OBJECTIVE To study the toxicokinetics and tissue distribution characteristics of alpha-amanitin in rats.METHODS The tail venous blood was collected from SD rats before and 5,10,20,30 and 45 min,1,1.5,2.5,4 and 8 h after intraperitoneal injection of alpha-amanitin(1.5 mg·kg-1),and the concentration of alpha-amanitin in blood was determined by liquid chromatography-mass spectrometry(LC-MS/MS).DAS 2.0 software was used to analyze and plot the drug-time curve with toxicokinetic parame-ters.Based on the toxicokinetics results,18 SD rats were randomly divided into three groups.The rats were sacrificed,and left ventricular arterial(LVA)blood and 9 types of tissue samples involving the heart,liver,spleen,lung,kidney,whole brain,small intestine,stomach wall and testis were collected 15 min,40 min and 2.5 h after dosing,and the concentrations of alpha-amanitin were measured by LC-MS/MS to obtain the tissue distribution results of alpha-amanitin in SD rats.RESULTS Toxicokinetics studies revealed that the peak blood concentration(Cmax)was(633±121)μg·L-1,the elimination half-life(T1/2)was(0.72±0.37)h,and the peak time(Tmax)was(0.52±0.16)h.The total clearance rate(CLz)was(1.62±0.26)L·h·kg-1,the area under the curve(AUC0-t)was(946±183)μg·h·L-1,and the mean reten-tion time(MRT0-t)was(1.18±0.17)h.The apparent volume of distribution(Vz)was(1.65±0.86)L·kg-1.The results of tissue distribution study showed that alpha-amanitin was widely distributed in SD rats with the highest concentration in the kidney,followed by the lung,small intestines,stomach wall,LVA blood and liver,but was low in the heart,spleen,testicles and other tissues,and very low in the brain.Alpha-amanitin was absorbed and eliminated quickly,peaked at 40 min in each tissue,and the concen-tration was minimized after 2.5 h.CONCLUSION The absorption and elimination of alpha-amanitin by intraperitoneal injection are rapid in SD rats,and the blood concentration reaches the peak about 31 min after administration,but can not be detected 4 h later.Alpha-amanitin is mainly distributed in the kidney,followed by the tissues and metabolic organs with rich blood flow,such as the lung,small intestines,stomach wall,LVA blood and liver.The content of alpha-amanitin is low in the heart,spleen,testicles and other tissues,and very low in the brain.It is speculated that it may have toxic targeting effect on the kidney and low blood-brain barrier permeability.

Respiratory viruses constantly undergo adaptive changes in long-term competition with the host，and are now able to alter the host metabolism to promote their own replication.As an extremely important part of host cell metabolism，glucose metabolism is closely related to respiratory virus infections.It is known that respiratory viruses can activate aerobic glycolysis in host cells through a variety of mechanisms to rapidly generate ATP，lactate and a series of intermediate metabolites.On one hand，aerobic glycolysis can facilitate viral invasion，replication，and evasion of immune surveillance；on the other hand，it can modulate the functional activities of host immune cells，thereby maintaining immune homeostasis during the elimination of viruses.This shows that respiratory viruses compete with host immune cells for glucose，and the one with the competitive advantage can affect the prognosis and regression of the disease.Therefore，this paper mainly discusses the role of aerobic glycolysis in the pathogenesis of respiratory virus infections，to provide new ideas for the fight against respiratory virus infections.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective:To investigate the epidemiological and clinical characteristics of human parainfluenza viruses (HPIVs) infection among hospitalized children with community-acquired pneumonia (CAP) in China, and provide basic data for diagnosis, treatment and prevention of HPIVs infection.Methods:From November 2014 to February 2020, 5 448 hospitalized children with CAP were enrolled in 14 hospitals in 11 provinces and municipalities directly under the Central Government in southern China and northern China. Nasopharyngeal aspirates or throat swabs were collected, and the nucleic acids of 18 types respiratory viruses including HPIV1-4 were screened by suspension array technology. Demographic data and clinical information were collected for statistical analysis.Results:The total detection rate of HPIVs in 5 448 children with CAP was 8.83% (481/5 448), and the detection rate in males was higher than that in females (62.79% vs. 37.21%; χ2=0.000, P=0.992). The detection rate of HPIVs in 1~< 3 years age group was higher than that in other age groups, and the difference was statistically significant ( χ2=61.893, P<0.001). The detection rate of HPIVs in the northern region was higher than that in the southern region (9.02% vs 8.65%), but the difference was not statistically significant ( χ2=0.239, P=0.625). The prevalence of HPIV1-4 in northern and southern China was not completely same. HPIV1 was mainly prevalent in autumn in both northern and southern regions. HPIV2 was prevalent in summer in northern China, and the detection rate was low in southern China. HPIV3 reached its peak in both spring and summer in both northern and southern China, but its duration was longer in southern China than in northern China. HPIV4 is mainly popular in autumn in both southern China and northern China. Among 481 children infected with HPIVs, 58.42% (281/481) were infected with HPIV alone, and the main clinical manifestations were cough (90.75%) and fever (68.68%). Out of the HPIV-positive cases, 42.62% (205/481) were co-infected with another type of HPIV or a different virus, while 11.43% (55/481) had co-infections with two or more different viruses. HPIV3 was the most common type of co-infection with other viruses. HPIV3 infection accounted for the largest proportion (76.80%) in 47 HPIVs-positive children with severe pneumonia. Conclusions:HPIVs is one of the most important pathogens causing CAP in children in China, and children under 3 years of age are the main populations of HPIVs infection. The prevalence characteristics of all types of HPIVs in children in the north and south are not completely same. HPIV3 is the dominant type of HPIV infections and causes more severe diseases.

Objective:To investigate the knowledge, attitudes, and practices (KAP) of pulse oximetry among pediatric healthcare providers in China and analyze the factor influencing the KAP.Methods:A self-developed questionnaire was used for an online research on the KAP of 11 849 pediatric healthcare providers from 31 provinces, autonomous regions, and municipalities of China from March 11 to 14, 2022.The factors influencing the KAP of pulse oximetry among pediatric healthcare providers were examined by Logistic regression. Results:The scores of KAP, of pulse oximetry were 5.57±0.96, 11.24±1.25 and 11.19±4.54, respectively.The corresponding scoring rates were 69.61%, 74.95%, and 55.99%, respectively. Logistic regression results showed that the gender and working years of pediatric healthcare providers, the region they were located, and whether their medical institution was equipped with pulse oximeters were the main factors affecting the knowledge score (all P<0.05). Main factors influencing the attitude score of pediatric healthcare providers included their knowledge score, gender, educational background, working years, region, medical institution level, and whether the medical institution was equipped with pulse oximeters (all P<0.05). For the practice score, the main influencing factors were the knowledge score, gender, age, and whether the medi-cal institution was equipped with pulse oximeters (all P<0.05). Conclusions:Chinese pediatric healthcare providers need to further improve their knowledge about and attitudes towards pulse oximetry.Pulse oximeters are evidently under-used.It is urgent to formulate policies or guidelines, strengthen education and training, improve knowledge and attitudes, equip more institutions with pulse oximeters, and popularize their application in medical institutions.

Aim To observe the effeet of changes in miR-124 expression on the proliferation, apoptosis, migration and invasion of HCC eells and its mecha¬nism.Methods The expression levels of miR-124 and ZEB2 were deteeted in HepG2 eells.CCK8, flow cytometry, Edu and Fran swell were used to deteet the effeets of miR-124 and ZEB2 on eell proliferation, ap¬optosis, migration and invasion.Dual lueiferase and target genes were used to prediet the targeting relation¬ship between miR-124 and ZEB2.The effeet of miR- 124 and ZEB2 on proliferation, apoptosis, migration and invasion-related protein expression was deteeted by Western blot.Results The expression of miR-124 in HepG2 eells was lower than that in normal liver eells L-02, while ZEB2 and miR-124 showed the opposite trend.The results of bioinformaties prediction and dual lueiferase showed that the expression of ZEB2 was neg¬ atively correlated with the expression of miR-124.Overexpression of miR-124 and silencing ZEB2 signifi¬cantly inhibited cell proliferation activity, migration and invasion ability compared with the control group; silencing miR-124 and overexpression of ZEB2 signifi¬cantly promoted cell proliferation activity, migration and invasion ability.Western blot results showed that overexpression of miR-124 and silencing ZEB2 signifi¬cantly promoted Bax expression and inhibited Bcl-2, PCNA, MMP2 and MMP9 expression levels.Silencing miR-124 and overexpression ZEB2 were the opposite.Conclusion miR-124 could negatively regulate the effects of ZEB2 on the proliferation, migration and in¬vasion of HCC cells.

Objective: To observe the clinical efficacy of acupuncture plus MOTOmed intelligent motor training in treating children with spastic cerebral palsy, and analyze the effects on lower limb motor function, intelligence development level, immune function and cerebral hemodynamics.Methods: A total of 42 children with spastic cerebral palsy were selected as the observation objects, and enrolled into the observation group. Another 42 cases treated in the same period were selected as the control group. Both groups received MOTOmed intelligent motor training, and the observation group was given additional acupuncture therapy, and the control group was given additional conventional rehabilitation treatment. After 2 consecutive treatment courses, the psychomotor development index (PDI) and mental development index (MDI) of Children's Developmental Center of China (CDCC) scale, the scores of gross motor function measure (GMFM) scale and modified Ashworth scale (MAS), and the changes in CD3+, CD4+, CD8+ and CD4+/CD8+ were observed. The peak systolic velocity (PSV) and mean flow velocity (MFV) of the anterior cerebral artery (ACA), middle cerebral artery (MCA) and posterior cerebral artery (PCA) were observed and measured. The clinical efficacy was evaluated. Results: Compared with the same group before treatment, the scores of GMFM, PDI and MDI, levels of CD3+, CD4+ and CD4+/CD8+, PSV and MFV levels of ACA, MCA and PCA in both groups were significantly increased after treatment (all P<0.05), while the CD8+ level had no significant change (both P>0.05). After treatment, the total effective rate of lower limb spasm in the observation group was 90.5％, significantly higher than 71.4％ in the control group (P<0.05). The scores of GMFM, PDI and MDI, the levels of CD3+ and CD4+, PSV and MFV, and the levels of ACA, MCA and PCA in the observation group were all significantly higher than those in the control group (all P<0.05). There were no significant differences in the CD8+ level and CD4+/CD8+ between the groups (all P>0.05). Conclusion: Acupuncture plus MOTOmed intelligent motor training has a better clinical efficacy than conventional rehabilitation plus MOTOmed intelligent motor training in treating children with spastic cerebral palsy, and is also superior in improving lower limb motor function and the level of intellectual development. And the mechanism may be related to the improvement of cerebral hemodynamics.

BACKGROUND: Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis. METHODS: We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician's global assessment (sPGA) at week 12. RESULTS: The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P < 0.05) and placebo (13.9%, P < 0.05) groups. The proportion of patients achieving an sPGA score 0 or 1 was 66.3% in the benvitimod group and 63.9% in the calcipotriol group, which were both significantly higher than that in the placebo group (34%, P < 0.05). In the long-term follow-up study, 50.8% of patients experienced recurrence. After retreatment with 1% benvitimod, 73.3% of patients achieved an sPGA score of 0 or 1 again at week 52. Adverse events included application site irritation, follicular papules, and contact dermatitis. No systemic adverse reactions were reported. CONCLUSION: During this 12-week study, benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis. TRIAL REGISTRATION Chinese Clinical Trial Registry (ChiCTR), ChiCTR-TRC-13003259; http://www.chictr.org.cn/showprojen.aspx?proj=6300.
Double-Blind Method ; Follow-Up Studies ; Humans ; Ointments ; Psoriasis/drug therapy* ; Resorcinols ; Severity of Illness Index ; Stilbenes ; Treatment Outcome

【Objective】 To investigate the risk factors of long- term adverse cardiovascular outcomes for coronary artery disease patients after gastrointestinal bleeding and evaluate the value of AIMS65 score and Glasgow- Blatchford score（GBS） for predicating these outcomes among those patients.【Methods】 All coronary artery disease patients with gastrointestinal bleeding were enrolled in the study from 2014 to 2016. All demographic data and clinical data for hospitalized coronary artery disease patients with gastrointestinal bleeding were retrospectively analyzed and all patients were divided into two groups according to whether the main outcomes occurred or not in order to detect their clinical features ， risk factors，and the prediction value of two score systems.【Results】Seventy patients showed the adverse cardiovascular outcomes among all patients. The area under the curve（AUC）that AIMS65 and GBS predicate the main outcomes were 0.59（P=0.035）and 0.51（P=0.039），respectively. The result of univariate analysis showed that age ，diabetes ，prior myocardial infarction ，hemoglobin ，prior proton- pump inhibitor use during hospital stay and blood transfusion were the risk factors. After multivariate analysis ，anemia ，high blood pressure and diabetes are independent risk factors.【Conclusions】 The GBS and AIMS65 both have a low specificity and sensitivity. Anemia ，high blood pressure and diabetes are independent risk factors of adverse cardiovascular outcomes after gastrointestinal bleeding.

Objective:Our study was aimed to analyze the therapeutic effect of early sequential enteral nutrition on postoperative rehabilitation in patients with gastric cancer.Methods:Patients with gastric cancer receiving surgery at our hospital from 2016 to 2017 included and the clinical information was prospective collected and analyzed.Patients were randomly divided into two groups using random number table.Patients in group A were sequentially given amino acid type,short peptide type and then whole protein type,while those in group B received whole protein formulation only.The recovery of gastrointestinal function,postoperative systemic inflammatory response,six-minutes walking test,and enteral nutrition-related complications were compared between the two groups.Results:A total of 71 patients were included in this study (Group A 36 cases,Group B 35 cases).There was no significant difference in terms of the restart anal exhaust between the two groups (P ＞ 0.05).Patients in group A had a significantly shorter postoperative hospitalization (t =4.070;P ＜ 0.01) and the earlier restoration of oral intake than that of Group B (t =3.400;P =0.001).One week after surgery,the levels of CRP (t =2.547;P =0.013) and IL-6 (t =3.172;P =0.002) were significant lower in group A when compared with group B.In addition,patients in group A had a significant higher six minutes walk steps than those in Group B [(416.1 + 36.7) m vs (358.9 ± 32.7) m;t =6.927,P ＜ 0.01].However,no significant difference in enteral nutrition-related complications was found between the two groups (P ＞ 0.05).Conclusion:In patients with gastric cancer,early sequential enteral nutrition can effectively accelerate the postoperative rehabilitation.