Objective To evaluate the effect of cytochrome P450 3A5(CYP3A5)genetic polymorphism on the blood drug concentration of tacrolimus(TAC)in patients with lupus nephritis(LN),to determine the appropriate initial dose for LN patients of different genotypes and the differences in time to remission,and to analyze factors associated with LN prognosis.Methods Patients with active LN attending the outpatient clinic of the Department of Rheumatology and Immunology,West China Hospital,Sichuan University were enrolled.Their CYP3A5 genotypes were determined.According to the different genotypes,the patients were assigned to two groups,the AA+GA group,or the rapid metabolism group with the genotype CYP3A5*1/*1,i.e.,AA+CYP3A5*1/*3,and the GG group,or the slow metabolism group with the genotype CYP3A5*3/*3.The basic information,clinical manifestations,history of other diseases,and medication history of the enrolled patients were collected.According to the principle of simple random grouping,patients in each group were randomly divided into two subgroups,receiving TAC at initial doses of 0.05 mg/(kg·d)and 0.075 mg/(kg·d),respectively.Data on laboratory test indicators,including TAC blood drug concentration,blood pressure,and other relevant clinical follow-up indicators,were collected each month from each group.Patients were also evaluated each month for their clinical remission status.When patients in the 0.05 mg/(kg·d)initial dose group did not achieve clinical remission after 2 months,the TAC dose was increased to 0.075 mg/(kg·d),and the patients were observed until the end of the 6th month.Patients in the 0.075 mg/(kg·d)initial dose group were observed for 6 months,regardless of their remission status.Results In the LN patient subgroups receiving TAC at the same initial dose,the cumulative remission rate of patients with the GG genotype was higher than that of patients with the AA+GA genotype,but only in the 0.05 mg/(kg·d)initial dose group,the difference in cumulative remission rate between the two genotypes was statistically significant(P<0.05).According to a comparison of patients with the same genotype who received TAC at different initial doses,the remission rate of patients receiving 0.075 mg/(kg·d)initial dose was higher than that of the 0.05 mg/(kg·d)initial dose group,but only in patients with AA+GA genotype,the difference in remission rate between the two initial dose groups was statistically significant(P<0.05).Whether it was different genotypes in the same TAC initial dose group or different TAC initial doses of the same genotype,there was no statistically significant difference in the time to achieve complete remission(P>0.05).Regardless of the different initial TAC doses,patients with the GG genotype maintained higher TAC blood concentrations than those with the AA+GA genotype throughout the course of treatment.TAC blood concentration during treatment(OR=1.941;95%CI,1.47-2.563;P<0.001),CYP3A5*1 genotype carrier status(OR=0.161;95%CI,0.053-0.492;P=0.001),and the initial TAC dose(OR=0.205;95%CI,0.113-0.371;P<0.001)were all significant factors influencing treatment efficacy.When TAC blood concentration was higher,patients with the GG genotype receiving TAC at an initial dose of 0.075 mg/(kg·d)were more likely to achieve clinical remission.There were no statistically significant differences in the incidence of adverse reactions between subgroups with the same genotype but receiving TAC at different initial doses(P>0.05).Conclusion The efficacy of TAC in treating LN patients is correlated with CYP3A5 genotypes,TAC blood drug concentration,and TAC initial dose.The blood drug concentration of TAC is influenced by CYP3A5 genotypes,with the TAC blood drug concentrations of the slow metabolism group being higher than that of the fast metabolism group.When the TAC blood drug concentration reaches 6-10 ng/mL,it is more likely for LN patients to achieve clinical remission.

【Objective】 To analyze the height growth of children aged 6 - 15 years in Nanning, Guangxi Zhuang Autonomous Region, so as to provide evidence for the assessment of local children′s height development. 【Methods】 A total of 25 225 children aged 6 - 15 years were selected to get their physical examination data from 41 primary schools in Nanning by stratified cluster sampling method in December 2021.Then the height data were compared with the current domestic standards. 【Results】 The average height of boys in Nanning was lower than the national standard before the age of 10 years and 7 months, and the gap with the national standard gradually narrowed after the age of 10 years and 7 months. The average height of boys in Nanning City exceeded the national standard between the age of 11 years and 1 month and 13 years and 6 months, and then lagged behind the national standard again after the age of 13 years and 7 months. The mean height of girls in Nanning City was lower than the national standard height in several age groups, and it was more obvious before the age of 9 years and 7 months. The proportion of height ≤-2s,≤-s,≥ +s and ≥+2s in boys aged 6 to 15 years in Nanning City fluctuated from 2.59% to 6.04%, 12.09% to 23.43%, 7.18% to 18.79% and 0.93% to 3.14%, respectively; the total proportions were 4.56%, 17.46%, 11.35% and 1.74%, respectively; the minimum/maximum proportion values of each height group were at 11 years old /8 years old, 14 years old/8 years old, 8 years old/12 years old, and 6 years old/11 years old, respectively. The proportions of girls aged 6 - 15 years in Nanning City with height ≤-2s, ≤-s, ≥+s, and ≥+2s fluctuated from 2.06% to 5.19%, 9.35% to 25.15%, 8.21% to 15.80% and 1.23% to 3.49%, respectively; the total proportions were 3.38%, 16.91%, 11.97% and 2.29%, respectively; and the minimum/maximum proportion values of each height group were at 13 years old/6 years old, 12 years old/6 years old, 7 years old/12 years old, and 6 years old/11 years old, respectively. 【Conclusions】 The overall height level of children in Nanning is still lower than the national level, with short prepubertal basal heights, an earlier age of onset of accelerated pubertal height, and a shorter duration of accelerated pubertal height in boys. Strengthening pre-pubertal height management and emphasizing the onset and duration of children′s pubertal development, especially the height development of boys during puberty, can help improve the adult lifelong height of children in this region.

Objective:To test the reliability and validity of the general procrastination scale (GPS) in the application of middle school students.Methods:The Chinese version of GPS, the irrational procrastination scale(IPS), and the Maslach burnout inventory(MBI) were utilized to survey 10 825 middle school students in Harbin City through stratified random sampling, and 4 498 students were retested after 4 weeks. Statistical analysis was performed using SPSS 27.0 and Mplus 8.0.Results:The entries were well differentiated.Exploratory and confirmatory factor analysis indicated that GPS was composed of two factors, including active avoidance and lack of planning.The model fit was good (CFI=0.914, TLI=0.901, RMSEA=0.069, SRMR=0.072). GPS was positively correlated with the total scores of IPS and MBI ( r=0.753, 0.677, both P<0.001). The Cronbach's α coefficient of GPS was 0.864, the folded half reliability was 0.870, and the retest reliability after 4 weeks was 0.756. Conclusion:The GPS has good reliability and validity among middle school students, which provides a standard for measuring the procrastination level of middle school students and carrying out related research.

The patient 1,a 13-year-old boy,was admitted due to"recurrent oral ulcers for 3 years,abdominal pain for 8 months,and perianal ulcers for 10 days";The patient 2,a 3-year-old boy,was admitted due to"recurrent abdominal pain,diarrhea,and fever for over 3 months".Genetic testing of both patients revealed"deficiency in ELF4,X-linked"(DEX),and the patients were diagnosed with Behcet's disease-like syndrome due to deficiency in ELF4,accordingly.The patient 1 was successively given intravenous methylprednisolone pulses and oral prednisone and mesalazine for symptomatic treatment.The patient 2 was successively treated with corticosteroids combined with enteral nutrition,as well as oral mercaptopurine.Subsequently,both patients showed improvements in symptoms and were discharged.

Objective: To investigate the efficacy of antibacterial peptides in the adjuvant therapy of stage Ⅲ periodontitis. Methods: Fifty-one patients were randomly divided into simple mechanical curettage group, minocycline hydrochloride group and antibacterial peptide group according to the treatment mode. Three groups received periodontal sequential treatment, and after the ultrasonic supragingival scaling, they were performed with curettage, root surface planing, polishing and flushing. After treatment in the minocycline hydrochloride group and the biological antibacterial peptide group, minocycline hydrochloride ointment and biological antibacterial peptide periodontal gel were injected into the periodontal pocket respectively. The mechanical curettage group did not take medicine. Periodontal checklists at baseline and 90 d after treatment were recorded to compare differences of the three groups in periodontal probing depth (PD), bleeding index (BI) and attachment level (AL). Enzyme-linked immunosorbent assay (ELSIA) was used to detect the change of tumour necrosis factor-α (TNF-α), interleukin (IL)-1β by collecting the gingival crevicular fluid of the three sets at baseline, 7 d after treatment and 90 d after treatment. Results: There was no statistically significant difference in periodontal clinical examination indexes(PD,BI,AL) and contents of TNF-α and IL-1β in the gingival crevicular fluid between the three groups at baseline (P>0.05). At 7 and 90 d after treatment, all indexes in the three groups were improved compared with those before treatment. The comparison between groups showed that in periodontal pockets with PD≤5 mm, there was no statistically significant difference in the indicators between the three groups. In periodontal pockets with PD≥6 mm, the minocycline hydrochloride group and the bio-antibacterial peptide group had no statistically significant difference in various indicators, but they were all better than the mechanical scaling group. Conclusion Basic periodontal therapy is an important treatment for stage Ⅲ periodontitis. Minocycline hydrochloride and biological antibacterial peptides are both effective adjuvant drugs for deep periodontal pockets with PD≥6 mm.

Objective:This study aims to investigate the effects of Zhibao Sanbian Pills on learning and memory ability and explore its mechanism.Methods:Cognitive decline and memory impairment in mice was induced by scopolamine. Morris water maze test, platform jumping test and dark avoidance test were used to evaluate the learning and memory ability of mice. TCMSP, TCMID database and literature search were used to search the chemical components of Zhibao Sanbian Pills. The potential active components were screened through ADMETlab 2.0. The targets were predicted by Swiss Target Prediction. GO function and KEGG pathway enrichment analysis were conducted through the Metascape database, and a PPI network was constructed for MCODE module analysis.Results:Compared with the model group, the latency of water maze test in the high-dose group of Zhibao Sanbian Pills was shortened ( P<0.05), and the time of platform quadrant and the number of crossing increased ( P<0.05). 863 active components and 401 potential targets of Zhibao Sanbian Pills were collected. The enrichment analysis of MCODE, GO and KEGG pathways found that the action pathways of Zhibao Sanbian Pills to improve cognitive impairment involve neuroactive ligand receptor pathway, calcium signal pathway, Rap1 signal pathway, PI3K-Akt signal pathway, MAPK signal transduction pathway, 5-hydroxytryptamine receptor pathway, etc. Conclusion:Zhibao Sanbian Pills have the potential to improve the learning and memory ability of mice, which may be realized through MAPK signaling pathway and other neural related signaling pathways.

Objective:To investigate the value of central vein sign (CVS) and iron deposition on quantitative susceptibility imaging (QSM) of 3.0 T MRI in differentiating multiple sclerosis (MS) from neuromyelitis optica spectrum disease (NMOSD).Methods:This study was a retrospective study. A total of 54 MS patients and 49 NMOSD patients were enrolled from July 2018 to December 2020 in People′s Hospital of Leshan and the First Affiliated Hospital of Chongqing Medical University. All patients underwent conventional MRI and three-dimensional enhanced T 2*-weighted angiography (3D-ESWAN), and ESWAN-filtered phase and QSM were reconstructed from 3D-ESWAN data. First, brain lesions of MS and NMOSD were screened on proton density (PD)-T 2WI, and then the location of lesions, CVS and nodular/annular iron deposition were observed on phase and QSM images. The χ 2 test was used to compare the differences in intracranial lesion location, CVS and iron deposition between MS and NMOSD patients. Receiver operating characteristic curve and area under the curve (AUC) were used to assess the efficiency of CVS and QSM iron deposition to differentiate MS from NMOSD. Results:A total of 968 MS lesions were observed in 54 MS patients, of which CVSs were found in 354 lesions and 227 CVSs were located around the lateral ventricles, 117 in deep white matter (DWM) and 10 in the cortex/subcortex; 372 lesions showed nodular iron deposition, and 193 lesions ring iron deposition on QSM. Totally 247 brain lesions were observed in 41 of 48 patients with NMOSD, of which CVSs were found in 4 lesions and 1 located around the lateral ventricle, 3 located in the DWM; 3 lesions showed nodular iron deposition on QSM. There were significant differences in cortex/subcortex lesions, CVS and iron deposition between MS and NMOSD patients (χ 2 were 29.33, 115.66 and 258.21, respectively, all P<0.001). The AUC of CVS for differentiating MS from NMOSD was 0.941 (95%CI 0.887-0.994), with a sensitivity of 96.3% and a specificity of 91.8%; the AUC of iron deposition for differentiating MS from NMOSD was 0.969 (95%CI 0.930-1.000), with a sensitivity of 100% and a specificity of 93.9%. Conclusion:CVS and iron deposition on 3.0 T MRI are distinct radiologic features of MS lesions from those of NMOSD lesions, and have certain value in the differential diagnosis.

OBJECTIVE To sort out and analyze the expression and provisions of drug standards in the text of the newly revised Drug Administration Law ，and to explore the connotation and legal positioning of drug registration standards so as to provide reference for the rational application and interpretation of relevant provisions of drug standards in Drug Administration Law . METHODS Through the review of the evolution of drug standard management in China ，the legal provisions of drug standard in the Drug Administration Law were analyzed. Comparative study and literature research methods were used to analyze the legal expression and connotation of drug standards. RESULTS & CONCLUSIONS There were different expressions about “national drug standards ”“drug standards ”and“quality standards ”in the current provisions of the newly revised Drug Administration Law ； the legal position of the provincial-level standard for the preparation of Chinese herbal pieces was not clear ，and there may be insufficient legal regulation in the enforcement of drug administration. It is necessary to make an administrative interpretation for the content of relevant drug standards and provisions ，and further clarify the legal attributes of drug standards in the processing of provincial Chinese herbal pieces in order to promote the standardized management of Chinese herbal pieces.

Alzheimer's disease （AD） is a deleterious neurodegenerative disorder， which has become a significant public health concern and economic burden. The pathogenesis of AD is complex and involves several hypotheses such as amyloid β-protein （Aβ） deposition， Tau protein hyperphosphorylation， oxidative stress， and inflammation. There is an urgent need for a holism-based comprehensive intervention with multi-pathway， multi-level， and multi-target characteristics， which demonstrates the unique advantage of traditional Chinese medicine （TCM）. Therefore， it is of great significance to conduct and promote research on TCM treatment of AD. Danggui Shaoyaosan （DSS） from the Synopsis of Golden Chamber （《金匮要略》） by ZHANG Zhongjing （150 AD-219 AD） was originally designed for reliving gynecological ailments. It is a classic TCM formula that modulates liver and spleen and dispels blood stasis and water retention. Since the late 1980s when Japanese researchers reported its therapeutic effect on AD， it has been widely used in the clinic with clear effects. The elucidation of the mechanism of this formula helps exert its effects. Hereby， this paper reviewed relative research progress and made an analysis in terms of attenuating aberrant accumulation of Aβ and hyperphosphorylated Tau protein， anti-inflammatory and antioxidant activities， mediating neurotransmitters， ameliorating lipid metabolism， modulating gut microbiota， reduced neuron apoptosis， decreasing intracellular Ca²⁺ overloading， and increasing the expression of estradiol. This paper is expected to provide references for understanding the scientific connotation of DDS in the treatment of AD and lay a solid foundation for further investigation.

ObjectiveTo investigate the mechanism of Danggui Shaoyaosan （DSS） in the improvement of the cognitive ability of SAMP8 mice with Alzheimer's disease （AD） via regulating the ubiquitin-proteasome pathway （UPP）. MethodFifteen SAMR1 mice were used as a normal group， and 60 SAMP8 mice were randomly divided into a model group and DSS high， medium， and low-dose groups （57.6， 28.8， and 14.4 g·kg^-1·d^-1）， with 15 mice in each group. Intragastric administration was conducted for eight continuous weeks. Place navigation and spatial capacity were evaluated by Morris water maze. Pathological structure changes in neurons in the hippocampal CA1 area was detected by hematoxylin-eosin （HE） staining. The protein expression levels of hippocampal β-amyloid protein（Aβ） and phosphorylation（p）-Tau were determined by immunohistochemical staining （IHC） and enzyme-linked immunosorbent assay （ELISA）， and the mRNA and protein expression levels of hippocampal ubiquitin （Ub）， ubiquitin ligase E3 （E3）， 26S proteasome， ubiquitin carboxyl terminal hydrolase-1 （UCHL1）， and UCHL3 were determined by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultAs compared with the normal group， the escape latency was prolonged in the model group （P<0.05） with the reduced number of crossing platform quadrants and time ratio in the platform quadrant （P<0.05）. The model group decreased neurons and condensed cell bodies in the CA1 area， and increased β-amyloid precursor protein （β-APP） and p-Tau positive cells （P<0.05）. In the model group， the protein expression levels of Aβ and p-Tau were increased （P<0.05）， the mRNA and protein expression levels of Ub were increased （P<0.05）， and the mRNA and protein expression levels of E3， 26S proteasome， UCHL1， and UCHL3 were decreased （P<0.05）. As compared with the model group， the escape latency was shortened in the DSS high and medium-dose groups （P<0.05） with an increased number of crossing platform quadrants and residence time ratio （P<0.05）. The pathological changes in CA1 of each DSS group were significantly improved， and the number of β-APP positive staining cells decreased （P<0.05）. The number of p-Tau positive staining cells decreased in the DDS medium and low-dose groups （P<0.05）. The protein expression levels of Aβ and p-Tau in each DDS group decreased （P<0.05）， and the mRNA expression level of Ub in each group decreased （P <0.05）. The mRNA expression levels of 26S， E3， and UCHL3 in the DDS high and medium-dose groups increased （P<0.05）， and the mRNA expression level of UCHL1 in the DDS medium-dose group increased （P<0.05）. The protein expression level of Ub in each DDS group decreased， and the protein expression levels of 26S， E3， UCHL1+3 in the DDS high and medium-dose groups increased （P<0.05）. ConclusionDSS can improve the cognitive ability of SAMP8 mice， and its mechanism may be related to the reduction of the abnormal deposition of Aβ and p-Tau via decreasing the expression of Ub and increasing that of E3， 26S， UCHL1， and UCHL3 in the UPP.