Comparative Analysis of Ketamine and Fentanyl Combined with Dexmedetomidine for Lumbar Anesthesia in Proximal Femur Fractures Among the Elderly.

Objective: This study aimed to compare the effects of ketamine and fentanyl combined with dexmedetomidine in lumbar anesthesia for proximal femur fractures among elderly patients. Design: This study employed a prospective, randomized controlled trial (RCT) design. Settings: The study was conducted at Beijing Jishuitan Hospital. Participants: A total of 100 elderly patients with proximal femur fractures who underwent lumbar anesthesia between January 2022 and January 2023. Intervention: Participants were divided into two groups: the ketamine group (n=49) and the fentanyl group (n=51). The ketamine group received ketamine combined with dexmedetomidine, while the fentanyl group received fentanyl combined with dexmedetomidine. Outcome Measures: The following outcome measures were assessed and compared between the two groups: (1) hemodynamic indexes; (2) visual analogue scale (VAS) scores; (3) stress reaction indexes; (4) Incidence of adverse effects. These comparisons were made using the random number table method. Results: No significant differences were observed in systolic blood pressure (SBP), transcutaneous oxygen saturation (SPO2), and heart rate (HR) between the two groups at each time point (P > .05). SBP and HR of both groups were lower than baseline (T0) from T1 onwards. Throughout the surgery, SBP and HR exhibited a decreasing trend with operation time, followed by an increase post-operation. SPO2 showed minimal fluctuations during surgery in both groups. Preoperatively, VAS scores were comparable between groups (P > .05). However, at 12h, 24h, and 48h post-surgery, VAS scores were significantly lower in the ketamine group (P < .05). Stress indicator levels were similar preoperatively (P > .05), but postoperatively, serum cortisol (Cor), epinephrine (E), and norepinephrine (NE) levels were lower in the ketamine group (P < .05). Conclusion: Dexmedetomidine combined with ketamine demonstrates safety and efficacy in the elderly. It significantly reduces postoperative pain and stress reactions while decreasing the incidence of adverse reactions.

Panobinostat (LBH589) combined with AM1241 induces cervical cancer cell apoptosis through autophagy pathway.

PURPOSE: The study aims to investigate the apoptotic effects of combining LBH589 and AM1241 (a selective CB2 receptor agonist) on cervical cancer cells and elucidating the mechanism of this combined therapy, which may provide innovative strategies for treating this disease. METHODS: The viability of the cervical cancer cells was measured by cell counting kit-8 (CCK-8) assay, and the synergistic effect was analyzed using SynergyFinder. Cell proliferation was tested by cell cloning. The apoptosis and reactive oxygen species (ROS) production in cervical cancer cells were analyzed by flow cytometry. Western blot and quantitative real-time PCR (qRT-PCR) were employed to determine changes in protein and gene levels of pathway-related factors. RESULTS: By the results of cytotoxicity assay, SiHa cells were selected and treated with 0.1 µM LBH589 and 4 µM AM1241 for 24 h for subsequent experiments. The combination of both was synergistic as determined by bliss, ZIP, HSA and LOEWE synergy score. Plate cloning results showed that LBH589 combined with AM1241 inhibited the proliferation of cervical cancer cells compared to individual drug. Additionally, compared with LBH589 alone, the combination of LBH589 and AM1241 induced autophagy by increasing LC3II/LC3I and decreasing P62/GAPDH, leading to a significantly higher rate of apoptosis. Pharmacological inhibition of also inhibited apoptosis. Consistently, we found that the endoplasmic reticulum, DNA damage repair pathway were induced after co-administration. Furthermore, cellular ROS increased after co-administration, and apoptosis was inhibited by the addition of ROS scavenger. CONCLUSION: LBH589 combined with AM1241 activated the endoplasmic reticulum emergency pathway, DNA damage repair signaling pathway, oxidative stress and autophagy pathway, ultimately promoting the apoptosis of cervical cancer cells. These findings suggest that the co-administration of LBH589 and AM1241 may be a new treatment plan for the treatment of cervical cancer.

Solamargine Alleviates Proliferation and Metastasis of Cervical Cancer Cells by Blocking the CXCL3-Mediated Erk Signaling Pathway.

Solamargine has unique antitumor efficacy in a variety of cancers. The study is to explore the role of solamargine in cervical cancer. HeLa and SiHa cells were exposed to solamargine treatment at divergent concentrations (0, 5, 10, and 20 µM). The antitumor role of solamargine in cervical cancer cells was determined by cell counting kit 8 (CCK-8), colony formation, scratch test, transwell assay, and western blot. The expression of mRNAs regulating the extracellular regulated protein kinases (Erk) pathway in solamargine-treated cells was detected by qRT-PCR. Rescue experiments were conducted to explore the effect of C-X-C motif chemokine ligand 3 (CXCL3). Following that, we inhibited Erk1/2 by PD98059 to investigate the interplay between CXCL3 and Erk pathway in solamargine-treated cells by measuring migration, invasion, and related matrix metalloproteinase (MMP) expressions. Solamargine inhibited the viability, proliferation, migration, and invasion of cervical cancer cells in a dose-dependent manner. The expression of p-Erk1/2 was downregulated by solamargine. CXCL3 overexpression abrogated the antitumor effect of solamargine on cervical cancer cells. The inhibition of the Erk signaling pathway restored the inhibiting role of solamargine which interfered with CXCL3 overexpression, in invasion, migration, and expressions of MMP-2 and MMP-9 in cervical cancer cells. Moreover, solamargine inhibited the growth of tumor in vivo xenograft model. Solamargine alleviated proliferation and metastasis of cervical cancer cells by blocking the CXCL3-mediated Erk signaling pathway.

Circ_0009035 regulates the progression of cervical cancer by targeting miR-1305/CREBRF axis.

Circular RNAs (circRNAs) have a crucial role in the occurrence of many diseases, such as tumors. Yet the roles of circ_0009035 (circRACGAP1) in cervical cancer are not fully characterized. The expression levels of circRACGAP1, miR-1305 and cAMP-responsive element-binding protein 3 regulatory factor (CREBRF) were detected by using real-time quantitative PCR or western blot. Cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine, colony formation assay, transwell assay and tube formation assay were used to detect cell proliferation, migration and invasion and angiogenesis, respectively. Flow cytometry assay was used to analyze the cell apoptosis. Dual-luciferase reporter assay and RNA immunoprecipitation assay were performed to analyze the targeting about miR-1305 and circ_0009035 or CREBRF. Xenograft model was built to study the role of circ_0009035 in vivo. Immunohistochemistry was used to detect the expression of Ki67, epithelial cadherin and vimentin. First, we found that circ_0009035 expression was significantly upregulated in tumor cells and tissues; second, knockdown of circ_0009035 could inhibit cell proliferation, migration and invasion and promote cell apoptosis. Subsequently, circ_0009035 was found to be able to target miR-1305, and the expression of miR-1305 in tumor tissues and cells was significantly lower. MiR-1305 inhibitor could restore cell-related progression of cervical cancer inhibited by si-circ_0009035. Finally, miR-1305 could target CREBRF, and circ_0009035 could regulate CREBRF expression by targeting miR-1305, thereby affecting cervical cancer tumorigenesis. In summary, our study confirmed that circ_0009035 could influence the development of cervical cancer through the targeted regulation of miR-1305/CREBRF.

Primary female genital system lymphoma complicated by a recurrent mucinous borderline ovarian tumor: a case report and review of the literature.

BACKGROUND: Primary female genital system lymphoma (PFGSL) is an infrequent entity. All genital organs may be affected, and most PFGSLs are localized to the cervix, uterine body, and ovaries. The clinical manifestations are nonspecific, which complicates a timely diagnosis. We report an unexpected case of PFGSL and discuss the disease characteristics by reviewing the literature. CASE PRESENTATION: A 48-year-old G3/P2 woman presented to the Department of Gynecology with a physical examination. Ultrasound examination and CT revealed pelvic masses. The woman underwent surgical treatment because of the pelvic masses and underwent a hysterectomy for a recurrent mucinous borderline ovarian tumor. However, the results of the postoperative pathological examination showed diffuse large B-cell lymphoma of the endometrium. After four courses of chemotherapy, the woman was in good condition. The clinical manifestations were nonspecific, which made a timely diagnosis complex. CONCLUSION: This case highlights the importance of the difficulty in detecting early PFGSL early and how easily nonspecific manifestations can be ignored. It may lead to missing the best time for early treatment.

Discovery of a novel IL-15 based protein with improved developability and efficacy for cancer immunotherapy.

Interleukin-15 (IL-15) can promote both innate and adaptive immune reactions by stimulating CD8+/CD4+ T cells and natural killer cells (NK) while showing no effect in activating T-regulatory (Treg) cells or inducing activation-associated death among effector T cells and NK cells. Thus, IL-15 is considered as one of the most promising molecules for antitumor immune therapy. To improve the drug-like properties of natural IL-15, we create an IL-15-based molecule, named P22339, with the following characteristics: 1) building a complex of IL-15 and the Sushi domain of IL-15 receptor α chain to enhance the agonist activity of IL-15 via transpresentation; 2) through a rational structure-based design, creating a disulfide bond linking the IL-15/Sushi domain complex with an IgG1 Fc to augment its half-life. P22339 demonstrates excellent developability, pharmacokinetic and pharmacodynamic properties as well as antitumor efficacy in both in vitro assessments and in vivo studies. It significantly suppresses tumor growth and metastasis in rodent models, and activates T effector cells and NK cells in cynomolgus monkey. Overall, these data suggest that P22339 has a great potential for cancer immunotherapy.

GRP137 promotes cell proliferation and metastasis through regulation of the PI3K/AKT pathway in human ovarian cancer.

PURPOSE: Ovarian cancer is one of the leading causes of death for women worldwide. The present study aims to investigate the role of G protein-coupled receptor 137 (GPR137) in the biological activities of ovarian cancer cells. METHODS: (QUERY: Please supply Methods for Abstract) RESULTS: G protein-coupled receptor 137 was highly expressed in clinical ovarian cancer tissues and exhibited the highest protein levels in SKOV3 cells and OVCAR3 cells. Knockdown of GPR137 caused significant decreases in cell proliferative rates and colony formation abilities in SKOV3 cells and OVCAR3 cells and also inhibited the in vivo tumorigenesis in a xenograft model. It was observed that knockdown of GPR137 inhibited cell motility by up to 40% in SKOV3 cells and approximately 65% in OVCAR3 cells in wound-healing assay. Cell migration abilities were consistently inhibited by 68.2% in SKOV3 cells and 59.3% in OVCAR3 cells, whereas cell invasion abilities were inhibited by 64.0% and 74.2% in SKOV3 and OVCAR3 cells, respectively, after knockdown of GPR137. When GPR137 was depleted, epithelial markers were increased, while mesenchymal markers decreased. CONCLUSIONS: Our data suggest that GPR137 plays pro-oncogenic roles in ovarian cancer via regulation of the PI3K/AKT pathway. These observations might pave new insights into therapeutic strategies against human ovarian cancer.

Aloesin Suppresses Cell Growth and Metastasis in Ovarian Cancer SKOV3 Cells through the Inhibition of the MAPK Signaling Pathway.

Aloesin is an active constituent of the herb aloe vera and plays a crucial role in anti-inflammatory activity, ultraviolet protection, and antibacterium. We investigated the role and possible mechanisms of aloesin in the cell growth and metastasis of ovarian cancer. It was found that aloesin inhibited cell viability and cell clonality in a dose-dependent manner. It arrests the cell cycle at the S-phase and induced apoptosis in SKOV3 cells. In an in vivo experiment, it was observed that aloesin inhibited tumor growth. Moreover, it inhibited migration and invasion of cancer in SKOV3 cells. Interestingly, members from the mitogen-activated protein kinase (MAPK) signaling family became less phosphorylated as the aloesin dose increased. This suggests that aloesin exerts its anticancer effect through the MAPK signaling pathway. Our data also highlights the possibility of using aloesin as a novel therapeutic drug for ovarian cancer treatment.

The effects of platelet apheresis on blood saving and coagulation in bilateral total hip replacement: A prospective study on 60 patients.

BACKGROUND: Preoperative platelet rich plasma (PRP) harvest has been used in cardiopulmonary surgery for more than 10 years. There is no previous study dealing with PRP in bilateral total hip replacement. This study was to investigate the effects of PRP on blood saving and blood coagulation function in patients with bilateral total hip replacement. PATIENTS AND METHODS: A prospective, randomized, clinical trial was conducted. Sixty patients were enrolled, including 30 patients undergoing PRP in the PRP group and 30 controls. The surgery time, total transfusion volume, blood loss, allogenic blood transfusion, autologous blood transfusion, urine volume, drainage volume, some blood parameters (including Fibrinogen, D-dimer, Prothrombin time, international normalizedratio, activated partial thromboplastin time, Platelet, Haemoglobin B), thrombelastogram (TEG) and blood-gas parameters were studied in the perioperative stage. The measurement data were analyzed statistically. RESULTS: There was no statistical difference between the two groups in baseline characteristics, surgery time, total transfusion volume, blood loss, autologous blood transfusion, etc. Allogenic blood transfusion in the PRP group was less than the control group with statistical difference (p = 0.024). Fibrinogen in the PRP group was higher than the control group (p = 0.008). Among the TEG indicators, activated clotting time and coagulation time K in the PRP group were less than the control group. Clotting rate and maximum amplitude in the PRP group were higher. The blood-gas parameters presented no statistical difference. CONCLUSION: The results suggested that PRP probably played a positive role in blood coagulation function as well as blood saving in patients with bilateral total hip replacement.

The efficacy of simultaneous bilateral axillary brachial plexus block under the guidance of neurostimulator or ultrasound: a prospective study.

PURPOSE: This study was designed to investigate the risk of local anesthetic toxicity and efficacy of simultaneous bilateral axillary brachial plexus block performed under the guidance of ultrasound or a neurostimulator. METHODS: One hundred and twenty patients who were anesthetized with bilateral axillary plexus block simultaneously between February 2012 and March 2014 were enrolled in the study. The patients were anesthetized under the guidance of a neurostimulator (group N, n = 60) or ultrasound (group U, n = 60). The block performance time, procedure-related pain, adverse events, total and free plasma concentrations of ropivacaine, and other data were recorded. The comparison was analyzed statistically. RESULTS: The block performance time, and onset of the sensory and motor block, of group N was longer than that of group U (p < 0.001). The procedure-related pain of group N was more serious than that of group U (p < 0.05). The patient satisfaction rate of group U was higher than that of group N (p < 0.05). The total plasma concentrations of ropivacaine in group N were comparable to those of group U, except for the value at 50 min after injection (p < 0.05). The free plasma concentrations of ropivacaine of group N at 5 min were significantly higher than that of group U (p < 0.001). No apparent serious adverse events were observed perioperatively in both groups. CONCLUSIONS: Simultaneous bilateral axillary brachial plexus block guided by neurostimulator or ultrasound in bilateral distal upper extremity surgery seems to have a low risk of local anesthetic toxicity and to be effective. The ultrasound-guided block is superior in terms of providing the same degree of anesthesia with shorter duration, less pain, and faster onset of sensory and motor blockades, which is important in clinical practice.

Serum proteomics of early postoperative cognitive dysfunction in elderly patients.

BACKGROUND: Studies on postoperative cognitive dysfunction (POCD) have attracted extensive attention and achieved significant progress. However, the diagnosis of POCD is not very satisfactory as no specific biomarkers have been classified. The aim of the present study was to evaluate differences in serum protein composition between POCD and Non-POCD patients, identify potential biomarkers associated with early POCD, and study the mechanism underlying POCD. METHODS: Sixty-eight elderly patients (age ≥ 65 years) received isoflurane inhalation anesthesia for arthroplasty surgeries. One day before and seven days after the surgery, these patients were subjected to a neuropsychological test and venous blood sample collection. Postoperative cognitive dysfunction was determined using Z test scores. Based on the results, the patients were divided into POCD and non-POCD groups. Twenty-five randomly chosen blood samples obtained seven days after the surgery from each group were analyzed on a Bruker ultraFlex(TM) time of flight (TOF)/TOF mass spectrophotometer. The resulting peptide fingerprints were compared with those from the pre-surgery samples to identify differences in serum protein composition. The model designed to distinguish between a non-POCD group and a POCD group were established and validated. Three proteins with the most significant changes were selected for further characterization. RESULTS: Thirty-three cases were diagnosed as POCD. Using the Clinprotools software, 58 polypeptides were found to display differential expression (P < 0.05). Using a support vector algorithm method, seven differential peaks were isolated to establish a diagnostic model to distinguish POCD patients from normal individuals. The prediction rate and recognition rate were 96.89% and 100%, respectively. Validation of this model showed that the accuracy rates were 100% and 85% using samples from the POCD and non-POCD groups, respectively. Protein analysis also led to the identification of fibrinopeptide A (FPA) as a potential biomarker for POCD. CONCLUSIONS: Arthroplastic surgery under isoflurane inhalation anesthesia causes differential serum protein expression in elderly patients. These differentially expressed proteins may contribute to the diagnosis of early POCD, which may provide a basis for identifying the underlying mechanism of POCD development.

[Misdiagnosis of 3 cases lymphoma due to misjudgement of immunohistochemistry].

OBJECTIVE: To recognize the importance of analyzing the result of immunohistochemical staining correctly. METHOD: Review of the three misdiagnosed cases lymphoma and exploring the causes of misdiagnosis through reviewing their clinics, histopathology and immunohistochemistry. RESULTS: Case 1 of lymphocyte rich classical Hodgkin's lymphoma (LRCHL) was misdiagnosed as follicular lymphoma (FL) initially, the RS cells were overlooked morphologically and wrongly determined BCL-2 and CD20-positive cells as tumor cells immunohistochemically; also once misdiagnosed as nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) because the CD20-negative RS misjudged cells as the positives. Case 2 of AML tumor cells expressed TdT, CD7 and CD43 unspecifically, which misdiagnosed as T-cell lymphoblastic lymphoma (T-LBL). Case 3 of type B1 thymoma was misdiagnosed as T-LBL, because CK wasn't expressed satisfactorily resulting in neglecting neoplastic epithelial cells, and lymphocytes in the background were TdT and CD99-positive. CONCLUSION: The diagnosis of lymphoma should be based on morphology, immunohistochemistry, clinics, and genetics. Moreover, the correct judgment of immunohistochemical staining is essential to make right diagnosis.

[Effect of propofol on the activation of nuclear factor-kappa B and expression of inflammatory cytokines in cerebral cortex during transient focal cerebral ischemia-reperfusion: experiment with rats].

OBJECTIVE: To investigate the effect of propofol on the activation of nuclear factor-kappa B (NF-kappa B) and the expression of inflammatory cytokines, such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and intercellular adhesion molecule-1 (ICAM-1) in cerebral cortex during transient focal cerebral ischemia-reperfusion, and to discuss the probable mechanism of its protective effect. METHODS: Ninety male Wistar rats were randomly divided into 3 equal groups: sham operation group undergoing sham operation; ischemia/reperfusion (I/R) group undergoing thread embolism of the left middle cerebral artery occlusion (MCAO) to cause focal ischemia for 2 hours and then undergoing reperfusion; and propofol group undergoing peritoneal injection of propofol 2 hours before the ischemia-reperfusion of MCAO. Then the rats in the 3 groups were re-divided into subgroups of 5 rats, totally 18 subgroups, to be decapitated 2, 3, 6, 12, 24, and 72 hours after reperfusion for the latter 2 groups, and their brains were taken out and fixed. Immunohistochemistry was used to detect the translocation of NF-kappaB in the neurons and the expression of IL-1, TNF-alpha, and ICAM-1 in the brain. Western blotting was used to detect the expression of NF-kappa B. The opposite non-ischemic cortexes were used as controls. RESULTS: Two to 24 hours after the reperfusion NF-kappaB was significantly translocated from the cytoplasm into the nucleus; however, NF-kappa B remained in the cytoplasm of bilateral cortexes in the sham operation groups, and the nonischemic cortexes in the I/R and protofol groups. The translocation of NF-kappa B from cytoplasm into nucleus was significantly inhibited in the ischemic cortex of the propofol group. The expression values of NF-kappa B in the nuclei of ischemic cortexes in the I/R group 2 to 24 hours after reperfusion were significantly higher than those in the sham operation group and the nonischemic cortexes of the I/R and propofol groups (all P < 0.01). The expression values of NF-kappa B in the ischemic cortex of the propofol group 2 to 24 hours after reperfusion was significantly lower than that of the I/R group (all P < 0.05). The expression values of IL-1, TNF-alpha, and ICAM-1 in the ischemic cortexes were significantly higher than that in the cortex of the sham operation group and those in the nonischemic cortexes of the I/R group and propofol group (P < 0.01 or P < 0.05) and the expression values of IL-1, TNF-alpha, and ICAM-1 in the propofol group were all significantly lower than those in the I/R group (all P < 0.05). CONCLUSION: Propofol inhibits the inflammatory reaction by inhibiting the NF-kappa B activation during focal ischemia-reperfusion which may be one of the mechanisms of its neuroprotective function.