Nine compounds were isolated and purified from 90% ethanol extract of Alstonia mairei Lévl by using various chromatographic methods, including silica gel, SephadexLH-20, MCI Gel and ODS column chromatography, combined with semi-preparative liquid phase separation methods. Modern spectroscopic methods (1D and 2D NMR, UV, IR, MS, etc.) were used to identify the structures of the isolated compounds. They were identified as mairoside A (1), 3′,6-di-O-sinaloylsucrose (2), myristic acid (3), methyl myristate (4), ethyl myristate (5), 3,4,5-trimethoxycinnamic acid (6), 3,4,5-trimethoxybenzoic acid (7), vinoline (8), kaempferol-3-O-rutinoside (9), among which compound 1 is a new glycoside, compounds 4 and 5 are new natural products, and the nuclear magnetic data of compound 4 were reported for the first time.

ObjectiveTo investigate the analgesic effect of Tuina at the "Weizhong （BL 40）" on neuropathic pain in a rat model of chronic constriction injury （CCI） of the sciatic nerve and its potential central spinal mechanisms. MethodsThirty-two Sprague-Dawley rats were randomly divided into four groups （8 rats in each group）， sham-operated group， model group， Tuina group， and blockade group. The CCI model was established in the model group， Tuina group， and the blockade group by ligating the sciatic nerve with catgut， while the sham-operated group underwent only sciatic nerve exposure without ligation. From postoperative day 4 to day 14， rats in the Tuina group and the blockade group received Tuina manipulation at the "Weizhong （BL 40）" using a dynamic pressure distribution measurement system （5 N pressure， 2 Hz frequency， 10 min per session， once daily）. The blockade group also received intraperitoneal injections of the microglial inhibitor minocycline （10 mg/kg） once daily. The sham-operated and the model group underwent the same handling and fixation as the Tuina group without actual Tuina. Mechanical withdrawal threshold （MWT） and paw withdrawal latency （PWL） were measured before surgery and on day 3， 7， 10， and 14 post-surgery. Transmission electron microscopy was used to evaluate sciatic nerve injury and repair， measuring axon diameter and total myelinated fiber diameter to calculate the g-ratio. Western Blotting was performed to detect the protein levels of ionized calcium-binding adapter molecule 1 （Iba-1）， CD206， CD68， interleukin-10 （IL-10）， and β-endorphin （β-EP） precursor pro-opiomelanocortin （POMC） in the ipsilateral spinal dorsal horn. ResultsCompared with the sham-operated group， the model group showed significantly reduced MWT and PWL on day 3， 7， 10， and 14 （P＜0.01）. Compared with the model group， the Tuina group and the blockade group showed increased MWT and PWL on day 10 and 14 （P＜0.05）. Compared with the Tuina group， the blockade group exhibited higher MWT on day 7， 10， and 14， and higher PWL on day 10 （P＜0.05）. Sciatic nerve pathological morphology revealed intact and well-structured myelin in the sham-operated group， while the model group exhibited myelin collapse， distortion， and myelin ovoid formation. The Tuina group displayed partially irregular myelin with occasional myelin collapse， whereas the blockade group exhibited partial myelin irregularities and phospholipid shedding. Compared with the sham-operated group， the model group showed a decreased g-ratio and increased levels of Iba-1 and CD68 in the spinal dorsal horn （P＜0.05 or P＜0.01）. Compared with the model group， the Tuina group and the blockade group exhibited an increased g-ratio and reduced Iba-1 and CD68 levels. Additionally， the Tuina group showed elevated levels of CD206， IL-10， and POMC， whereas the blockade group had decreased CD206 levels （P＜0.05）. ConclusionTuina at "Weizhong （BL 40）" alleviates neuropathic pain in CCI rats， potentially by regulating microglial activation in the spinal cord， inhibiting M1 polarization while promoting M2 polarization， and activating the IL-10/β-EP pathway to exert analgesic effects.

Objective To compare therapeutic efficacy of anticoagulation alone and combining with intervention for treating severe cerebral venous thrombosis(CVT).Methods Data of 65 severe CVT patients were retrospectively analyzed.The patients were divided into anticoagulation group(n=32)or combined group(n=33)according to therapeutic methods.The modified Rankin scale(mRS)score at admission and discharge,the prognosis of patients,vascular recanalization rate as well as incidence of complications during follow-up period were compared between groups.Results No significant difference of mRS scores at admission was found between groups(P＞0.05),while mRS scores of combined group were lower than of anticoagulation group at discharge(P＜0.05).The rate of good prognosis at discharge(84.85%vs.59.38%),6 months after discharge(87.88%vs.65.63%)and 12 months after discharge(93.94%vs.75.00%)in combined group were all higher than those in anticoagulation group(all P＜0.05).The vascular recanalization rate in combined group was higher than that in anticoagulant group(100%vs.75.00%,P＜0.05).At the end of follow-up,no significant difference of complication incidence was found between groups(15.15%vs.18.75%,P＞0.05).Conclusion For patients with severe CVT,anticoagulation combined with interventional therapy could significantly alleviate clinical symptoms and improve prognosis compared with anticoagulation alone.

Objective To observe the value of stent implantation for treating idiopathic intracranial hypertension(IIH)complicated with venous sinus stenosis(VSS).Methods Data of 54 patients with IIH complicated with VSS who underwent stent implantation were retrospectively analyzed.The papillary edema grade,lumbar puncture-opening pressure(LP-OP)and trans-stenotic pressure gradient of venous sinus(ΔP)before and after stent implantation were compared,and the symptom improvement and treatment-related complications during the follow-up period were recorded.Results Totally 60 stents were successfully implanted in 54 patients.Before stent implantation,the papillary edema grade was 3(3,3),LP-OP was(391.39±92.62)mmH2O and the ΔP was 18.50(15.00,25.00)mmHg,which decreased to 1(0,1),(208.80±62.31)mmH2O and 1.25(0.88,2.55)mmHg after stent implantation,respectively,all with significant differences(all P＜0.001).Clinical symptoms improved after stent implantation in all 54 patients.At the end of follow-up,disappearance of headache,papillary edema,visual disorder,abducent nerve paralysis and tinnitus were noticed in 30(30/37,81.08%),38(38/45,84.44%),41(41/45,91.11%),8(8/10,80.00%)and 9 cases(9/10,90.00%),respectively.Treatment-related complications occurred in 4 cases(4/54,7.41%),all improved after intervention.Conclusion Stent implantation was effective and safe for treating IIH complicated with VSS.

Objective:To perform molecular diagnosis and pedigree analysis for one case with α-thalassemia who does not conform to the genetic laws,and explore the effects of a newly discovered rare mutation(HBA2:c.*12G＞A)on clinical phenotypes.Methods:Blood samples of the proband and her family members were collected for blood routine analysis,and the hemoglobin components were analyzed by capillary electrophoresis.The common α-and β-globin gene loci in Chinese population were detected by conventional techniques(Gap-PCR,RDB-PCR).The α-globin gene sequences(HBA1,HBA2)were analyzed by Sanger sequencing.Results:By analyzing the test results of proband and her family members,the genotype of the proband was-α3,7/HBA2:c.*12G＞A,her father was HBA2:c.*12G＞A heterozygous mutation carrier.Conclusion:This study identifies a rare α-globin gene mutation(HBA2:c.*12G＞A)that has not been reported before.It is found that heterozygous mutation carriers present with static α-thalassemia.

Objective:To explore the levels of regulatory T cells(Tregs)and cytokines IL-35,TGF-β and IL-10 in peripheral blood of hemophilia A(HA)patients with F Ⅷ inhibitor and their clinical significance.Methods:43 HA patients admitted to the Hematology Department of the Affiliated Hospital of North China University of Science and Technology from October 2019 to December 2020 were selected,including 6 cases with F Ⅷ inhibitor and 37 cases without FⅧ inhibitor.In addition,20 healthy males who underwent physical examinations were selected as healthy controls.Flow cytometry was used to detect the levels of CD4+CD25+CD127-Tregs in peripheral blood of the HA patients and healthy controls,and ELISA assay was used to detect the expression levels of IL-35,TGF-β and IL-10 in serum,and their differences between different groups were compared.Results:Compared with the healthy control group,the level of Tregs in HA patients was decreased,and the level of Tregs in the FⅧ inhibitor positive group was the lowest,the difference was statistically significant(P＜0.05).There was no significant difference in the expression level of Tregs in HA patients of different severity levels.The serum IL-35,TGF-β,and IL-10 levels in both FⅧ inhibitor negative and positive groups were significantly lower than those in healthy control group,and those in FⅧ inhibitor positive group were significantly lower than those in FⅧ inhibitor negative group(all P＜0.05).Conclusion:The decrease of Tregs,IL-35,TGF-β,and IL-10 levels in HA patients may be related to the formation of FⅧ inhibitors.

Objective:To investigate the effect of genetic polymorphism of MTHFR C677T (rs1801133) on methotrexate (MTX) related toxicity in pediatric mature B-cell lymphoma patients. Methods:Fifty-eight intermediate and high risk patients under 18 years of age with mature B-cell lymphoma who received 5 g/m2 MTX (24 h intravenous infusion) in Sun Yat-sen University Cancer Center from August 2014 to December 2021 were included,and their toxicity of high-dose MTX (HD-MTX) were monitored and analyzed. Results:Among the 58 pediatric patients,the number of CC,CT,and TT genotypes for MTHFR C677T was 33,19 and 6,respectively. A total of 101 courses of HD-MTX therapy were counted,of which plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion were observed in 35 courses,≤0.2 μmol/L in 66 courses. Inter-group comparison showed that plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion increased the risk of developing oral mucositis (P<0.05). Compared with wild-type (CC genotype),patients in the mutant group (CT+TT genotype) were more likely to develop myelosuppression,manifested as anemia,leucopenia,neutropenia and thrombocytopenia. However,plasma MTX level at 48 h was not associated with MTHFR C677T gene polymorphism. Conclusion:The risk of developing oral mucositis in children with mature B-cell lymphoma is associated with plasma MTX concentration. Polymorphism of MTHFR C677T gene is not related to plasma MTX concentration in children with mature B-cell lymphoma,but is related to grade Ⅲ to Ⅳ hematological toxicity.

Objective:To evaluate the efficacy and safety of θ short burst rapid pulse stimulation(TBS)in treating schizophrenia by meta-analysis.Methods:Randomized controlled trials(RCTS)on TBS in the treatment of schizophrenia were searched from CNKI,Wanfang,VIP,China Biomedicine,Web of science,PubMed,Embase and Cochrane Library databases to December 2022.The main study indicator was the Positive and Negative Symptoms Scale(PANSS).Risk quality assessment of the included literatures was performed by two reviewers and statistical analysis was performed using RevMan5.3.Results:A total of 13 RCTS with 641 patients were included.Meta-anal-ysis showed that TBS targeting the left dorsolateral prefrontal cortex(DLPFC)with intervention duration longer than 2 weeks decreased the PANSS total scores(WMD=-4.63,95％CI:-5.75--3.51,P＜0.001),positive symptom scores(WMD=-1.13,95％CI:-2.00--0.26,P＜0.05),negative symptom scores(WMD=-2.51,95％CI:-2.77--1.53,P＜0.001)and general psychopathological symptom scores(WMD=-1.20,95％CI:-1.80--0.60,P＜0.001).The adverse reactions of TBS included dizziness,and no serious adverse e-vents were reported.Conclusion:TBS has high safety,and stimulation of left dorsolateral prefrontal cortex targets for more than 2 weeks could effectively improve psychiatric symptoms in patients with schizophrenia.

AIM To study the effects of Liangxue Heying Formula on vascular inflammatory injury in a rat model of thromboangiitis obliterans(TAO).METHODS The rats were randomly divided into the sham operation group,the model group and the low,medium and high dose Liangxue Heying Formula groups(2.25,4.5,9 g/kg).With the rat TAO model successfully established by injection of 0.1 mL sodium laurate(10 mg/mL)into the femoral artery of hind limbs,corresponding doses of drugs by gavage were administered upon the rats.Subsequently,the rats had their morphological changes of the affected limbs observed and assessed;their changes of blood flow in hind limbs scanned by laser Doppler flowmetry;their plasma levels of TNF-α,IL-6,ICAM-1 and VCAM-1 detected by ELISA;their histopathological changes of femoral artery and vein observed by HE staining;and their protein expressions of TNF-α,IL-6,JAK2,p-JAK2,STAT3,p-STAT3,ICAM-1 and VCAM-1 in femoral artery detected by Western blot.RESULTS Compared with the sham operation group,the model group displayed increased morphological score of the affected limb(P＜0.01);decreased blood perfusion ratio of the affected side/healthy side(P＜0.01);increased plasma levels of TNF-α,IL-6,ICAM-1 and VCAM-1(P＜0.01);more existence of thrombotic infiltration containing a larger number of inflammatory cells in femoral artery and femoral vein tissue,and increased protein expressions of TNF-α,IL-6,p-JAK2,p-STAT3,ICAM-1 and VCAM-1 in femoral artery(P＜0.01).Compared with the model group,the medium and high dose Liangxue Heying Formula groups demonstrated decreased morphological score of the affected limb(P＜0.01);increased blood perfusion ratio of the affected side/healthy side(P＜0.01);reduced infiltration of thrombus and inflammatory cells in femoral artery and femoral vein tissue,and decreased protein expressions of IL-6 and p-STAT3 in femoral artery tissue(P＜0.01).All Liangxue Heying Formula groups shared decreased plasma levels of TNF-α,IL-6,ICAM-1 and VCAM-1(P＜0.05,P＜0.01);and reduced protein expressions of TNF-α,ICAM-1,VCAM-1 and p-JAK2 in femoral artery(P＜0.01).CONCLUSION Liangxue Heying Formula can improve the systemic inflammatory state of TAO rats by inhibiting the activation of endothelial cells and reducing vascular inflammatory injury possibly due to the mechanism associated with the regulation of the JAK2/STAT3 signaling pathway.

Objective To establish an evaluation index system for medical services provided by primary diagnosis physi-cian groups in tertiary public hospitals,using the Delphi method and Analytic Hierarchy Process(AHP).Methods Based on existing policies and relevant literature,initial indicators were formulated.The Delphi method was used in two rounds to deter-mine the index system,with a participation rate of 100%and high expert authority coefficients(Round 1:Cr=0.851,Round 2:Cr=0.839).The AHP was then applied to calculate the weights of the indicators.Results The evaluation index system for medical services provided by primary diagnosis physician groups was established through two rounds of expert consultations.The AHP yielded the weights of the indicators,with four primary indicators:internal processes(0.406),finance(0.288),learning and growth(0.208),and customer(0.098),and 25 secondary indicators.The consistency ratio(CR)values for the weights of the indicators were all less than 0.01.Conclusion The proposed index system is scientific and feasible for evaluating medical services provided by primary diagnosis physician groups in tertiary public hospitals.It can be applied in hospital department man-agement to further enhance the quality of medical services and the level of hospital refinement management.