC patients, 103 (37.6 %) patients developed postoperative complications. The occurrence of postoperative complications was found to be associated with a significantly higher tumor recurrence (76.2 % vs. 56.6 %, P = 0.002) and a lower 5-year overall survival rate (27.7 % vs. 42.1 %; P = 0.037) as compared with those without complications. Regarding the recurrence pattern, early recurrence (≤2 years) was more frequently seen in patients with complications than that in patients without complications (54.5 % vs.38.6 %; P = 0.011). Multivariate analysis indicated that postoperative complications occurrence was an independent risk factor for early recurrence (odds ratio [OR] 2.223; 95 % confidence intervals [95 % CI] 1.161-4.258, P = 0.016) and poor overall survival (OR 1.413; 95 % CI, 1.012-1.971, P = 0.042). CONCLUSIONS: The results of the present study indicate that the occurrence of postoperative complications is a predictive factor for HCC recurrence after curative hepatectomy, especially for early recurrence.

Safety and long-term outcomes of anatomic left hepatic trisectionectomy for intermediate and advanced hepatocellular carcinoma.

BACKGROUND AND AIM: Anatomic left hepatic trisectionectomy (ALHT) is a complex hepatic resection, and its outcomes in hepatocellular carcinoma (HCC) still remain unclear. This paper focuses on the assessment of the safety and long-term effects of ALHT on intermediate and advanced HCC patients with tumors that occupy the left liver lobe. METHODS: This study performed a retrospective analysis of consecutive HCC patients who underwent ALHT in a single-center cohort between December 2004 and December 2011. RESULTS: ALHT was performed on 34 intermediate and advanced HCC patients (0.05%) of 17064 HCC patients who had undergone hepatic resection. Among them, 12 (33.3%) developed postoperative complications. Based on the multivariate analysis, we found that a serum prealbumin level of 170 mg/L is associated with an increased risk of morbidity (P=0.008). The one-year, two-year, three-year, and five-year overall survival rates were 61%, 27%, 11%, and 11%, respectively. The median overall survival was 13 months (range, 2-89 months). Based on the multivariate analysis, we also found that patients with an A/G ratio <1.5 are more likely to have poor prognosis than those with an A/G ratio ≥ 1.5 (P=0.014). Multiple tumors are associated with worse outcomes (P=0.020). CONCLUSIONS: ALHT is safe for intermediate and advanced HCC patients with tumors that occupy the left lobe and with preoperative Child-Pugh class A liver function. Low preoperative serum prealbumin level may increase the risk of postoperative complications. Although early intrahepatic recurrence rate is high, some patients, especially those with a single tumor and normal A/G ratio, exhibit long-term survival.

Prognosis after resection of hepatitis B virus-related hepatocellular carcinoma originating from non-cirrhotic liver.

BACKGROUND: Long-term prognosis after resection of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) originating from non-cirrhotic liver is not fully clarified. METHODS: A total of 183 patients who underwent curative hepatectomy for HCC without cirrhosis were classified into two groups: HBV infection group (n = 124) and non-HBV infection group (n = 59). Long-term postoperative outcomes were compared between the two groups. RESULTS: The 5-year postoperative overall survival (OS) and disease-free survival (DFS) were 42.6 and 39.0 %, respectively, in the HBV infection group versus 52.3 and 46.5 % in the non-HBV infection group (both p > 0.05). When patients were subdivided according to TNM stages, OS in stages II or III HCC patients was similar between the two groups. In contrast, OS and DFS were significantly worse in stage I patients with HBV infection than those in stage I patients without HBV infection (p = 0.041 and 0.038, respectively). Preoperative serum HBV DNA >4 log10 copies/mL and vascular invasion were independent factors associated with poor prognosis (p = 0.034 and 0.017, respectively) for patients with HBV infection. CONCLUSIONS: After hepatic resection for HCC in non-cirrhotic liver, patients with HBV infection with early-stage tumors had worse prognosis than patients without HBV infection, possibly due to the carcinogenetic potential of viral hepatitis in the remnant liver. Antiviral therapy should be considered after hepatectomy in patients with high HBV DNA levels.

Efficacy of surgical resection for pulmonary metastases from hepatocellular carcinoma.

BACKGROUND: The lung is one of the most common sites for extrahepatic metastasis from hepatocellular carcinoma (HCC). This study aimed to assess the efficacy of surgical resection for pulmonary metastases from HCC. MATERIAL AND METHODS: The medical records of 9 patients who underwent pulmonary metastasectomy from HCC at 2 institutions were retrospectively studied, together with a review of studies reporting the outcomes of at least 5 patients in the Chinese and English languages. RESULTS: There were no perioperative deaths or major complications. The 1-, 3-, and 5-year overall survival rate after surgery was 100%, 44.4%, and 33.3%, respectively. A total of 19 studies involving 443 patients who underwent pulmonary metastasectomy for metastasis of HCC were included in the literature review. The median mortality rate was 0% (range, 0-7.1%). The median survival ranged from 10.7 to 77 (median=33.2) months, and the 5-year overall survival rate ranged from 11.5% to 75% (median=36%). CONCLUSIONS: Surgical resection is a safe and effective treatment in selected patients with pulmonary metastases from HCC.

Hepatic resection for multiple hepatocellular carcinoma less than 5 cm: a prospective comparative study.

BACKGROUND/AIMS: Treatment of multiple hepatocellular carcinoma (HCC) remains a critical issue. In addition, the prognosis and prognostic factors of multiple HCC after hepatic resection are rarely prospectively documented. METHODOLOGY: The clinicopathologic and follow-up data of 81 patients who underwent curative resection of HCC between January 2008 and January 2009 were prospectively collected. Patients were categorized according to the size of the largest tumor: group A (n = 40, two or three HCCs with maximum tumor diameter > 3 cm and < or = 5 cm) and group B (n = 41, two or three HCCs with maximum tumor diameter < or = 3 cm). The two groups were compared for clinicopathologic data and survival results. RESULTS: The 1-, 2-, 3-, and 4-year survival rates of group A were 75.0%, 58.0%, 50.0%, and 44.0%, respectively, while the survival rates of group B were 93.0%, 80.0%, 66.0%, and 47.0%, respectively. The 1-, 2-, 3-, and 4-year disease-free survival rates of group A were 43.0%, 30.0%, 23.0%, and 15.0%, respectively, comparing to 71.0%, 54.0%, 44.0%, and 36.0% in group B, respectively. The median overall cumulative survival time of group A and group B were 36.0 and 44.5 months, respectively (P = 0.322). The median disease-free survival time of group A was 10.0 months and was significantly shorter than that of group B (30.0 months, P = 0.011). CONCLUSIONS: Resection may provide comparative survival benefits even for patients with multiple HCCs with maximum tumor diameter > 3 cm and < or = 5 cm.

[Application of total hemihepatic vascular exclusion in liver resection for patients with hepatocellular carcinoma and impaired liver function].

OBJECTIVE: To study the clinical value of total hemihepatic vascular exclusion (THHVE) in liver resection for patients with hepatocellular carcinoma (HCC) and impaired liver function. METHODS: The data of 70 patients who underwent liver resection for HCC with impaired liver function between January 2009 and October 2011 were analyzed retrospectively. THHVE was applied in 38 patients (THHVE group), Pringle maneuver in 25 patients (Pringle group) and no vascular occlusion in 7 patients. In the THHVE group, 36 patients were male, 2 were female, average age was (54 ± 9) years. And in Pringle group, 23 patients were male, 2 were female, average age was (53 ± 10) years. Total intraoperative blood loss, blood transfusion rate, clamping time, postoperative complication rate, postoperative hospital stay and postoperative liver function were compared between the THHVE and Pringle group. RESULTS: Total blood loss ((317 ± 186) ml vs. (506 ± 274) ml, t = -3.025, P = 0.004) and transfusion rate (10.5% vs. 32.0%, χ(2) = 4.509, P = 0.034) were significantly lower in the THHVE group than in the Pringle group. Although the clamping time was longer ((21 ± 5) minutes vs. (17 ± 5) minutes, t = 3.209, P = 0.002), the total bilirubin levels on postoperative day 3 and 7 and ALT levels on postoperative day 1, 3, 7 were significantly lower in the THHVE group than in the Pringle group, and the pre-albumin level on postoperative day 7 was higher in the THHVE group than in the Pringle group. Total complication rate (26.3% vs. 52.0%, χ(2) = 4.291, P = 0.038) and major complication rate (7.9% vs. 28.0%, χ(2) = 4.565, P = 0.033) were lower in the THHVE group than in the Pringle group. And postoperative hospital stay duration was shorter in the THHVE group than in the Pringle group ((14.0 ± 2.6) d vs. (16.4 ± 4.0) d, t = -2.625, P = 0.012). CONCLUSIONS: THHVE is a safe and effective technique in liver resection for patients with HCC and impaired liver function. It is associated with less blood loss, lower transfusion requirements, better postoperative liver function recovery, lower postoperative complication rate and shorter postoperative hospital stay.

Neuroprotective effects of oxymatrine on hypoxic-ischemic brain damage in neonatal rats by activating the Wnt/ß-catenin pathway.

Neuronal apoptosis is a major pathological process associated with neurological dysfunction in neonates after hypoxic-ischemic brain damage (HIBD). Our previous study demonstrated that oxymatrine (OMT) exerts potential neuroprotective effects on neonatal rats subjected to hypoxic-ischemic insult. However, the underlying molecular mechanism remains unclear. In this study, we investigated the effects of OMT-mediated neuroprotection on neonatal HIBD by attempting to determine its effect on the Wnt/ß-catenin signaling pathway and explored the underlying mechanism. Both 7-day-old rat pups and primary hippocampus neurons were used to establish the HIBD and oxygen-glucose deprivation (OGD) injury models, respectively. Our results demonstrated that OMT treatment significantly increased cerebral blood flow and reduced S100B concentration, infarct volume, and neuronal apoptosis in neonatal rats. In vitro, OMT markedly increased cell viability and MMP level and decreased DNA damage. Moreover, OMT improved the mRNA and protein levels of Wnt1 and ß-catenin, inhibited the expression of DKK1 and GSK-3ß, enhanced the nuclear transfer of ß-catenin, and promoted the binding activity of ß-catenin with Tcf-4; however, it downregulated the expression of cleaved caspase-3 and cleaved caspase-9. Notably, the introduction of XAV-939 (a Wnt/ß-catenin signaling inhibitor) reversed the positive effects of OMT both in vivo and in vitro. Collectively, our findings demonstrated that OMT exerted a neuroprotective effect on neonatal HIBD by inhibiting neuronal apoptosis, which was partly via the activation of the Wnt/ß-catenin signaling pathway.

Protective effects of leonurine hydrochloride on pyroptosis in premature ovarian insufficiency via regulating NLRP3/GSDMD pathway.

BACKGROUND: Premature ovarian insufficiency is common in clinically infertile patients. The NOD-like receptor family pyrin domain-containing 3 (NLRP3)/Gasdermin D (GSDMD) signaling pathway plays a key role in premature ovarian insufficiency. Leonurine (Leo) is one of the important active ingredients extracted from Leonurus japonicus Houttuyn, which can inhibit NLRP3 activation. However, whether leonurine hydrochloride plays a protective role in premature ovarian insufficiency through actions on NLRP3/GSDMD signaling is not yet known. METHODS: After cyclophosphamide-induced premature ovarian insufficiency was established in female mice, Leo was injected intraperitoneally over four weeks to evaluate the ovarian function and anti-pyroptosis effects using the metrics of fertility, serum hormone level, ovary weight, follicle number, expression of NLRP3/GSDMD pathway-related proteins, and serum IL-18 and IL-1ß levels. RESULTS: Intraperitoneal administration of leonurine hydrochloride was found to significantly protect fertility and maintain both serum hormone levels and follicle number in mice with premature ovarian insufficiency. Mice treated with leonurine hydrochloride consistently resisted cyclophosphamide-induced ovarian damage by inhibiting the activation of NLRP3 inflammasome, Caspase-1 and GSDMD in both ovarian tissue and granulosa cells, which led to lower levels of IL-18 and IL-1ß in the serum (p < 0.05, p < 0.01, p < 0.001). CONCLUSION: Intraperitoneal administration of leonurine hydrochloride prevents cyclophosphamide-induced premature ovarian insufficiency in mice by inhibiting NLRP3/GSDMD-mediated pyroptosis.

Targeting the chemokine ligand 2-chemokine receptor 2 axis provides the possibility of immunotherapy in chronic pain.

Chronic pain affects patients' physical and psychological health and quality of life, entailing a tremendous public health challenge. Currently, drugs for chronic pain are usually associated with a large number of side effects and poor efficacy. Chemokines in the neuroimmune interface combine with their receptors to regulate inflammation or mediate neuroinflammation in the peripheral and central nervous system. Targeting chemokines and their receptor-mediated neuroinflammation is an effective means to treat chronic pain. In recent years, growing evidence has shown that the expression of chemokine ligand 2 (CCL2) and its main chemokine receptor 2 (CCR2) is involved in its occurrence, development and maintenance of chronic pain. This paper summarises the relationship between the chemokine system, CCL2/CCR2 axis, and chronic pain, and the CCL2/CCR2 axis changes under different chronic pain conditions. Targeting chemokine CCL2 and its chemokine receptor CCR2 through siRNA, blocking antibodies, or small molecule antagonists may provide new therapeutic possibilities for managing chronic pain.

Neuroprotective strategies for neonatal hypoxic-ischemic brain damage: Current status and challenges.

Neonatal hypoxic-ischemic brain damage (HIBD) is a prominent contributor to both immediate mortality and long-term impairment in newborns. The elusive nature of the underlying mechanisms responsible for neonatal HIBD presents a significant obstacle in the effective clinical application of numerous pharmaceutical interventions. This comprehensive review aims to concentrate on the potential neuroprotective agents that have demonstrated efficacy in addressing various pathogenic factors associated with neonatal HIBD, encompassing oxidative stress, calcium overload, mitochondrial dysfunction, endoplasmic reticulum stress, inflammatory response, and apoptosis. In this review, we conducted an analysis of the precise molecular pathways by which these drugs elicit neuroprotective effects in animal models of neonatal hypoxic-ischemic brain injury (HIBD). Our objective was to provide a comprehensive overview of potential neuroprotective agents for the treatment of neonatal HIBD in animal experiments, with the ultimate goal of enhancing the feasibility of clinical translation and establishing a solid theoretical foundation for the clinical management of neonatal HIBD.

Cidan Capsule in Combination with Adjuvant Transarterial Chemoembolization Reduces Recurrence Rate after Curative Resection of Hepatocellular Carcinoma: A Multicenter, Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded. RESULTS: As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug. CONCLUSIONS: Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).