Objective: To investigate the effect of auricular therapy on sleep improvement and the GABAergic system pathway in a rat model of insomnia and to explore its possible mechanism. Methods: According to the random number table, 60 male SD rats were randomly divided into blank control, model, auricular point sticking, auricular bloodletting, and auricular bloodletting combined with sticking groups, with 12 rats per group. Insomnia was induced by intraperitoneal injection of p-chlorophenylalanine. After establishing the insomnia model, 36 rats were treated once a day with auricular point sticking or bloodletting for 5 consecutive days. After the intervention, the general condition and body weight of rats were observed; the righting reflex test was used to detect the sleep latency and duration; HE staining was used to observe the morphology of hypothalamic neuron cells; and an enzyme-linked immunosorbent assay was used to detect the GABA and glutamate content in rat serum. Immunohistochemistry(IHC) and real-time fluorescence quantitative PCR were used to detect GABA ARα1 and GABA ARγ2 protein and mRNA expression in the hypothalamus of rats, and Western blotting(WB) was used to detect GABA ARα1, GABA ARγ2, GAD65/67, GAT-1, and GABA-T protein expression in the hypothalamus of rats. Results: Compared with the blank control group, the model group had a lower body weight, a significantly shorter sleep duration (P<0.05), severe damage to the morphological structure of hypothalamic neurons with disordered cell arrangement, larger intercellular gaps, enlarged cell bodies, and a vacuolated appearance. All the intervention groups had significantly higher body weight and longer sleep duration than the model group (P<0.05). Compared with the other intervention groups, the auricular point sticking group had a longer sleep duration (P<0.05), and the hypothalamic neuron cells in all intervention groups improved, with the auricular point sticking group showing more apparent improvement. The model group had a lower GABA and higher glutamate contents, and GABA ARα1, GABA ARγ2, and GAD65/67 protein expression in the hypothalamus were lower than in the blank control group. In contrast, GAT-1 and GABA-T protein expression was higher, and GABA ARα1 and GABA ARγ2 mRNA expression was lower (P<0.05). The serum GABA content in the auricular point sticking and auricular bloodletting groups was higher, and the serum glutamate content in the auricular point sticking and auricular bloodletting combined sticking groups was lower than in the model group. GABA ARα1 mRNA expression in the hypothalamus of each intervention group was significantly increased, and GABA ARγ2 mRNA expression in the hypothalamus of the auricular point sticking and auricular bloodletting combined sticking groups increased. GABA ARα1(IHC, WB), GABA ARγ2(WB), and GAD65/67 protein expression in the hypothalamus of the auricular point sticking group increased, whereas GAT-1 and GABA-T protein expression decreased. GABA ARα1 and GABA ARγ2 protein expression(IHC, WB) in the hypothalamus of the auricular bloodletting group increased, whereas GABA-T protein expression decreased. GABA ARγ1(IHC) and GABA ARγ2(WB) protein expression in the hypothalamus of the auricular bloodletting combined sticking group increased, whereas GAT-1 and GABA-T protein expression decreased (P<0.05). Compared with in the inventation groups, the serum GABA content in the auricular point sticking group increased, the serum glutamate content decreased, GABA ARα1 and GABA ARγ2 mRNA expression in the hypothalamus increased, and GABA ARα1(IHC), GAD65/67 protein expression increased. In contrast, GABA-T protein expression decreased (P<0.05), and GABA ARγ2 protein expression(IHC) in the hypothalamus of the auricular bloodletting group increased (P<0.05). Conclusion Auricular therapy, particularly auricular point sticking, may have modulated the GABAergic system pathway by upregulating hypothalamic GABA ARα1, GABA ARγ2, and GAD65/67 protein expression while downregulating GAT-1 and GABA-T protein expression to alleviate symptoms in an insomnia rat model.

Objective: To assess the dynamic changes of microcirculation at acupoints in patients with primary dysmenorrhea and cold congelation and blood stasis syndrome using laser speckle blood flow imaging. Methods: Patients with primary dysmenorrhea and cold coagulation and blood stasis syndrome (primary dysmenorrhea group, n=53) and healthy female college students(control group, n=57) who met the inclusion and exclusion criteria from October 2020 to July 2022 were enrolled at Hebei University of Chinese Medicine. On the premenstrual and first day of menstruation, a laser speckle blood flow imaging system was used to measure the microcirculation blood flow perfusion on the surface of acupoints related to the conception, thoroughfare, and governor vessels, and stomach, spleen, and bladder meridians in the abdomen and lumbosacral regions. The dynamic changes in microcirculation were calculated based on the difference in average blood flow perfusion at each acupoint before and after menstruation. Receiver operating curve (ROC) analysis was used to analyze the diagnostic efficacy of dynamic changes in microcirculation on the surface of each acupoint. The microcirculation sensitization rate of acupoints was calculated. Results: Compared with the control group, the dynamic changes in microcirculation at the following acupoints in the primary dysmenorrhea group were increased (P<0.05): conception vessel (Yinjiao[CV7], Qihai[CV6], Shimen[CV5], Guanyuan[CV4]); left thoroughfare vessel (left Huangshu[KI16], left Zhongzhu[KI15], left Siman[KI14], left Qixue[KI13], left Dahe[KI12], left Henggu[KI11]); left stomach meridian (left Tianshu[ST25], left Wailing[ST26], left Qichong[ST30]); left spleen meridian (left Daheng[SP15], left Fujie[SP14]); right thoroughfare vessel (right Huangshu[KI16], right Zhongzhu[KI15], right Siman[KI14], right Qixue[KI13], right Dahe[KI12], right Henggu[KI11]); right stomach meridian (right Wailing[ST26], right Daju[ST27], right Shuidao[ST28], right Guilai[ST29], right Qichong[ST30]); and right spleen meridian (right Fujie[SP14]). The area under the ROC curve of conception vessel (Yinjiao[CV7], Qihai[CV6], Shimen[CV5], Guanyuan[CV4]), thoroughfare vessel (right Siman[KI14], left Huangshu[KI16], right Qixue[KI13], right Zhongzhu[KI15], right Dahe[KI12], left Zhongzhu[KI15], left Siman[KI14], right Huangshu[KI16], left Qixue[KI13], right Henggu[KI11], left Henggu[KI11], left Dahe[KI12]); stomach meridian (left Tianshu[ST25], right Guilai[ST29], left Wailing[ST26], right Shuidao[ST28], right Daju[ST27], right Wailing[ST26], right Qichong[ST30], left Qichong[ST30]), and spleen meridian (left Daheng[SP15], left Fujie[SP14], right Fujie[SP14]) was 0.610-0.682 (P<0.05). Compared with the control group, the sensitization rate of some acupoints in the primary dysmenorrhea group increased (P<0.05). Conclusion With the onset of menstruation, the blood flow perfusion of some acupoints in the abdomen (thoroughfare, and conception vessels, and stomach and spleen meridians) of patients with primary dysmenorrhea and cold blood coagulation and blood stasis syndrome increased, and the status of acupoints changed from a resting state to an active state. These acupoints are sensitive in patients with primary dysmenorrhea and cold blood coagulation and blood stasis syndrome and have a certain diagnostic efficacy, providing a basis for further analyzing the efficacy and mechanism of acupuncture and moxibustion to treat primary dysmenorrhea with cold blood coagulation and blood stasis syndrome.

OBJECTIVE To provide a reference for optimizing the market access process for over-the-counter drugs （OTC） in China. METHODS Based on literature review， questionnaire survey was designed and distributed via the Wenjuanxing platform to respondents from pharmaceutical enterprises， drug regulatory agencies， industry associations， medical institutions and universities. The collected survey data were then subjected to statistical analysis. RESULTS A total of 154 questionnaires were collected， all of which were valid. Among the respondents， 58.5% were from pharmaceutical enterprises， 18.8% were from the field of drug regulation， and the remaining 22.7% were from universities and medical institutions. More than half of the respondents had been working for 10 years or more. A total of 89.6% of the respondents called for the establishment of an independent review system for OTC. Additionally， 88.3% believed it was necessary to establish an OTC monograph system based on China’s national conditions. Meanwhile， 73.4% of respondents believed it was necessary to standardize the monograph inclusion procedures and processes， while 77.3% thought the specific process for switching prescription drugs to OTC status should be improved. Furthermore， 91.0% of the respondents considered that real-world data/evidence could contribute to simplifying the OTC market approval pathway， although challenges related to data quality and data accessibility were acknowledged. CONCLUSIONS The review cycle for China’s OTC market access mechanism is relatively long. A localized adaptation and optimization path of “institutional reconstruction-technological innovation-regulatory innovation” in a trinity is proposed to provide a decision-making basis for establishing a scientific and efficient OTC regulatory system with international experience serving as a reference.

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD⁺), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD⁺ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
Humans ; NAD/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Nicotinamide Phosphoribosyltransferase/metabolism* ; Cytokines/metabolism* ; Quinones ; Oxidoreductases

Objective:To investigate the long-term efficacy of self-designed posterior atlas polyaxial screw-plate in the treatment of unstable atlas fracture.Methods:A retrospective case series study was conducted to analyze the clinical data of 20 patients with unstable atlas fracture who were admitted to Affiliated Honghui Hospital of Xi′an Jiaotong University from January 2011 to April 2013, including 14 males and 6 females, aged 23-60 years [(42.7±8.6)years]. All the patients were treated with internal fixation using self-designed posterior atlas polyaxial screw-plate. The operation time and intraoperative bleeding volume were recorded. The fracture reduction was evaluated by CT scan at 3 days after surgery. The bone healing was observed by X-ray (anterior-posterior and lateral views of the cervical spine) and CT scan at 9 months after surgery. The delayed spinal cord injuries were evaluated by Frankel grade at 1 and 2 years after surgery and at the last follow-up. The Visual Analogue Scale (VAS) before surgery, at 3 months, 1 year, 2 years after surgery and at the last follow-up were compared. The axial rotation, flexion and extension range of the cervical spine at 3 months, 1 year, 2 years after surgery and at the last follow-up were compared. Intraoperative and postoperative complications were observed.Results:All the patients were followed up for 121-148 months [(135.0±6.8)months]. The operation duration was 68-122 minutes [(86.0±14.1)minutes], with the intraoperative blood loss of 90-400 ml [(120.0±67.9)ml]. The CT scan of the cervical spine at 3 days after surgery showed all satisfactory fracture reduction. Satisfactory bone reunion was observed at 9 months after surgery. All patients were scaled as Frankel grade E at 1 year, 2 years and at the last follow-up after surgery, with no delayed spinal cord injuries observed. The VAS scores of the cervical spine at 3 months, 1 year, 2 years after surgery and at the last follow-up were 2.0(1.3, 3.0)points, 1.0(1.0, 1.8)points, 1.0(0.3, 1.0)points and 1.0(0.3, 1.0)points, which were significantly lower than that before surgery [7.0(6.0, 7.8)points] ( P<0.05), with significantly lower scores at 1-, 2-year after surgeny and at the last follow-up than at 3 months after surgery ( P<0.05). There were no significant differences among the other time points ( P>0.05). The axial rotation ranges of the cervical spine were (103.0±8.3)°, (128.3± 11.4)° and (129.8±13.6)° at 1 year, 2 years after surgery and at the last follow-up respectively, which were significantly higher than that at 3 months after surgery [(85.3±7.0)°] ( P<0.05); It was further improved at 2 years after surgery and at the last follow-up compared with that at 1 year after surgery ( P<0.05), with no significant difference at the last follow-up compared with that at 2 years after surgery ( P>0.05). The flexion and extension range of the cervical spine at 1 year, 2 years after surgery and at the last follow-up were (65.5±4.8)°, (78.3±6.5)° and (79.3±6.9)° respectively, which were significantly higher than that at 3 months after surgery [(54.3±4.4)°] ( P<0.05); It was further improved at 2 years after surgery and at the last follow-up compared with that at 1 year after surgery ( P<0.05), with no significant difference between the last follow-up and 2 years after surgery ( P>0.05). No intraoperative injuries such as arteriovenous injury were observed. No incision infection or dehiscence occurred after surgery, with no complications caused by long-term bed rest such as lung or urinary tract infection, pressure sore formation or deep vein thrombosis occurred. No loosening or breakage of the screw and atlas plate was observed at the long-term follow-up. One patient had mild cervical pain, snap during rotation, and limited range of motion at the last follow-up. Conclusion:Self-designed posterior atlas polyaxial screw-plate has merits including small surgical wounds, satisfactory reduction, solid fixation, obvious pain relief, effective preservation of the previous cervical motion, few complications, and satisfactory long-term efficacy in the treatment of unstable atlas fracture.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most prevalent chronic liver disease globally,with only one Food and Drug Administration(FDA)-approved drug for its treatment.Given MASLD's complex pathophysiology,ther-apies that simultaneously target multiple pathways are highly desirable.One promising approach is dual-modulation of the famesoid X receptor(FXR),which regulates lipid and bile acid metabolism.However,FXR agonists alone are insufficient due to their limited anti-inflammatory effects.This study aimed to dto identify natural products capable of both FXR activation and inflammation inhibition to provide a comprehensive therapeutic approach for MASLD.Potential FXR ligands from the Natural Product Library were predicted via virtual screening using the Protein Preparation Wizard module in Schrodinger(2018)for molecular docking.Direct binding and regulation of candidate compounds on FXR were analyzed using surface plasmon resonance(SPR)binding assay,reporter gene ana-lysis,and reverse transcription-polymerase chain reaction(RT-PCR).The anti-inflammatory properties of these compounds were eval-uated in AML12 cells treated with tumor necrosis factor-alpha(TNF-α).Dual-function compounds with FXR agonism and inflamma-tion inhibition were further identified in cells transfected with Fxr siRNA and treated with TNF-α.The effects of these dual-function compounds on lipid accumulation and inflammation were evaluated in cells treated with palmitic acid.Results revealed that 17 natural products were predicted via computational molecular docking as potential FXR agonists,with 15 exhibiting a strong affinity for FXR recombinant protein.Nine isoflavone compounds significantly enhanced FXR reporter luciferase activity and the mRNA expressions of Shp and Ostb.Structure-activity relationship analysis indicated that introducing isopropyl or methoxy groups at the C7 position or a methoxy group at the C6 position could enhance the agonistic efficacy of isoflavones.Three compounds(2,6,and 8)were identified as dual-function natural products functioning as FXR agonists and inflammatory inhibitors,while one compound(12)acted as an FXR agonist to inhibit inflammation.These natural products protected hepatocytes against palmitic acid-induced lipid accumulation and in-flammation.In conclusion,compounds 2,6,and 8(genistein,biochanin A,and 7-methoxyisoflavone,respectively)were identified as dual-function bioactive products that transactivate FXR and inhibit inflammation,serving as potential candidates or lead compounds for MASLD therapy.

The combination of Artificial Intelligence(AI)and medical applications has derived a large number of uses and scenarios,which has engaged and changed the healthcare industry from multiple dimensions,such as diagnosis and treatment processes,data fusion,and empowered medical devices,etc.AI large model is a machine learning model based on huge parameter scales and complexity,with a high degree of accuracy and extensive generalization capabilities.In facing the problems such as rapid growth of the data in medical scenarios,data multimodality,large and complex knowledge graphs,AI large model connects the medical processes such as diagnosis,decision-making,treatment and management by series connection,which further broadens and extends the space of AI's medical applications,which will highly utilizes medical data.In view that,we summarized the typical application scenarios of conventional AI and large models in the application of medical field,and discussed the problems of large models in data governance,modal fusion and credibility,so as to promote the landing and application of the combination of large models and medical treatment.

OBJECTIVE: To explore the safety and effectiveness of one-stage posterior eggshell osteotomy and long-segment pedicle screw fixation in the treatment of ankylosing spondylitis kyphosis combined with acute thoracolumbar vertebral fracture. METHODS: A clinical data of 20 patients with ankylosing spondylitis kyphosis combined with acute thoracolumbar spine fracture, who were treated with one-stage posterior eggshell osteotomy and long-segment pedicle screw fixation between April 2016 and January 2022, was retrospectively analyzed. Among them, 16 cases were male and 4 cases were female; their ages ranged from 32 to 68 years, with an average of 45.9 years. The causes of injury included 10 cases of sprain, 8 cases of fall, and 2 cases of falling from height. The time from injury to operation ranged from 1 to 12 days, with an average of 7.1 days. The injured segment was T ₁₁ in 2 cases, T ₁₂ in 2 cases, L ₁ in 6 cases, and L ₂ in 10 cases. X-ray film and CT showed that the patients had characteristic imaging manifestations of ankylosing spondylitis, and the fracture lines were involved in the anterior, middle, and posterior columns and accompanied by different degrees of kyphosis and vertebral compression; and MRI showed that 12 patients had different degrees of nerve injuries. The operation time, intraoperative bleeding, intra- and post-operative complications were recorded. The visual analogue scale (VAS) score and Oswestry disability index (ODI) were used to evaluate the low back pain and quality of life, and the American spinal cord injury association (ASIA) classification was used to evaluate the neurological function. X-ray films were taken, and local Cobb angle (LCA) and sagittal vertical axis (SVA) were measured to evaluate the correction of the kyphosis. RESULTS: All operations were successfully completed and the operation time ranged from 127 to 254 minutes (mean, 176.3 minutes). The amount of intraoperative bleeding ranged from 400 to 950 mL (mean, 722.5 mL). One case of dural sac tear occurred during operation, and no cerebrospinal fluid leakage occurred after repair, and the rest of the patients did not suffer from neurological and vascular injuries, cerebrospinal fluid leakage, and other related complications during operation. All incisions healed by first intention without infection or fat liquefaction. All patients were followed up 8-16 months (mean, 12.5 months). The VAS score, ODI, LCA, and SVA at 3 days after operation and last follow-up significantly improved when compared with those before operation ( P<0.05), and the difference between 3 days after operation and last follow-up was not significant ( P>0.05). The ASIA grading of neurological function at last follow-up also significantly improved when compared with that before operation ( P<0.05), including 17 cases of grade E and 3 cases of grade D. At last follow-up, all bone grafts achieved bone fusion, and no complications such as loosening, breaking of internal fixation, and pseudoarthrosis occurred. CONCLUSION One-stage posterior eggshell osteotomy and long-segment pedicle screw fixation is an effective surgical procedure for ankylosing spondylitis kyphosis combined with acute thoracolumbar vertebral fracture. It can significantly relieve patients' clinical symptoms and to some extent, alleviate the local kyphotic deformity.
Humans ; Male ; Female ; Animals ; Adult ; Middle Aged ; Aged ; Spinal Fractures/surgery* ; Pedicle Screws ; Spondylitis, Ankylosing/surgery* ; Quality of Life ; Retrospective Studies ; Egg Shell/injuries* ; Thoracic Vertebrae/injuries* ; Lumbar Vertebrae/injuries* ; Kyphosis/surgery* ; Osteotomy ; Fracture Fixation, Internal/methods* ; Fractures, Compression/surgery* ; Treatment Outcome