Lidocaine, an anesthetic drug, protects Neuro2A cells against cadmium toxicity

Purpose: To investigate the neuroprotective effect of lidocaine in Neuro2A cells Methods: Differentiated N2a cells were used in this study. Cell viability and neuroprotection were assessed using dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and trypan blue assays, while Bax/Bcl-2 expression was assayed by western blotting. Mitochondrial membrane potential, reactive oxygen species and calcium levels were measured using flow cytometry. Results: Lidocaine protected differentiated N2a cells against cadmium-induced toxicity, and also attenuated cadmium toxicity-induced changes in mitochondrial membrane potential (MMP), reactive oxygen species (ROS) and calcium (Ca2+) levels. Furthermore, Bax/Bcl-2 ratio, which was disrupted by cadmium, and cadmium-induced apoptosis, were reversed by lidocaine. Conclusion: Lidocaine protects differentiated N2a cells against cadmium-induced toxicity by reversing apoptosis. Thus, lidocaine is a potential neuroprotective agent

Hypaconitine confers protection on ketamine-induced neuronal injury in neonatal rat brain via a mechanism involving PI3K/Akt/Bcl-2 pathway

Purpose: To investigate the neuroprotective effect of hypaconitine against ketamine-induced neuronal injury in the brains of neonatal rats, and the underlying mechanism of action. Methods: Seven day-old Sprague-Dawley pups weighing 15.0 to 20.0 g (mean weight = 17.5 ± 2.5 g), and aged 7 days were used for this study. The pups were sacrificed, and their forebrains isolated and used to prepare cell suspensions. The isolated cells were treated with ketamine (100 µM) or varied concentrations of hypaconitine (0.1 – 2 µM) or LY294002 (10 µM). The cells were trypsinized and cultured at 37 °C in 10 % fetal bovine serum (FBS) supplemented Dulbecco's modified Eagle's medium (DMEM) in a humidified incubator containing 5 % CO2. Cell viability was determined using MTT assay, while TUNEL assay was used to determine the extent of apoptosis in the cells. The expressions of pAkt, Bcl-2 and caspase-3 were determined using Western blotting. Results: There were only few viable cells in the ketamine-treated group, and cell viability was significantly and dose-dependently increased in hypaconitine-treated groups (p < 0.05). The extent of apoptosis was significantly higher in ketamine-treated cells than in control cells, but treatment with hypaconitine significantly reduced the number of apoptotic cells (p < 0.05). However, in the presence of LY294002 (a PI3K-specific inhibitor), the effect of hypaconitine on neuronal cell apoptosis was significantly reversed (p < 0.05). The expressions of p-Akt and Bcl-2 were significantly down-regulated while the expression of caspase-3 was significantly upregulated in ketamine-treated neuronal cells, when compared with control group (p < 0.05). However, in cells treated with hypaconitine, the expressions of p-Akt and Bcl-2 were significantly upregulated, while the expression of caspase-3 was significantly down-regulated (p < 0.05). Treatment of neuronal cells with hypaconitine in the presence of LY294002 significantly reversed the effect of hypaconitine on the expressions of p-Akt, Bcl-2 and caspase-3 (p < 0.05). Conclusion: These results suggest that hypaconitine ameliorates ketamine-induced neuronal injury in neonatal rats via a mechanism involving the PI3K/Akt/Bcl-2 pathway

Evaluation of efficacy and safety of gefitinib as monotherapy in Chinese patients with advanced non-small cell lung cancer and very poor performance status

<p>Abstract</p> <p>Background</p> <p>This paper reports the outcome of gefitinib for Chinese advanced NSCLC patients with poor performance status (PS) at the Peking Union Medical College Hospital.</p> <p>Methods</p> <p>From Oct 2002 to Apr. 2006, 42 advanced NSCLC patients with PS 3/4 received gefitinib 250 mg/day treatment. Median survival (MS) were calculated using the Kaplan-Meier method and a Cox regression model was used to find main factors affecting MS.</p> <p>Results</p> <p>Adverse events (AEs) were generally mild (grade 1 and 2) and reversible. The most frequent AEs were rash 72.2% (26/42) and diarrhea 44.4% (26/42). The objective tumor response rate and stable disease rate were 40.5% and 26.2% respectively, and median survival(MS) of all patients was 10.1 months (95% confidential interval CI, 3.4 ~ 16.8), and progression-free survival(PFS) was 5.7 months (95% CI, 4.5 ~ 6.9). The MS were significantly related with objective response of gefitinib. Objective responses was significantly related with rashes induced with gefitinib.</p> <p>Conclusion</p> <p>Our study suggest that treatment with gefitinib may be well tolerated and beneficial for Chinese patients with poor PS, and the safety and efficacy were similar to patients with good PS.</p

Advances in basic research, clinical diagnosis and treatment of pancreatic cancer in 2023

Pancreatic cancer is a highly malignant digestive tract tumor with hidden symptoms, limited treatment options and rapid progression. With an increasing incidence rate year by year, pancreatic cancer has increasingly become a prominent issue endangering public health, causing a huge social burden. Although there was no significant improvement in survival rates for pancreatic cancer patients in the past two decades, recent progress in epidemiology, basic research and clinical research of pancreatic cancer has accelerated significantly compared to the past. Some findings have already enabled a small proportion of pancreatic cancer patients to achieve better survival. This article provided a review of the significant progress made in research, diagnosis and treatment of pancreatic cancer in 2023

Dietary epicatechin improves survival and delays skeletal muscle degeneration in aged mice

We recently reported that epicatechin, a bioactive compound that occurs naturally in various common foods, promoted general health and survival of obese diabetic mice. It remains to be determined whether epicatechin extends health span and delays the process of aging. In the present study, epicatechin or its analogue epigallocatechin gallate (EGCG) (0.25% w/v in drinking water) was administered to 20-mo-old male C57BL mice fed a standard chow. The goal was to determine the antiaging effect. The results showed that supplementation with epicatechin for 37 wk strikingly increased the survival rate from 39 to 69%, whereas EGCG had no significant effect. Consistently, epicatechin improved physical activity, delayed degeneration of skeletal muscle (quadriceps), and shifted the profiles of the serum metabolites and skeletal muscle general mRNA expressions in aging mice toward the profiles observed in young mice. In particular, we found that dietary epicatechin significantly reversed age-altered mRNA and protein expressions of extracellular matrix and peroxisome proliferator–activated receptor pathways in skeletal muscle, and reversed the age-induced declines of the nicotinate and nicotinamide pathway both in serum and skeletal muscle. The present study provides evidence that epicatechin supplementation can exert an antiaging effect, including an increase in survival, an attenuation of the aging-related deterioration of skeletal muscles, and a protection against the aging-related decline in nicotinate and nicotinamide metabolism.—Si, H., Wang, X., Zhang, L., Parnell, L. D., Ahmed, B., LeRoith, T., Ansah, T.-A., Zhang, L., Li, J., Ordovás, J. M., Si, H., Liu, D., Lai, C.-Q. Dietary epicatechin improves survival and delays skeletal muscle degeneration in aged mice. FASEB J. 33, 965–977 (2019)

Characteristics and potential biomarkers of flavor compounds in four Chinese indigenous chicken breeds

Chinese indigenous chickens have a long history of natural and artificial selection and are popular for their excellent meat quality and unique flavor. This study investigated six meat quality-related traits in Ningdu yellow, Baier yellow, Kangle, and Shengze 901 chickens. Two-dimensional gas chromatography-time-of-flight mass spectrometry was used to detect unique flavors in 24 breast muscle samples from the same phenotyped chickens. Overall, 685, 618, 502, and 487 volatile organic compounds were identified in Ningdu yellow, Baier yellow, Kangle, and Shengze 901 chickens, respectively. The flavor components were separated into eight categories, including hydrocarbons and aldehydes. Multivariate analyses of the identified flavor components revealed some outstanding features of these breeds. For example, the hydrocarbons (22.09%) and aldehydes (14.76%) were higher in Ningdu yellow chickens and the highest content of N, N-dimethyl-methylamine was in Ningdu yellow, Baier yellow, and Shengze 901 chickens, indicating the maximum attribution to the overall flavor (ROAV = 439.57, 289.21, and 422.80). Furthermore, we found that 27 flavor compounds differed significantly among the four Chinese breeds, including 20 (e.g., 1-octen-3-ol), two (e.g., 2-methyl-naphthalene), four (e.g., 2,6-lutidine), and one (benzophenone) flavor components were showed significant enrichment in Ningdu yellow, Baier yellow, Kangle, and Shengze 901 chickens, respectively. The flavor components enriched in each breed were key biomarkers distinguishing breeds and most were significantly correlated with meat quality trait phenotypes. These results provide novel insights into indigenous Chinese chicken meat flavors

Cervical HPV infection in Yueyang, China: a cross-sectional study of 125,604 women from 2019 to 2022

ObjectiveHuman papillomavirus (HPV) infection is currently the main cause of cervical cancer and precancerous lesions in women. The aim of this study was to investigate the epidemiological characteristics of HPV genotypes among women in Yueyang city and to provide a basis for the prevention and treatment of cervical cancer in this city.MethodsA cross-sectional study was conducted on 125,604 women who had received treatment from eight hospitals in Yueyang city from September 2019 to September 2022. Analysis of the prevalence of HPV in patients.ResultsThe prevalence of HPV was 20.5% (95%CI: 20.2–20.7%), of which the high-risk type (HR-HPV) accounted for 17.5% (95%CI: 17.3–17.7%) and the low-risk type (LR-HPV) accounted for 5.0% (95%CI: 4.9–5.1%). Among the HR-HPV subtypes, the top five in prevalence, from the highest to the lowest, were HPV52 (5.1%), HPV16(2.7%), HPV58 (2.6%), HPV53 (2.4%), and HPV51 (1.7%). The main LR-HPV infection types were HPV81 (2,676 cases, OR = 2.1%; 95%CI, 2.0–2.1%). Among the infected patients, 19,203 cases (OR = 74.3%; 95%CI, 73.8–74.9%) had a single subtype, 4,673 cases (OR = 18.1%; 95%CI, 17.6–18.6%) had two subtypes, and 1957 cases (OR = 7.6%; 95%CI, 7.3–7.9%) had three or more subtypes. HPV prevalence is highest among women &lt;25 years, 55–64 years and ≥ 65 years of age.ConclusionThe prevalence of HPV in women in Yueyang city was 20.5%, with HR-HPV being dominant. As women aged &lt;25 years, 55–64 years, and ≥ 65 years are at a relatively higher risk, more attention should be paid to them for prevention and control of HPV infections

Electroacupuncture stimulation modulates functional brain connectivity in the treatment of pediatric cerebral palsy: a case report

BackgroundPediatric cerebral palsy (CP) is a non-progressive brain injury syndrome characterized by central motor dysfunction and insufficient brain coordination ability. The etiology of CP is complex and often accompanied by diverse complications such as intellectual disability and language disorders, making clinical treatment difficult. Despite the availability of pharmacological interventions, rehabilitation programs, and spasticity relief surgery as treatment options for CP, their effectiveness is still constrained. Electroacupuncture (EA) stimulation has demonstrated great improvements in motor function, but its comprehensive, objective therapeutic effects on pediatric CP remain to be clarified.MethodsWe present a case of a 5-year-old Chinese female child who was diagnosed with CP at the age of 4. The patient exhibited severe impairments in motor, language, social, and cognitive functions. We performed a 3-month period of EA rehabilitation, obtaining resting state functional magnetic resonance imaging (rs-fMRI) of the patient at 0 month, 3 months and 5 months since treatment started, then characterized brain functional connectivity patterns in each phase for comparison.ResultsAfter a 12-month follow-up, notable advancements were observed in the patient’s language and social symptoms. Changes of functional connectivity patterns confirmed this therapeutic effect and showed specific benefits for different recovery phase: starting from language functions then modulating social participation and other developmental behaviors.ConclusionThis is a pioneering report demonstrating the longitudinal effect of EA stimulation on functional brain connectivity in CP patients, suggesting EA an effective intervention for developmental disabilities (especially language and social dysfunctions) associated with pediatric CP

Whole exome sequencing identifies frequent somatic mutations in cell-cell adhesion genes in chinese patients with lung squamous cell carcinoma

Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21%, and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion, and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy

The Invasion and Metastasis Promotion Role of CD97 Small Isoform in Gastric Carcinoma

CD97 is over-expressed in the majority of gastric adenocarcinomas and is associated with its dedifferentiation and aggressiveness. Our previous results demonstrated that out of three CD97 isoforms tested, only the small one was able to promote increased invasiveness in vitro. Based on these data we further aimed to investigate the role of CD97 small isoform in gastric cancer progression in vivo by employing the cells with a stable CD97 small isoform knock-down and an orthotopic gastric cancer mouse model. We could demonstrate that the knock down of CD97/EGF1,2,5, led to a significant decrease in the number of cells penetrating the gelatin coated membrane as compared with control cells. In the gastric cancer mouse model, both the hypodermic and the orthotopic yielded tumor masses of the CD97/EGF1,2,5kd group and were significantly smaller than the control. Metastatic tumor cell number in early metastatic regional lymph nodes on post-operative day 42 was distinctly decreased in the CD97/EGF1,2,5kd group as compared with the SGC-NS group, and was accompanied with the downregulation of CD44, VEGFR, CD31 and CD97. We concluded in this study that CD97 small isoform not only supported gastric cancer local growth, but also promoted metastatic spread in orthotopically implanted mouse model suggesting involvement of the CD97 small isoform in the preparation of (pre)metastatic niche