Effects of oxycodone hydrochloride sustained-release tablets and morphine hydrochloride sustained-release tablets on peripheral blood T cell levels in advanced lung squamous cell carcinoma with moderate to severe cancer pain.

Objective: To investigate the effects of morphine hydrochloride sustained-release tablets and oxycodone hydrochloride sustained-release tablets on T-cell levels in advanced lung squamous cell carcinoma(LUSC) with moderate to severe cancer pain. Methods: A retrospective study was used, ninety-eight patients who were admitted to The First Affiliated Hospital of Hebei North University for treatment of advanced LUSC with moderate to severe cancer pain between January 2021 and December 2021 were randomized into two groups(n=49 each) using the sealed envelope system. The reference group was treated with morphine hydrochloride sustained-release tablets, while the experimental group received oxycodone hydrochloride sustained-release tablets to compare pain relief rates(PRRs), levels of T cells, pain intensity, et al. Blood samples were collected for lymphocyte levels by flow cytometry. Results: The experimental group had significantly higher level than the reference group(P<0.05). Before administration, the two groups did not differ greatly in levels of T-cell subsets or pain scores on the visual analog scale(P>0.05, respectively). At 15 days of administration, the Treg level in the experimental group was higher than in the reference group; T helper 17 and 22 cells were reduced in both groups, and the decrease was more pronounced in the experimental group. At seven and 15 days of administration, the experimental group had a VAS score significantly lower than the reference group(P<0.05). The total adverse reaction rate was significantly lower in the experimental group as compared with the reference group(P<0.05). Conclusions: Oxycodone hydrochloride sustained-release tablets demonstrate desirable efficacy and safety in advanced LUSC with moderate to severe cancer pain by modulating T-cells in the body and improving the PRR.

Diabetic ketoacidosis induced by nivolumab in invasive mucinous adenocarcinoma of the lung: a case report and review of the literature.

Background: Nivolumab is the first programmed cell death receptor 1 (PD-1) inhibitor approved in China. Compared with chemotherapy, nivolumab has shown advantages of good efficacy and safety in the treatment of a variety of tumors. However, due to its short time of use in China and lack of safety experience, clinical understanding of its adverse reactions has not been sufficiently elucidated. In recent years, cases of diabetic ketoacidosis caused by nivolumab have been reported in the emergency department, which has aroused our concern. Case Description: Here we present a serious case of diabetic ketoacidosis in a 69-year-old woman with invasive mucinous adenocarcinoma of the lung, which occurred following therapy with the PD-1 inhibitor nivolumab and dendritic cell/cytokine-induced killer cell (DC/CIK) immunotherapy. She presented with diabetic ketoacidosis 5 days after the second cycle of nivolumab administration. The patient presented with dry mouth symptoms, a maximum blood glucose of 511.2 mg/dL, hemoglobin A1c (HbA1c) level of 7.4%, urine ketone body value of 3+, and extracellular fluid residual alkali level of -3.8 mmol/L. Normal saline and insulin was initiated. The patient had no history of obesity or family history of diabetes. She received a single dose of 3.75 mg of dexamethasone treatment during this period of time which resulted in cough improvement, but did not explain the onset of the diabetes. She was treated with insulin, sitagliptin phosphate tablets and acarbose tablets. Diabetic ketoacidosis was considered an immune-related toxicity caused by nivolumab, and consequently, treatment with nivolumab was suspended. Patient was maintained under insulin treatment with a blood glucose levels normalization. Conclusions: The incubation period of nivolumab-induced diabetic ketoacidosis is dispersive and the clinical risk is high. Patients need life-long insulin therapy. Blood glucose and HbA1c should be monitored routinely before and during nivolumab immunotherapy to avoid the occurrence of diabetic ketoacidosis. After the occurrence of diabetic ketoacidosis, insulin should be used to actively control blood glucose and do a good job in medication education to ensure long-term compliance of patients. Nivolumab should only be initiated if the patient has a clinical benefit under stable glucose control.

Network pharmacology analysis of the mechanism of Huisheng oral liquid in the treatment of lung cancer.

Background: To study the active ingredient and possible mechanism of Huisheng oral liquid in the treatment of lung cancer by network pharmacology. Methods: The active ingredient and drug targets of Huisheng oral liquid were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID), and lung cancer targets were screened using the Gene Expression Omnibus (GEO) database. The drug targets of the effective components of Huisheng oral liquid were matched with disease targets and the obtained intersecting targets were imported into the Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) database to construct a protein-protein interaction (PPI) network. R software and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used for Gene Ontology (GO) and KEGG enrichment analyses, and Cytoscape software was used to construct a Huisheng oral liquid component target-lung cancer target network. The function and pathway of the therapeutic target of Huisheng oral liquid for lung cancer were analyzed. Results: A total of 1,376 differentially expressed genes (DEGs) of lung cancer were obtained, and 185 potential effective components of Huisheng oral liquid in the treatment of lung cancer were obtained, including quercetin, luteolin, kaempferol, and baicalein. There were 36 intersecting targets between Huisheng oral liquid and lung cancer, and the key targets for lung cancer treatment were CDKN1A, CCNB1, MDM2, CDK1, ErbB2, E2F1, EGFR, etc. Huisheng oral liquid mainly regulates the p53 signaling pathway. Conclusions: The mechanism of Huisheng oral liquid in the treatment of lung cancer is mainly reflected in regulating tumor cell apoptosis, inhibiting angiogenesis, and improving immunity.

Adverse skin reactions induced by sintilimab in advanced lung squamous carcinoma: a case report and review of the literature.

Background: Sintilimab is an immune checkpoint inhibitor (ICI). It can induce immune-related Adverse Events (irAEs). Severe adverse skin reactions are rare, but the mortality rate is high. We report the first case of successful treatment of adverse skin reactions using traditional Chinese medicine (TCM). Case Description: Here we present the case of a 67-year-old male with advanced lung squamous carcinoma. After 8 cycles of chemotherapy, the patient's disease progressed and the treatment regimen was adjusted to sintilimab combined with albumin paclitaxel and cisplatin. Thirty-two days after this cycle, the patient reported a sporadic rash with pruritus on the face, front chest, and both upper limbs. The area of rash was 40%, and the adverse reaction was grade 3. The level of interleukin-related indicators was above normal. The patient's skin symptoms disappeared after treatment with hormones, TCM, and other drugs. The patient's adverse skin reaction was due to an immune-related toxicity caused by sintilimab, so treatment with sintilimab was suspended. The albumin-paclitaxel plus cisplatin regimen was continued to treat lung cancer. Conclusions: Although rare, case of fatal adverse reaction caused by sintilimab have been reported. We recommend early monitoring and recognition of symptoms. During management, high-dose hormones combined TCM may be helpful.

Vitexin protects against ischemia/reperfusion-induced brain endothelial permeability.

Brain endothelial permeability plays a crucial role in blood-brain barrier (BBB), but the permeability enhancement in cerebral ischemia reperfusion (I/R). Vitexin has certain neuroprotective effects, but the effect brain endothelial permeability in I/R injury was unknown. In this study, the effects of Vitexin on endothelial permeability and the underlying mechanisms in human brain microvascular endothelial cells (HBMEc) I/R injury model were investigated. Cell viability, lactate dehydrogenase (LDH), inflammation and apoptosis were detected. The effects of Vitexin on BBB integrity tight junction, matrix metalloproteinases (MMP) were also investigated. The mechanism was confirmed by PI3K inhibitor and NOS inhibitor in normal or eNOS siRNA transfection HBMEc. Vitexin significantly reduced LDH, Caspase 3 level, alleviated inflammation, also could maintain BBB integrity, increased tight junction proteins expression and inhibited MMP. The mechanism is related to reduction of intracellular NO and ONOO-, regulated eNOS, iNOS activity. Vitexin significantly preserved eNOS phosphorylation in response to the activated Akt. Moreover, combined with PI3K inhibitor or low dosage of NOS inhibitor, totally abolished Vitexin-induced eNOS phosphorylation, the protected effect was also attenuated, but still significantly between model cells. However, combined with high dosage NOS inhibitor which both inhibited the eNOS phosphorylation and iNOS, the protected effect of Vitexin was abrogated. In addition, eNOS silencing cells were used to further clarify the regulatory role of Vitexin on iNOS. Our findings showed that Vitexin could play a protective role in I/R-induced brain endothelial permeability by simultaneously increase eNOS phosphorylation and inhibit iNOS.

Toosendanin mediates cisplatin sensitization through targeting Annexin A4/ATP7A in non-small cell lung cancer cells.

Cisplatin (CDDP) is used in the treatment of non-small cell lung cancer (NSCLC), but due to the development of resistance, the benefit has been limited. Toosendanin (TSN) has shown therapeutic effects on NSCLC; however, the role of TSN on CDDP sensitization in NSCLC remains unknown. The antitumor effects of TSN and CDDP sensitization mediated by TSN were explored. TSN was added in various amounts to measure dose- and time-dependent cytotoxicity. Intracellular CDDP was detected by high-performance liquid chromatography. The protein levels of ATP7A, ATP7B, hCTR1, MRP-2, P-gp and Annexin A4 (Anxa4) were analyzed. The tests were conducted using normal NSCLC (A549 cell line) and CDDP-resistant cells (A549/DDP cell line). Anxa4 promotes CDDP resistance by regulating ATP7A, so Anxa4 was overexpressed and silenced and also transfected with pcMV6 or siRNA/ATP7A, respectively. Mechanistic investigations revealed that TSN decreased relative viability in NSCLC cells. Remarkably, TSN significantly enhanced CDDPsensitization in invalid doses. TSN downregulated Anxa4 expression, enhanced intracellular CDDP, and had no effect on MRP-2, P-gp, ATP7A, ATP7B or hCTR1. Subsequently, overexpression of Anxa4 led to a significant decrease in intracellular CDDP concentration. The adjustment of CDDP concentration regulated by TSN disappeared in Anxa4 or ATP7A-silenced cells. TSN also enhanced CDDP sensitization in single ATP7A-overexpressing cells, but had no effect on cells with simultaneous ATP7A overexpression and Anxa4 silencing. The present study suggests that TSN can mediate CDDP sensitization in NSCLC through downregulation of Anxa4.