Gallbladder cancer (GBC) is a highly aggressive malignancy, which poses significant challenges for timely diagnosis, resulting in a dismal prognosis. Chemotherapy serves as a primary treatment option in cases where surgery is not feasible. However, the emergence of chemoresistance poses a significant challenge to the effectiveness of chemotherapy, ultimately resulting in a poor prognosis. Despite extensive research on mechanisms of chemotherapeutic resistance in oncology, the underlying mechanisms of chemoresistance in GBC remain poorly understood. In this review, we present the findings from the last decade on the molecular mechanisms of chemotherapeutic resistance in GBC. We hope that these insights may provide novel therapeutic and experimental targets for further investigations into this lethal disease.

The supraclavicular block (SCB) and the infraclavicular block (ICB) are introduced to meet upper extremity surgery, where the transducer or the insertion point is placed superiorly and inferiorly at the approximate midpoint of the clavicle, respectively. These two approaches are highly appealing since they clearly exhibited each cord and its associated anatomy. In addition, it directed the needle accurately with real-time imaging by ultrasound guidance. Therefore, it brought higher success rates and fewer complications. Numerous trials have recently been conducted to examine the SCB and ICB regarding the new approach, injection techniques, block dynamics, and complication of hemidiaphragmatic paresis. It was found that both approaches could improve block effectiveness and postoperative analgesia for upper extremity surgery, according to recent studies at the level of the clavicular brachial plexus block. However, there is still a lack of work comparing the clinical performance and effectiveness of both approaches with ultrasonography. This review aims to outline the current available data from clinical trials along with case reports about these two approaches and to describe the findings published in the literature during the previous 5 years. Based on these findings, we attempt to determine whether there exists a one-size-fits-all approach that has the potential to meet upper extremity surgery.

Synthesis of nanoparticles using natural organic substances has attracted more attention due to avoiding inorganic toxicity. This work aimed to synthesize copper oxide nanoparticles (CuONPs) using Caesalpinia sappan heartwood extract as a reducing agent. The effects of pH of synthesis reaction were investigated. The obtained CuONPs were characterized using UV-visible spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy dispersive X-ray spectroscopy. Their particle size, size distribution, and zeta potential were determined using photon correlation spectrophotometry. Candida albicans is a major cause of chronic fungal infections due to its biofilms leading to severe drug resistance problems. In this study, in vitro antifungal and antibiofilm activities as well as killing kinetics of the synthesized CuONPs against C. albicans were investigated. Additionally, fungal biofilm was observed by using confocal laser scanning microscopy. The results showed that the pH of the synthesis reaction played an important role in the physicochemical properties and antifungal activities of the obtained CuONPs. CuONPs synthesized at pH 10 and 12 showed the relatively small and narrow size distribution with high negative zeta potential and time-dependent killing kinetics. Confocal laser scanning microscopy confirms obvious fungal biofilm reduction and increased fungal cell death after exposure to CuONPs. These findings suggest the optimal pH of CuONPs synthesis using C. sappan extract as a reducing agent. The results on antifungal and antibiofilm activities indicate that the obtained CuONPs can be a promising agent for treating fungal infection.

Ferroptosis is a form of regulated cell death (RCD) triggered by iron-dependent lipid peroxidation and is closely associated with the occurrence and progression of hepatocellular carcinoma (HCC). The lncRNA SNHG1 (small nucleolar RNA host gene 1) has been shown to play an oncogenic role in HCC, but its function in RCD other than autophagy and apoptosis is still unknown. Here, we investigated the correlation between SNHG1 and 156 typical markers of five RCD types based on RNA sequencing data from The Cancer Genome Atlas database and showed the negative regulators of ferroptosis FANCD2 (Fanconi anemia complementation group D2) and G6PD (glucose-6-phosphate dehydrogenase) to be the most highly and fifth most highly correlating factors with SNHG1, respectively. A competitive endogenous RNA network of SNHG1 – miR-199a-5p/3p – FANCD2/G6PD was constructed bioinformatically. In vitro experiments showed that overexpression of the miR-199a precursor led to a decrease in expression of SNHG1, FANCD2, and G6PD, whereas knockdown of SNHG1 decreased expression of FANCD2 and G6PD but increased levels of miR-199a-5p and miR-199a-3p in HCC cells (Huh7 and HepG2). In addition, knockdown of SNHG1 increased erastin-mediated ferroptosis, iron accumulation, and lipid peroxidation. These results suggest that SNHG1 upregulates FANCD2 and G6PD by sponging miR-199a, thereby inhibiting ferroptosis in HCC. Moreover, a signature based on expression of SNHG1, FANCD2, and G6PD was identified as being associated with overall survival and the immunological microenvironment in HCC. Collectively, this study identified the SNHG1–miR-199a–FANCD2/G6PD axis in HCC, which is a potential marker for the prognosis and therapy of this tumor.

Although pregnancy success rates are raised with assisted reproductive technology, it still cannot meet clinical demands. Kunling Pill (KLP), a traditional Chinese medicine, is widely used in various gynecological disorders, particularly in improving fertility and pregnancy rates. However, the underlying mechanism of how KLP affects pregnancy outcomes remains unclear. This study aimed to explore the effects and mechanisms of KLP on endometrial receptivity. Firstly, a retrospective trial was conducted to validate the efficacy of KLP on repeated implantation failure (RIF) patients. The result indicated a significant increase in the proportion of live birth in KLP group (30.56%) compared to the control group (16.89%). Secondly, network pharmacology methods predicted the active components and network targets of KLP. Endometrial receptivity is closely associated with the activation of inflammatory factors, predicting the function of KLP on the immune system. The estrogen and apoptotic signaling pathways were also highlighted in the gene ontology enrichment analysis. Thirdly, a decreased endometrial receptivity model was established by controlled ovarian hyperstimulation (COH) in female C57BL/6 mice, divided into the COH and KLP groups. Normal female mice are as control group. In vivo, KLP administration could increase endometrial thickness and the number of endometrial glands and pinopodes. In the endometrium, KLP supplementation upregulated the expressions of estrogen receptor α, progesterone receptor, endothelial nitric oxide synthase, and integrin αVβ3 in the murine uterus and reduced serum levels of estrogen and progesterone. KLP regulated the uterine immune cells and inhibited cell apoptosis in the ovary via Bcl-2/Bax/caspase-3 pathway. In conclusion, KLP administration raised the live birth rate in RIF patients to optimize medication regimens, mainly because KLP ameliorated impaired endometrial receptivity.

Apolipoprotein E (ApoE), a ligand for low-density lipoprotein receptors, is strongly induced during osteogenesis and has a physiologic role in regulating osteoblast function, but the mechanisms of its action are still unclear. The study aims to elucidate the influence and molecular mechanisms of ApoE on bone formation. An ovariectomy-induced osteoporotic model were conducted in ApoE knockout (ApoE^-/-) mice to study the effect of ApoE on the bone system. Bone quality were assessed through bone mineral density and histomorphometric analysis. To investigate the underlying role and mechanisms of ApoE during osteogenesis, primary osteoblasts from the calvariums of newborn ApoE^-/- or wild-type (WT) mice were cultured in the osteoblastic differentiation medium in vitro for further research. Our animal experiment data showed that ApoE^-/- mice exhibited bone loss, exacerbated by estrogen deprivation after ovariectomy. ApoE deficiency attenuated osteoblast activity and inhibited osteoblast osteogenesis, accompanied by decreased osterix expression. ApoE deficiency did not affect primary osteoblast viability and collagen-1 expression. Moreover, osteoprotegerin expression in ApoE^-/- osteoblasts was reduced compared to WT controls. Our study demonstrated that ApoE gene deficiency contributed to bone loss and attenuated osteogenesis by down-regulating osterix expression.

A large amount of clinical evidence has revealed that ketamine can relieve fentanyl-induced hyperalgesia. However, the underlying mechanism is still unclear. In the current study, a single dose of ketamine (5 mg/kg or 10 mg/kg), TAK-242 (3 mg/kg), or saline was intraperitoneally injected into rats 15 min before four subcutaneous injections of fentanyl. Results revealed that pre-administration of ketamine alleviated fentanyl-induced hyperalgesia according to hind paw-pressure and paw-withdrawal tests. High-dose ketamine can reverse the expression of toll-like receptor-dimer (d-TLR4), phospho- nuclear factor kappa-B (p-NF-κB, p-p65), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) 1 d after fentanyl injection in the spinal cord. Moreover, fentany-linduced-hyperalgesia and changes in the expression of the aforementioned proteins can be attenuated by TAK-242, an inhibitor of TLR4, as well as ketamine. Importantly, TLR4, p-p65, COX-2, and IL-1β were expressed in neurons but not in glial cells in the spinal cord 1 d after fentanyl injection. In conclusion, results suggested that a single dose of ketamine can relieve fentanyl-induced-hyperalgesia via the TLR4/NF-κB pathway in spinal cord neurons.

Sotorasib, an oral small-molecule inhibitor, reportedly exerts promising activity against Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant tumors. However, the currently administered dose may fail to represent the optimal dose based on the therapeutic efficacy. Herein, we developed a simple and sensitive method using high-performance liquid chromatography with ultraviolet (HPLC-UV) to measure the sotorasib concentration in human plasma. The sotorasib calibration curve exhibited linearity across the concentration range of 0.10-20.0 μg/mL (r² = 0.9999). The coefficients of intra- and inter-day validation ranged between 0.79-9.75% and 3.01-6.13%, respectively. The assay accuracy ranged between –3.14 and 5.18%, with > 98.5% recovery. Subsequently, we applied the developed method to estimate sotorasib concentrations in a patient with KRAS G12C-mutated non-small cell lung cancer. We anticipate that our HPLC-UV method will be valuable for assessing the safety and efficacy of sotorasib in larger patient cohorts.

Inflammatory bowel disease (IBD) is a non-specific chronic intestinal inflammatory disorder. Pharmacotherapy serves as the main treatment strategy for IBD; however, the current medications have certain limitations, such as inefficacy and a tendency to induce tolerance, thereby requiring the development of innovative drugs to fulfill therapeutic requirements. A model of acute colitis induced with a solution of approx. 3% dextran sulfate sodium (DSS) has been widely used in preclinical drug development. Nevertheless, this model has some drawbacks, including rapid disease progression leading to mortality in some mice and disparities between the inflammatory characteristics of mice and the pathological features of human IBD. The current study found that mice freely consuming a lower concentration of a DSS solution (1-1.5%) for 10-15 days exhibited milder colitis symptoms. Continued consumption of the DSS solution for 15-20 days resulted in chronic inflammation in colon tissue, accompanied by a significant increase in the proportion of Th1 cells, indicating the involvement of adaptive immune responses. Subsequently, mice were treated with mesalazine or Centella triterpenes while concurrently consuming the DSS solution for 10 days. The treated mice had significant improvements in body weight and colon length compared to the control group. The advantages of this subacute model include minimal mortality among experimental mice and the fact that intestinal mucosal inflammation in mice resembles the pathological features of human IBD, enabling the assessment of drug efficacy against IBD.

This study aimed to investigate the effect of anti-Mullerian hormone (AMH) on the pregnancy outcome of infertility assisted by IVF/Micro-Insemination/Embryo Transfer Infertility Assistance (IVF/ICSI-ET). A total of 324 patients under the age of 35 who received IVF/ICSI-ET assistance in our center were included in this analysis. AMH levels of these patients were measured by chemiluminescence method and divided into clinical pregnancy group (175 cases) and non-pregnancy group (149 cases) according to the final pregnancy outcome. The relationship between the two groups' pregnancy outcomes and AMH levels was analyzed. The above association was re-evaluated after excluding patients with polycystic ovary syndrome. There was no significant difference in age, body mass index (BMI), follicle-stimulating hormone (FSH), and 2 pronucleus (PN) between clinical and non-clinical pregnancy groups. Compared with the clinical pregnancy group, the level of AMH in the non-pregnancy group was significantly lower (p < 0.05). A higher AMH level was closely related to better IVF/ICSI-ET assisted pregnancy outcome in vitro. After excluding AMH abnormalities, the AMH level was still significantly associated with pregnancy outcomes of in vitro IVF/ICSI-ET-assisted pregnancy. Our results show a correlation between AMH level and pregnancy outcome of in vitro IVF/ICSI-ET assisted pregnancy. For women under age 35, lower AMH levels may be one of the predictors of adverse pregnancy outcomes. For patients with low AMH level, it is suggested to strengthen monitoring to ensure the safety and smoothness of the pregnancy process.