OBJECTIVE To optimize the simmering technology of Rheum palmatum from Menghe Medical School and compare the difference of chemical components before and after processing. METHODS Using appearance score， the contents of gallic acid， 5-hydroxymethylfurfural （5-HMF）， sennoside A+sennoside B， combined anthraquinone and free anthraquinone as indexes， analytic hierarchy process （AHP）-entropy weight method was used to calculate the comprehensive score of evaluation indicators； the orthogonal experiment was designed to optimize the processing technology of simmering R. palmatum with fire temperature， simmering time， paper layer number and paper wrapping time as factors； validation test was conducted. The changes in the contents of five anthraquinones （aloe-emodin， rhein， emodin， chrysophanol， physcion）， five anthraquinone glycosides （barbaloin， rheinoside， rhubarb glycoside， emodin glycoside， and emodin methyl ether glycoside）， two sennosides （sennoside A， sennoside B）， gallic acid and 5-HMF were compared between simmered R. palmatum prepared by optimized technology and R. palmatum. RESULTS The optimal processing conditions of R. palmatum was as follows: each 80 g R. palmatum was wrapped with a layer of wet paper for 0.5 h， simmered on high heat for 20 min and then simmered at 140 ℃， the total simmering time was 2.5 h. The average comprehensive score of 3 validation tests was 94.10 （RSD＜1.0%）. After simmering， the contents of five anthraquinones and two sennosides were decreased significantly， while those of 5 free anthraquinones and gallic acid were increased to different extents； a new component 5-HMF was formed. CONCLUSIONS This study successfully optimizes the simmering technology of R. palmatum. There is a significant difference in the chemical components before and after processing， which can explain that simmering technology slows down the relase of R. palmatum and beneficiate it.

AIM To identify the endophytic fungus G-(JK)-2 from Orixa japonica Thunb.and to study its secondary metabolites and their α-glucosidase inhibitory activities.METHODS Through the ITS sequence,the evolutionary tree that identifies the endophytic fungus G-(JK)-2 was established.Then 45 days rice solid medium of endophytic fungus G-(JK)-2 was extracted by methanol,and then by ethyl acetate.The ethyl acetate extract was separated and purified by silica gel chromatography,Sephadex LH-20,and semi-preparative HPLC.The structures of obtained compounds were identified by physicochemical properties and spectral data.Their α-glucosidase inhibitory activities were evaluated by PNPG method.RESULTS The endophytic fungus G-(JK)-2 from O.japonica was identified as Fusarium nematophilum.Thirteen compounds were isolated and identified as p-hydroxybenzaldehyde(G1),4-hydroxyacetophenone(G2),anhydromevalonolactone(G3),flazine(G4),salicylic acid(G5),p-hydroxybenzoic acid(G6),di-(2-ethylhexyl)-phthalate(G7),terephthalic acid bis(2-ethyl-hexyl)ester(G8),thymine(G9),uridine(G10),adenosine(G11),2′-deoxyuridine(G12),nicotinic acid(G13).The inhibitory effect of each compound on α-glucosidase was in sequence of G4>G11>G10>G13>G12.CONCLUSION All compounds are first isolated from the endophytic fungi of the O.japonica,and G10,G11,G13 are first isolated from the endophytic fungi of Fusarium.G4 and G11 have mild inhibition to α-glucosidase.

Objective To explore the effect of back Tuina on motor behavior,oxidative stress and in-flammation in rats with chronic fatigue syndrome(CFS).Methods Twenty-four Sprague-Dawley rats were randomly divided into a blank group,a model group and a Tuina group,each of 8,according to a random number table.The CFS rat model was prepared by means of forced weight-bearing swimming combined with chronic stress stimulation in 21 days.After modeling,the Tuina group was given daily 20-minute Tuina for 14 days.The general condition semi-quantitative score,exhaustion swimming time and open field experiment(OFE)distance of all groups were recorded.After the experiment,sam-ples were collected,and the histopathological changes of the vertical spine muscles were observed by hematoxylin and eosin(HE)staining.The cross-sectional area and diameter of muscle fibers were calcu-lated using Image Pro Plus software,and the frequency distribution diagram of cross-sectional area of muscle fibers was processed by using the Origin software.The contents of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and peroxisome proliferator-activated receptor γ-coactivator 1α(PGC-1α)and tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6 in the serum of rats were mea-sured.Results After the intervention,the general condition semi-quantitative score of the Tuina group was significantly lower than the model group(P<0.01),while the exhaustion swimming time and OFE distance were significantly higher than the latter group(P<0.05,P<0.01).(2)HE staining showed that the significant atrophy of erector spinal muscle cells in the model group,was significantly relieved in the Tuina group.(3)Compared with the blank group,the contents of SOD,GSH-Px and PGC-1α in erectus muscles decreased significantly(P<0.01),while those of TNF-α,IL-1β and IL-6 in the se-rum of the model group increased significantly(P<0.01).However,compared with model group,the contents of SOD,GSH-Px and PGC-1α in erectus muscle increased significantly(P<0.05,P<0.01),while those of TNF-α,IL-1β and IL-6 of the Tuina group decreased significantly(P<0.05,P<0.01).Conclusion Tuina in the back can regulate the oxidative stress response,reliever the inflammatory re-sponse and improve the motor behavior of CFS rats.

Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.

Fever of unknown origin(FUO)is a difficulty in clinical diagnosis and treatment.Patients with FUO come to seek medical consultation usually with fever as the main complaint,and the accompanying symptoms and signs are generally atypical.The pathogenesis of FUO remains conflicting in the field of modern western medicine,and its treatment is still focused on empirical anti-inflammatory management,which has the deficiency of delayed diagnosis,limited therapeutic options,poor therapeutic effects,and obvious adverse reactions.In the field of traditional Chinese medicine(TCM),FUO generally results from the dysfunction of zang-fu organs and the imbalance of yin and yang,and has the clinical features of long duration of illness,unknown etiology,complexity of illness,recurrent attacks,and difficult to be cured.Based on the six-meridian syndrome differentiation,Chief Physician LI Chuang-Peng pointed out that the pathogenesis of FUO is characterized by the combined disease of shaoyin and yangming,and put forward the therapeutic principle of warming shaoyin and unblocking yangming.He proposed the use of Dahuang Fuzi Decoction(mainly composed of Rhei Radix et Rhizoma and Aconiti Lateralis Radix Praeparata)plus Yiyi Fuzi Baijiang Powder(mainly composed of Coicis Semen,Aconiti Lateralis Radix Praeparata and Patriniae Herba)to subside fever and eliminate pathogen,together with Asari Radix et Rhizoma for guiding the medicine directly to the shaoyin.Moreover,therapies of strengthening and activating spleen and stomach,nourishing yin to produce fluid,and unblocking the blood vessels can be used for eliminating the pathogen and supporting the healthy qi.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the role of calprotectin S100 A8/A9 complex in evaluating the condition of children with severe Mycoplasma pneumoniae pneumonia(SMPP).Methods A prospective study was conducted among 136 children with Mycoplasma pneumoniae pneumonia(MPP)and 30 healthy controls.According to the severity of the condition,the children with MPP were divided into mild subgroup(40 children)and SMPP subgroup(96 children).The levels of S100 A8/A9 complex and related inflammatory factors were compared between the MPP group and the healthy control group,as well as between the two subgroups of MPP.The role of S100 A8/A9 in assessing the severity of MPP was explored.Results The MPP group had a significantly higher level of S100 A8/A9 than the healthy control group,with a significantly greater increase in the SMPP subgroup(P<0.05).The multivariate logistic regression analysis showed that the increases in serum C reactive protein(CRP)and S100A8/A9 were closely associated with SMPP(P<0.05).The receiver operating characteristic(ROC)curve analysis showed that the combined measurement of serum S100 A8/A9 and CRP had an area under the ROC curve of 0.904 in predicting SMPP,which was significantly higher than the AUC of S100 A8/A9 or CRP alone(P<0.05),with a specificity of 0.718 and a sensitivity of 0.952.Conclusions S100 A8/A9 is closely associated with the severity of MPP,and the combination of S100 A8/A9 with CRP is more advantageous for assessing the severity of MPP in children.

Objective To investigate the effects of propranolol on the proliferation,apoptosis,migration,and tube formation ability of human umbilical vein endothelial cells(HUVEC),as well as its impact on the expression of sex-determining region Y-box 18(SOX18),matrix metalloproteinase-7(MMP-7),and vascular endothelial growth factor A(VEGFA).Methods HUVEC were treated with different concentrations of propranolol,and cell viability was assessed using the CCK-8 method to determine the optimal concentration and treatment duration.The experiment consisted of a control group and groups treated with different concentrations of propranolol(50,100,150 μmol/L).Apoptosis,migration,and tube formation of HUVEC were observed using flow cytometry,wound healing assays,and tube formation assays.Western blot and real-time quantitative PCR were used to detect the expression levels of SOX18,MMP-7,and VEGFA proteins and mRNA.Results Compared to the control group,the apoptosis rate in the propranolol treatment groups increased significantly(P<0.05),and it rose significantly with increasing drug concentration(P<0.05).The wound healing rate decreased in the propranolol treatment groups,and both the number of tube formation nodes and total tube length were reduced(P<0.05).The expression levels of SOX18,MMP-7,and VEGFA proteins and mRNA were downregulated in the propranolol treatment groups(P<0.05).Conclusions Propranolol can inhibit the proliferation,migration,and tube formation ability of HUVEC and promote cell apoptosis,resulting in decreased expression levels of SOX18,MMP-7,and VEGFA.

Objective To explore the characteristics of blood pressure in the elderly patients with hypertensive cerebral small vessel disease(CSVD)and their correlation with traditional Chinese medicine(TCM)syndrome types.Methods A retrospective analysis was conducted in 189 elderly patients with essential hypertension.With reference to the presence or absence of CSVD,the patients were divided into CSVD group(87 cases)and non-CSVD group(102 cases).The blood pressure related parameters and clinical data obtained by four diagnostic methods of TCM in the two groups were collected,and then the characteristics of blood pressure and their correlation with TCM syndromes were analyzed with statistical methods.Results(1)CSVD group had higher values than non-CSVD group in the ambulatory blood pressure parameters of 24-hour systolic blood pressure(24hSBP),24-hour diastolic blood pressure(24hDBP),daytime systolic blood pressure(DSBP),daytime diastolic blood pressure(DDBP),nighttime systolic blood pressure(NSBP),nighttime diastolic blood pressure(NDBP),24-hour pulse pressure(24hPP),daytime pulse pressure(DPP),nighttime pulse pressure(NPP),maximum SBP,morning SBP,daytime SBP load and nighttime SBP load(P＜0.01).(2)The analysis of blood pressure variability showed that the mean value of nighttime SBP standard deviation(NSSD)in CSVD group was higher than that in the non-CSVD group(P＜0.01).(3)The analysis of circadian rhythm of blood pressure showed that there was significant difference in the comparison of circadian rhythm of ambulatory blood pressure between the two groups(P＜0.05):non-CSVD group was predominated by non-dipper type blood pressure(50 cases,49.02%)and dipper type blood pressure(31 cases,30.39%),and CSVD group was predominated by non-dipper type blood pressure(38 cases,43.68%)and super-dipper type blood pressure(31 cases,35.63%).(4)Logistic regression analysis showed that 24hSBP(OR=1.296,95%CI:1.112-1.511),maximum SBP(OR=1.074,95%CI:1.006-1.146),morning SBP(OR=1.064,95%CI:1.013-1.118),abnormal circadian rhythm of blood pressure(OR=3.736,95%CI:1.663-8.390)were the influence factors of CSVD(P＜0.05 or P＜0.01).(5)The analysis of the distribution of TCM syndrome types showed that non-CSVD group was dominated by accumulation of excess phlegm-damp syndrome(58.82%)and yin deficiency and yang hyperactivity syndrome(21.57%),and CSVD group was dominated by yin deficiency and yang hyperactivity syndrome(51.72%)and accumulation of excess phlegm-damp syndrome(21.84%).(6)The analysis of blood pressure in patients with various syndrome types showed that the DPP of patients with accumulation of excess phlegm-damp syndrome in the CSVD group was significantly higher than that in the non-CSVD group(P＜0.01),and the 24hDBP and NDBP of patients with yin deficiency and yang hyperactivity syndrome in the CSVD group were significantly higher than those in the non-CSVD group(P＜0.01).Conclusion It is indicated that 24hSBP,maximum SBP,elevated morning SBP,and abnormal blood pressure circadian rhythms may be the important risk factors for the hypertensive CSVD in the elderly.Elderly hypertensive patients with accumulation of excess phlegm-damp syndrome should pay more attention to the mean daytime pulse pressure,and elderly hypertensive patients with yin deficiency and yang hyperactivity syndrome should pay more attention to monitoring DBP.The dynamic observation and early control of the blood pressure is helpful for the prevention and treatment of CSVD in the elderly patients with hypertension.

Objective To investigate the clinical efficacy and safety of Yiqi Huatan Tongluo Prescription(mainly composed of Fici Simplicissimae Radix,Notoginseng Radix et Rhizoma,Pinelliae Rhizoma Praeparatum,Poria,Nelumbinis Folium,and Glycyrrhizae Radix et Rhizoma,etc.)combined with drug-coated balloon(DCB)in the treatment of coronary heart disease(CHD)and to observe its effect on low-shear related serological indicators.Methods A total of 106 patients with CHD of qi deficiency and phlegm stasis obstructing collateral type who were scheduled to undergo percutaneous coronary intervention were randomly divided into a treatment group and a control group,with 53 cases in each group.The control group was treated with drug-eluting stent implantation,and the treatment group was treated with DCB.After the operation,the control group was given conventional antiplatelet aggregation drugs,and the treatment group was given oral administration of Yiqi Huatan Tongluo Prescription.The medication for the two groups lasted for 12 weeks.The changes in the serum levels of monocyte chemoattractant protein 1(MCP-1),interleukin 1 β(IL-1β)and vascular endothelial growth factor(VEGF)in the two groups were observed before and after treatment.Moreover,the traditional Chinese medicine(TCM)syndrome efficacy after treatment and the incidence of adverse events one year after operation were compared between the two groups.Results(1)After 12 weeks of treatment,the total effective rate for TCM syndrome efficacy of the treatment group was 88.68％(47/53),and that of the control group was 75.47％(40/53).The intergroup comparison(tested by chi-square test)showed that the TCM syndrome efficacy in the treatment group was significantly superior to that in the control group(P＜0.05).(2)The analysis of indicators related to endothelial dysfunction in the blood flow with low shear stress showed that after treatment,the levels of serum MCP-1,IL-1βand VEGF in the control group presented no obvious changes(P＞0.05),but the serum levels of MCP-1 and IL-1β in the treatment group were significantly lowered compared with those before treatment(P＜0.05).The intergroup comparison showed that the decrease of serum MCP-1,IL-1β and VEGF levels in the treatment group was significantly superior to that in the control group(P＜0.05).(3)The one-year follow-up after the operation showed that the total incidence of adverse events in the treatment group was 18.87％(10/53),and that in the control group was 20.75％(11/53).There was no significant difference between the two groups(P＞0.05).Conclusion Yiqi Huatan Tongluo Prescription combined with DCB has definite action on the targets related to endothelial dysfunction in coronary blood flow with low shear stress,which is conducive to reducing inflammatory response,improving the symptoms of angina pectoris and enhancing clinical efficacy.The incidence of adverse events did not increase one year after operation,indicating good safety and effectiveness.