ObjectiveTo explore the molecular mechanisms by which serum containing Gegen Qinlian Tang （GQT） inhibits glycolysis and enhances chemotherapy sensitivity in 5-fluorouracil （5-FU）-resistant colorectal cancer （CRC） cells based on the cyclin-dependent kinase 16 （CDK16）/MYC proto-oncogene （MYC） pathway. MethodsHCT-116/5-FU cells were treated with different concentrations （5%， 10%， 20%， 30%） of GQT-containing serum. Cell viability and 5-FU sensitivity were assessed using the cell counting kit-8 （CCK-8） assay， and the experimental concentrations of 5-FU and GQT for subsequent experiments were determined. Cell proliferation and apoptosis under individual 5-FU， GQT， and combined 5-FU + GQT treatments were evaluated using 5-ethynyl-2′-deoxyuridine （EDU） staining and annexin V-FITC/PI double staining， respectively. Glucose consumption， adenosine triphosphate （ATP） production， and lactate levels were measured by colorimetric assays. Expression levels of glycolysis-related proteins， CDK16， MYC， and phosphorylated MYC were detected by Western blot. Co-immunoprecipitation （CoIP） was used to examine the protein interaction between CDK16 and MYC， and cycloheximide （CHX） treatment was applied to assess the effect of CDK16 overexpression on MYC protein stability. ResultsCCK-8 assays showed that 2.5 mg·L^-1 5-FU significantly inhibited HCT-116 cell viability in a dose-dependent manner. In HCT-116/5-FU cells， significant inhibition was observed only at 5 mg·L^-1 5-FU （P<0.05）， which was used for model establishment. Compared with 5-FU alone， addition of 5% GQT-containing serum significantly suppressed HCT-116/5-FU cell viability （P<0.05）， with stronger inhibition at higher serum concentrations. Thus， 5% GQT-containing serum was used in subsequent experiments. Compared with the control group， 5-FU， GQT， and 5-FU + GQT treatments all significantly reduced cell proliferation （P<0.05） and increased apoptosis （P<0.01）. The 5-FU + GQT combination showed superior inhibition of proliferation compared with 5-FU or GQT alone （P<0.01）， accompanied by more pronounced reductions in glucose consumption， ATP production， and lactate generation （P<0.01）. Additionally， compared with control， 5-FU， and GQT groups， the 5-FU + GQT group exhibited stronger suppression of MYC and its phosphorylated forms （P<0.01） and greater inhibition of glycolytic enzymes， including hexokinase 2 （HK2）， 3-phosphoinositide-dependent protein kinase 1 （PDK1）， lactate dehydrogenase A （LDHA）， and pyruvate kinase M2 （PKM2） （P<0.01）. CDK16， MYC， and MYC phosphorylation expression levels were significantly downregulated in the 5-FU + GQT group compared with the 5-FU group （all P<0.01）. MYC protein stability decreased in a time-dependent manner in the 5-FU + GQT group （P<0.05）， which was rescued by CDK16 overexpression （P<0.05）. ConclusionGQT significantly enhances the sensitivity of HCT-116/5-FU cells to 5-FU， potentially by inhibiting CDK16 and thereby reducing MYC-mediated glycolysis.

ObjectiveTo explore the molecular mechanisms by which serum containing Gegen Qinlian Tang （GQT） inhibits glycolysis and enhances chemotherapy sensitivity in 5-fluorouracil （5-FU）-resistant colorectal cancer （CRC） cells based on the cyclin-dependent kinase 16 （CDK16）/MYC proto-oncogene （MYC） pathway. MethodsHCT-116/5-FU cells were treated with different concentrations （5%， 10%， 20%， 30%） of GQT-containing serum. Cell viability and 5-FU sensitivity were assessed using the cell counting kit-8 （CCK-8） assay， and the experimental concentrations of 5-FU and GQT for subsequent experiments were determined. Cell proliferation and apoptosis under individual 5-FU， GQT， and combined 5-FU + GQT treatments were evaluated using 5-ethynyl-2′-deoxyuridine （EDU） staining and annexin V-FITC/PI double staining， respectively. Glucose consumption， adenosine triphosphate （ATP） production， and lactate levels were measured by colorimetric assays. Expression levels of glycolysis-related proteins， CDK16， MYC， and phosphorylated MYC were detected by Western blot. Co-immunoprecipitation （CoIP） was used to examine the protein interaction between CDK16 and MYC， and cycloheximide （CHX） treatment was applied to assess the effect of CDK16 overexpression on MYC protein stability. ResultsCCK-8 assays showed that 2.5 mg·L^-1 5-FU significantly inhibited HCT-116 cell viability in a dose-dependent manner. In HCT-116/5-FU cells， significant inhibition was observed only at 5 mg·L^-1 5-FU （P<0.05）， which was used for model establishment. Compared with 5-FU alone， addition of 5% GQT-containing serum significantly suppressed HCT-116/5-FU cell viability （P<0.05）， with stronger inhibition at higher serum concentrations. Thus， 5% GQT-containing serum was used in subsequent experiments. Compared with the control group， 5-FU， GQT， and 5-FU + GQT treatments all significantly reduced cell proliferation （P<0.05） and increased apoptosis （P<0.01）. The 5-FU + GQT combination showed superior inhibition of proliferation compared with 5-FU or GQT alone （P<0.01）， accompanied by more pronounced reductions in glucose consumption， ATP production， and lactate generation （P<0.01）. Additionally， compared with control， 5-FU， and GQT groups， the 5-FU + GQT group exhibited stronger suppression of MYC and its phosphorylated forms （P<0.01） and greater inhibition of glycolytic enzymes， including hexokinase 2 （HK2）， 3-phosphoinositide-dependent protein kinase 1 （PDK1）， lactate dehydrogenase A （LDHA）， and pyruvate kinase M2 （PKM2） （P<0.01）. CDK16， MYC， and MYC phosphorylation expression levels were significantly downregulated in the 5-FU + GQT group compared with the 5-FU group （all P<0.01）. MYC protein stability decreased in a time-dependent manner in the 5-FU + GQT group （P<0.05）， which was rescued by CDK16 overexpression （P<0.05）. ConclusionGQT significantly enhances the sensitivity of HCT-116/5-FU cells to 5-FU， potentially by inhibiting CDK16 and thereby reducing MYC-mediated glycolysis.

Since the promulgation of the first Drug Administration Law of the People's Republic of China 40 years ago in 1984, China has undergone four main stages in the traditional Chinese medicine(TCM) regulation: the initial establishment of TCM regulation rules(1984-1997), the formation of a modern TCM regulatory system(1998-2014), the reform of the review and approval system for new TCM drugs(2015-2018), and the construction of a scientific regulation system for TCM(2019-2024). Over the past five years, a series of milestone achievements of TCM regulation in China have been achieved in the six aspects, including its strategic objectives and the establishment of a science-based regulatory system, the reform of the review and approval system for new TCM drugs, the optimization and improvement of the TCM standard system and its formation mechanism, comprehensive enhancement of regulatory capabilities for TCM safety, international harmonization of TCM regulation and its role in promoting innovation. Looking ahead, centered on advancing TCMRS to establish a sound regulatory framework tailored to the unique characteristics of TCM, TCM regulation will evolve into new reform patterns, advancing and extending across eight critical fronts, including the legal framework and policy architecture, the review and approval system for new TCM drugs, the quality standard and management system of TCM, the comprehensive quality & safety regulation and traceability system, the research and transformation system for TCMRS, AI-driven innovations in TCM regulation, the coordination between high-quality industrial development and high-level regulation, and the leadership in international cooperation and regulatory harmonization. In this way, a unique path for the development of modern TCM regulation with Chinese characteristics will be pioneered.
Humans ; China ; Drugs, Chinese Herbal/standards* ; History, 20th Century ; History, 21st Century ; Medicine, Chinese Traditional/trends*

In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of Agathis dammara, including 11 previously unreported compounds: dammaradione (1), dammarones D-G (2, 5, 14, 15), dammaric acids B-F (8-12), and dammarol (16). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure-activity relationship (SAR) analysis was conducted. Araucarone (3) and dammaric acid C (9), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic β cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into β cells in zebrafish.
Zebrafish ; Animals ; Diterpenes/isolation & purification* ; Insulin-Secreting Cells/cytology* ; Glucose/metabolism* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; Structure-Activity Relationship ; Plant Extracts/pharmacology* ; Regeneration/drug effects*

ObjectiveTo investigate the effects of foliar fertilizer of nano-calcium carbonate and calcium nitrate tetrahydrate on the agronomic traits， carbohydrate and endogenous hormone contents of Dendrobium officinale planted for 1 year under greenhouse cultivation， in order to provide scientific basis for fertilization to improve the yield and quality of D. officinale. MethodsSingle-factor experimental design was adopted. Starting from early spring， D. officinale was treated with foliar spraying according to corresponding fertilizers. Three treatment groups were established based on different fertilizers， namely， a blank group（clear water）， a nano-calcium carbonate group（0.727 g·L^-1 nano-calcium carbonate water-soluble fertilizer）， and a calcium nitrate tetrahydrate group（1.091 g·L^-1 calcium nitrate tetrahydrate water-soluble fertilizer）. The frequency of spraying was three times per month， and the entire treatment process lasted for nine months. The effects of various treatments on the traits and relative chlorophyll content of D. officinale were dynamically monitored. Sampling was conducted at three specific time points：August 2， 2023， September 8， 2023， and November 1， 2023， respectively. The contents of glucose and mannose in D. officinale stems were determined by high performance liquid chromatography（HPLC）， the content of soluble sugars in D. officinale stems and leaves was determined by phenol method， and enzyme-linked immunosorbent assay（ELISA） was used to detect the concentrations of cytokinin and auxin. ResultsCompared with the blank group， the treatments with nano-calcium carbonate and calcium nitrate tetrahydrate could significantly increase stem length， stem node number， leaf number， and tiller number. Among them， during the harvesting period in November， the stem length and tiller number， which are indicators related to the yield of D. officinale， increased by 60.85% and 19.23% after treatment with calcium nitrate tetrahydrate， and by 32.54% and 28.85% after treatment with nano-calcium carbonate， respectively. Compared with the blank group， treatments with nano-calcium carbonate and calcium nitrate tetrahydrate could promote the accumulation of sucrose in the stems and leaves of D. officinale to varying degrees， as well as the accumulation of polysaccharides， mannose， and glucose in the stems. In addition， nano-calcium carbonate treatment also facilitated the accumulation of fructose in the stems and leaves of D. officinale. Specifically， during the harvesting period in November， polysaccharides and mannose， which were the main active ingredients in D. officinale stems， increased by 28.48% and 29.36% after treatment with calcium nitrate tetrahydrate， and by 39.91% and 82.62% after treatment with nano-calcium carbonate， respectively. In addition， compared with the blank group， the concentrations of auxin in the stems and leaves of D. officinale were significantly increased after treatment with calcium nitrate tetrahydrate（P<0.05）. Similarly， the concentrations of cytokinin and auxin in the stems of D. officinale were also elevated after treatment with nano-calcium carbonate. Correlation analysis further indicated that elongation growth and tillering of D. officinale stems after foliar spraying of nano-calcium carbonate and calcium nitrate tetrahydrate might be related to the accumulation of carbohydrates in the stems and leaves and the synergistic effect of auxin and cytokinin. ConclusionIn production practice， spraying nano-calcium carbonate and calcium nitrate tetrahydrate can promote the accumulation of cytokinin， auxin， and carbohydrate contents in the stems and leaves of D. officinale， and promote tillering and elongation growth of the stems.

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Objective:To evaluate the clinical efficacy of endoscopic treatment of superficial non-ampullary duodenal adenoma.Methods:A retrospective analysis was performed on the clinical data and follow-up information of patients diagnosed with superficial duodenal non-ampullary adenomas via preoperative endoscopy and treated endoscopically at Peking University First Hospital between January 2013 and January 2024. The overall en bloc resection rate, complete resection rate of the lesion, perioperative complications, and recurrence rates were evaluated. Patients were categorized into three groups based on their treatment modality: endoscopic mucosal resection (EMR)（ n=46）, endoscopic submucosal dissection (ESD)（ n=16）, and modified ESD (ESD with snare, ESD-S)（ n=24）. Comparative analyses were conducted to evaluate operative time, en bloc resection rate, and complete resection rate among the three groups. Results:Among 86 patients, the overall en bloc and complete resection rates were 87.2% (75/86) and 86.0% (74/86), respectively. No case of delayed bleeding was observed during the perioperative period. Intraoperative perforation occurred in two patients, both of whom improved following conservative management. Delayed perforation was noted in four patients, and three of them were successfully managed with surgical intervention, while one case was resolved after conservative treatment. During the follow-up period, local recurrence was identified in two patients. Following re-treatment with endoscopy and continuous surveillance, no further recurrence was observed. The operative times for the EMR group, ESD-S group, and ESD group were 4 (1-36) minutes, 25 (5-190) minutes, and 46 (5-150) minutes, respectively. Significant differences were observed in operative times among the three groups ( Hc=49.892, P<0.001). The en bloc resection rates for the EMR, ESD-S, and ESD groups were 80.4% (37/46), 91.7% (22/24), and 100.0% (16/16), respectively. The complete resection rates were 80.4% (37/46), 91.7% (22/24), and 93.8% (15/16) for the respective groups. Conclusion:Endoscopic treatment demonstrates favorable efficacy and safety for superficial non-ampullary duodenal adenoma. In addition to traditional EMR and ESD, ESD-S is also an effective procedure for endoscopic treatment of non-ampullary duodenal adenoma.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

OBJECTIVE: To explore the differences in clinical efficacy between enhanced workflows and express workflows in robotic-assisted total hip arthroplasty(THA). METHODS: A retrospective analysis was conducted on 46 patients who underwent robotic-assisted THA between November 2020 and May 2021. They were divided into the enhanced workflows group and the express workflows group based on the surgical methods. There were 20 patients in the enhanced workflows group, including 11 males and 9 females;aged from 51 to 78 years old with an average of (67.30±7.52) years old. The BMI ranged from 18.24 to 24.03 kg·m^-2 with an average of(23.80±3.01) kg·m^-2. There were 26 patients in the express workflows group, including 12 males and 14 females;aged from 57 to 84 years old with a mean age of (67.58±7.29) years old, and their BMI ranged from 19.72 to 30.08 kg·m^-2 with an average of (24.41 ±2.92) kg·m^-2. The operation time, hospital stay, and perioperative complications of the patients were recorded. The postoperative acetabular prosthesis anteversion angle, abduction angle, limb length, and offset distance data were measured. The Harris hip score at the latest follow-up was recorded. RESULTS: All patients completed the surgery as planned and were followed up, with the follow-up period ranging from 47 to 54 months with a mean of (49.78±1.85) months and the length of hospital stay ranging from 2 to 11 days with an average of (6.57±1.82 ) days. The operation time of enhanced workflows group was (93.41±16.41) minutes, which was longer than that of the express workflow groups (75.19±18.36) minutes, and the difference was statistically significant (P<0.05). In enhanced workflows group, the postoperative acetabular anteversion angle was (19.20±4.46)°, the limb length discrepancy was (-1.55±9.13) mm, and changes of the offset was (-5.15±6.77) mm. The corresponding values in express workflows group were (20.46±3.29)°, (2.19±4.39) mm, and (-2.39±4.34) mm, respectively. There was no statistically significant difference in these indicators between the two groups(P>0.05). One patient in the enhanced workflows group developed deep venous thrombosis after surgery. No cases of dislocation or periprosthetic infection. At the latest follow-up, all patients had well-positioned prostheses without loosening. Harris hip score was (90.50±1.67) points in enhanced workflows group and (90.73±2.36) points in the express workflows group, with no statistically significant difference between the two groups (P>0.05). CONCLUSION The clinical efficacy of robot assisted total hip arthroplasty technology is satisfactory. The enhanced workflows will increase the surgical time. For patients with normal anatomical hip joint disease, this study did not find significant advantages in joint stability and functional scoring for the enhanced workflows.
Humans ; Arthroplasty, Replacement, Hip/methods* ; Male ; Female ; Aged ; Middle Aged ; Robotic Surgical Procedures/methods* ; Retrospective Studies ; Aged, 80 and over ; Workflow ; Treatment Outcome

Objective To investigate the effect and mechanism of hypoxia inducible factor-1 α/aquaporin-4(HIF-1α/AQP4)pathway in high altitude cerebral edema(HACE)after blood-brain barrier injury in rats.Methods Adult male SD rats(n=40)were randomly divided into two groups:control group(Ctrl,n=20)and high altitude cerebral edema group(HACE,n=20).The rats in the control group were reared in Xining(altitude 2261 m)for 4 days,and the rats in HACE group were reared in low-pressure simulation chamber(altitude 5000 m)for 4 days.Brain water content was measured by the method of dry and wet weight.The intracranial structure,morphology and signal changes of small animals were observed through T2 weighted image of 7.0 T MRI.The morphological changes of neurons and the apoptosis of nerve cells in the CA1 region of hippocampal tissue were observed by the staining of Nissl and TUNEL.Immunohistochemical staining was performed to observe the extravasation of immunoglobulin G(IgG).The expressions of HIF-1α,AQP4,matrix metalloproteinase-9(MMP-9),claudin-5,occludin and zonula occludens-1(ZO-1)in the tissue of hippocampal were detected by the method of Western blotting and immunofluorescent staining.Results The brain water content increased significantly in the HACE group(P＜0.05).The neurons in CA1 region of hippocampal tissue were atrophic and deformed,the arrangement of neurons was disordered in the HACE group.The number of neurons decreased significantly,the apoptosis of nerve cells increased significantly,and the IgG exudates obviously in the CA1 region of hippocampal tissue in the HACE group.The expressions of HIF-1α,AQP4 and MMP-9 proteins increased significantly,while claudin-5,occludin and ZO-1 proteins decreased significantly in the CA1 region of hippocampal tissue,which detected by the method of Western blotting and immunofluorescent staining(P＜0.05).Conclusion Acute high-altitude hypoxia can induce to blood-brain barrier disruption through the HIF-1α/AQP4 pathway,resulting in high-altitude cerebral edema.