Objective To explore the changes in brain structure after short-term withdrawal therapy in patients with alcohol use disorder(AUD).Methods A total of 28 male patients with AUD were included,and brain MRI scans were performed at the time of enrollment and 2-3 weeks after standardized treatment.The total volume of brain tissue,gray matter,white matter and cerebrospi-nal fluid volume before and after treatment were measured by voxel-based morphometry(VBM)technology,and the gray matter volume of each brain region of the whole brain was measured and statistically analyzed according to the automated anatomical labeling(AAL)template.Results Compared with the baseline data,after 2-3 weeks of standardized treatment,the volume of gray matter in brain tissue increased significantly,and the volume of cerebrospinal fluid decreased significantly.Compared with before treatment,the brain regions with increased gray matter volume in the left hemisphere were distributed in the medial and paracingulate gyrus,central sulcus cover,anterior wedge lobe and insula,and the brain regions with increased gray matter volume in the right hemisphere were distributed in the anterior cingulate gyrus,paracingulate gyrus,central sulcus cover,amygdala,superior temporal gyrus,middle temporal gyrus,transverse temporal gyrus,anterior cuneiformus,posterior central gyrus,superior marginal gyrus,peritaloid cortex and insula.Conclusion Patients with AUD experience some increases in gray matter volume,especially in the prefrontal lobe,after short-term withdrawal therapy.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

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.

OBJECTIVES: To investigate the cerebral metabolism in the patients with type 2 diabetes mellitus-associated cognitive dysfunction (T2DACD) and explore the mechanism of electroacupuncture (EA) at the acupoints for Tiaozang Xingshen (adjusting zangfu function and rescuing the spirit) in treatment of T2DACD, using magnetic resonance spectroscopy. METHODS: Fifteen patients with T2DACD (observation group) and 22 healthy subjects (control group) were enrolled. In the observation group, the patients were treated with EA for Tiaozang Xingshen at Baihui (GV 20) and Shenting (GV 24), and bilateral Feishu (BL 13), Pishu (BL 20), Shenshu (BL 23), Zusanli (ST 36), Sanyinjiao (SP 6), Hegu (LI 4) and Taichong (LR 3). EA was operated with disperse-dense wave, 2 Hz/100 Hz in frequency and 0.1 mA to 1.0 mA in current intensity; 30 min each time, once daily. One course of EA consisted of 5 treatments, at the interval of 2 days and the intervention lasted 8 courses. Before treatment in the control group, before and after treatment in the observation group, the score of Montreal cognitive assessment scale (MoCA), the score of clinical dementia rating (CDR), Flanker paradigm, Stroop paradigm, Nback paradigm, the score of self-rating anxiety scale (SAS), the score of self-rating depression scale (SDS), and the score of Hamilton depression rating scale (HAMD) were evaluated separately; the glycolipid metabolic indexes (fasting plasma glucose [FPG], glycosylated hemoglobin type A1c [HbA1c], total cholesterol [TC], triacylglycerol [TG], high-density lipoprotein cholesterol [HDL-C] and low-density lipoprotein cholesterol [LDL-C]) were determined；with the magnetic resonance spectroscopy technique adopted, the metabolites in the basal ganglia area were detected. The correlation analysis was performed for the metabolite values with MoCA score, CDR score , Flanker paradigm, Stroop paradigm, and Nback paradigm. RESULTS: Before treatment, compared with the control group, in the observation group, MoCA score was lower (P<0.001), CDR score and the levels of FPG and HbA1c were higher (P<0.001); the reaction times of Flanker non-conflict, Flanker conflict, Stroop neutrality, Stroop congruence, Stroop conflict, and 1-back were prolonged (P<0.05, P<0.001), and the accuracy of Flanker conflict, Stroop conflict, and 1-back decreased (P<0.05, P<0.01); the ratio of N-acetyl aspartate (NAA) to creatine (Cr) in the left basal ganglia area was dropped (P<0.001), and that of myo-inositol (MI) to Cr in the right side increased (P<0.05). In the observation group after treatment, compared with the levels before treatment, MoCA score was higher (P<0.001), the scores of CDR, SAS and HAMD were reduced (P<0.01, P<0.05), the reaction times of Flanker conflict and Stroop conflict shortened (P<0.001, P<0.05), and the accuracy of Flanker conflict and 1-back increased (P<0.001, P<0.05); the ratio of NAA to Cr in the left basal ganglia area and that of the gamma-aminobutyric acid (GABA) to Cr in the right increased (P<0.05), that of MI to Cr in the right decreased (P<0.05). Before treatment, in the observation group, the ratio of MI to Cr in the right basal ganglia area was positively correlated with the reaction time of Stroop congruence (r=0.671, P=0.012) and this ratio was positively correlated with the reaction time of Stroop conflict (r=0.576, P=0.039). CONCLUSIONS Electroacupuncture for "adjusting zangfu function and rescuing the mind" improves the cognitive function of T2DACD patients, which may be related to the regulation of NAA, MI and GABA levels in the basal ganglia.
Humans ; Electroacupuncture ; Acupuncture Therapy ; Acupuncture Points ; Diabetes Mellitus, Type 2/therapy* ; Glycated Hemoglobin ; Cognitive Dysfunction/therapy* ; Cholesterol ; gamma-Aminobutyric Acid

Objective:To explore the clinical efficacy of modern rehabilitation techniques combined with Traditional Chinese Medicine (TCM) external application in the treatment of knee stiffness.Methods:Prospective cohort study. A total of 80 patients with knee stiffness meeting the entry criteria admitted to the People's Hospital of Bozhou from January 2019 to December 2021 were selected and divided into the observation group ( n=40) and the control group ( n=40) according to the random ball touching method. Both groups were given routine physiotherapy. The control group was treated with TCM external application on the basis of the physiotherapy, and the observation was treated with modern rehabilitation techniques on the basis of the treatment of the control group. The goniometer was used to measure the knee flexion and extension before and after treatment, and the VAS scale was used to assess the knee pain. Fug l-Meyer motor function score was used to evaluate lower extremity motor function. Results:After treatment, the knee flexion [(96.43 ± 4.63) ° vs. (89.58 ± 4.67) °, t=6.59] in the observation group was higher than that of the control group ( P<0.01), and the extension [(8.32 ± 2.03) ° vs. (11.69 ± 2.37) °, t=6.83] in the control group was lower than that of the control group ( P<0.01); VAS score (2.06 ± 0.49 vs. 3.65 ± 0.76, t=11.12) was lower than that of the control group ( P<0.01), and Fugl Meyer motor function score (28.97 ± 3.76 vs. 20.43 ± 3.04, t=11.17) was higher than that of the control group ( P<0.01). Conclusion:The application of modern rehabilitation techniques combined with TCM external application in the treatment of knee stiffness can improve the range of motion of the knee joint, reduce the VAS score of pain, and improve the motor function.

Peripheral bacterial infections without impaired blood-brain barrier integrity have been attributed to the pathogenesis of Parkinson's disease (PD). Peripheral infection promotes innate immune training in microglia and exacerbates neuroinflammation. However, how changes in the peripheral environment mediate microglial training and exacerbation of infection-related PD is unknown. In this study, we demonstrate that GSDMD activation was enhanced in the spleen but not in the CNS of mice primed with low-dose LPS. GSDMD in peripheral myeloid cells promoted microglial immune training, thus exacerbating neuroinflammation and neurodegeneration during PD in an IL-1R-dependent manner. Furthermore, pharmacological inhibition of GSDMD alleviated the symptoms of PD in experimental PD models. Collectively, these findings demonstrate that GSDMD-induced pyroptosis in myeloid cells initiates neuroinflammation by regulating microglial training during infection-related PD. Based on these findings, GSDMD may serve as a therapeutic target for patients with PD.

OBJECTIVE: To compare the mid-term clinical effect of arthroscopic surgery versus conservative treatment on the middle aged early knee osteoarthritis (EKOA) patients, with the hope to provide clinical evidence for their individual therapy. METHODS: A total of 145 middle aged EKOA patients(182 knees) who received arthroscopic surgery or conservative treatment from January 2015 to December 2016 were retrospectively enrolled, including 35 males and 110 females, aged from 47 to 79 years old with an average of (57.6±6.9) years old, and the duration of disease ranged from 6 to 48 months with an average of(14.6±8.9) months. According to treatment method, patients were divided into arthroscopic surgery group (47 patients, 58 knees) and conservative treatment group(98 patients, 124 knees). Before treatment, patients presented with symptoms of knee joint, such as pain, swelling, locking, limited flexion and extension, and weakness, as well as abnormal findings in knee X-ray (without or suspicious joint space narrow, and a few of osteophyte formation) or in knee MRI (injury or degeneration of articular cartilage or meniscus, loose body in the joint cavity and synovial hyperemia edema, etc). Related data were collected, including duration of knee symptoms, presence of meniscus injury, loose body in the joint cavity or mechanical symptoms such as locking, and visual analogue scale (VAS) and Lysholm knee function score before treatment and at the latest follow-up. Statistical analysis was performed to compare the differences in VAS or Lyshilm score before or after treatment between the low groups and within each group. RESULTS: Patients in the two groups were followed up from 60 to 76 months. In the arthroscopic surgery group, the incision healing was good and no surgical complications occurred. There were no significant differences in age, gender, BMI and follow-up time between the two groups(P>0.05). Before treatment, compared with conservative group, duration of symptoms in the arthroscopic group was longer (P<0.001), comorbidity rates of meniscus injury (P<0.001), free body (P=0.001) and mechanical symptoms (P<0.001) were higher, VAS (P<0.001) and Lysholm score (P<0.001) were worse. At the final follow-up, VAS and Lysholm score in either the conservative group or the arthroscopic group were significantly better than before treatment (P<0.05), while no significant differences between the two groups were found. The VAS was (1.5±1.2) scores in the arthroscopic group and (1.6±1.0)scores in the conservative group(P=0.549), and the Lysholm score was (84.9±12.5) scores in the arthroscopic group and (84.2±9.9) scores in the conservative group (P=0.676). CONCLUSION Both arthroscopic surgery and conservative treatment have satisfactory intermediate clinical effect middle- aged patients with EKOA, without statistically differences. However, most of the patients before surgery in the arthroscopic treatment group had mechanical locking symptoms caused by meniscus injury or loose body. Therefore, for the middle-aged EKOA patients with mechanical locking symptoms or without obtaining satisfactory outcome after conservative treatment, arthroscopic surgery may be considered.
Male ; Middle Aged ; Female ; Humans ; Aged ; Osteoarthritis, Knee/surgery* ; Retrospective Studies ; Arthroscopy/methods* ; Treatment Outcome ; Knee Joint/surgery*

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

Background and Objectives: Chronic inflammation of bone tissue often results in bone defects and hazards to tissue repair and regeneration. Cannabidiol (CBD) is a natural cannabinoid with multiple biological activities, including anti-inflammatory and osteogenic potential. This study aimed to investigate the efficacy and mechanisms of CBD in the promotion of bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation in the inflammatory microenvironment. Methods: and Results: BMSCs isolated from C57BL/6 mice, expressed stem cell characteristic surface markers and pre-sented multidirectional differentiation potential. The CCK-8 assay was applied to evaluate the effects of CBD on BMSCs’ vitality, and demonstrating the safety of CBD on BMSCs. Then, BMSCs were stimulated with lipopolysaccharide (LPS) to induce inflammatory microenvironment. We found that CBD intervention down-regulated mRNA expression levels of inflammatory cytokines and promoted cells proliferation in LPS-treated BMSCs, also reversed the protein and mRNA levels downregulation of osteogenic markers caused by LPS treatment. Moreover, CBD intervention activated the cannabinoid receptor 2 (CB2) and the p38 mitogen-activated protein kinase (MAPK) signaling pathway. While AM630, a selective CB2 inhibitor, reduced phosphorylated (p)-p38 levels. In addition, AM630 and SB530689, a selective p38 MAPK inhibitor, attenuated the enhancement of osteogenic markers expression levels by CBD in inflammatory microenvironment, respectively. Conclusions CBD promoted osteogenic differentiation of BMSCs via the CB2/p38 MAPK signaling pathway in the inflammatory microenvironment.

Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response. However, single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways. The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications. To circumvent this issue, we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle (PNM) for cancer therapy. PNM was engineered by integrating the PI3K/mTOR inhibitor PF-04691502 (PF) and the broad spectrum CDK inhibitor flavopiridol (Flav) into a single nanoplatform, which showed tumor-specific accumulation, activation and deep penetration in response to the high glutathione (GSH) tumoral microenvironment. The codelivery of PF and Flav could trigger gasdermin E (GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response. Furthermore, the combination of PNM-induced immunogenic pyroptosis with anti-programmed cell death-1 (αPD-1) immunotherapy further boosted the antitumor effect and prolonged the survival time of mice. Collectively, these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/mTOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.