Advances in the use of local anesthetic extended-release systems in pain management.

Pain management remains among the most common and largely unmet clinical problems today. Local anesthetics play an indispensable role in pain management. The main limitation of traditional local anesthetics is the limited duration of a single injection. To address this problem, catheters are often placed or combined with other drugs in clinical practice to increase the time that local anesthetics act. However, this method does not meet the needs of clinical analgesics. Therefore, many researchers have worked to develop local anesthetic extended-release types that can be administered in a single dose. In recent years, drug extended-release systems have emerged dramatically due to their long duration and efficacy, providing more possibilities for the application of local anesthetics. This paper summarizes the types of local anesthetic drug delivery systems and their clinical applications, discusses them in the context of relevant studies on local anesthetics, and provides a summary and outlook on the development of local anesthetic extended-release agents.

Levels of vitamin A and selenium of children with cystic echinococcosis in Aba Tibetan and Qiang and Garze Tibetan Autonomous Prefecture, Sichuan, China.

OBJECTIVE: The aim of this study was to review the levels of vitamin A and selenium in children with echinococcosis in Ganzi and Aba. METHODS: Twenty-six children with cystic echinococcosis and 104 apparently healthy controls from the Aba and Garze Tibetan Autonomous Prefecture of Sichuan province in China were recruited. The serum levels of selenium and vitamin A of the cases and controls were detected and stratified by sex and age. RESULTS: The results showed that the ratio of boys to girls was 1:1.36. Compared with the healthy controls, the vitamin A serum levels of the cases significantly declined. The rate of selenium deficiency was high in the cases, but there was no significant difference compared with the control group. Additionally, the lower the vitamin A serum level, the higher the risk for developing echinococcosis. CONCLUSIONS: To improve management strategies in children with cystic echinococcosis, or possibly to prevent the disease, children living in high-risk areas for cystic echinococcosis should be given supplemental vitamin A and encouraged to consume a vitamin A-rich diet containing paw-paw, carrot, palm oil, or fish. Children with vitamin A deficiency in high-risk areas should be screened for cystic echinococcosis.

Berberine targets the electron transport chain complex I and reveals the landscape of OXPHOS dependency in acute myeloid leukemia with IDH1 mutation.

Metabolic reprogramming, a newly recognized trait of tumor biology, is an intensively studied prospect for oncology medicines. For numerous tumors and cancer cell subpopulations, oxidative phosphorylation (OXPHOS) is essential for their biosynthetic and bioenergetic functions. Cancer cells with mutations in isocitrate dehydrogenase 1 (IDH1) exhibit differentiation arrest, epigenetic and transcriptional reprogramming, and sensitivity to mitochondrial OXPHOS inhibitors. In this study, we report that berberine, which is widely used in China to treat intestinal infections, acted solely at the mitochondrial electron transport chain (ETC) complex I, and that its association with IDH1 mutant inhibitor (IDH1mi) AG-120 decreased mitochondrial activity and enhanced antileukemic effect in vitro andin vivo. Our study gives a scientific rationale for the therapy of IDH1 mutant acute myeloid leukemia (AML) patients using combinatory mitochondrial targeted medicines, particularly those who are resistant to or relapsing from IDH1mi.

Exploring the pharmacological mechanisms of Shuanghuanglian against T-cell acute lymphoblastic leukaemia through network pharmacology combined with molecular docking and experimental validation.

CONTEXT: Due to the poor prognosis of T-cell acute lymphoblastic leukaemia (T-ALL), there is an urgent need to identify safer and more cost-effective drugs. OBJECTIVE: This study evaluated the antitumour activity of Shuanghuanglian (SHL) on T-ALL cells and elucidated the mechanism. MATERIALS AND METHODS: Jurkat and Molt4 cells were treated with SHL (0.1, 0.2 and 0.4 mg/mL) for 24 and 48 h. The controls were treated with RPMI 1640 containing 10% foetal bovine serum. Cell viability was evaluated through Cell Counting Kit-8 assay. Patterns of death and signalling pathway alterations caused by SHL were identified by network pharmacology combined with GO enrichment analysis and then were verified by Hoechst 33342 staining, Annexin V-FITC/PI staining and Western blotting. Interactions of the active ingredients with targets were analysed by molecular docking. RESULTS: The IC50 values of SHL in Jurkat and Molt4 cells were 0.30 ± 0.10 and 0.48 ± 0.07 mg/mL, respectively, at 24 h and 0.27 ± 0.05 and 0.30 ± 0.03 mg/mL at 48 h. In T-ALL, 117 target genes of SHL were mainly enriched in the apoptosis and NOTCH signalling pathways. SHL induced apoptosis was confirmed by Hoechst 33342 staining and flow cytometry. The protein levels of cleaved caspase-7 and cleaved PARP were significantly increased but those of cleaved NOTCH1 and MYC were reduced. The active ingredients of SHL can interact with γ-secretase.Discussion and conclusions: SHL induces apoptosis in T-ALL cells via the NOTCH1-MYC pathway and may be a potential drug for the treatment of T-ALL.

Oral Lactobacillus reuteri LR06 or Bifidobacterium BL5b supplement do not produce analgesic effects on neuropathic and inflammatory pain in rats.

BACKGROUND: Previous studies have reported that certain bacteria exert visceral antinociceptive activity in visceral pain and may also help to relieve neuropathic and inflammatory pain. OBJECTIVE: The aim of this study was to explore the analgesic effect of Lactobacillus reuteri LR06 (LR06) or Bifidobacterium BL5b (BL5b) in chronic pain in vivo. DESIGN: Rats were randomly assigned into four groups: sham, Chronic Constriction Injury (CCI)/Complete Freund's Adjuvant (CFA) + control, CCI/CFA + LR06, and CCI/CFA + BL5b. Rats from the probiotic groups were treated with 1 x 109 cfu (LR06 or BL5b) daily through gavage for 14 days after a pain model was successfully established. Mechanical and thermal hyperalgesia were used to assess the analgesic effect of the probiotics. Iba1 was used to verify the microglial inflammatory reaction in the different groups. RESULTS: The results showed that probiotics L. reuteri LR06 or Bifidobacterium BL5b had no significant antinociception effects in chronic pain rats. The chronic pain-induced activation of microglia (Iba1) was not relieved by probiotics in CCI/CFA-induced neuropathic or inflammatory pain rats. CONCLUSION: Our results suggested that L. reuteri LR06 or Bifidobacterium BL5b had no antinociceptive effects on CCI-induced neuropathic pain and CFA-induced inflammatory pain in rats.

Effects of Intravenous Patient-Controlled Sufentanil Analgesia and Music Therapy on Pain and Hemodynamics After Surgery for Lung Cancer: A Randomized Parallel Study.

OBJECTIVE: Postoperative pain is caused by surgical injury and trauma; is stressful to patients; and includes a series of physiologic, psychological, and behavioral reactions. Effective postoperative analgesia helps improve postoperative pain, perioperative safety, and hospital discharge rates. This study aimed to observe the influence of postoperative intravenous sufentanil patient-controlled analgesia combined with music therapy versus sufentanil alone on hemodynamics and analgesia in patients with lung cancer. METHODS: This was a randomized parallel study performed in 60 patients in American Society of Anesthesiologists class I or II undergoing lung cancer resection at the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University. Patients were randomly assigned to a music therapy (MT) group and a control (C) group. The MT group underwent preoperative and postoperative music intervention while the C group did not. Both groups received intravenous patient-controlled sufentanil analgesia. The primary outcome was the visual analogue scale (VAS) score at 24 hours after surgery. The secondary outcomes included hemodynamic changes (systolic blood pressure, diastolic blood pressure, heart rate), changes on the Self-Rating Anxiety Scale (SAS), total consumption of sufentanil, number of uses, sedation, and adverse effects. The postoperative sufentanil dose and analgesia frequency were recorded. RESULTS: Compared with the C group, the MT group had significantly lower VAS score, systolic and diastolic blood pressure, heart rate, and SAS score within 24 hours after surgery (p < 0.01). In addition, postoperative analgesia frequency and sufentanil dose were reduced in the MT group (p < 0.01). CONCLUSIONS: Combined music therapy and sufentanil improves intravenous patient-controlled analgesia effects compared with sufentanil alone after lung cancer surgery. Lower doses of sufentanil could be administered to more effectively improve patients' cardiovascular parameters.

[Spinal anesthesia with low dose sufentanil-bupivacaine in transurethral resection of the prostate].

OBJECTIVE: To explore the clinical efficacy of intrathecally administered low dose sufentanil-bupivacaine in transurethral resection of the prostate (TURP). METHODS. Ninety patient (ASA I - III) undergoing TURP were randomly divided into 3 groups (n = 30); Group A, B and C. Group A received 7.5 mg bupivacaine + 5 microg sufentanil + 10% glucose; Group B received 7.5 mg bupivacaine + 7.5 microg sufentanil + 10% glucose; Group C received 15 mg bupivacaine + 10% glucose. The volume was 3 mL in every group. SP, DP, HR, SpO2, the degree of motor and sensory blockade and the side effect were observed. RESULTS: SP/DP was significantly decreased in Group C than that in Group and Group B (p<0.05), HR and SpO2 in group B were decreased to different degrees 15 min after the injection (p<0.05). The complete recovery time of motor nerve blockade and the regression time of sensory blockade were obviously prolonged in Group C (p<0.05). There were no significant differences in analgesic effect among the three groups during the operation, but the incidence of pruritus was higher in both group A and Group B than that in Group C during the first 24 hours after the injection. CONCLUSION: Spinal anesthesia with low dose sufentanil-bupivacaine possesses relatively steady hemodynamics. The blockade degree of motor and sensory blockade in this spinal anesthesia is lower than that in standard spinal bupivacaine in TURP.

[Influence of ganciclovir and astragalus membranaceus on proliferation of hematopoietic progenitor cells of cord blood after cytomegalovirus infection in vitro].

OBJECTIVE: Cytomegalovirus (CMV) infection was greatly common in the world. CMV infection produces usually mild or asymptomatic infections in individuals with normal immune responses, whereas it may cause serious disease in immunosuppressive patients. Clinical manifestations include suppression of myelopoiesis, a mononucleosis like syndrome, hepatosplenomegaly, lymphadenopathy, thrombocytopenia, and hemolytic anemia. In patients undergoing bone marrow transplantation CMV remains the most common infectious causes of morbidity and mortality. But the treatment drugs with specific effect for CMV was fewer at the present. This study was to investigate the effect of CMV on proliferation of colony forming unit granulocyte-macrophage (CFU-GM), CFU-erythroid (CFU-E), brust forming unit-erythroid (BFU-E), CFU-multipotential (CFU-Mix) and CFU-megakaryocyte (CFU-Mk) progenitor cells of cord blood (CB) with the presence of ganciclovir (GCV) and astragalus membranaceus in vitro. METHODS: Twenty CB samples were collected from fetal umbilical vein of normal term spontaneous delivery neonates. The colony forming unit-assay was applied to observe the suppression effect of CMV-AD169 strain on CFU-GM, CFU-E, BFU-E, CFU-Mix and CFU-Mk of CB with the presence of GCV and astragalus membranaceus in vitro. The technique of PCR was used to demonstrate the existence of CMV-AD169 DNA in the colony cells of cultured CFU-GM, CFU-E, BFU-E, CFU-Mix and CFU-Mk. RESULTS: (1) The numbers of CFU-GM, CFU-E, BFU-E, CFU-Mix and CFU-Mk colonies in CMV infection groups were significantly less than those in blank and mock group, respectively. The last time of colonies in groups with CMV infection was significantly shorten compared with the blank and mock group. (2) CMV-DNA was positively detected in the colony cells of CMV infection groups by PCR, while negative in the control groups. (3) The lasting time of CFU-GM, CFU-E, BFU-E, CFU-Mix and CFU-Mk colonies infected with CMV extended significantly with the presence of astragalus membranaceus and GCV, and the numbers of those increased significantly compared with the CMV infection group, respectively. The increasing rate of colonies was 27.2%, 45.2%, 49.1%, 39.0% and 11.9% with astragalus membranaceus group, 37.4%, 74.2%, 71.7%, 67.4% and 38.9% with GCV group, 53.6%, 83.8%, 88.7%, 87.8% and 61.5% with astragalus membranaceus and GCV group, respectively. CONCLUSIONS: The differentiation and proliferation of CFU-GM, CFU-E, BFU-E, CFU-Mix and CFU-Mk were significantly inhibited after infected with CMV-AD169 strain. The suppression effect of CMV-AD169 on CFU-GM, CFU-E, BFU-E, CFU-Mix and CFU-Mk was inhibited with the presence of GCV and astragalus membranaceus in vitro. This suggested that CMV-AD169 may be inhibited or killed by GCV and Astragalus Membranaceus in vitro.