Objective:To evaluate the impact of three small compounds, namely sodium diethyldithiocarbamate (DTC), levamisole (LMS) and imiquimod (Imi), on the immunogenicity and protective efficacy of the candidate antigen PA0833 from Pseudomonas aeruginosa ( Pa) and analyze the underlying mechanisms. Methods:PA0833 was formulated with aluminum adjuvant and the above small compounds, respectively. BALB/c mice were immunized with these vaccines intramuscularly on days 0, 14 and 21. Serum samples were collected and the levels of PA0833-specific IgG were measured by ELISA. The protective efficacy of these vaccines was evaluated by assessment of survival rates, body weights, clinical scores, inflammatory factors, and histopathological changes after infecting the immunized mice with Pa PAO1 strains. Besides, the mice were injected with DTC intramuscularly for seven consecutive days to analyze the mechanism of DTC in enhancing immune response using transcriptome sequencing and flow cytometry. Results:All these small compounds were capable of effectively enhancing the immunogenicity of PA0833 formulated with aluminum adjuvant, reducing bacterial loads in lung tissues, inhibiting the secretion of TNF-α, IL-6 and IL-1β, and improving mouse survival rates upon Pa infection. DTC was more effective than the other two compounds. Transcriptome sequencing identified 121 up-regulated genes and 18 down-regulated genes in DTC-treated group as compared with PBS control group. These differentially expressed genes were significantly enriched in immune pathways, with a strong activation of the IL-17 pathway. Flow cytometry analysis demonstrated significant activation of dendritic cells and proliferation of Th17 cells in splenocytes in DTC-treated group as compared with PBS control group. Conclusions:All three small compounds are able of effectively enhance antigen immunogenicity with DTC being the most effective, indicating that DTC can be used as a novel adjuvant in vaccine development.

Octapeptin has strong antibacterial activity against Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii, while it also has activity against some Gram-positive bacteria. This study used natural octapeptin A3 and B3 as lead compounds for structural modification. Twenty-one peptide derivatives (including A3 and B3) containing eight amino acid residues were prepared by solid-phase synthesis, and evaluated for antibacterial activity and renal cytotoxicity. Among them, three compounds 6, 7 and 17 exhibited broad-spectrum antibacterial activity and significantly enhanced the activity for Gram-positive bacteria while maintaining the activity of Gram-negative bacteria. Several compounds improved the activity for Pseudomonas aeruginosa. Compound 7 was active against all test strains and had relatively low renal cytotoxicity. The results provide a basis for the further development of novel polypeptide antibiotics.

ObjectiveTo explore the distribution characteristics of traditional Chinese medicine （TCM） syndrome elements of macroangiopathy in patients with type 2 diabetes mellitus （T2DM） and the key elements of occurrence， development and progression of disease. MethodsA multicenter cross-sectional study was conducted to enroll 445 T2DM patients from five hospitals， and according to the presence or absence of macroangiopathy， the patients were divided into a T2DM group （120 cases） and a diabetic macroangiopathy （DM） group （325 cases）. Patients in DM group were divided into grade Ⅰ， Ⅱ， Ⅲ and Ⅳ according to the peripheral vascular color Doppler ultrasound results and the vascular anomalies classification standard. The general data including gender， age， duration of T2DM and body mass index （BMI） were collected， and the data of four examinations were obtained for syndrome differentiation. According to the diagnostic criteria of TCM syndrome elements， the patients can be divided into 9 patterns including qi deficiency， blood deficiency， yin deficiency， yang deficiency， qi stagnation， blood stasis， excess heat， and excess cold. The general data and distribution of TCM syndrome elements were compared between the two groups. The distribution of TCM syndrome elements in different vascular anomalies grades in the DM group was analyzed. Logistic regression analysis was used to explore the influence of various TCM syndrome elements on the occurrence of macroangiopathy in T2DM. ResultsThere was no significant difference in gender and BMI between groups （P＞0.05）. The age and duration of diabetes in the DM group were older and longer than those in the T2DM group （P＜0.01）. With the increase of age and prolonged course of disease， the severity of diabetic macroangiopathy increases gradually （P＜0.05 or P＜0.01）. There was no significant difference in BMI and course of disease among the different TCM syndrome elements （P＞0.05）. The average age of patients with blood stasis syndrome was the oldest （P＜0.05）. There was significant difference in gender distribution between the excess heat syndrome and yin deficiency syndrome （P＜0.05）. A total of 240 TCM syndrome elements were extracted from the T2DM group， while 731 TCM syndrome elements extracted from the DM group. The top two high-frequency syndrome elements in the two groups were qi deficiency and yin deficiency， with a frequency of larger than 50%. The distribution of phlegm-damp syndrome and blood-stasis syndrome were significantly higher in the DM group than in the T2DM group （P＜0.01）. There were significant differences in the distribution of qi deficiency syndrome， yin deficiency syndrome， phlegm-damp syndrome， blood stasis syndrome， and excess heat syndrome among different grades of vascular anomalies （P＜0.01）； qi deficiency and yin deficiency were both high-frequency TCM syndrome elements in patients at grades 0 to Ⅲ； phlegm-damp syndrome increased in frequency with the progression of the disease from grades 0 to Ⅳ， and the frequency of blood stasis syndrome showed an overall upward trend. The frequency of phlegm-dampness syndrome increased from grades 0 to Ⅳ with the progression of the disease， and the frequency of blood stasis syndrome showed an overall upward trend. Logistic regression analysis showed that phlegm-damp syndrome and blood stasis syndrome were important TCM syndrome elements related to the vascular anomalies degree of macrovascular disease in T2DM （P＜0.05 or P＜0.01）. ConclusionQi deficiency and yin deficiency are the basic TCM syndrome elements throughout the whole process of T2DM and diabetic macrovascular disease. Phlegm-damp and blood stasis are related to the degree of vascular anomalies in diabetic macrovascular disease and are the key TCM syndrome elements in the progression of macroangiopathy in T2DM.

Background Comorbid attention-deficit/hyperactivity disorder(ADHD)and emotional dysregulation may represent a distinct subtype of ADHD,which is characterized by an increased risk of anxiety or depressive disorder and a poor clinical prognosis,so research is urgently required to explore its unique executive functioning profile and clinical characteristics.However,there is limited research comparing the clinical symptoms and executive function in children with ADHD in terms of the presence or absence of emotional dysregulation.Objective To explore the executive function and clinical characteristics of ADHD children with emotional dysregulation.Methods From June 2020 to December 2023,118 children aged 7 to 12 with ADHD attending the Mental Health Center of West China Hospital,Sichuan University and fulfilling the Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5)diagnostic criteria were enrolled.Children were classified into emotional dysregulation group(n=68)and non-emotional dysregulation group(n=50)based on the standard T-scores of Achenbach's Child Behavior Checklist(CBCL)-anxious/depressed,aggressive behavior and attention problems subscales.All children were then subjected to complete the Chinese version of Swanson Nolan and Pelham,Version IV Scale-parent form(SNAP-IV),Chinese Wechsler Intelligence Scale for Children(C-WISC),Weiss Functional Impairment Scale-Parent form(WFIRS-P)and 4 tests of the Cambridge Neuropsychological Test Automated Battery(CANTAB):①Stockings of Cambridge(SOC)testing spatial planning.②Intradimensional-extradimensional Set Shifting(IED)testing cognitive/attentional flexibility,adjusting the total errors across the task.③Spatial Working Memory(SWM)testing spatial working memory.④Rapid Visual Information Processing(RVP)testing sustained attention.Results The SNAP-IV Inattention,Hyperactivity/Impulsivity and Oppositional Defiant Disorder domain scores and total score were all higher in emotional dysregulation group compared with non-emotional dysregulation group(t=3.206,5.088,6.316,6.553,P<0.01).The WFIRS-P family,school learning,life skills,self-concept,social activities and risky activities domain scores and total score were all higher in emotional dysregulation group compared with non-emotional dysregulation group(t=6.074,4.406,4.143,3.984,6.575,6.662,8.254,P<0.01).In CANTAB,emotional dysregulation group made more total adjusted errors across the IED task compared with non-emotional dysregulation group(t=2.168,P<0.05).Conclusion Children with ADHD who exhibit emotional dysregulation have been observed to experience more severe core symptoms,impaired social functioning and poorer performance on tests assessing executive function,particularly in the area of cognitive flexibility.

Objective:To study the trinucleotide repeats of GCN (GCA, GCT, GCC, GCG) encoding Alanine in exon 3 of the PHOX2B gene among healthy individuals from southwest China and two patients with Congenital central hypoventilation syndrome (CCHS). Methods:The number and sequence of the GCN repeats of the PHOX2B gene were analyzed by capillary electrophoresis, Sanger sequencing and cloning sequencing of 518 healthy individuals and two newborns with CCHS, respectively. Results:Among the 1036 alleles of the 518 healthy individuals, five alleles were identified, including (GCN) 7, (GCN) 13, (GCN) 14, (GCN) 15 and (GCN) 20. The frequency of the (GCN) 20 allele was the highest (94.79%). And five genotypes were identified, which included (GCN) 7/(GCN) 20, (GCN) 13/(GCN) 20, (GCN) 14/(GCN) 20, (GCN) 15/(GCN) 20, (GCN) 20/(GCN) 20. The homozygous genotypes were all (GCN) 20/(GCN) 20, and the carrier rate was 89.58%. Four GCN sequences of the (GCN) 20 homozygous genotypes were identified among the 464 healthy individuals. The GCN repeat numbers in the exon 3 of the PHOX2B gene showed no significant difference between the expected and observed values, and had fulfilled the, Hardy-Weinberg equilibrium. The genotypes of the two CCHS patients were (GCN) 20/(GCN) 25 and (GCN) 20/(GCN) 30, respectively. Conclusion:It is important to determine the GCN repeats and genotypic data of the exon 3 of the PHOX2B gene among the healthy individuals. The number of GCN repeats in 518 healthy individuals was all below 20. The selection of appropriate methods can accurately detect the polyalanine repeat mutations (PARMs) of the PHOX2B gene, which is conducive to the early diagnosis, intervention and treatment of CCHS.

Fluorescent carbon dots(CDs)were synthesized via a solvothermal method with citric acid and urea as raw materials,and ethylene glycol as reaction solvent.The micromorphology,crystal structure,elemental composition,surface functional group,and optical property of as-synthesized CDs were characterized.The excitation-dependent fluorescence property of CDs was investigated,and the effects of synthesis conditions including reaction temperature,reaction time and raw materials on excitation and emission wavelengths of the CDs were also discussed.Then,a series of CDs-based fluorescent composites were prepared by combining CDs with starch,nano-silica,montmorillonite,kaoline,kieselguhr and magnesium oxide,respectively.Finally,the CDs-starch composites were used for latent fingerprint development on smooth substrates,and the qualitative as well as quantitative evaluation of the contrast,sensitivity and selectivity in fingerprint development were also made.Enhanced development of latent fingerprints was thus achieved by the aid of the excitation-dependent fluorescence property of CDs-starch composite combined with the optical filtering technique,which could decrease the background noise interference to a great extent.Experimental results showed that,the contrast between fingerprint(developing signal)and substrate(background noise)was obvious,exhibiting a strong contrast;the minutiae of papillary ridges were clear,indicating a high sensitivity;the adsorption between CDs-starch composites and fingerprint residues was specific,showing a good selectivity.

Objective To observe the clinical effect of Peiyuan Yangxin(cultivating vital essence and nourishing heart)acupuncture and moxibustion method combined with Gubu Pills in the treatment of type 2 diabetes mellitus complicated with osteoporosis(T2DOP).Methods A total of 70 patients with T2DOP were randomly divided into treatment group and control group,with 35 cases in each group.The control group was treated with conventional hypoglycemic and calcium supplementation.On the basis of the control group,the treatment group was treated with Peiyuan Yangxin acupuncture and moxibustion method combined with Gubu Pills for eight weeks.After two months of treatment,the clinical efficacy of the two groups was evaluated,and the changes of serum osteocalcin(OC),total type 1 collagen amino acid extension peptide(PINP),β-collagen special sequence(β-CTX),inorganic phosphorus(P)and glycosylated hemoglobin(HbA1c)were observed before and after treatment.The changes of pain Visual Analogue Scale(VAS),Hamilton anxiety scale(HAMA)and diabetes specific quality of life scale(DSQL)scores were compared before and after treatment between the two groups.The safety and adverse reactions of the two groups were evaluated,and the recurrence rate and rehospitalization rate of the two groups were counted.Results(1)After treatment,the serum OC,PINP,β-CTX and P levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving serum OC,PINP,β-CTX and P levels,with a statistically significant difference(P＜0.05).(2)After treatment,the HbA1c level of patients in both groups was significantly improved(P＜0.05),and the treatment group was significantly superior to the control group in improving HbA1c level,with statistically significant differences(P＜0.05).(3)After treatment,the VAS,HAMA and DSQL scores of patients in the two groups were significantly improved(P＜0.05),and the treatment group was significantly superior to the control group in improving VAS,HAMA and DSQL scores,with statistically significant differences(P＜0.05).(4)The total effective rate was 88.57％(31/35)in the treatment group and 68.57％(24/35)in the control group.The efficacy of the treatment group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(5)The recurrence in the treatment group was significantly less than that in the control group,and the difference was statistically significant(P＜0.05).(6)There were no statistically significant differences of the incidence of adverse reactions between the two groups of patients(P＞0.05).Conclusion Peiyuan Yangxin acupuncture and moxibustion method combined with Gubu Pills in the treatment of T2DOP can significantly reduce the pain and anxiety symptoms of patients,improve the biochemical indexes of bone metabolism,thereby improving the quality of life of patients,increasing the effective rate of treatment,and reducing the recurrence rate and the rate of rehospitalization in the short term.

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.