As the brain's resident immune cells, microglia perform crucial functions such as phagocytosis, neuronal network maintenance, and injury restoration by adopting various phenotypes. Dynamic imaging of these phenotypes is essential for accessing brain diseases and therapeutic responses. Although numerous probes are available for imaging pro-inflammatory microglia, no PET tracers have been developed specifically to visualize anti-inflammatory microglia. In this study, we present an ¹⁸F-labeled PET tracer (QTFT) that targets the P2Y₁₂, a receptor highly expressed on anti-inflammatory microglia. [¹⁸F]QTFT exhibited high binding affinity to the P2Y₁₂ (14.43 nmol/L) and superior blood-brain barrier permeability compared to other candidates. Micro-PET imaging in IL-4-induced neuroinflammation models showed higher [¹⁸F]QTFT uptake in lesions compared to the contralateral normal brain tissues. Importantly, this specific uptake could be blocked by QTFT or a P2Y₁₂ antagonist. Furthermore, [¹⁸F]QTFT visualized brain lesions in mouse models of epilepsy, glioma, and aging by targeting the aberrantly expressed P2Y₁₂ in anti-inflammatory microglia. In a pilot clinical study, [¹⁸F]QTFT successfully located epileptic foci, showing enhanced radioactive signals in a patient with epilepsy. Collectively, these studies suggest that [¹⁸F]QTFT could serve as a valuable diagnostic tool for imaging various brain disorders by targeting P2Y₁₂ overexpressed in anti-inflammatory microglia.

Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Objective To evaluate the clinical efficacy of Chevron minimally-invasive osteotomy and internal fixation with ISO intramedullary plate plus traditional Chinese medicine(TCM)bone-setting manipulations for the treatment of moderate hallux valgus.Methods A retrospective study was conducted.A total of 49 patients(62 feet)with moderate hallux valgus were treated with Chevron minimally-invasive osteotomy and internal fixation with ISO intramedullary plate,and were given TCM bone-setting manipulations before the operation,during the operation,and after the operation.The efficacy was evaluated by using the Visual Analogue Scale(VAS)score and the American Orthopedic Foot and Ankle Society(AOFAS)forefoot score after the operation.Before the operation and 12 months after the operation,the hallux valgus angle(HVA),intermetatarsal angle(IMA)between the first and second metatarsal bone,and the distal metatarsal articular angle(DMAA)showed by X-ray imaging in the weight-bearing position of the foot were recorded.Results(1)All of the 49 patients were followed up for 12 to 24 months,with a mean of(20.6±3.1)months.(2)The X-ray imaging assessment showed that 12 months after the operation,the mean HVA,IMA and DMAA values of the 49 patients(62 feet)were significantly lower than those before the operation,and the differences were all statistically significant(P＜0.01).(3)Twelve months after the operation,the pain VAS score of 49 patients was(3.14±1.21)points,which was significantly lower than the preoperative score points(7.26±2.52),and the difference was statistically significant(P＜0.01).(4)The assessment of joint function showed that 12 months after the operation,the scores of various AOFAS items of pain,function and hallux alignment as well as the overall AOFAS scores of 49 patients were significantly higher than those before the operation,and the differences were statistically significant(P＜0.01).(5)For the 62 feet in 49 patients,the excellent efficacy was achieved in 53 feet,good efficacy was achieved in 7 feet,and fair efficacy was achieved in 2 feet,with the fine rate of 96.77%(60/62).Conclusion For the treatment of moderate hallux valgus,the application of Chevron minimally-invasive osteotomy and internal fixation with ISO intramedullary plate plus TCM bone-setting manipulations is effective on promoting the reset of hallux-metatarsophalangeal joint,restoring the balance of the joint,and maintaining the equilibrium state of the joint through postoperative rehabilitation guidance.The combined therapy exerts certain efficacy,reduces the recurrence rate,and eventually achieves the early rehabilitation after the operation.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

Objective To evaluate the association between diabetic retinopathy (DR) and mean ocular perfusion pressure (MOPP) in patients with type 2 diabetes mellitus (T2DM).Methods Patients from the Fushun Diabetic Retinopathy Cohort Study (FS-DIRECT), a communitybased prospective cohort study conducted in northeast China, were included in this study. The presence and severity of DR were determined by grading fundus photographs according to the Early Treatment Diabetic Retinopathy Study (ETDRS) retinopathy scale. Systolic and diastolic blood pressure (SBP and DBP) were recorded using an electronic sphygmomanometer. Intraocular pressure (IOP) was measured using an iCare rebound tonometer. MOPP was calculated using the formula MOPP = 2/3 [DBP + 1/3(SBP ? DBP)] ? IOP.Results In total, 1,857 patients who had gradable fundus photography and MOPP data were enrolled in this study. Male patients had a higher MOPP than female patients (52.25 ± 8.75 vs. 50.96 ± 8.74mmHg, P = 0.002). Overall, both male and female patients with any type of DR, non-proliferative DR (NPDR), or non-sight-threatening DR (non-STDR) had significantly higher MOPP relative to patients without DR. Increased MOPP (per 1 mmHg) was in turn associated with the presence of any type of DR [odds ratio (OR) = 1.03, 95％ confidence interval (CI) : 1.02–1.04], NPDR (OR = 1.0395％ CI: 1.02–1.04),and non-STDR (OR = 1.03, 95％ CI: 1.01–1.04) after adjusting for confounders. Increased MOPP (per 1 mmHg) was also associated with an increased likelihood of macular edema (OR = 1.02, 95％ CI:1.01–1.04).Conclusions The results suggest that increased MOPP was associated with DR and macular edema in northeastern Chinese patients with T2DM.

Objective To analyze the death trend of children under 5 years old in Lanzhou and establish the time series model to predict the mortality and incidence of children under 5 years old in Lanzhou in 2019. Methods Descriptive epidemiological method was used to analyze the mortality of children under 5 years old in Lanzhou from January 2010 to December 2018. SPSS 21.0 software was used to construct time series analysis model, selecting the best model and predict the mortality of children under 5 years old in Lanzhou in 2019. Results A total of 1 650 deaths of children under 5 years old were reported in Lanzhou from 2010 to 2018. The number of deaths reported by boys and girls was 871 and 774 respectively, with an average annual mortality rate of 6.23‰. In recent years, the overall mortality rate of children under 5 years old in Lanzhou had declined. The majority of deaths among children under 5 years old were neonates, accounting for 65.27%. Simple seasonal model was the best model by comparing different models. The model could well fit the monthly death cases of children under 5 years old in Lanzhou from 2010 to 2018. It is predicted that the total number of deaths of children under 5 years old in Lanzhou will be 140 in 2019, which is similar to the number of deaths in 2018. Conclusions The mortality rate of children under 5 years old in Lanzhou is decreasing year by year. Simple seasonal model can better reflect the mortality trend of children under 5 years old in Lanzhou and make short-term prediction.

Objective To discuss the clinical curative effect of percutaneous vertebroplasty(PVP)combined with percutaneous pedicle screw fixation for thoracolumbar fracture.Methods Retrospectively analyzed the clinical data of 43 patients with thoracolumbar fracture who underwent PVP combined with percutaneous pedicle screw fixation in our hospital from November 2015 to June 2017.Those patients included 28 males and 15 females,and the age of patients ranged from 50 to 66 years old,with an average age of(58.26 ±3.67)years old.The func-tional outcome were evaluated by VAS scores and ODI scores before and after the operation.The sagittal Cobb angle was used to evaluate the reduction of fracture.Results All these patients all successfully completed the operation,and there was no complications after operation.The operation time ranged from 60 to 126 min,with an average time of(96.07 ±15.69)min;the blood loss ranged from 60 to 180 min,with an average time of(113.26 ±24.7)min.All the patients were followed up for 4 to 23 months,with an average time of(12.07 ±4.01)months. The VAS score,ODI score and sagittal Cobb angle were significantly decreased in the last follow -up period compared with those before surgery,and the difference was statistically significant(P<0.05).Conclusion PVP combined with percutaneous pedicle screw fixation in the treatment of thoracolumbar fracture has smaller incision,less blood loss,shorter operation time and better improvement of local pain,func-tional movement and kyphosis.

AIM To observe the curative effects of Modified Buzhong Yiqi Decoction (Codonopsis Radix,Astragali Radix,Atractylodis macrocephalae Rhizoma,ect.) on perioperative period of intertrochanteric fractures in elderly patients with Qi deficiency and blood stasis type.METHODS One hundred and twenty cases of elderly intertrochanteric fractures were randomly divided into treatment group and control group,60 cases in each group.All patients underwent closed fracture reduction and proximal femoral nail anti-rotation (PFNA) fixation.During the perioperative period,the control group only received conventional treatment,while the treatment group received conventional treatment and Modified Buzhong Yiqi Decoction once a day.The levels of interleukin-6 (IL-6),interleukin-10 (IL-10) and tumor necrosis factor (TNF-α) of both groups in preoperative and in the 1st day,the 7th day,the 14th day of postoperative were observed and compared.The complications and the curative effects according to the Harris score also were observed and compared between the two groups.RESULTS In preoperative,there was no significant difference in levels of IL-6,IL-10 and TNF-α between the two groups (P ＞ 0.05).The levels of IL-6 and TNF-α in the 1 st day of postoperative in the control group were significantly higher than those in the treatment group (P ＜0.05,P ＜0.01).And the levels of IL-10 were similar between the two groups (P ＞0.05).In addition,in the 7th day and the 14th day of postoperative,the levels of IL-6,IL-10 and TNF-α in both groups were all decreased,moreover,the descent degree in treatment group was more significant than those in the control group (P ＜ 0.05,P ＜ 0.01).The treatment group had the lower incidence of complications and the higher curative effects than those in the control group,both differences were statistically significant (P ＜0.05).CONCLUSION Modified Buzhong Yiqi Decoction applying to the perioperative period of femoral intertrochanteric fractures in elderly patients with Qi deficiency and blood stasis,can effectively reduce the perioperative inflammatory response,reduce the incidence of postoperative complications,and improve the curative effects.So it has a positive effect on the rehabilitation for the traumatic patients and is worthy of clinical promotion.

OBJECTIVETo evaluate the sedative and hypnotic effects of Foshouningshen decoction (FSNSD) and study its effects on expressions of 5-hydroxy tryptamine (5-HT) and 5-HT1A receptor (5-HTR) in the hippocampus in a rat model of insomnia.

METHODSMale KM mice were divided into control group, estazolam (0.4 mg/kg daily) group, and low-, moderate-, and high-dose FSNSD groups (daily dose of 12, 24, and 48 g/kg, respectively). After corresponding treatments for 1 week, the mice underwent sleep-inducing test with subthreshold and threshold doses of sodium pentobarbital. Forty-eight male SD rats were randomized into control group, insomnia model group, estazolam group (0.2 mg/kg daily), and low-, moderate-, and high-dose FSNSD groups (with daily dose of 6, 12, and 24 g/kg, respectively). Rat models of insomnia were established by intraperitoneal injection of 4-cholro-dl-phenylalanine (PCPA) at the daily dose of 350 mg/kg for 3 days, after which the rats received corresponding treatments via gavage for 1 week. The performance of the rats in open field test was recorded and the hippocampal expression of 5-HT was detected using ELISA; the expressions of 5-HTR protein and mRNA in the hippocampus were detected using immunohistochemistry and real-time PCR, respectively.

RESULTSIn the sleep-inducing test with a subthreshold dose of sodium pentobarbital, the mice treated with high-dose FSNSD showed a significantly higher rate of sleep onset than the control mice (P<0.05); in the test with a threshold dose of sodium pentobarbital, treatment with moderate- and high-dose FSNSD resulted in significantly prolonged sleeping time (P<0.01) and shortened sleep latency (P<0.05) in the mice. The rats in insomnia model group showed increased total distance in open field test (P<0.05) with significantly decreased content of 5-HT (P<0.01) and expressions of 5-HTR protein and mRNA in the hippocampus (P<0.01). Treatment of the rats with estazolam or high-dose FSNSD obviously decreased the total distance in open field test (P<0.05) and increased the content of 5-HT (P<0.05) and expressions of 5-HTR (P<0.01) in the hippocampus of rats with insomnia.

CONCLUSIONFSNSD can produce therapeutic effects on insomnia possibly by increasing 5-HT content and expressions of 5-HTR in the hippocampus.

OBJECTIVETo evaluate the expression of HMGB1 protein in tissue specimens of laryngeal squamous cell carcinoma (LSCC) and adjacent normal mucosa, and explore the correlation of HMGB1 protein expression with clinicopathologic features and prognosis in LSCC.

METHODSNinty-three cases of LSCC and 5 cases of adjcent mucosal tissue samples were included in this study. Immunohistochemical staining was performed on paraffin-embedded tissue specimens to examine the HMGB1 protein expression. The data were futher correlated with the clinicopathological features and prognosis of the LSCC patients.

RESULTSThe positive rates of HMGB1 expression in LSCC specimens was 87.1%, significantly higher than that in the adjcent normal mucosa samples (46.7%, P = 0.001), and its overexpresion was closely correlated with T stage (Chi2 = 10.878, P = 0.004), clinical stage (Chi2 = 21.115, P < 0.01), metastasis (Chi2 = 28.298, P < 0.01) and recurrence (Chi2 = 14. 923, P = 0.001) in patients with LSCC. Patients with HMGB1 overexpression had both poorer disease-free survival and poorer overall survival compared with that in patients with low HMGB1 expression (Chi2 = 13.815, Chi2 = 11.912; Both P < 0.01). Univariate and multivariate Cox regression analyses revealed that HMGBI expression is an independent prognostic factor for patients with LSCC.

CONCLUSIONSThe results of this study demonstrate that HMGB1 protein expression is significantly increased in LSCC tissues, and HMGB1 protein overexpression is associated with a poorer prognosis in patients with LSCC. These results suggest that HMGB1 may play a critical role in the initiation and progression of LSCC, implicating HMGB1 may become a valuable marker for the prediction of prognosis in patients with LSCC.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; metabolism ; pathology ; surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; HMGB1 Protein ; metabolism ; Humans ; Laryngeal Neoplasms ; metabolism ; pathology ; surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Proportional Hazards Models ; Survival Rate