Phosphatidylinositol 4 kinases are the initial and key molecules of the phosphatidyl inositol signaling pathway.Among them,the phosphatidylinositol 4-kinaseⅢ β(PI4KⅢβ)is in-volved in the synthesis of the Golgi PI4P pool,playing a vital role in numerous physiological processes.Meanwhile,the en-zyme is an important host factor mediating the replication of some pathogenic RNA viruses,and participating in other patho-logical processes such as bacterial infection and malaria.In ad-dition,studies have shown that the function of PI4KⅢβ is regu-lated by numerous factors,including host and viral protein bind-ing partners.This review will discuss the structure and the phys-iopathology regulatory mechanism of PI4KⅢβ.

This study was aimed at investigating the pathogenic and molecular characteristics of Klebsiella pneumoniae(KP)in fecal samples of diarrhea cases in a district of Beijing.Fecal samples from diarrhea cases in an outpatient department in a district of Beijing from 2018 to 2021 were collected,and used for isolation and culture of KP.The KP strains isolated strains were subjected to drug resistance phenotype testing and whole-genome sequencing.Multilocus sequence typing and whole-genome phyletic evolution analysis were performed on the sequencing results.The cases'epidemiological and clinical characteristics were analyzed.From 2018 to 2021,1 103 fecal samples were collected and detected.The total detection rate of KP was 10.43％(115/1 103),and the infection rate of KP mixed with other diarrhea-causing pathogens was 42.61％(49/115).The positivity rate was slightly high(12.47％,61/489)a-mong females and was highest in young adults 16-45 years of age.Small peaks were observed in January,April to May,and August to September.The gastrointestinal symptoms in cases were mainly nausea and watery stool,and the suspicious food was unknown.Ampicillin,tetracycline,and sulfafurazole were the top three antibiotics to which these 115 KP strains showed resistance,and 29 strains were resistant to multiple antibiotics.The strains were divided into 72 sequence types,among which ST23 was dominant.According to the phylogenetic tree,the strains were divided into four main branches,among which 14 ST23 strains had a very close genetic relationship with the highly virulent NTUH-K2044 reference strain.KP infection persisted in fecal samples from diarrhea cases in the district of Beijing.Women and young adults were particularly susceptible.The drug resistance of KP strains in this region was very serious,and the ST types were diverse.Moreover,the ST23 pathogenic strains were closely related to high virulence strains.

AIM To analyze the metabolites of nobiletin in rats in vivo based on characteristic ions.METHODS Ten rats were assigned into administration group and control group,and given intragastric administration of the 0.5％CMC-Na suspension of nobiletin(250 mg/kg)and 0.5％CMC-Na solution,respectively,after which plasma,urine and feces were collected,solid phase extraction method was adopted in pretreatment,UHPLC-HRMS analysis was performed.The candidate metabolites were systematically described according to diagnostic product ions,chromatographic retention time,accurate molecular weight and neutral loss fragments,after which accurate metabolites were obtained in the established metabolite data set with-CH3(m/z 15)characteristic ions as a baits.RESULTS A total of 64 metabolites were identified,whose main metabolic pathways were glucuronidation,sulfation,hydrogenation and their compound reactions.CONCLUSION This experiment elucidates the metabolites of nobiletin in rats in vivo,which provides a new reference for its further development.

Objective:To observe the clinical efficacy of exercise-based acupuncture in treating ischemic stroke and its effects in improving the patient's motor function and daily living ability. Methods:A total of 106 patients with motor dysfunction due to cerebral infarction were randomized into a trial group and a control group,each consisting of 53 cases.Both groups received conventional rehabilitation;in addition,the control group was given point-toward-point acupuncture at scalp points,and the trial group was offered exercise-based acupuncture,3 times weekly for 4 consecutive weeks.Before treatment,after 2 and 4 weeks of treatment,and at the 2-month follow-up,the Fugl-Meyer assessment(FMA)scale,Lovett scale for muscle strength,modified Ashworth scale(MAS),and activities of daily living(ADL)scale were used to assess the patient's motor function,muscle strength,muscle tension,and daily living ability. Results:After treatment,both groups gained improvements in motor function and daily living ability;after 4-week treatment and at the 2-month follow-up,the trial group had higher FMA and ADL scores than the control group(P<0.05).The MAS score decreased after treatment in both groups;after 2 and 4 weeks of treatment and at the 2-month follow-up,the MAS score was lower in the trial group than in the control group(P<0.05).After the intervention,the Lovett score increased in both groups;after 4 weeks of treatment,the Lovett score was higher in the trial group than in the control group(P<0.05). Conclusion:Based on routine rehabilitation,exercise-based acupuncture and scalp point-toward-point acupuncture both can improve the motor function and daily living ability in ischemic stroke patients;exercise-based acupuncture performs better than scalp point-toward-point acupuncture.

Objective To analyze the antimicrobial susceptibility,molecular types,serotypes,virulence factors and resistance mechanisms of Streptococcus agalactiae(S.agalactiae)isolated from pregnant women with ad-vanced maternal age in Tangshan City,and provide basic data for the treatment,prevention and control of S.aga-lactiae infection.Methods 42 strains of S.agalactiae isolated from pregnant women with advanced maternal age in North China University of Science and Technology Affiliated Hospital as well as Tangshan Maternal and Child Health Hospital were collected.Detection of antimicrobial susceptibility and whole genome sequencing of 13 antimi-crobial agents were performed.Results The percentage of tetracycline,erythromycin,levofloxacin,and chloram-phenicol concurrently resistant strains was 7.1％,35.7％of the strains presented multidrug resistance to erythro-mycin,clindamycin,and levofloxacin.The carriage rates of resistance genes ermB and tetM were 66.7％and 47.6％,respectively.29 strains(69.0％)exhibited mutations in both gyrA and parC fluoroquinolone resistance determi-nants.42 strains of S.agalactiae belonged to 4 serotypes,namely ⅠB(35.7％),Ⅲ(33.3％),Ⅴ(26.2％),andⅠA(4.8％);and 11 sequence types(STs),with the highest proportion being ST10(35.7％)and ST19(31.0％);as well as 6 clonal complexes(CCs),among which CC19(42.9％)and CC12(35.7％)had the highest proportion.All S.agalactiae carried virulence factor-encoding genes of cfb,cylE,and pavA.Conclusion The molecular types and serotypes of S.agalactiae carried by pregnant women with advanced maternal age in Tangshan City pre-sent polymorphism,with obvious multidrug resistance,and carry multiple types of drug resistance genes and viru-lence genes.

Objective:To explore the effects of ultra-high dose rate pulsed electron beams on Caenorhabditis elegans ( C. elegans). Methods:The adult wild-type strain (N2) of C. elegans was synchronized and cultured to L4 stage, and then randomly divided into control group (SHAM group), conventional radiotherapy dose rate group (CONV group) and ultra-high dose rate radiation group (UHDR group). The CONV and UHDR groups were exposed to 3 Gy of the pulsed electron beam at dose rates of 0.3 and 200 Gy/s, respectively. After irradiation, the egg-laying capacity of each group was assessed, and the developmental progress, motility, and survival rates each were evaluated at day 3, 6, and 10. Results:On the 3 rd day post-irradiation, both the CONV and UHDR groups showed shorter body lengths compared to the SHAM group ( t=4.81, 4.83, P<0.05), with no significant differences in body width ( P>0.05). On the 6 th and 10 th days, the CONV group showed a significant reduction in both body length and width compared to the SHAM group ( t=3.18-3.63, P<0.05), whereas the UHDR group displayed a significant increase in body length ( t=-9.85, -2.87, P<0.05) with no significant change in body width. When comparing the UHDR group to the CONV group on day 6 and 10, a significant increase in body width was observed ( t=-4.43, -3.37, P<0.05). Motor activity, including head swinging and body bending, significantly decreased in the CONV and UHDR groups compared to the SHAM group on day 6 ( t=2.91, 3.52, 3.97, 2.71, P<0.05), with no significant differences among the three groups by day 10 ( P>0.05). Egg-laying capacity significantly reduced in both irradiated groups compared to the SHAM group ( t=1.72, 5.54, P<0.05), while the UHDR group exhibited higher fecundity than the CONV group ( t=-5.99, P<0.05). Lifespan was significantly shortened in the CONV group compared to the SHAM group ( χ2=8.49, P<0.05), whereas the survival time of the UHDR group was not significantly differ from that of the SHAM group ( P>0.05). Conclusions:Exposure to a conventional electron beam result in developmental delays, reduced mobility, decreased fecundity, and a shortened lifespan in C. elegans. However, only slight side effects were observed when C. elegans were exposed to an ultra-high dose rate pulsed electron beam at the same dosage.

Acute hepatic porphyria （AHP） is a rare disease with abnormal heme metabolism， and breakthroughs have been made in the treatment of this disease in recent years. In addition to conventional treatment methods， this article reviews new therapies for AHP that are in the stage of initial clinical application or are still in the research stage， including RNAi therapy， enzyme replacement therapy， genetic supplementation of DNA or mRNA， drug molecular chaperones， and glycine transporter inhibitors for reducing heme synthesis. Moreover， this article also reviews the treatment of AHP-related comorbidities and complications， such as hyponatremia and posterior reversible encephalopathy syndrome. High glucose infusion is the main treatment method for AHP in China， and the improvement in diagnosis and increased attention to rare diseases in China has promoted the development of the diagnosis and treatment of AHP， and it is expected to explore more suitable treatment methods for AHP in the Chinese population in the future.

【Objective】 To measure and analyze foot development indicators of children under 3 years old, in order to provide basis for the correct clinical assessment of children foot development. 【Methods】 A total of 5 894 children under 3 years old who took physical examination in the Child Health Care Department of Xi′an People′s Hospital from August 2022 to March 2023 were randomly selected. Foot length, foot width, the ratio of foot width to length and arch index were measured by image processing system, and were compared among different age groups and sex groups. 【Results】 1) Foot length, foot width and arch index of children under 3 years old increased significantly with age, while the ratio of foot width to length decreased significantly with age(F=1 345.23, 396.21,184.65, 287.03, P<0.05). 2) There was no statistical significance in foot length, foot width and arch index between left and right foot of children under 3 years old(P>0.05). 3) Foot length and foot width of boys were greater than those of girls in all age groups, and the difference was statistically significant(tfoot length:3.45 - 10.19, tfoot width: 3.77 - 9.21, P<0.05). There was no significant difference in arch index between boys and girls in all age groups(P>0.05). 【Conclusion】 Foot shape of children under 3 years old changes with age, there are differences in foot length and width between boys and girls.

Since the approval of gemtuzumab ozogamicin,an antibody-drug conjugate(ADC)targeting CD33 in 2000,13 ADC drugs have been approved by the FDA.Although these drugs have clearly improved the survival of patients with various types of advanced cancers,their significant toxicity has compromised their therapeutic benefits.The adverse reactions of ADC drugs are complex and include on-target and off-target toxicities,where the payload drug is a determining factor.Antibody and linker may also affect the degree of toxicity.Combination therapy becomes an important strategy in anticancer treatment because of its increased efficiency,but treatment-related adverse reactions also increase accordingly.This review comprehensively analyzes the toxicity mechanisms of current ADC drugs and proposes various optimization strategies,including but not limited to optimizing linker molecules,upgrading antibody design,and changing drug administration strategies,to improve the overall safety profile of ADC drugs.

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.