OBJECTIVE To explore the influencing factors for successful detoxification in patients undergoing methadone maintenance therapy. METHODS A retrospective selection of 161 methadone maintenance therapy patients from the South Branch of Zhongshan Second People’s Hospital （including methadone maintenance treatment sites in Shiqi District， Xiqu District， Development Zone of Zhongshan City） from January 1， 2012， to January 1， 2025， was conducted as the study object. Data collected included patients’ sociodemographic information， drug abuse history， laboratory test results， medication records， etc. Patients were divided into the unsuccessful detoxification group and the successful detoxification group based on whether methadone detoxification was achieved. Univariate， univariate Cox regression， and multivariate Cox proportional hazards regression were used for influencing factor analysis， and the Kaplan-Meier method was employed for survival analysis. RESULTS Among the 161 methadone maintenance therapy patients， 96 were in the successful detoxification group and 65 in the unsuccessful detoxification group， yielding a successful detoxification rate of 59.63%. Multivariate Cox proportional hazards regression analysis revealed that age， registered residence status， age at first drug use， and duration of drug abuse were key influencing factors for successful detoxification in methadone maintenance therapy patients （P＜0.05）. Specifically， the successful detoxification rate for patients with Zhongshan local registered residence was 8.364 times higher than that for patients with non-local registered residence； for every 1-year increase in patient age， the successful detoxification rate decreased by 22.7%； for every 1-year increase in age at first drug use， the successful detoxification rate rose by 33.4%； and for every 1-year increase in duration of drug abuse， the successful detoxification rate increased by 33.5%. Survival analysis showed that the successful detoxification rate in the methadone low-dose group （≤30.8 mg） was significantly higher than that in the methadone high-dose group （＞30.8 mg） （P＝0.015）， and the successful detoxification rate in the population with Zhongshan local registered residence was significantly higher than that in those with non-local registered residence （P＜0.001）. CONCLUSIONS Age， registered residence status， age at first drug use， and duration of drug abuse are key influencing factors for successful detoxification in patients undergoing methadone maintenance therapy， and the last methadone dose may be associated with successful detoxification.

OBJECTIVE To establish management index system for rational drug use of key monitoring drugs， and provide reference for the management of key monitoring drugs in the hospitals. METHODS First， the management index system for rational drug use of key monitoring drugs was drafted by collecting the evidence from related medical literature. Next， using a modified Delphi method， twenty experienced experts from the fields of pharmacy， medical practice， healthcare insurance， and finance were selected to participate in two rounds of questionnaire consultations. Based on the expert enthusiasm coefficient， authority coefficient， degree of opinion concentration， and degree of coordination， the final indicators were determined to establish a management index system for rational drug use of key monitored drugs in medical institutions. RESULTS The expert enthusiasm coefficients reached 100% in both rounds of consultation. In first-level， second-level and third-level indicators， the authority coefficients of experts were 0.89， 0.86 and 0.87， and coordination coefficients of the experts in importance score were 0.300 （P＜ 0.05）， 0.125 （P＜0.05） and 0.139 （P＜0.05）， respectively. The average score for the importance of all indicators reached over 3.5， in which the full score ratio ranged from 35% to 100%. Except that the variation coefficient of a third-level indicator “number of specifications purchased for key monitored drugs” was 0.26， the variation coefficients of rest indicators were less than or equal to 0.25. Based on the results of expert consultation， final version of the management index system established in this study， including two first-level indicators （drug procurement and use， and rational drug use）， five second-level indicators （such as the accessibility， cost-effectiveness） and twenty third-level indicators （such as the number of specifications purchased for key monitored drugs， the increase in the cost of key monitored drugs）. CONCLUSIONS The management index system established in this study possesses high reliability and strong operability， and may provide a reference for the management of key monitoring drugs in the hospitals.

BACKGROUND:3D organoids have characteristics that resemble physiological tissues and to some extent mimic organ function,making them excellent models for applications ranging from basic development/stem cell research to personalized medicine. OBJECTIVE:To review and discuss the types of diseases and application areas such as tumor modeling that organoids can be applied to,as well as their regulatory status and challenges. METHODS:With"organoid,stem cell,disease model,3D printing technology,medical field"as Chinese and English search terms,we searched PubMed,Elsevier,WanFang,and CNKI databases to summarize and analyze organoid products at home and abroad,summarize the application of organoid technology in the medical field,and prospect the future development of organoid products in the medical field. RESULTS AND CONCLUSION:Organoids can break the limitations of traditional cell and animal models,avoid the ethical problems existing in clinical research,and have a high similarity to the source organ,a more similar performance to the physiology and pathology of human systems,and genetic stability,which has great advantages in current research.Organoids have been applied in the following fields:efficacy evaluation studies(preclinical models),including intestinal organoids,kidney organoids,liver organoids,gallbladder organoids,lung organoids,brain organoids,heart organoids,skin organoids,and reproductive system organoids;research on infectious diseases;cancer research and precision therapy;regenerative medicine;immune organoids.Although the United States,the European Union and China do not have perfect regulatory provisions,they are trying to promote the formulation of organoid regulatory laws and regulations.In China,although no organoid medical device products have been listed for the time being,its related regenerative medicine products have made breakthroughs.

Objective:This study aimed to compare the effects of cochlear implantation（CI） on vestibular function in patients with large vestibular aqueduct syndrome（LVAS） and in patients with extremely severe deafness with normal inner ear structure. Methods:A total of 28 LVAS patients and 28 patients with normal inner ear structure who suffered from extremely severe deafness were selected. The parameters of caloric tests, bone conduction evoked cervical vestibular-evoked myogenic potentials（cVEMP）, bone conduction evoked ocular vestibular-evoked myogenic potentials（oVEMP） and video head impulse tests（v-HIT） were compared between the two groups before and after CI. The data were analyzed using SPSS 26.0 software. Results:There was no significant difference in the results of the preoperative caloric test, v-HIT, and oVEMP（P1, N1） between the LVAS group and the control group（P>0.05）. Compared to the control group, the LVAS group exhibited a shorter cVEMP P1[（13.41±0.71）ms vs （16.28±0.89）ms, P<0.000 1], shorter N1[（19.83±0.54）ms vs （28.18±1.56）ms, P<0.000 1], higher amplitude[（123.60±83.80）μV vs （73.92±79.85）μV, P=0.049 4] and higher oVEMP amplitude[（16.60±13.87）μV vs （9.96±10.47）μV, P=0.028 5] before CI. The abnormal rate of caloric test increased in both groups after CI（25.00% vs 57.14%, P=0.028 8, 32.14% vs 82.14%, P=0.000 3, respectively）. There was no significant difference in the v-HIT parameters in both groups before and after the operation. As for the LVAS group, there was no statistically significant difference in cVEMP and oVEMP induction rates before and after operation. In the control group, there was a decrease in cVEMP induction rate（96.42% vs 64.28%, P=0.005 2） and oVEMP induction rate（96.42% vs 57.14%, P=0.000 9） after CI. LVAS group showed a shorter cVEMP P1[（13.41±0.71）ms vs （10.30±0.60）ms, P<0.000 1]; shorter cVEMP N1[（19.86±0.53）ms vs （18.97±1.33）ms, P=0.004 7]; decreased amplitude[（124.50±84.86）μV vs （64.35±61.57）μV, P=0.001 0] and shorter oVEMP amplitude[（15.92±13.03）μV vs （9.16±9.20）μV, P=0.009 9] after CI. The oVEMP N1 in the control group was longer than that before operation[（11.73 ± 0.91）ms vs （13.35 ± 2.60）ms, P=0.019 6], whereas there was no significant difference in other VEMP parameters after CI. Conclusion:Before CI, there was no significant difference in the results of the caloric test and v-HIT between the LVAS group and the control group, but the LVAS group exhibited increased sensitivity to acoustic stimulation-induced myogenic potentials. After CI, the function of the semicircular canal was impaired in both groups in the low-frequency area, and remained largely unaffected in the high-frequency area. Additionally, the function of the otolith in the LVAS group was less affected than that in the control group after CI, which may be related to the fact that the enlarged vestibular aqueduct of the LVAS patients acted as the third window of the inner ear.
Humans ; Vestibular Aqueduct/physiopathology* ; Cochlear Implantation ; Male ; Female ; Vestibular Evoked Myogenic Potentials ; Deafness/physiopathology* ; Child ; Adolescent ; Adult ; Young Adult ; Hearing Loss, Sensorineural/physiopathology* ; Vestibular Function Tests

Objective:To explore the molecular basis for an individual with Bel subtype of the ABO blood type due to a novel c. 620T>C variant gene, and assess its impact on the structure of GTB transferase.Methods:An individual who had visited the First Affiliated Hospital of Zhengzhou University on February 11, 2023 was selected as the study subject. ABO phenotyping was initially conducted with serological methods, which was followed by direct sequencing of 7 exons of the ABO gene. Subsequently, single-strand sequencing was carried out by using allele-specific primers, and the variant in the B transferase was homology-modeled using the Modeller software. The impact of the variant on the transferase′s spatial structure was analyzed with the PyMOL software. Results:The serological phenotype of the patient was identified as the Bel subtype. Direct sequencing revealed that she has harbored a novel c. 620T>C variant, resulting in a p. Leu207Pro substitution in the polypeptide chain. Combined with single-strand sequencing, her genotype was ultimately determined as ABO* BELnew/ ABO* O.01.02. Three-dimensional protein structure modeling showed that, compared with the wild type, the distance of one hydrogen bond between Proline and Glycine at position 272 has increased, along with disappearance of another hydrogen bond. Conclusion:The novel c. 620T>C (p.Leu207Pro) variant of B allele may affect the structural stability of the glycosyltransferase. The weakened enzyme activity in turn may lead to reduced B antigen expression, manifesting as the Bel subtype by serological analysis.

Objective:To explore the RH genotype for a female with RhD(-) blood type and its molecular basis. Methods:A 26-year-old female who had attended the outpatient clinic of the First Affiliated Hospital of Zhengzhou University in August 2019 was selected as the study subject. Peripheral blood samples were collected from the proband and her parents for Rh phenotyping with gel card method. PCR-sequence-based typing (PCR-SBT) and DNA sequencing were used to determine the RHD zygosity and RH genotype of the proband and her parents. Homology modeling of Rh proteins was performed with bioinformatic software, and protein structural alterations caused by the variant was simulated by molecular dynamics. This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No. 2023-KY-0870-003). Results:Serological tests showed that the proband and her father both had weakened e antigen of the Rh phenotype. PCR-SBT and DNA sequencing showed that the genotypes of the proband and her parents were dce/ dCE, dce/ DcE and dCE/ DcE, respectively. And the genotypes of the RHD and RHCE of the proband were RHD*01N.01/ RHD*01N.16, RHCE*01.01/RHCE*04, respectively. Protein simulation and molecular dynamics analysis revealed that the ce_16C variant resulted from RHCE* ce (c.48G>C) may alter the structure of intracellular and extracellular loops, mainly affecting the mobility of extracellular loops 2, 6 and intracellular loops 3, 4. Conclusion:Variant of the RHCE* ce allele c. 48G>C probably underlay the weakened e antigen in this proband.

Objective:To investigate the distribution characteristics of cognition-related lifestyles of elderly in communities and explore the integrated effects on early cognitive decline.Methods:The participants were from the Project of Prevention and Intervention of Neurodegenerative Disease for Elderly in China. A total of 2 537 older adults aged ≥60 years without dementia in the 2015 baseline survey and the 2017 follow-up survey were included. The information about their cognition-related lifestyles, including physical exercise, social interaction, leisure activity, sleep quality, smoking status, and alcohol consumption, were collected through questionnaire survey and the integrated scores were calculated. Multivariate logistic regression analysis was used to assess the association between integrated cognition-related lifestyle score and early cognitive decline.Results:In the 2 537 older adults surveyed, 28.7% had score of 5-6, while only 4.8% had high scores for all 6 healthy lifestyles. Significant differences in healthy lifestyle factor distributions were observed between men and women. Multivariate logistic regression model showed that the risks for early cognitive decline in the older adults who had lifestyle score of 4 and 5-6 were lower than that in those with lifestyle score of 0-3 ( OR=0.683, 95% CI: 0.457-1.019; OR=0.623, 95% CI: 0.398-0.976; trend P=0.030). In the women, the risks for early cognitive decline was lower in groups with score of 4 and 5-6 than in group with score of 0-3 ( OR=0.491, 95% CI: 0.297-0.812; OR=0.556, 95% CI: 0.332-0.929; trend P=0.024). Conclusion:Cognition-related healthy lifestyles are associated with significantly lower risk for early cognitive decline in the elderly, especially in women.

BACKGROUND:Exercise as a viable non-pharmacological treatment has the potential to reverse skeletal muscle aging that deteriorates with age.The role of autophagy in the skeletal muscle aging process is indispensable.During skeletal muscle aging,Atg genes involved in regulating autophagy regulate the autophagic process in either a facilitative or inhibitory manner to improve the physiological morphology of skeletal muscle.However the specific molecular mechanisms of autophagy in the exercise regulation of skeletal muscle aging remain puzzling. OBJECTIVE:To search for general patterns of the effects of autophagic mechanisms on skeletal muscle aging during exercise through a review of articles in this field. METHODS:(1)CNKI and Web of Science were searched,reviewed,and screened for relevant literature using the keywords of"Atg genes(proteins),autophagy,exercise,and skeletal muscle aging"to lay the theoretical foundation for the full-text analysis.(2)The comparative analysis method was used to compare the similarities and differences among the included documents to provide reasonable theoretical support for the arguments.By the further comparative analysis of the literature,the relationship between relevant indicators was clarified,to provide the ideas for the full-text analysis. RESULTS AND CONCLUSION:Atg family-mediated autophagy is indispensable for delaying skeletal muscle aging.Atg genes involved in regulating autophagy regulate the autophagic process in either a facilitative or inhibitory manner to improve the physiological morphology and function of skeletal muscle.Different exercise patterns,such as age,time,or intensity at initiation,may have heterogeneous effects on the expression of autophagy-related proteins,but long-term aerobic exercise regulates Atg-related proteins,induces skeletal muscle autophagy,and delays the loss of muscle mass.

BACKGROUND:Aging is an irreversible process that is characterized by genes,diet and environment.As a central regulator of growth and development,mammalian target of rapamycin(mTor)can regulate the negative effects caused by aging,exercise and poor diet,which are correlated with the activity of mTor and its complexes.However,the relationship between these factors,such as mTor and the effect of exercise on aging,is still unclear. OBJECTIVE:To study the relationship between exercise,high fat/high salt diet and mTor in aging,so as to have a more comprehensive understanding of the prevention and treatment mechanism of aging. METHODS:(1)Literature retrieval was conducted in the core database of Web of Science and CNKI,using the keywords of"mTor gene,exercise,high fat/high salt diet,aging,"thereby providing theoretical support for this review.(2)Comparative analysis provided a theoretical basis for this thesis by carefully reading the obtained effective literature and comparing the differences among various literatures.(3)Through the comparative analysis of similarities and differences between the included articles,we could define each index and their relationship,so as to clarify the ideas of this review. RESULTS AND CONCLUSION:mTor is closely related to aging.Through the literature analysis,we believe that two complexes of mTor,mTorC1 and mTorC2,play important roles in aging,exercise and skeletal muscle growth and development.In addition,mTor-mediated S6K1,Akt,FOXO,and 4E-BP1 signaling pathways are strongly associated with exercise,high-fat diet,high-salt diet,and skeletal muscle/heart aging.

Objective To establish a highly sensitive,stable,and universally applicable ultra-high-performance liquid mass spectrometry tandem method(UPLC-MS/MS)for simultaneous determination of nirmatrelvir and ritonavir blood concentrations in human plasma.Methods The separation was performed on an ACQUITY UPLC BEH C18 column(2.1 mm× 50 mm,1.7 μm)with gradient elution,and the mobile phase consisted of 0.1％formic acid-water and 100％acetonitrile at the flow rate of 0.3 mL·min-1.The column temperature was 45℃,and the injection volume was 2 μL.Electrospray ionization as ion source(ESI+)was used as the ion source and multiple reactions monitoring mode(nirmatrelvir m/z 500.20→319.10,nirmatrelvir-D9 m/z 508.59→328.10,ritonavir m/z 721.30→426.10,13C,2H3-ritonavir m/z 725.30→426.10)was adopted.Thirty patients with coronavirus disease 2019(COVID-19)treated with nirmatrelvir and ritonavir at the People's Hospital of Changxing County in Jan.2023 were selected to measure their steady-state trough concentrations of nirmatrelvir and ritonavir after 3 days of treatment.Results The linear range of nirmatrelvir was 0.100-10.0 μg·mL-1(R2=0.997 2),and the linear range of nirmatrelvir was 0.050-5.00 μg·mL-1(R2=0.995 2).The recovery rates of nirmatrelvir and lopinavir were both＞90％and the intra-batch and inter-batch precision relative standard deviations(RSDs)were both＜10％.Additionally,the recovery ranges for nirmatrelvir and lopinavir were 91.5％-97.0％,and the matrix effects ranged from 92.4％to 97.7％.The results of clinical samples showed that the plasma concentrations of nirmatrelvir and ritonavir in patients with COVID-19 varied greatly among individuals.Conclusion The method for simultaneous determination of nirmatrelvir and ritonavir concentrations in human plasma established in this study is convenient,highly specific,highly accurate,with high precision,which is suitable for monitoring the concentrations of nirmatrelvir and ritonavir in patients.