OBJECTIVE To further standardize the technical operations and management processes throughout therapeutic drug monitoring （TDM）， clarify the clinical value of TDM implementation， improve the scientific validity and reliability of monitoring results， and provide a solid reference basis for the formulation and optimization of clinical individualized precision dosing regimens. METHODS The Guidelines for the Management of Therapeutic Drug Monitoring were formulated in accordance with the latest definition of guidelines by the Institute of Medicine of the National Academies and the standard guideline development methodology of the World Health Organization， and in compliance with the requirements of the appraisal of guidelines for research and evaluation. A modified Delphi method was adopted to establish the research question system； evidence-based medicine research methods were applied to systematically search multiple databases to screen the latest and most comprehensive evidence. Evidence was graded and evaluated based on the evidence grading system of the Chinese Evidence-Based Medicine Center， and the grading criteria for recommendation strength from the Oxford Centre for Evidence-Based Medicine were used to determine the recommendation strength. The recommendation opinions were formed through multidisciplinary expert consensus. RESULTS The Guidelines for the Management of Therapeutic Drug Monitoring cover four core modules， including TDM application indications， technical procedures， result interpretation and clinical application， and quality control， involving 18 primary research questions， 34 secondary research questions， and yield 82 recommendations. CONCLUSIONS The guidelines systematically standardize the key technical links and management requirements of the whole TDM process， provide scientific and operable standardized tools， help improve the standardization level of TDM work， promote the translation of monitoring results into clinical decision-making， and provide strong support for precision personalized medicine and ensuring the safety and rationality of medication use.

OBJECTIVE To standardize the main processes and related technical links of the clinical comprehensive evaluation of drugs， and provide guidance and reference for improving the quality of comprehensive evaluation evidence and its transformation and application value. METHODS The construction of Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs was based on the standard guideline formulation method of the World Health Organization （WHO）， strictly followed the latest definition of guidelines by the Institute of Medicine of the National Academy of Sciences of the United States， and conformed to the six major areas of the Guideline Research and Evaluation Tool Ⅱ. Delphi method was adopted to construct the research questions； research evidence was established by applying the research methods of evidence-based medicine. The evidence quality classification system of the Chinese Evidence-Based Medicine Center was adopted for evidence classification and evaluation. The recommendation strength was determined by the recommendation strength classification standard formulated by the Oxford University Evidence-Based Medicine Center， and the recommendation opinions were formed through the expert consensus method. RESULTS & CONCLUSIONS The Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs covers 4 major categories of research questions， including topic selection， evaluation implementation， evidence evaluation， and application and transformation of results. The formulation of this guideline has standardized the technical links of the entire process of clinical comprehensive evaluation of drugs， which can effectively guide the high-quality and high-efficient development of this work， enhance the standardized output and transformation application value of evaluation evidence， and provide high-quality evidence support for the scientific decision-making of health and the rationalization of clinical medication.

Objective In this paper,CiteSpace(V6.3.R1)was used to sort out and summarize the experimental study on the mechanism and development trend of acupuncture intervention in Alzheimer's disease(AD),so as to provide basis and suggestions for subsequent research.Methods Relevant literatures on the mechanism of acupuncture intervention in AD were retrieved from CNKI database from March 1997 to March 2024.CiteSpace(V6.3.R1)software was used to visually display keywords,draw corresponding maps,and discuss the hot spots of acupuncture intervention mechanism in AD.Results After screening,a total of 397 articles were included in this study.The mechanism of acupuncture intervention in AD mainly focuses on the regulation of synaptic plasticity,regulation of neurotransmitter release,regulation of neuroinflammation,regulation of apoptosis,influence on mitochondrial autophagy,anti-oxidative stress and so on.Conclusion Acupuncture intervention in AD has developed rapidly,involving Notch1/Hes signaling pathway,Shh signaling pathway,NF-κB signaling pathway,PI3K/Akt signaling pathway and other signaling pathways.The research heat of TCM acupuncture intervention in AD continues to rise,and various research teams have harvested rich research results,diversified research hotspots,and in-depth exploration of acupuncture treatment of AD has rich clinical value.

Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

Objective:This study aims to improve the management level and quality of horizontal scientific research contracts in hospitals, reduce the risk of contract management, and explore an efficient mode of information management of horizontal scientific research contract management.Methods:Taking a Tertiary Grade A hospital as an example, this study described and summarized the management status of horizontal scientific research contracts from 2018 to 2022, sorted out the potential risks and prevention and control nodes of the review, signing, performance, and archiving of horizontal scientific research contracts in the whole cycle management process, and designed an information management model according to the relevant elements of risk prevention and control and the standardized requirements of contract management, thereby developing information platform related functions.Results:The horizontal research contract management function of the clinical research platform based on the integration concept was available to meet the requirements of risk prevention and control of horizontal research contracts, and the contract review and signing cycle of the information management mode was shortened by 33.33% and 31.95% respectively compared with the traditional management mode. The platform realized a standardized whole process management of contract submission, review, repair and revision, signing, performance, and filing.Conclusions:Information management can effectively reduce the risk of horizontal scientific research contract management. It is necessary to strengthen the docking and interaction function with other information platforms and further explore the information auxiliary function to improve the refined management effect of horizontal scientific research contracts.

Objective To exploring the expression of microRNA-93-5p(miRNA-93-5p)and neuregulin protein 1(NRG1)in thyroid cancer tissues and their relationship with clinicopathological characteristics and survival prognosis.Methods Frozen tissue specimens of 136 patients with thyroid diseases who underwent surgical treatment in the hospital from January 2018 to May 2020 were selected,including 84 cases of thyroid cancer(thyroid cancer group),52 cases of benign thyroid diseases(benign thyroid disease group),and another 40 cases of normal thyroid tissues(control group).The relative expression levels of miRNA-93-5p and the positive expression rate of NRG1 in the tissues of the thyroid cancer group,the benign thyroid disease group and the control group were compared,and the relationship between the expression of miRNA-93-5p and NRG1 in patients with thyroid cancer and the clinicopathological characteristics was analyzed.Multivariate Logistic regression was used to analyze the influencing factors of miRNA-93-5p and NRG1 expression.Kaplan-Meier survival curve was used to analyze the relationship between the expression of miRNA-93-5p and NRG1 and survival prognosis in patients with thyroid cancer.Results There were statistically significant differences in the relative expression levels of miRNA-93-5p and the positive expression rate of NRG1 among the thyroid cancer group,the benign thyroid disease group and the control group(P＜0.05).The relative expression level of miRNA-93-5p in thyroid cancer tissues was negatively correlated with the positive expression rate of NRG1(r=-0.216,P=0.013).The proportion of tumor maximum diameter＞1 cm,the rate of moderate and low differentiation,the rate of capsular invasion,the rate of lymphatic metastasis,and the proportion of TNM stage Ⅲ+Ⅳ in the miRNA-93-5p high-expression group were higher than those in the miRNA-93-5p low-ex-pression group(P＜0.05),and the above indicators in the NRG1 high-expression group were all lower than those in the NRG1 low-expression group(P＜0.05).Multivariate Logistic regression analysis revealed that the maximum diameter of the tumor,degree of differentiation,capsular invasion,lymphatic metastasis and TNM stage were all influencing factors for the expression of miRNA-93-5p and NRG1.The 3-year cumulative survival rate of the miRNA-93-5p high-expression group was lower than that of the miRNA-93-5p low-expres-sion group(P＜0.05),and the 3-year cumulative survival rate of the NRG1 high-expression group was higher than that of the NRG1 low-expression group(P＜0.05).Conclusion In thyroid cancer tissues,miRNA-93-5p is highly expressed and NRG1 is lowly expressed.Both can be used as biomarkers for evaluating the survival prognosis of patients.

Objective In this paper,CiteSpace(V6.3.R1)was used to sort out and summarize the experimental study on the mechanism and development trend of acupuncture intervention in Alzheimer's disease(AD),so as to provide basis and suggestions for subsequent research.Methods Relevant literatures on the mechanism of acupuncture intervention in AD were retrieved from CNKI database from March 1997 to March 2024.CiteSpace(V6.3.R1)software was used to visually display keywords,draw corresponding maps,and discuss the hot spots of acupuncture intervention mechanism in AD.Results After screening,a total of 397 articles were included in this study.The mechanism of acupuncture intervention in AD mainly focuses on the regulation of synaptic plasticity,regulation of neurotransmitter release,regulation of neuroinflammation,regulation of apoptosis,influence on mitochondrial autophagy,anti-oxidative stress and so on.Conclusion Acupuncture intervention in AD has developed rapidly,involving Notch1/Hes signaling pathway,Shh signaling pathway,NF-κB signaling pathway,PI3K/Akt signaling pathway and other signaling pathways.The research heat of TCM acupuncture intervention in AD continues to rise,and various research teams have harvested rich research results,diversified research hotspots,and in-depth exploration of acupuncture treatment of AD has rich clinical value.

Objective:This study aims to improve the management level and quality of horizontal scientific research contracts in hospitals, reduce the risk of contract management, and explore an efficient mode of information management of horizontal scientific research contract management.Methods:Taking a Tertiary Grade A hospital as an example, this study described and summarized the management status of horizontal scientific research contracts from 2018 to 2022, sorted out the potential risks and prevention and control nodes of the review, signing, performance, and archiving of horizontal scientific research contracts in the whole cycle management process, and designed an information management model according to the relevant elements of risk prevention and control and the standardized requirements of contract management, thereby developing information platform related functions.Results:The horizontal research contract management function of the clinical research platform based on the integration concept was available to meet the requirements of risk prevention and control of horizontal research contracts, and the contract review and signing cycle of the information management mode was shortened by 33.33% and 31.95% respectively compared with the traditional management mode. The platform realized a standardized whole process management of contract submission, review, repair and revision, signing, performance, and filing.Conclusions:Information management can effectively reduce the risk of horizontal scientific research contract management. It is necessary to strengthen the docking and interaction function with other information platforms and further explore the information auxiliary function to improve the refined management effect of horizontal scientific research contracts.

Objective:To evaluate the effect of Kuntai capsules combined with progestin-primed ovarian stimulation (PPOS) protocol on the ovarian response, laboratory parameters and embryo transfer outcomes of expected poor ovarian response (POR) patients undergoing invitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. Methods:A retrospective cohort study was performed at Center for Reproductive Medicine, Jiangxi Maternal and Child Health Hospital from June 2020 to July 2023. A total of 1 733 expected POR patients were enrolled and divided into the PPOS only group (control group) and the Kuntai capsules combined with PPOS regimen group (trial group). After a 1∶1 propensity score matching, 423 cases were included in each group. Further analyses and comparisons were made between the two groups, concerning the ovarian stimulation outcomes, embryo laboratory parameters and pregnancy rates after the first frozen-thawed embryo transfer cycles. The primary outcome measure was the number of oocytes retrieved.Results:No statistically significant difference was found in baseline characteristics after matching between the two groups (all P>0.05). Compared with control group, the number of oocytes retrieved did not differ significantly in the trial group ( P=0.295). The level of luteinizing hormone (LH) on the trigger day [3.3 (2.2, 5.0) U/L], the number of available blastocysts formed [1 (0, 1)] and the available blastocyst formation rate [46.2% (85/184)] in the trial group were significantly higher than those in control group [2.9 (1.9, 4.5) U/L, P=0.004; 0 (0, 1), P=0.034; 30.0% (48/160), P=0.002]. However, there were no significant differences in the duration and dosage of gonadotropin used, progesterone and estradiol levels on the trigger day, incidence of premature LH surge, number/rate of fertilized oocytes, number/rate of cleaved embryos, number/rate of high-quality embryos, as well as rate of unavailable embryos (all P>0.05). Compared with control group, the trial group demonstrated comparable implantation rate, clinical pregnancy rate, early miscarriage rate, ongoing pregnancy rate and live birth rate after the first frozen-thawed embryo transfer cycles (all P>0.05). Conclusion:Compared with the PPOS only regimen, the combination of Kuntai capsules and PPOS did not increase the number of oocytes retrieved but could increase the number and rate of available blastocysts formed in expected POR patients.

Objective:To explore the clinical application value of third-generation sequencing technology in preimplantation genetic testing (PGT) of an ATR-X syndrome pedigree with chromosomal microduplication.Methods:The study selected a pedigree with a suspected ATR-X syndrome child at Assisted Reproductive Center of Jiangxi Maternal and Child Health Hospital in October 2022. After chromosome copy number variation sequencing (CNV Seq) detection, it was found that the female carried a 550 kb heterozygous microrepeat with unclear clinical significance in the Xq21.1 region, which involved partial sequences of the ATRX gene. The third generation long read sequencing technology was used to detect the female genome sequence, determine the physical location of the insertion of the above repeat into the genome, clarify the pathogenicity of the repeat, and obtain a single nucleotide polymorphism (SNP) haplotype linked to the above micro repeat inheritance. After the couple's full informed consent, PGT was performed to assist pregnancy. One haploid embryo without pathogenic microduplication was selected for transfer. To verify the consistency with PGT test results, amniocentesis prenatal diagnosis was performed in the second trimester after successful pregnancy, and the fetus was followed up after birth. Results:The results of the third generation long read sequencing and Sanger sequencing verification showed that the Xq21.1 microrepeat carried by the female was inserted into the genome chrX: 76804463-76804464 (GRCh37/hg19), which is an intra tandem repeat of the ATRX gene, and it is predicted that it may cause damage to the normal function of the ATRX protein. After one cycle of PGT treatment, 27 oocytes were obtained and 13 blastocysts were successfully developed after intracytoplasmic sperm injection (ICSI). Through genetic testing, it was found that two blastocysts were haploid embryos without carrying the aforementioned pathogenic microduplication. After thawing and transferring one of the blastocysts, the pregnancy was achieved, and the prenatal diagnosis results of amniocentesis in the second trimester were consistent with the PGT results. In November 2023, at 39 +5 weeks of pregnancy, a female live baby was delivered by natural delivery, and she is in good health. Conclusion:The third-generation sequencing technology has significant advantages in PGT detection of clinically ambiguous microreplicates with functional deficiency due to its long read length characteristics. It can not only determine the location of microreplicates inserted into the genome and determine their pathogenicity, but also obtain SNP haplotypes that are linked to the target mutation, thus preparing for subsequent embryo detection.