Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective To analyse the acupoint selection rules of acupuncture in the treatment of non-small cell lung cancer,and to provide reference for clinical application.Methods The clinical research,practitioner's experience and academic thought of acupuncture treatment for non-small cell lung cancer were retrieved to obtain the acupuncture prescriptions of modern practitioners for the treatment of non-small cell lung cancer.Based on the statistical methods of acupoint frequency,prescription rules,acupoint clustering and core combination,the core theoretical system and acupoint selection rules of acupuncture treatment of non-small cell lung cancer by modern practitioner were analyzed.Results According to the inclusion and exclusion criteria,94 acupuncture prescriptions were finally included.There were eight acupoints used more than 20 times,which were Zusanli(ST36),Neiguan(PC6),Feishu(BL13),Sanyinjiao(SP6),Qihai(RN6),Guanyuan(RN4),Hegu(LI4)and Zhongwan(RN12).The top three high-frequency acupoint combinations were Zusanli-Neiguan,Zusanli-Sanyinjiao and Qihai-Zusanli;correlation analysis showed that the correlation strength of Zusanli-Neiguan was the highest,followed by Zusanli-Sanyinjiao and Zusanli-Hegu.The cluster analysis showed that the acupoints with frequency＞10 times could be divided into three categories.Category 1 includes:Zusanli,Neiguan,Sanyinjiao,Hegu;category 2 includes Guanyuan,Qihai,Zhongwan,Xuehai(SP10),Taichong(LR3);category 3 consists of two parts,one is Danzhong(RN17),Tiantu(RN22),Fenglong(ST40),Taiyuan(LU9);the second is Feishu(BL13),Lieque(LU7),Chize(LU5),Zhongfu(LU1),Xinshu(BL15),Gaohuang(BL43),Fengmen(BL12).Conclusion The core acupoints for acupuncture treatment of non-small cell lung cancer include four categories:① invigorating the spleen and benefiting qi:Zusanli,Sanyinjiao,Zhongwan and Fenglong;②replenishing and supplementing original qi:Guanyuan,Qihai and Gaohuang;③regulating qi and broadening the chest:Danzhong,Neiguan,Tiantu and Fengmen;④ diffusing the lung and ventilating qi:Feishu,Hegu,Chize and Lieque.The three treatment methods of replenishing qi,regulating qi and venting pathogen are the basis of acupuncture treatment of advanced non-small cell lung cancer.The core idea of acupuncture treatment of non-small cell lung cancer focuses on supplementation,supplemented by dredging,and to dredge and supplement simultaneously.

Aim To investigate the effects of puerarin on the proliferation,migration,and apoptosis of glio-blastoma cells and the underlying mechanisms.Meth-ods Differentially expressed genes associated with gli-oma and mitochondrial disease were analyzed using the GEO database.Cytotoxicity was detected by CCK-8 as-say.Cell migration was detected by the scratch wound healing assay and Transwell assay.Cell proliferation was assessed by EdU assay.Apoptosis level was meas-ured by TUNEL assay.Mitochondrial membrane poten-tial was detected by Mito-Tracker assay.ATP contents were detected using the ATP kit.The protein expres-sion levels were detected by Western blot.Antitumor efficacy of puerarin was analyzed using subcutaneous xenograft.Results There were 178 genes co-related differentially expressed genes in glioma and mitochon-drial disease.Core genes of co-related differentially ex-pressed genes were screened by GO and KEGG enrich-ment analyses,and the interaction networks.Among them,ubiquitin C(UBC)level was highly expressed in tissues of glioma patients.Puerarin could bind to UBC and reduce UBC expression at the animal and cell levels.Puerarin treatment inhibited the growth of glio-ma and decreased cell proliferation,migration and pro-moted cell apoptosis signals.Meantime,puerarin treat-ment also reduced mitochondrial membrane potentials and ATP contents,and down-regulated the levels of UBC related proteins.Conclusion Puerarin inhibits the proliferation,migration and promotes apoptosis of glioma cells.The mechanism of induction of mitochon-drial dysfunction is involved.

Objective To explore the property of projection neurons in the pathway from the medial prefrontal cortex(mPFC)to the thalamic paraventricular nucleus(PVT)and to investigate the effect of modulation of the pathway on physiological pain and acute pain in mice.Methods Three knock-in mice with glutamate decarboxylase 67-green fluorescent protein(GAD67-GFP)were used in morphological tracing experiments,and twenty-seven C57 mice were used for behavioral observation experiments.Cholera toxin subunit B(CTB)was injected into the PVT of GAD67-GFP transgenic mice,and the properties of mPFC neurons projected to PVT were observed.The mPFC-PVT pathway was activated or inhibited by chemogenetics to observe the effects on physiological pain,such as mechanical pain,thermal pain,cold pain,and on acute inflammatory pain induced by capsaicin in mice.Results CTB-labeled neurons in the mPFC were mainly distributed in layer Ⅴ and layer Ⅵ and not double-labeled with GAD67-GFP.Chemogenetic activation of the mPFC-PVT pathway decreased the mechanical pain threshold significantly(P＜0.0001)and shortened the thermal pain latency(P＜0.001),but had no obvious effects on cold pain.Inhibition of this pathway increased the mechanical pain threshold significantly(P＜0.05).Activation of the pathway increased the paw licking time(P＜0.05)in acute inflammatory pain induced by capsaicin.Conclusion mPFC-PVT pathway is a non GABAergic projection and its activation can promote mechanical pain,thermal pain,and acute inflammatory pain induced by capsaicin in mice.

Objective: To explore the family rehabilitation model for children with scar contracture after hand burns and observe its efficacy. Methods: A retrospective non-randomized controlled study was conducted. From March 2020 to March 2021, 30 children with scar contracture after deep partial-thickness to full-thickness burns of hands, who met the inclusion criteria, were hospitalized in the Burn Center of PLA of the First Affiliated Hospital of Air Force Medical University. According to the rehabilitation model adopted, 18 children (23 affected hands) were included in a group mainly treated by family rehabilitation (hereinafter referred to as family rehabilitation group), and 12 children (15 affected hands) were included in another group mainly treated by hospital rehabilitation (hereinafter referred to as hospital rehabilitation group). In the former group, there were 11 males and 7 females, aged (4.8±2.1) years, who began rehabilitation treatment (3.1±0.8) d after wound healing; in the latter group, there were 7 males and 5 females, aged (4.6±2.1) years, who began rehabilitation treatment (2.8±0.7) d after wound healing. The children in hospital rehabilitation group mainly received active and passive rehabilitation training in the hospital, supplemented by independent rehabilitation training after returning home; after 1-2 weeks of active and passive rehabilitation training in the hospital, the children in family rehabilitation group received active and passive rehabilitation training at home under the guidance of rehabilitation therapists through WeChat platform. Both groups of children were treated for 6 months. During the treatment, they wore pressure gloves and used hand flexion training belts and finger splitting braces. Before treatment and after 6 months of treatment, the modified Vancouver scar scale, the total active movement of the hand method, and Carroll quantitative test of upper extremity function were used to score/rate the scar of the affected hand (with the difference of scar score between before treatment and after treatment being calculated), the joint range of motion (with excellent and good ratio being calculated), and the function of the affected limb, respectively. Data were statistically analyzed with independent sample t test, equivalence test, Fisher's exact probability test, and Mann-Whitney U test. Results: The differences of scar scores of the affected hands of children in family rehabilitation group and hospital rehabilitation group between after 6 months of treatment and those before treatment were 3.0 (2.0, 7.0) and 3.0 (2.0, 8.0) respectively (with 95% confidence interval of 2.37-5.38 and 1.95-5.91). The 95% confidence interval of the difference between the differences of the two groups was -2.43-2.21, which was within the equivalent boundary value of -3-3 (P<0.05). The excellent and good ratios of joint range of motion of the affected hand of children in family rehabilitation group and hospital rehabilitation group were 3/23 and 2/15 respectively before treatment, and 15/23 and 12/15 respectively after 6 months of treatment. The ratings of joint range of motion of the affected hand of children in family rehabilitation group and hospital rehabilitation group after 6 months of treatment were significantly higher than those before treatment (with Z values of 3.58 and 2.30, respectively, P<0.05), but the ratings of joint range of motion of the affected hand between the two groups were similar before treatment and after 6 months of treatment (with Z values of 0.39 and 0.55, respectively, P>0.05). The functional ratings of the affected limbs of children in family rehabilitation group and hospital rehabilitation group after 6 months of treatment were significantly higher than those before treatment (with Z values of 3.98 and 3.51, respectively, P<0.05), but the functional ratings of the affected limbs between the two groups were similar before treatment and after 6 months of treatment (with Z values of 1.27 and 0.38, respectively, P>0.05). Conclusions: The WeChat platform assisted rehabilitation treatment with mainly family rehabilitation, combined with hand flexion and extension brace can effectively reduce the scarring after children's hand burns, improve the joint range of motion of the affected hands, and promote the recovery of affected limb function. The effect is similar to that of hospital-based rehabilitation providing an optional rehabilitation, treatment method for children who cannot continue to receive treatment in hospital.
Male ; Female ; Humans ; Child ; Cicatrix/therapy* ; Retrospective Studies ; Treatment Outcome ; Wound Healing ; Hand Injuries/rehabilitation* ; Wrist Injuries ; Contracture/etiology* ; Burns/complications*

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Aim To investigate the protective effect of hesperidin (HES) on cardiorenal damage induced by DOCA/Salt hypertension and the underlying mechanisms. Methods Eighteen male SD rats were randomly divided into normal group (Ctrl), model group (DOCA/Salt), and DOCA/Salt with hesperidin group (DOCA/Salt + HES). HES was administered for four weeks. Blood pressure, serum creatinine and blood urea nitrogen were measured. The pathological changes in heart and kidney were examined by HE, Masson and Sirius red staining. The expression of α-SMA, collagen I and TGF-β were detected by Western blot. The mRNA levels of Nlrp3, TNF-α, IL-1β, IL-6 and NOXs were measured using qRT-PCR. Results Compared with the model group, HES administration significantly attenuated the occurrence of DOCA/Salt hypertension, improved renal function indicators of hypertensive rats, reduced renal and cardiac fibrosis, deduced the expression of α-SMA, collagen I and TGF-β, inhibited the expression of Nlrp3, TNF-α, IL-1β and IL-6, and decreased the expression of NOXs in renal and cardiac tissues. Conclusions HES can delay the occurrence of hypertension and protect against hypertension-induced renal and cardiac tissue damage, which may be related to the reduction of inflammatory reaction and oxidative stress by HES.

BACKGROUND: The validation of various risk scores in elderly patients with comorbid atrial fibrillation (AF) and acute coronary syndrome (ACS) has not been reported. The present study compared the predictive performance of existing risk scores in these patients. METHODS: A total of 1252 elderly patients with AF and ACS comorbidities (≥ 65 years old) were consecutively enrolled from January 2015 to December 2019. All patients were followed up for one year. The predictive performance of risk scores in predicting bleeding and thromboembolic events was calculated and compared. RESULTS: During the 1-year follow-up, 183 (14.6%) patients had thromboembolic events, 198 (15.8%) patients had BARC class ≥ 2 bleeding events, and 61 (4.9%) patients had BARC class ≥ 3 bleeding events. For the BARC class ≥ 3 bleeding events, discrimination of the existing risk scores was low to moderate, PRECISE-DAPT (C-statistic: 0.638, 95% CI: 0.611-0.665), ATRIA (C-statistic: 0.615, 95% CI: 0.587-0.642), PARIS-MB (C-statistic: 0.612, 95% CI: 0.584-0.639), HAS-BLED (C-statistic: 0.597, 95% CI: 0.569-0.624) and CRUSADE (C-statistic: 0.595, 95% CI: 0.567-0.622). However, the calibration was good. PRECISE-DAPT showed a higher integrated discrimination improvement (IDI) than PARIS-MB, HAS-BLED, ATRIA, and CRUSADE (P < 0.05) and the best decision curve analysis (DCA). For thromboembolic events, the discrimination of GRACE (C-statistic: 0.636, 95% CI: 0.608-0.662) was higher than CHA2DS2-VASc (C-statistic: 0.612, 95% CI: 0.584-0.639), OPT-CAD (C-statistic: 0.602, 95% CI: 0.574-0.629) and PARIS-CTE (C-statistic: 0.595, 95% CI: 0.567-0.622). The calibration was good. Compared to OPT-CAD and PARIS-CTE, the IDI of the GRACE score slightly improved (P < 0.05). However, NRI analysis showed no significant difference. DCA showed that the clinical practicability of thromboembolic risk scores was similar. CONCLUSIONS The discrimination and calibration of existing risk scores in predicting 1-year thromboembolic and bleeding events were unsatisfactory in elderly patients with comorbid AF and ACS. PRECISE-DAPT showed higher IDI and DCA than other risk scores in predicting BARC class ≥ 3 bleeding events. The GRACE score showed a slight advantage in predicting thrombotic events.

N-methyl-D-aspartate receptor (NMDAR),an important ionic glutamate receptor and a ligand and voltage-gated ion channel characterized by complex composition and functions and wide distribution,plays a key role in the pathological and physiological process of diseases or stress states.NMDAR can mediate apoptosis through different pathways such as mitochondrial and endoplasmic reticulum damage,production of reactive oxygen species and peroxynitrite,and activation of mitogen-activated protein kinase and calpain.This paper reviews the structure,distribution,and biological characteristics of NMDAR and the mechanisms of NMDAR-mediated apoptosis.
Apoptosis ; Humans ; Mitogen-Activated Protein Kinases/metabolism* ; Reactive Oxygen Species/metabolism* ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Signal Transduction