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.

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 It compared the power consumption and electrical parameters between Thulium fiber laser devices(TFL)and Holmium laser devices(HoL)in transurethral enucleation of prostate(TUEP).Methods A sin-gle surgeon conducted TUEP by THL or HoL in 10 patients respectively.The enucleation efficiency,the laser energy output and the electric parameters were recorded and analyzed.Results The data from both groups of surgeries were tested for normal distribution,and the t-test found that the difference in the enucleation efficiency between the two surgeries was not statistically significant(P=0.818),and the energy consumption indexes of the two devices were comparable.The difference in the total kilojoules of laser emission between the two lasers during surgery was not statistically significant(P=0.148),but the power consumption of the thulium laser was about one-tenth of that of the holmium laser(P＜0.001),suggesting that the former utilised electrical energy significantly more efficiently than the latter.The maximum current of the HoL was significantly higher than that of the TFL(P＜0.001),requiring a spe-cial high-power power outlet.Conclusion TFL was superior to HoL in terms of lower power consumption,higher en-ergy-efficient and electrical convenient in transurethral enucleation of the prostate.

Objective It compared the power consumption and electrical parameters between Thulium fiber laser devices(TFL)and Holmium laser devices(HoL)in transurethral enucleation of prostate(TUEP).Methods A sin-gle surgeon conducted TUEP by THL or HoL in 10 patients respectively.The enucleation efficiency,the laser energy output and the electric parameters were recorded and analyzed.Results The data from both groups of surgeries were tested for normal distribution,and the t-test found that the difference in the enucleation efficiency between the two surgeries was not statistically significant(P=0.818),and the energy consumption indexes of the two devices were comparable.The difference in the total kilojoules of laser emission between the two lasers during surgery was not statistically significant(P=0.148),but the power consumption of the thulium laser was about one-tenth of that of the holmium laser(P＜0.001),suggesting that the former utilised electrical energy significantly more efficiently than the latter.The maximum current of the HoL was significantly higher than that of the TFL(P＜0.001),requiring a spe-cial high-power power outlet.Conclusion TFL was superior to HoL in terms of lower power consumption,higher en-ergy-efficient and electrical convenient in transurethral enucleation of the prostate.

Objective Postoperative delirium(POD)has become a critical challenge with severe consequences and increased incidences as the global population ages.However,the underlying mechanism is yet unknown.Our study aimed to explore the changes in metabolites in three specific brain regions and saliva of older mice with postoperative delirium behavior and to identify potential non-invasive biomarkers. Methods Eighteen-month-old male C57/BL6 mice were randomly assigned to the anesthesia/surgery or control group.Behavioral tests were conducted 24 h before surgery and 6,9,and 24 h after surgery.Complement C3(C3)and S100 calcium-binding protein B protein(S100beta)levels were measured in the hippocampus,and a metabolomics analysis was performed on saliva,hippocampus,cortex,and amygdala samples. Results In total,43,33,38,and 14 differential metabolites were detected in the saliva,hippocampus,cortex,and amygdala,respectively."Pyruvate""alpha-linolenic acid"and"2-oleoyl-1-palmitoy-sn-glycero-3-phosphocholine"are enriched in one common pathway and may be potential non-invasive biomarkers for POD.Common changes were observed in the three brain regions,with the upregulation of 1-methylhistidine and downregulation of D-glutamine. Conclusion Dysfunctions in energy metabolism,oxidative stress,and neurotransmitter dysregulation are implicated in the development of POD.The identification of changes in the level of salivary metabolite biomarkers could aid in the development of noninvasive diagnostic methods for POD.

Objective It compared the power consumption and electrical parameters between Thulium fiber laser devices(TFL)and Holmium laser devices(HoL)in transurethral enucleation of prostate(TUEP).Methods A sin-gle surgeon conducted TUEP by THL or HoL in 10 patients respectively.The enucleation efficiency,the laser energy output and the electric parameters were recorded and analyzed.Results The data from both groups of surgeries were tested for normal distribution,and the t-test found that the difference in the enucleation efficiency between the two surgeries was not statistically significant(P=0.818),and the energy consumption indexes of the two devices were comparable.The difference in the total kilojoules of laser emission between the two lasers during surgery was not statistically significant(P=0.148),but the power consumption of the thulium laser was about one-tenth of that of the holmium laser(P＜0.001),suggesting that the former utilised electrical energy significantly more efficiently than the latter.The maximum current of the HoL was significantly higher than that of the TFL(P＜0.001),requiring a spe-cial high-power power outlet.Conclusion TFL was superior to HoL in terms of lower power consumption,higher en-ergy-efficient and electrical convenient in transurethral enucleation of the prostate.

Objective It compared the power consumption and electrical parameters between Thulium fiber laser devices(TFL)and Holmium laser devices(HoL)in transurethral enucleation of prostate(TUEP).Methods A sin-gle surgeon conducted TUEP by THL or HoL in 10 patients respectively.The enucleation efficiency,the laser energy output and the electric parameters were recorded and analyzed.Results The data from both groups of surgeries were tested for normal distribution,and the t-test found that the difference in the enucleation efficiency between the two surgeries was not statistically significant(P=0.818),and the energy consumption indexes of the two devices were comparable.The difference in the total kilojoules of laser emission between the two lasers during surgery was not statistically significant(P=0.148),but the power consumption of the thulium laser was about one-tenth of that of the holmium laser(P＜0.001),suggesting that the former utilised electrical energy significantly more efficiently than the latter.The maximum current of the HoL was significantly higher than that of the TFL(P＜0.001),requiring a spe-cial high-power power outlet.Conclusion TFL was superior to HoL in terms of lower power consumption,higher en-ergy-efficient and electrical convenient in transurethral enucleation of the prostate.

Objective It compared the power consumption and electrical parameters between Thulium fiber laser devices(TFL)and Holmium laser devices(HoL)in transurethral enucleation of prostate(TUEP).Methods A sin-gle surgeon conducted TUEP by THL or HoL in 10 patients respectively.The enucleation efficiency,the laser energy output and the electric parameters were recorded and analyzed.Results The data from both groups of surgeries were tested for normal distribution,and the t-test found that the difference in the enucleation efficiency between the two surgeries was not statistically significant(P=0.818),and the energy consumption indexes of the two devices were comparable.The difference in the total kilojoules of laser emission between the two lasers during surgery was not statistically significant(P=0.148),but the power consumption of the thulium laser was about one-tenth of that of the holmium laser(P＜0.001),suggesting that the former utilised electrical energy significantly more efficiently than the latter.The maximum current of the HoL was significantly higher than that of the TFL(P＜0.001),requiring a spe-cial high-power power outlet.Conclusion TFL was superior to HoL in terms of lower power consumption,higher en-ergy-efficient and electrical convenient in transurethral enucleation of the prostate.

Objective It compared the power consumption and electrical parameters between Thulium fiber laser devices(TFL)and Holmium laser devices(HoL)in transurethral enucleation of prostate(TUEP).Methods A sin-gle surgeon conducted TUEP by THL or HoL in 10 patients respectively.The enucleation efficiency,the laser energy output and the electric parameters were recorded and analyzed.Results The data from both groups of surgeries were tested for normal distribution,and the t-test found that the difference in the enucleation efficiency between the two surgeries was not statistically significant(P=0.818),and the energy consumption indexes of the two devices were comparable.The difference in the total kilojoules of laser emission between the two lasers during surgery was not statistically significant(P=0.148),but the power consumption of the thulium laser was about one-tenth of that of the holmium laser(P＜0.001),suggesting that the former utilised electrical energy significantly more efficiently than the latter.The maximum current of the HoL was significantly higher than that of the TFL(P＜0.001),requiring a spe-cial high-power power outlet.Conclusion TFL was superior to HoL in terms of lower power consumption,higher en-ergy-efficient and electrical convenient in transurethral enucleation of the prostate.

Objective To optimize the screening methods for antiallergic activity of two Chinese medicines in vitro and compare the antiallergic activity of five medicine pairs in vitro.Methods The degranulation assay of RBL-2H3 cells was optimized,and the activity of the five drugs on inhibiting mast cell degranulation was compared by toluidine blue staining and the release of β-HEX and histamine(HIS).The hyaluronidase inhibition test was optimized to compare the hyaluronidase inhibition effect of five Chinese medicine pairs.Results In the experiment of degranulation of RBL-2H3 cells,5 medicine pairs could inhibit β-HEX release from model cells to different degrees(P<0.05),including Schizonepetae Herba-Saposhnicovia divaricata,Ephedrae Herba-Asarum,Saposhnicovia divaricata-Radix Angelicae dahuricae,Rhizoma Chuanxiong-Asarum.The β-HEX release rate in the supernatant of degranulated model cells was significantly increased(P<0.05)after coculture with Flos Magnoliae-Fructus Xanthii.All the five medicine pairs could reduce HIS release in the supernatant of degranulated model cells.In the hyaluronase inhibition rate test,the hyaluronase inhibition rate of each medicine pair was Rhizoma Chuanxion-Asarum>Saposhnicovia divaricate-Radix Angelicae dahuricae>Schizonepetae Herba-Saposhnicovia divaricate>Ephedrae Herba-Asarum,among which Rhizoma Chuanxiong-Asarum had the strongest anti-allergic activity.Conclusion The trend of antiallergic activity of different drugs obtained by the two methods is consistent in vitro,indicating that the two methods can be used for screening antiallergic activity in vitro.