Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

This study aims to explore the effects and mechanisms of 4'-O-methylbavachalcone(MeBavaC), an active compound from Psoraleae Fructus, in regulating white matter neuroinflammation to improve vascular cognitive impairment. Male Sprague-Dawley(SD) rats were randomly divided into four groups: sham group, model group, high-dose MeBavaC group(14 mg·kg~(-1)), and low-dose MeBavaC group(7 mg·kg~(-1)). The rat model of chronic cerebral hypoperfusion(CCH) was established using bilateral common carotid artery occlusion. The Morris water maze test was performed to evaluate the learning and memory abilities of the rats. Luxol fast blue staining, Nissl staining, immunofluorescence, immunohistochemistry, and transmission electron microscopy were utilized to observe the morphology and ultrastructure of the white matter myelin sheaths, axon integrity, the morphology and number of hippocampal neurons, and the loss and activation of glial cells in the white matter. Transcriptome analysis was performed to explore the potential mechanisms of white matter injury induced by CCH. Western blot and quantitative real-time polymerase chain reaction(qRT-PCR) assays were conducted to measure the expression levels of NOD-like receptor protein 3(NLRP3), absent in melanoma 2(AIM2), gasdermin D(GSDMD), cysteinyl aspartate-specific proteinase-1(caspase-1), interleukin-18(IL-18), interleukin-1β(IL-1β), erythropoietin(EPO), nuclear factor erythroid 2-related factor 2(Nrf2), and heme oxygenase-1(HO-1) in the white matter of rats. The results showed that compared with the model group, MeBavaC significantly improved the learning and memory abilities of rats with CCH, improved the damage of white matter myelin sheath, maintained axonal integrity, reduced the loss of hippocampal neurons and oligodendrocytes in the white matter, inhibited the activation of microglia and the proliferation of astrocytes in the white matter, and suppressed the NLRP3/AIM2/caspase-1/GSDMD pathway. The expression levels of inflammatory cytokines IL-1β and IL-18 were significantly reduced, while EPO expression and the expression of Nrf2/HO-1 antioxidant pathway were notably elevated. In conclusion, MeBavaC can alleviate cognitive impairment in rats with CCH and suppress neuroinflammation in cerebral white matter. The mechanism of action may involve activation of EPO activity, promotion of endogenous antioxidant pathways, and inhibition of neuroinflammation in the white matter. This study suggests that MeBavaC exhibits antioxidant and anti-neuroinflammatory effects, showing potential application in improving cognitive dysfunction.
Animals ; Male ; Rats, Sprague-Dawley ; NF-E2-Related Factor 2/immunology* ; Rats ; Chalcones/administration & dosage* ; Cognitive Dysfunction/metabolism* ; Signal Transduction/drug effects* ; Neuroinflammatory Diseases/drug therapy* ; Heme Oxygenase-1/metabolism* ; Humans ; Heme Oxygenase (Decyclizing)/genetics*

OBJECTIVES: This systematic review examines recent pharmacoeconomic literature on denosumab' cost-effectiveness for bone metastasis treatment, providing evidence-based insights to guide healthcare policy decisions. METHODS: A comprehensive literature search was performed across Cochrane, PubMed, EMBASE (Ovid), CNKI, and Wanfang databases to identify original articles published between 2017 and 2023. Key words consisted of bone metastases, denosumab, and cost-effectiveness in the search strategy. The methodological quality of the included studies was assessed utilizing the revised Consolidated Health Economic Evaluation Reporting Standards (CHEERS 2022). Data was extracted regarding methodological characteristics and cost-effectiveness analyses. RESULTS: A total of 111 studies were retrieved, of which 6 met the inclusion criteria. All included studies were based on clinical trials and published literature data and exhibited high methodological quality. Up to 83% (5 out of 6) of comparisons demonstrated that denosumab was more cost-effective or dominant compared to zoledronic acid. The adjusted incremental cost-effectiveness ratios varied substantially by tumor type, ranging from CZK 436,339.09 to USD 136,234 per skeletal-related event avoided and from CZK 61,580.95 to USD 118,392.11 per quality-adjusted life year gained. CONCLUSIONS The majority of the included studies support denosumab as a more cost-effective treatment option for bone metastases in solid tumors compared to zoledronic acid. The application of CHEER (2022) enhances the reliability of pharmacoeconomic evaluations.
Denosumab/therapeutic use* ; Humans ; Bone Neoplasms/economics* ; Cost-Benefit Analysis

OBJECTIVE: To investigate the effects of astragaloside IV (AS-IV) on podocyte injury of diabetic nephropathy (DN) and reveal its potential mechanism. METHODS: In in vitro experiment, podocytes were divided into 4 groups, normal, high glucose (HG), inositol-requiring enzyme 1 (IRE-1) α activator (HG+thapsigargin 1 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups. Additionally, podocytes were divided into 4 groups, including normal, HG, AS-IV (HG+AS-IV 20 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups, respectively. After 24 h treatment, the morphology of podocytes and endoplasmic reticulum (ER) was observed by electron microscopy. The expressions of glucose-regulated protein 78 (GRP78) and IRE-1α were detected by cellular immunofluorescence. In in vivo experiment, DN rat model was established via a consecutive 3-day intraperitoneal streptozotocin (STZ) injections. A total of 40 rats were assigned into the normal, DN, AS-IV [AS-IV 40 mg/(kg·d)], and IRE-1α inhibitor [STF-083010, 10 mg/(kg·d)] groups (n=10), respectively. The general condition, 24-h urine volume, random blood glucose, urinary protein excretion rate (UAER), urea nitrogen (BUN), and serum creatinine (SCr) levels of rats were measured after 8 weeks of intervention. Pathological changes in the renal tissue were observed by hematoxylin and eosin (HE) staining. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expressions of GRP78, IRE-1α, nuclear factor kappa Bp65 (NF-κBp65), interleukin (IL)-1β, NLR family pyrin domain containing 3 (NLRP3), caspase-1, gasdermin D-N (GSDMD-N), and nephrin at the mRNA and protein levels in vivo and in vitro, respectively. RESULTS: Cytoplasmic vacuolation and ER swelling were observed in the HG and IRE-1α activator groups. Podocyte morphology and ER expansion were improved in AS-IV and IRE-1α inhibitor groups compared with HG group. Cellular immunofluorescence showed that compared with the normal group, the fluorescence intensity of GRP78 and IRE-1α in the HG and IRE-1α activator groups were significantly increased whereas decreased in AS-IV and IRE-1α inhibitor groups (P<0.05). Compared with the normal group, the mRNA and protein expressions of GRP78, IRE-1α, NF-κ Bp65, IL-1β, NLRP3, caspase-1 and GSDMD-N in the HG group was increased (P<0.05). Compared with HG group, the expression of above indices was decreased in the AS-IV and IRE-1α inhibitor groups, and the expression in the IRE-1α activator group was increased (P<0.05). The expression of nephrin was decreased in the HG group, and increased in AS-IV and IRE-1α inhibitor groups (P<0.05). The in vivo experiment results revealed that compared to the normal group, the levels of blood glucose, triglyceride, total cholesterol, BUN, blood creatinine and urinary protein in the DN group were higher (P<0.05). Compared with DN group, the above indices in AS-IV and IRE-1α inhibitor groups were decreased (P<0.05). HE staining revealed glomerular hypertrophy, mesangial widening and mesangial cell proliferation in the renal tissue of the DN group. Compared with the DN group, the above pathological changes in renal tissue of AS-IV and IRE-1α inhibitor groups were alleviated. Quantitative RT-PCR and Western blot results of GRP78, IRE-1α, NF-κ Bp65, IL-1β, NLRP3, caspase-1 and GSDMD-N were consistent with immunofluorescence analysis. CONCLUSION AS-IV could reduce ERS and inflammation, improve podocyte pyroptosis, thus exerting a podocyte-protective effect in DN, through regulating IRE-1α/NF-κ B/NLRP3 signaling pathway.
Podocytes/metabolism* ; Animals ; Diabetic Nephropathies/metabolism* ; Saponins/therapeutic use* ; Triterpenes/therapeutic use* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Male ; Rats, Sprague-Dawley ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Endoribonucleases/metabolism* ; Endoplasmic Reticulum Chaperone BiP ; Rats ; Diabetes Mellitus, Experimental/complications* ; Endoplasmic Reticulum/metabolism* ; Multienzyme Complexes

OBJECTIVE: High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory. Nogo-A is an important axonal growth inhibitory factor. However, its function in high-altitude hypoxia and its mechanism of action remain unclear. METHODS: In an in vivo study, a low-pressure oxygen chamber was used to simulate high-altitude hypoxia, and genetic or pharmacological intervention was used to block the Nogo-A/NgR1 signaling pathway. Contextual fear conditioning and Morris water maze behavioral tests were used to assess learning and memory in rats, and synaptic damage in the hippocampus and changes in oxidative stress levels were observed. In vitro, SH-SY5Y cells were used to assess oxidative stress and mitochondrial function with or without Nogo-A knockdown in Oxygen Glucose-Deprivation/Reperfusion (OGD/R) models. RESULTS: Exposure to acute high-altitude hypoxia for 3 or 7 days impaired learning and memory in rats, triggered oxidative stress in the hippocampal tissue, and reduced the dendritic spine density of hippocampal neurons. Blocking the Nogo-A/NgR1 pathway ameliorated oxidative stress, synaptic damage, and the learning and memory impairment induced by high-altitude exposure. CONCLUSION: Our results demonstrate the detrimental role of Nogo-A protein in mediating learning and memory impairment under high-altitude hypoxia and suggest the potential of the Nogo-A/NgR1 signaling pathway as a crucial therapeutic target for alleviating learning and memory dysfunction induced by high-altitude exposure. GRAPHICAL ABSTRACT available in www.besjournal.com.
Animals ; Oxidative Stress ; Hippocampus/metabolism* ; Rats ; Nogo Proteins/genetics* ; Male ; Rats, Sprague-Dawley ; Hypoxia/metabolism* ; Altitude ; Synapses ; Humans ; Altitude Sickness/metabolism*

Objective:To study the clinical safety and validity of retrograde new endoscopic field of vision in miniature pigs.Methods:6 live miniature pigs were selected as study subjects,En-doscopic Retrograde New View(ERNV)was selected.The performance,image quality and intraoper-ative and postoperative complications were evaluated.To evaluate whether all the experimental ani-mals could complete the relevant endoscopy.Verify ERNV's operating performance,including whether the duodenoscope can enter the biliary tract smoothly,and made sure whether the injection,suction,and instrument channels were unobstructed.Choledochoscope image clarity,color resolu-tion,image deformation and distortion,accurate evaluation of lumen conditions and clear observation of mucosal surface conditions were analyzed.Whether there were operant injuries such as bleeding and perforation,as well as adverse events such as respiratory depression and cardiac arrest.The sur-vival status and adverse reactions of all pigs were observed.Results:The choledochoscope was successfully inserted into the bile duct of 6 miniature pigs.The product had good operation perfor-mance and could enter the bile duct through the duodenoscope smoothly.The injection,suction and instrument channels were relatively smooth.In addition,the endoscopic images are clear,with better color resolution,and without image deformation and distortion,which can realize accurate evaluation of the conditions in the lumen and observe the mucosal surface conditions more clearly.No bile duct stenosis or dilatation occurred in all miniature pigs,and the bile duct mucosa was smooth,without hyperemia and edema,and no abnormal thickening or bending of mucous vessels.During the exami-nation,there were no operational injuries such as bleeding and perforation,and no adverse events such as respiratory depression and cardiac arrest occurred.The vital signs of all miniature pigs tended to be stable after operation,and the survival state was good,and there were no complications such as cholangitis,bleeding and perforation.Conclusion:ERNV has good clinical safety and efficacy,ex-cellent operation performance and excellent image quality,and is worthy of clinical application.

Objective To analyze the antigen recognition sites of commercial and homemade antibodies against aquaporin(AQP)9,and to identify the application effect.Methods Western blotting was used to compare the efficacy of three commercial antibodies and self-made antibody in identifying AQP9 genotypes.The antigen recognition sites of four antibodies and their specificities in practical applications were analyzed.Results Western blotting showed that protein bands of three commercial antibodies were detected in both WT and Aqp9-/-mice.The keyhole limpet hemocyanin(KLH)conjugated synthetic peptides corresponding to the three commercial antibodies were derived from rat,human and human,respectively.And The sequences of these three synthetic peptides were different from those of mice.AQP3/7 and AQP9 have similar molecular weight and were expressed in the liver with high homology.An obvious band of self-made antibody was observed at the 27 kD position in WT mice,but no band was observed at the corresponding position in Aqp9-/-mice.Conclusion Commercial antibodies 1 and 3 can be used to assist in the identification of genotypes in Aqp9-/-mice.Homemade antibodies can accurately identify genotypes at the protein level.

Purpose::Internal iliac artery ligation (IIAL) has been used as a damage control procedure to treat hemodynamically unstable pelvic fracture for many years. However, there is ongoing debate regarding the effectiveness and safety of this hemostatic method. Therefore, we performed a systematic literature review to assess the efficacy and safety of IIAL for pelvic fracture hemostasis.Methods::Three major databases, PubMed, Embase, and Google Scholar, were searched to screen eligible original studies published in English journals. Two reviewers independently read the titles, abstracts, and full texts of all literature. Articles were included if they reported the use and effects of IIAL.Results::A total of 171 articles were initially identified, with 22 fully meeting the inclusion criteria. Among the analyzed cases, up to 66.7% of patients had associated abdominal and pelvic organ injuries, with the urethra being the most frequently injured organ, followed by the bowel. The outcomes of IIAL for achieving hemostasis in pelvic fractures were found to be satisfactory, with an effective rate of 80%. Hemorrhagic shock was the leading cause of death, followed by craniocerebral injury. Notably, no reports of ischemic complications involving the pelvic organs due to IIAL were found.Conclusion::IIAL has a good effect in treating hemodynamically unstable pelvic fracture without the risk of pelvic organ ischemia. This procedure should be considered a priority for hemodynamically unstable pelvic fracture patients with abdominal organ injuries.

The purpose of this study was to identify the tick species native to Xindi Township,Yumin County,Xinjiang,China.Preliminary morphological identification of parasitic ticks collected from animals in the area was conducted with an ultra-depth of field three-dimensional VHX 600 digital stereo microscope.Total DNA of the ticks was extracted,amplified by PCR based on the COI and ITS2 gene loci,and the posi-tive PCR products were sequenced.The sequence were a-ligned with reference sequences from the NCBI database were aligned with the Basic Local Alignment Search Tool.A genet-ic phylogenetic tree was generated with the neighbor-joining method of MEGA 7.0 software to determine the evolutionary biological characteristics of ticks.Morphological identification showed that the ticks collected from Xindi Township of Yu-min County were consistent with the characteristics of Hya-lomma asiaticum.An evolutionary tree based on the COI and ITS2 gene sequences showed that the ticks collected in this study were clustered with known H.asiaticum sequences.The PCR products of COI and ITS2 were sequenced and compared,which confirmed that the collected tick species were H.asiaticum,in agreement with the morphological and molecular biological results.These findings help to clarify the distribution of ticks in Xindi Township of Xinjiang,and provide basic data for the analysis of tick genetic and evolutionary characteristics,as reference for surveillance and control of ticks in the Xinjiang Uygur Autonomous Region.

Objective:To analyze the immune reconstitution after BTKi treatment in patients with chronic lymphocytic leukemia(CLL).Methods:The clinical and laboratorial data of 59 CLL patients admitted from January 2017 to March 2022 in Fujian Medical University Union Hospital were collected and analyzed retrospectively.Results:The median age of 59 CLL patients was 60.5(36-78).After one year of BTKi treatment,the CLL clones(CD5+/CD19+)of 51 cases(86.4％)were significantly reduced,in which the number of cloned-B cells decreased significantly from(46±6.1)× 109/L to(2.3±0.4)× 109/L(P=0.0013).But there was no significant change in the number of non-cloned B cells(CD19+minus CD5+/CD19+).After BTKi treatment,IgA increased significantly from(0.75±0.09)g/L to(1.31±0.1)g/L(P＜0.001),while IgG and IgM decreased from(8.1±0.2)g/L and(0.52±0.6)g/L to(7.1±0.1)g/L and(0.47±0.1)g/L,respectively(P＜0.001,P=0.002).BTKi treatment resulted in a significant change in T cell subpopulation of CLL patients,which manifested as both a decrease in total number of T cells from(2.1±0.1)× 109/L to(1.6±0.4)× 109/L and NK/T cells from(0.11±0.1)× 109/L to(0.07±0.01)× 109/L(P=0.042,P=0.038),both an increase in number of CD4+cells from(0.15±6.1)× 109/L to(0.19±0.4)× 109/L and CD8+cells from(0.27±0.01)× 109/L to(0.41±0.08)× 109/L(both P＜0.001).BTKi treatment also up-regulated the expression of interleukin(IL)-2 while down-regulated IL-4 and interferon(IFN)-γ.However,the expression of IL-6,IL-10,and tumor necrosis factor(TNF)-α did not change significantly.BTKi treatment could also restored the diversity of TCR and BCR in CLL patients,especially obviously in those patients with complete remission(CR)than those with partial remission(PR).Before and after BTKi treatment,Shannon index of TCR in patients with CR was 0.02±0.008 and 0.14±0.001(P＜0.001),while in patients with PR was 0.01±0.03 and 0.05±0.02(P＞0.05),respectively.Shannon index of BCR in patients with CR was 0.19±0.003 and 0.33±0.15(P＜0.001),while in patients with PR was 0.15±0.009 and 0.23±0.18(P＜0.05),respectively.Conclusions:BTKi treatment can shrink the clone size in CLL patients,promote the expression of IgA,increase the number of functional T cells,and regulate the secretion of cytokines such as IL-2,IL-4,and IFN-γ.BTKi also promote the recovery of diversity of TCR and BCR.BTKi treatment contributes to the reconstitution of immune function in CLL patients.