Effectiveness and Safety of Chinese Herbal Injections Combined with SOX Chemotherapy Regimens for Advanced Gastric Cancer: a Bayesian Network Meta-Analysis.

Background: Randomized controlled trials (RCTs) have demonstrated that combining Chinese herbal injections (CHIs) with oxaliplatin plus tegafur (SOX) chemotherapy regimens improves clinical effectiveness and reduces adverse reactions in patients with advanced gastric cancer (AGC). These RCTs highlight the potential applications of CHIs and their impact on AGC patient prognosis. However, there is insufficient comparative evidence on the clinical effectiveness and safety of different CHIs when combined with SOX. Therefore, we performed a network meta-analysis to rank the clinical effectiveness and safety of different CHIs when combined with SOX chemotherapy regimens. This study aimed to provide evidence for selecting appropriate CHIs in the treatment of patients with AGC. Methods: We searched eight databases from their inception until March 2023. Surface Under the Cumulative Ranking Curve (SUCRA) probability values were used to rank the treatment measures, and the Confidence in Network Meta-Analysis (CINeMA) software assessed the grading of evidence. Results: A total of 51 RCTs involving 3,703 AGC patients were identified. Huachansu injections + SOX demonstrated the highest clinical effectiveness (SUCRA: 78.17%), significantly reducing the incidence of leukopenia (93.35%), thrombocytopenia (80.19%), and nausea and vomiting (95.15%). Shenfu injections + SOX improved Karnofsky's Performance Status (75.59%) and showed a significant reduction in peripheral neurotoxicity incidence (88.26%). Aidi injections + SOX were most effective in reducing the incidence of liver function damage (75.16%). According to CINeMA, most confidence rating results were classified as "low". Conclusion: The combination of CHIs and SOX shows promising effects in the treatment of AGC compared to SOX alone. Huachansu and Shenfu injections offer the greatest overall advantage among the CHIs, while Aidi injections are optimal for reducing the incidence of liver damage. However, further rigorous RCTs with larger sample sizes and additional pharmacological studies are necessary to reinforce these findings.

Chinese herbal injections in combination with radiotherapy for advanced pancreatic cancer: A systematic review and network meta-analysis.

Background: Advanced pancreatic cancer (APC) is a fatal disease with limited treatment options. This study aims to evaluate the effectiveness and safety of different Chinese herbal injections (CHIs) as adjuvants for radiotherapy (RT) in APC and compare their treatment potentials using network meta-analysis. Methods: We systematically searched three English and four Chinese databases for randomized controlled trials (RCTs) from inception to July 25, 2023. The primary outcome was the objective response rate (ORR). Secondary outcomes included Karnofsky performance status (KPS) score, overall survival (OS), and adverse events (AEs). The treatment potentials of different CHIs were ranked using the surface under the cumulative ranking curve (SUCRA). The Cochrane RoB 2 tool and CINeMA were used for quality assessment and evidence grading. Results: Eighteen RCTs involving 1199 patients were included. Five CHIs were evaluated. Compound Kushen injection (CKI) combined with RT significantly improved ORR compared to RT alone (RR 1.49, 95 % CrI 1.21-1.86). Kanglaite (KLT) plus RT (RR 1.58, 95 % CrI 1.20-2.16) and CKI plus RT (RR 1.49, 95 % CrI 1.16-1.95) were associated with improved KPS score compared to radiation monotherapy, with KLT+RT being the highest rank (SUCRA 72.28 %). Regarding AEs, CKI plus RT was the most favorable in reducing the incidence of leukopenia (SUCRA 90.37 %) and nausea/vomiting (SUCRA 85.79 %). Conclusions: CKI may be the optimal choice of CHIs to combine with RT for APC as it may improve clinical response, quality of life, and reduce AEs. High-quality trials are necessary to establish a robust body of evidence. Protocol registration: PROSPERO, CRD42023396828.

Severe fever with thrombocytopenia syndrome virus induces platelet activation and apoptosis via a reactive oxygen species-dependent pathway.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV) and with a high fatality rate. Thrombocytopenia is a major clinical manifestation observed in SFTS patients, but the underlying mechanism remains largely unclear. Here, we explored the effects of SFTSV infection on platelet function in vivo in severely infected SFTSV IFNar-/- mice and on mouse and human platelet function in vitro. Results showed that SFTSV-induced platelet clearance acceleration may be the main reason for thrombocytopenia. SFTSV-potentiated platelet activation and apoptosis were also observed in infected mice. Further investigation showed that SFTSV infection induced platelet reactive oxygen species (ROS) production and mitochondrial dysfunction. In vitro experiments revealed that administration of SFTSV or SFTSV glycoprotein (Gn) increased activation, apoptosis, ROS production, and mitochondrial dysfunction in separated mouse platelets, which could be effectively ameliorated by the application of antioxidants (NAC (N-acetyl-l-cysteine), SKQ1 (10-(6'-plastoquinonyl) decyltriphenylphosphonium) and resveratrol). In vivo experiments showed that the antioxidants partially rescued SFTSV infection-induced thrombocytopenia by improving excessive ROS production and mitochondrial dysfunction and down-regulating platelet apoptosis and activation. Furthermore, while SFTSV and Gn directly potentiated human platelet activation, it was completely abolished by antioxidants. This study revealed that SFTSV and Gn can directly trigger platelet activation and apoptosis in an ROS-MAPK-dependent manner, which may contribute to thrombocytopenia and hemorrhage during infection, but can be abolished by antioxidants.

Aging induces severe SIV infection accompanied by an increase in follicular CD8+ T cells with overactive STAT3 signaling.

The number of elderly people living with HIV is increasing globally, and the condition of this population is relatively complicated due to the dual effects of aging and HIV infection. However, the impact of HIV infection combined with aging on the immune homeostasis of secondary lymphoid organs remains unclear. Here, we used the simian immunodeficiency virus mac239 (SIVmac239) strain to infect six young and six old Chinese rhesus macaques (ChRMs) and compared the infection characteristics of the two groups in the chronic stage through multiplex immunofluorescence staining of lymph nodes. The results showed that the SIV production and CD4/CD8 ratio inversion in old ChRMs were more severe than those in young ChRMs in both the peripheral blood and the lymph nodes, especially when a large number of CD8+ T cells infiltrated the follicles and germinal centers. STAT3 in these follicular CXCR5+CD8+ T cells was highly activated, with high expression of granzyme B, which might be caused by the severe inflammatory milieu in the follicles of old ChRMs. This study indicates that aging may be a cofactor involved in SIV-induced immune disorders in secondary lymphoid tissues, affecting the effective antiviral activity of highly enriched follicular CXCR5+CD8+ cells.

Glucose Metabolism Disorder Induces Spermatogenic Dysfunction in Northern Pig-Tailed Macaques (Macaca leonina) With Long-Term SIVmac239 Infection.

Although spermatogenic dysfunction is widely found in patients with human immunodeficiency virus (HIV), the underlying reasons remain unclear. Thus far, potential hypotheses involving viral reservoirs, testicular inflammation, hormone imbalance, and cachexia show inconsistent correlation with spermatogenic dysfunction. Here, northern pig-tailed macaques (NPMs) exhibited marked spermatogenic dysfunction after long-term infection with simian immunodeficiency virus (SIVmac239), with significant decreases in Johnsen scores, differentiated spermatogonial stem cells, and testicular proliferating cells. The above hypotheses were also evaluated. Results showed no differences between SIV- and SIV+ NPMs, except for an increase in follicle stimulating hormone (FSH) during SIV infection, which had no direct effect on the testes. However, long-term SIVmac239 infection undermined pancreatic islet ß cell function, partly represented by significant reductions in cellular counts and autophagy levels. Pancreatic islet ß cell dysfunction led to glucose metabolism disorder at the whole-body level, which inhibited lactate production by Sertoli cells in testicular tissue. As lactate is the main energy substrate for developing germ cells, its decrease was strongly correlated with spermatogenic dysfunction. Therefore, glucose metabolism disorder appears to be a primary cause of spermatogenic dysfunction in NPMs with long-term SIVmac239 infection.

KIF23 promotes triple negative breast cancer through activating epithelial-mesenchymal transition.

BACKGROUND: KIF23 is a member of kinesin family, recent researches indicate KIF23 plays an important role in the proliferation and migration of malignant cancer cells. While the function and specific molecule mechanism of KIF23 in triple negative breast cancer remains unclear. METHODS: QRT-PCR and immunohistochemistry were conducted to analyze expression of KIF23 in triple negative breast cancer tissues and paired paracancer tissues. CCK-8 assay, colony formation assay, wound healing assay and transwell assay were applied for exploring phenotype changing of triple negative breast cancer cell lines MDA-MB-231 and BT549 after siRNA-induced knockdown of KIF23. Several bioinformatic databases were used for predicting miRNAs that combing with KIF23 mRNA and verified by dual luciferase reporter assay. Western blot assay was performed to explore downstream signaling pathway of KIF23. RESULTS: KIF23 was overexpressed in triple negative breast cancer, knockdown of KIF23 by siRNA inhibited proliferation and migration of TNBC cell lines MDA-MB-231 and BT549. Mechanistically, knockdown of KIF23 resulted in the suppression of Epithelial-Mesenchymal Transition. Meanwhile, miR-195-5p was downregulated in TNBC, and dual luciferase reporter assay indicated miR-195-5p could combine with 3'UTR of KIF23 thus promoting degradation of KIF23. CONCLUSIONS: KIF23 is a potential oncogene in triple negative breast cancer, miR-195-5p could combine with 3'UTR of KIF23. Our study reveals a new sight into triple negative breast cancer.

Fasting Plasma Glucose and Coronary Heart Disease in a Rural Population of North Henan, China.

Even in individuals without diabetes, the incidence of coronary heart disease (CHD) increases with the rise in fasting plasma glucose (FPG); however, the threshold of FPG for CHD in rural areas of China is unclear. We retrospectively examined 2,987 people. Coronary angiography records were used to determine the presence of CHD as well as its severity. Risk factors for CHD and the relationship between different levels of FPG and CHD were analyzed. After adjusting for age, hypertension, dyslipidemia, smoking, drinking, chronic kidney disease, and previous ischemic stroke, the incidence of CHD in nondiabetic women began to increase when FPG exceeded 5.2 mmol/L (odds ratio (OR) = 1.438, 95% confidence interval (CI) = 1.099-1.880, p=0.008), and the degree of coronary artery lesions also became more severe (OR = 1.406, 95% CI = 1.107-1.788, p=0.005). However, no such correlations were found in nondiabetic men. In conclusion, among the nondiabetic women in rural areas of northern Henan, both the incidence of CHD and the severity of lesions increased when FPG levels were greater than 5.2 mmol/L, while no significant correlation between FPG and CHD was observed in diabetes-free men.

Successful implementation of intestinal resection and anastomosis in non-human primates suggests the possibility of longitudinal intestinal research.

Intestinal biopsy is a basic experimental method for studying pathological changes in the intestinal tract during human immunodeficiency virus (HIV) infection. In this study, jejunal resection and anastomosis were successfully performed in 12 Chinese rhesus macaques ( Macaca mulatta). The sampled gut tissues were then examined by hematoxylin and eosin (H&E) staining, electron microscopy, flow cytometry, immunofluorescence detection, and RNA quality analysis to ensure suitability for histological, physiological, pathological, and immunological detection, as well as mechanistic analysis at the cellular and molecular level. Importantly, the surgery did not affect the ratio or number of immune cells in peripheral blood or the concentration of lipids, proteins, and vitamins in plasma, which are important indicators of nutritional status. Our results thus indicated that jejunal resection and anastomosis are feasible, and that immune homeostasis and intestinal barrier integrity are not altered by surgery. All macaques recovered well (except for one), with no postoperative complications. Therefore, this animal surgery may be applicable for longitudinal intestinal research related to diseases such as acquired immunodeficiency syndrome (AIDS).

A retrospective study of concurrent radiotherapy plus S-1 for treating advanced non-small cell lung cancer.

We investigated the efficacy of concurrent radiotherapy plus S-1 (CRS) for treating unresectable stage III advanced non-small-cell lung cancer (ANSCLC).Seventy five ANSCLC patients were included in this retrospective study. Of those, 40 patients were assigned to an intervention group, and received S-1 (orally at 40 mg/m) twice daily for 14 consecutive days. Then, concurrent radiotherapy was administered in 2 Gy fractions, 5 times weekly for a total dose of 60 Gy. The other 35 patients were assigned to a control group, and underwent concurrent radiotherapy (the same as the intervention group) and cisplatin (60 mg/m on day 1 (CRC). The outcome measurements included overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and toxicity.The 3-year ORR was 60.7% and 43.9% for intervention group and control group, respectively (P = .031). The median OS was 34.1 months and 25.3 months in the intervention and control groups, respectively (P = .041). The median PFS was 31.5 months for intervention group, while it was 22.4 months for control group (P = .048). No significant difference in toxicity was found between the 2 groups.The results demonstrated that the efficacy of CRS was superior to the CRC in ANSCLC patients with similar toxicity.

[Retracted] Production of interleukin­4 in CD133+ cervical cancer stem cells promotes resistance to apoptosis and initiates tumor growth.

Following the publication of this article, an investigation conducted internally within our Department has revealed that the data published in Fig.  5a are not reproducible. Consequently, confidence in the conclusions drawn from the reported results in the paper has been undermined and, as a result, all authors involved have unanimously agreed to the retraction of this article. All authors recognize the seriousness of this issue and apologize unreservedly to the editors, reviewers and readers. We are also in the process of examining other studies in the paper. We sincerely regret that this study has been compromised, and are committed to rapidly correcting the public record and implementing practices to prevent any recurrence of such a situation in the future. [the original article was published in Molecular Medicine Reports 13: 5068-5076, 2016; DOI: 10.3892/mmr.2016.5195].

Production of interleukin­4 in CD133+ cervical cancer stem cells promotes resistance to apoptosis and initiates tumor growth.

The cancer stem cell (CSC) theory suggests that cancer growth and invasion is dictated by the small population of CSCs within the heterogenous tumor. The aim of the present study was to elucidate the cause for chemotherapy failure and the resistance of CSCs to apoptosis. A total of ~2.3% cluster of differentiation (CD)133+ cancer stem­like side population (SP) cells were identified in cases of uterine cervical cancer. These CD133+ SP cells were found to potently initiate tumor growth and invasion, as they exhibit transcriptional upregulation of stemness genes, including octamer­binding transcription factor­4, B­cell­specific Moloney murine leukemia virus insertion site­1, epithelial cell adhesion molecule, (sex determining region Y)­box 2, Nestin and anti­apoptotic B cell lymphoma­2. In addition, the CD133+ SP cells showed resistance to multi­drug treatment and apoptosis. The present study further showed that the secretion of interleukin­4 (IL­4) in CD133+ cervical cancer SP cells promoted cell proliferation and prevented the SP cells from apoptosis. Following the neutralization of IL­4 with anti­IL­4 antibody, the CD133+ SP cells were more sensitive to drug treatment and apoptosis. Therefore, the data obtained in the present study suggested that the autocrine secretion of IL­4 promotes increased survival and resistance to cell death in CSCs.

[Evaluation of clinical effect of hysterectomy preserving the uterine artery].

OBJECTIVE: To discuss the clinical feasibility of hysterectomy that preserves the ascending branch and the ovarian branch of the uterine artery, and the effect on the ovary. METHODS: Fifty-two women who received hysterectomy with preservation of the ovaries, the so called divest due to benign gynecological disease were selected as the study group. It consisted of 35 patients who received subtotal-divest and 17 patients who received total-divest. Meanwhile, 38 cases who received traditional hysterectomy served as the control group. Two milliliter venous blood was taken and estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) were measured at 1 month preoperation, 1 month, 6 months, and 12 months postoperation from 30 women with age ranging from 36 - 45 years of the two groups each. All the patients in the study group received ultrasonography via vagina at 1 month preoperation and postoperation, respectively. RESULTS: Postoperatively, through vagina color ultrasound examination, in the 52 cases of study group, bilateral uterine arteries were not retained in 1 case, and unilateral uterine artery was not retained in 6 cases. The postoperative peak blood flow of uterine artery during systolic phase (Va) was (20 +/- 9) cm/s, and during diastolic phase (Vb) was (3.8 +/- 3.2) cm/s. Compared with the preoperative values, (29 +/- 8) cm/s, (7.1 +/- 3.4) cm/s, the velocity of blood was slowed obviously (P < 0.01). The postoperative resistance index (RI) (0.79 +/- 0.08), was not significantly different compared with the preoperative value (0.80 +/- 0.08) (P > 0.05). The operative time, bleeding volume, and the postoperative exhaust time had no significant difference between the two groups (P > 0.05). Comparing the hormone assay of two groups, there was a significant change at 6 months postoperation in the control group, but postoperation hormone assay had no significant change compared with the pre-operative result in study group. It indicated that the new approach did not affect the ovarian functions. CONCLUSION: The divest is applicable in clinics, and it can preserve the completeness of blood-supply and the function of the ovary.