Objective:The activation of astrocytes is an important process in the formation of chronic pain.This study aims to observe the activation of A1 reactive astrocytes in the medullary dorsal horn in the rat model of trigeminal neuralgia,and to explore the mechanism of central sensitization caused by A1 reactive astrocyte. Methods:The adult male rats were randomly divided into a sham group and a chronic constriction injury of infraorbital nerve(ION-CCI)group.The facial mechanical pain threshold and thermal withdrawal latency were measured before the operation and on the 1st,3rd,7th,10th,and 14th day after the operation.After pain behavior observation,the expression of glial fibrillary acidic protein(GFAP)in the medullary dorsal horn was observed by immunohistochemistry and immunofluorescence colocalization of GFAP,complement 3(C3)/S100A10,and 4',6-diamidino-2-phenylindole(DAPI)was analyzed.Primary astrocytes were cultured and randomly divided into a naive group and a DHK group.The DHK group was treated with 1 mmol/L of astrocyte activation inhibitor dihydrokainic acid(DHK).Fura-2/AM was used to stain the astrocytes and the calcium wave of the 2 groups under the stimulation of high potassium was recorded and compared.The expression of C3 was detected by Western blotting. Results:The facial mechanical pain threshold and thermal withdrawal latency of the ION-CCI group were significantly lower than those of the sham group(both P<0.05).There were a large number of GFAP positive astrocytes in the medullary dorsal horn of the ION-CCI group.The fluorescence intensity of GFAP in the ION-CCI group was higher than that in the sham group(P<0.05).GFAP and C3/S100A10 were co-expressed in astrocytes.Compared with the sham group,the fluorescence intensity of C3 and the protein expression of C3 in the ION-CCI group were increased(both P<0.05).The expression of C3 in ION-CCI group was significantly increased(P<0.05).Compared with the naive group,the C3 protein expression was significantly decreased in the DHK group(P<0.05).The intensity of calcium fluorescence was increased after high potassium stimulation in both groups.Furthermore,the peak and increase amplitude of calcium fluorescence in the naive group were much higher than those in the DHK group(both P<0.05). Conclusion:A1 reactive astrocytes in the medullary dorsal horn of trigeminal neuralgia model rats are increased significantly,which may participate in central sensitization of trigeminal neuralgia by impacting astrocyte calcium wave.

Objective To propose a family-centred health education program for family caregivers of Autistic children and investigate its clinical value.Methods Delphi method was used to establish a family-centred Autistic children care program for family caregivers looking after the Autistic children,which involved two rounds of expert consultation.The pre-and post-control method for different cases was employed in the study.Forty Autistic caregivers in our hospital from January 2022 to October 2022 were assigned to the control group and another 40 in our hospital from November 2022 to January 2023 were assigned to the observation group.The family caregivers of Autistic children in the control group received traditional care education,while those in the observation group was managed with the family-centred Autistic children health education program.The two groups were compared in terms of care burden,knowledge of health education,and evaluation of clinical symptom of Autistic children.Results The expert authority coefficient of the first round of expert consultation was 0.875 respectively and those in the second round was 0.900,respectively.The coefficient of variation of the coordination degree of each index was 0.04-0.20.Kendalls W scores of the two rounds were 0.794 and 0.786,respectively.A health education program for family-centred Autistic children caregiver was established to consist of three subjects:caregiver training,family-centred parental care and activation of positive emotions of autistic caregivers.Autism caregivers in both groups had completed the study.In comparison with the control group,the care burden of the observation group was significantly lower,the knowledge of health education was significantly higher,and the evaluation of children's clinical symptoms was better among the family caregivers of autistic children in the observation group(all P<0.05).Conclusions The family-centred autistic children care program for family caregivers is scientific and applicable.It is conducive to providing health education guidance for family caregivers of Autistic children,effectively reducing the care burden and enhancing the knowledge of health education.

Objective To investigate the correlation between baseline data,early treatment response and prognosis in children with acute lymphoblastic leukemia(ALL).Methods Ninety-two children with ALL were divided into the endpoint event group(19 cases)and the event-free survival group(73 cases)according to whether there was an endpoint event(recurrence or death).The age and gender at initial diagnosis were recorded.Initial white blood cell count(WBC),platelet count(PLT),immunophenotype,chromosome karyotype,fusion gene,prednisone test,bone marrow remission status on the 15th day of induction chemotherapy and minimal residual disease(MRD)on the 15th,33rd and 55th day of induction chemotherapy were detected.The correlation between the above baseline data and early treatment response and the occurrence of endpoint event in children with ALL was analyzed.Logistic regression was used to analyze influencing factors of endpoint events in children with ALL.Receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of baseline data and early treatment response to endpoint events in children with ALL.Results The proportion of WBC≥100×109/L at first diagnosis,prednisone poor reaction and positive MRD on the 33rd day of induction chemotherapy were higher in the endpoint event group than those in the event-free survival group(P<0.05),and there were no significance differences in remaining indicators(P>0.05).Logistic regression analysis showed that prednisone poor reaction and positive MRD on the 33rd day of induction chemotherapy were risk factors for endpoint event in children with ALL(P<0.05),and the combined value of the two indicators was better than that of a single indicator in predicting endpoint events in children with ALL.Conclusion Prednisone poor reaction and positive MRD on the 33rd day of induction chemotherapy are associated with recurrence and death in children with ALL.

Chronic pain is a disease that seriously affects people′s health and quality of life. Solving the challenges faced by chronic pain management, finding effective treatment methods, and improving the quality of life of chronic pain patients are important clinical issues that urgently need to be addressed. This article summarizes the etiology diagnosis, multidimensional evaluation, personalized treatment, prevention, and translation of pain research results for chronic pain, and looks forward to future treatment strategies for chronic pain.

Objective:To compare the clinical efficacy of ultrasound-guided spinal nerve block (SNB) and paraverteral nerve block (PVB) in treating postherpetic neuralgia.Methods:A total of 52 patients with postherpetic neuralgia who visited the Pain Clinic of the Xiangya Hospital, Central South University from February 2020 to December 2022 were selected and randomly divided into an ultrasound-guided SNB group and a PVB group using a random number table method, with 26 patients in each group. Patients in the SNB group received ultrasound-guided spinal nerve block therapy; The PVB group received ultrasound-guided paraverteral nerve block treatment. Visual Analog Scale (VAS) scores, 36-Item Short Form Survey (SF-36) scores, and total effective rate were observed in two groups of patients before treatment, 2 weeks after treatment, 1 month after treatment, 3 months after treatment, and 6 months after treatment. Complications during treatment were also observed.Results:The total effective rates of SNB group patients at 1, 3, and 6 months after treatment were significantly higher than those of PVB group (all P<0.05). After treatment, the VAS scores of both groups of patients at each time point were significantly reduced compared to before treatment (all P<0.05); The VAS scores of patients in the SNB group were lower than those in the PVB group at 1, 3, and 6 months after treatment, but the difference was not statistically significant (all P>0.05). There was no statistically significant difference in Physical Component Summary (PCS) and Mental Component Summary (MCS) scores between SNB and PVB groups before nerve block treatment (all P>0.05). The MCS and PCS scores of the two groups of patients were significantly higher than before treatment at 2 weeks, 1 month, 3 months, and 6 months after treatment (all P<0.05). The MCS scores of the SNB group were significantly higher than those of the PVB group at 2 weeks, 1 month, 3 months, and 6 months after treatment (all P<0.05), but there was no statistically significant difference in PCS scores between the two groups (all P>0.05). Both groups of patients did not experience any serious complications related to the treatment in this study during the follow-up period. Conclusions:Both ultrasound-guided spinal nerve block and paraverteral nerve block can safely and effectively treat postherpetic neuralgia. The clinical effect of ultrasound-guided spinal nerve block in treating postherpetic neuralgia is better than that of paraverteral nerve block.

Pain caused by surgery is an important clinical issue that seriously affects postoperative rehabilitation and health-related quality of life. Failure to effectively manage postoperative pain not only leads to a decrease in patient quality of life, increases medical expenses, but also has a negative impact on patient recovery. Therefore, it is of great clinical significance to address the challenges of acute postoperative pain management, find effective management strategies, and improve the quality of pain management. This article summarizes the current status of acute postoperative pain management in recent years, including the mechanism of pain occurrence, pain assessment methods, drug and non drug management strategies, and predictive factors for chronic postoperative pain. It also looks forward to future research directions and application prospects.

Objective:To explore a multimodal perioperative analgesia plan for patients undergoing microvascular decompression surgery for trigeminal neuralgia.Methods:Eighty patients who underwent microvascular decompression surgery for trigeminal neuralgia admitted to the Xiangya Hospital, Central South University from April 2017 to April 2019 were randomly divided into a nerve block group (group A) and a control group (group C) using a random number table method, with 40 patients in each group. The group A underwent surgical block of the lateral occipital and auricular nerves under ultrasound guidance before induction, with 3 ml of 0.5% ropivacaine used at each site. The group C did not undergo nerve block. Both groups received intravenous injections of midazolam, sufentanil, cisatracurium, etomidate, and lidocaine for anesthesia induction, followed by tracheal intubation and maintenance of anesthesia with propofol and remifentanil. After surgery, an analgesic pump was connected. The total amount of intraoperative use of sufentanil and remifentanil in both groups was recorded, as well as the pain Visual Analogue Scale (VAS) and postoperative anesthesia related complications at 2, 6, 24, and 48 hours after surgery.Resultsl:The total amount of sufentanil and remifentanil used during surgery in the group A was less than that in the group C (all P<0.05). The incidence of postoperative nausea and vomiting in the group A patients was lower than that in the group C ( P<0.05), and the nausea and vomiting score was also lower than that in the group C ( P<0.05). There was no statistically significant difference in the incidence of other postoperative complications (all P>0.05). There was a statistically significant difference in VAS scores between the two groups at 6 hours after surgery ( P<0.05). Conclusions:Occipital and auricular nerve blockade can reduce the amount of opioid drugs used during microvascular decompression surgery in patients with trigeminal neuralgia, thereby reducing the incidence of nausea and vomiting. The postoperative analgesic effect is good.

Objective:To retrospectively observe the effect of oxycodone on acute postoperative pain in patients undergoing thoracoscopic surgery.Methods:A retrospective analysis was conducted on the clinical data of 404 patients undergoing thoracoscopic thoracic surgery under combined general anesthesia at the Xiangya Hospital, Central South University from April 1, 2020 to September 30, 2021. They were divided into A group ( n=99, oxycodone group) and B group ( n=305, control group) based on whether oxycodone was used during the surgery. The two groups of patients were further matched 1∶1 using the nearest neighbor matching method. We compared the Visual Analogue Scale (VAS) of activity and resting pain and the incidence of moderate to severe pain between two groups of patients 24 hours after surgery, and observed the incidence and severity of pain related adverse reactions such as nausea, vomiting, itching, and dizziness. Resultsl:After matching the propensity scores of the two groups of patients, the balance was good ( SMD<0.20). There was no statistically significant difference between the groups in age, gender, body mass index, American Society of Anesthesiologist (ASA) grade, surgical time, intraoperative bleeding, and the use of antiemetics and analgesics during the perioperative period (all P>0.05). Compared with the control group, patients in the group A had a resting VAS [(2.03±1.61)points vs (1.62±1.31)points, P=0.049], and activity VAS [(4.13±1.72)points vs (3.51±1.79)points, P=0.013] was even lower, and the incidence of moderate to severe pain (VAS≥4) during activity was lower [59.6%(59/99) vs 37.4%(37/99), P=0.003]. There was no statistically significant difference in the incidence of analgesic related adverse reactions between the two groups ( P>0.05). Conclusions:Intravenous injection of oxycodone can effectively alleviate acute pain in patients undergoing thoracoscopic surgery within 24 hours, and reduce the incidence of moderate to severe pain during activity.

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 (IDH1^mi) 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 IDH1^mi.
Humans ; Oxidative Phosphorylation ; Berberine ; Electron Transport ; Mitochondria ; Leukemia, Myeloid, Acute ; Isocitrate Dehydrogenase

Objective:To evaluate the effect of intrathecal exosomes derived from human amniotic fluid (hAF exo) on neuropathic pain induced by spared nerve injury (SNI) in mice.Methods:Eighteen clean-grade healthy male Kunming mice, aged 7-8 weeks, weighing 30-35 g, were divided into 3 groups ( n=6 each) using a random number table method: sham operation group (Sham group), SNI group, and SNI+ hAF exo group. Spared nerve injury was produced by exposing the sciatic nerve and its branches and ligation and transection of tibial nerve and common fibular nerve in anesthetized mice. Another three mice were selected to develop the model of neuropathic pain after anesthesia. PKH-26 labeled hAF exo 7 μl was intrathecally injected on days 1, 2 and 3 after developing the model. The mice were sacrificed at 10 h after the end of administration, and the uptake of hAF exo by the dorsal horn of the injured lumbar enlargement of the spinal cord was observed with the fluorescence microscope. On 1, 2 and 3 days after developing the model, 1 μg/μl hAF exo 7 μl was intrathecally injected in SNI+ hAF exo group, and PBS 7 μl was intrathecally injected in Sham group and SNI group. The mechanical paw withdrawal threshold (MPWT) was measured at 1 day before and 1, 3, 5 and 7 days after operation. And then the mice were sacrificed after measurement of the pain threshold at 7 days after developing the model, and the ipsilateral lumbar enlargement of the spinal cord was taken for determination of the expression of CD11b, interleukin-1beta (IL-1β) and IL-10 by Western blot. Results:The dorsal horn of the lumbar enlargement of the spinal cord on the injured side could absorb hAF exo with the fluorescence microscope. Compared with Sham group, the MPWT was significantly decreased at 3-7 days after developing the model, the expression of CD11b and IL-1β was up-regulated ( P<0.05), and no significant change was found in the expression of IL-10 in SNI group ( P>0.05). Compared with SNI group, the MPWT was significantly increased at 3-7 days after developing the model, the expression of CD11b and IL-1β was down-regulated, and the expression of IL-10 was up-regulated in SNI+ hAF exo group ( P<0.05). Conclusions:Intrathecal exosomes derived from human amniotic fluid can alleviate neuropathic pain in mice, and the mechanism may be related to mediation of the polarization of microglia from M1 type to M2 type and attenuation of neuroinflammation.