Objective To explore the effect of transcranial direct current stimulation(tDCS)based on music therapy on insomnia. Methods From July,2023 to April,2024,70 patients with insomnia in the Fourth Affiliated Hospital of Soochow Univer-sity were randomly divided into control group(n=35)and observation group(n=35).Both groups accepted mu-sic therapy;moreover,the observation group accepted tDCS,and the control group accepted sham tDCS,for four weeks.They were assessed with Pittsburgh Sleep Quality Index(PSQI)total score and sub-score,Hamilton De-pression Scale 17-item(HAMD-17),Hamilton Anxiety Scale(HAMA),Chinese version of Stress Perception Scale(CPSS);and the relative power of resting-state electroencephalography(EEG)and mean blood flow veloci-ty(Vm)of each cerebral artery with transcranial Doppler were measured before and after treatment. Results Five cases dropped down in the control group,and four in the observation group.PSQI total score and sub-score,HAMD-17 score,HAMA score and CPSS score(|t|>3.503,P<0.01)in the observation group decreased after treatment,and were less in the observation group than in the control group(|t|>2.304,P<0.05),except sleep duration,sleep efficiency and CPSS scores.The relative power of δ and θ increased in the observation group,and decreased in α,β and γ(|t|>6.468,P<0.001),and were better in the observation group than in the control group(|t|>2.395,P<0.05).The Vm of each artery increased in the observation group(|t|>4.624,P<0.001),and were more in the observation group than in the control group(|t|>2.147,P<0.05). Conclusion tDCS based on music therapy may further improve sleep quality and EEG activity,increase cerebral blood flow velocity,and reduce adverse emotions in insomnia patients.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective To explore the effect and mechanism of Baicalein in the treatment of hyperuricemia.Methods The mouse model of hyperuricemia was established by yeast extract combined with potassium oxazinate.The effect and potential mechanism of Baicalein in the treatment of hyperuricemia were studied by biochemical indexes,pathological changes,non-target metabonomics and network pharmacology.Results Baicalein could reduce the contents of serum uric acid,creatinine and blood urea nitrogen,reduce the inflammatory injury of renal tissue,up-regulate the expression level of uric acid excretion protein and down-regulate the expression level of uric acid reabsorption protein.Nine disease-related targets such as BCL2,SIRT1 and XDH were screened by network pharmacology.Six key metabolic pathways including nicotinic acid and nicotinamide metabolism,caffeine metabolism and purine metabolism were screened by metabonomics analysis.Conclusions Baicalein can treat hyperuricemia and reduce renal injury,and its mechanism may be related to the metabolic pathways of nicotinic acid and nicotinamide regulated by SIRT1 and quinolinate.

Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(Ⅳ)prodrug(C8Pt(Ⅳ))and Cet.The so-called antibody-platinum(Ⅳ)prodrugs conjugates,named Cet-C8Pt(Ⅳ),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(Ⅳ)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(Ⅳ)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(Ⅳ)prodrugs conjugates.

The in-depth study of the intervention of endometriosis （EMS） with Chinese medicines has revealed many pathways that can be regulated by Chinese medicines in the treatment of EMS. Chinese medicinal compound prescriptions， single Chinese herbal medicines， or their active ingredients treat EMS via the signaling pathways discussed in this paper. They can directly or indirectly regulate the expression of key molecules in the corresponding signaling pathways to inhibit the proliferation of endometriotic cells and the inflammatory changes of endometrial tissue， promote the apoptosis of endometriotic cells， change the pain threshold， and reduce endometriotic cell invasion， so as to achieve the therapeutic effects of inhibiting EMS progression， improving endometrial receptivity， and reducing ovarian injury. The following details are based on relevant studies conducted both at home and abroad. Curcumol can inhibit angiogenesis and promote cell apoptosis by blocking the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway. Icariin can reduce inflammation and promote cell apoptosis by blocking the nuclear factor-kappa B signaling pathway. Puerarin can suppress cell proliferation and promote cell apoptosis by inhibiting the mitogen-activated protein kinase （MAPK） signaling pathway and blocking the estrogen signaling pathway. Naringenin has the ability to activate the MAPK signaling pathway to promote cell apoptosis. Imperatorin can inhibit cell proliferation and promote cell apoptosis by inhibiting the phosphatidylinositol 3-kinase/protein kinase B signaling pathway. Resveratrol can inhibit cell proliferation and alleviate fibrosis and adhesion by blocking the transforming growth factor-beta signaling pathway. Paeonol can inhibit angiogenesis by blocking the hypoxia-inducible factor 1 signaling pathway. The above summary can serve as a reference for the future clinical treatment or experimental research of EMS with Chinese medicines.

ObjectiveTo investigate the effect of transcranial direct current stimulation (tDCS) combined with constraint-induced weight training (CIWT) on Pusher syndrome after stroke. MethodsA total of 60 stroke inpatients with Pusher syndrome in the First Affiliated Hospital of Soochow University from January to December, 2021 were randomly divided into tDCS group, CIWT group and combination group, with 20 cases in each group. The three groups accepted routine rehabilitation training, the tDCS group received anode tDCS, the CIWT group received CIWT of the affected lower limb, and the combination group received CIWT of the affected lower limb and tDCS, for eight weeks. They were assessed with Berg Balance Scale (BBS), Fugl-Meyer Assessment-Lower Extremities (FMA-LE), Burke Lateropulsion Scale (BLS) and Holden Walking Functional Ambulation Category (FAC) before and after treatment. ResultsAfter treatment, the scores of BBS, FMA-LE, BLS and FAC improved (|t| > 1.452, P < 0.05) in all the groups, and improved the most in the combination group (|F| > 1.827, P < 0.05). ConclusiontDCS combined with CIWT of the affected lower extremity can effectively improve the function of stroke patients with Pusher syndrome.

OBJECTIVE: To investigate whether gut microbiota disturbance after cardiopulmonary bypass (CPB) contributes to the development of perioperative neurocognitive disorders (PND). METHODS: Fecal samples were collected from healthy individuals and patients with PND after CPB to prepare suspensions of fecal bacteria, which were transplanted into the colorectum of two groups of pseudo-germ-free adult male SD rats (group NP and group P, respectively), with the rats without transplantation as the control group (n=10). The feces of the rats were collected for macrogenomic sequencing analysis, and serum levels of IL-1β, IL-6 and TNF-α were measured with ELISA. The expression levels of GFAP and p-Tau protein in the hippocampus of the rats were detected using Western blotting, and the cognitive function changes of the rats were assessed with Morris water maze test. RESULTS: In all the 3 groups, macrogenomic sequencing analysis showed clustering and clear partitions of the gut microbiota after the transplantation. The relative abundances of Klebsiella in the control group (P < 0.005), Akkermansia in group P (P < 0.005) and Bacteroides in group NP (P < 0.005) were significantly increased after the transplantation. Compared with those in the control group, the rats in group NP and group P showed significantly decreased serum levels of IL-1β, IL-6 and TNF-α and lowered expression levels of GFAP and p-Tau proteins (all P < 0.05). Escape platform crossings and swimming duration in the interest quadrant increased significantly in group NP (P < 0.05), but the increase was not statistically significant in group N. Compared with those in group P, the rats in group NP had significantly lower serum levels of IL-1β, IL-6 and TNF-α and protein expressions of GFAP and p-Tau (all P < 0.05) with better performance in water maze test (P < 0.05). CONCLUSION In patients receiving CPB, disturbances in gut mirobiota contributes to the development of PND possibly in relation with inflammatory response.
Male ; Animals ; Rats ; Rats, Sprague-Dawley ; Cardiopulmonary Bypass ; Gastrointestinal Microbiome ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; Neurocognitive Disorders

Objective:To explore the effect of repetitive transcranial magnetic stimulation (rTMS) combined with cognitive behavioral therapies (CBT) on the cognitive function and alcohol craving in patients with alcohol dependence.Methods:From March 2019 to September 2021, a total of 150 patients with alcohol dependence were enrolled and randomly divided into rTMS treatment group (rTMS+ sham CBT, n=41), CBT treatment group (CBT+ sham rTMS, n=34), rTMS+ CBT treatment group( n=36) and control group (sham rTMS+ sham CBT, n=39). At baseline (before treatment), 2nd week, 8th week, 12th week and 24th week, alcohol dependence scale (ADS) was used to evaluate the degree of alcohol dependence, the obsessive compulsive drinking scale (OCDS) was used to assess patients' drinking craving, and Montreal cognitive assessment scale (MoCA) was used to assess the overall cognitive level of patients.SPSS 23.0 statistical software was used to compare the differences of ADS, OCDS and MoCA scale scores of the four groups by repeated measure ANOVA and simple effect analysis. Results:(1)The patients in the four groups were evaluated with ADS scale at baseline, 12th week and 24th week respectively.The interaction of group×time( F=1.279, P=0.279) and the main effect of group were not significant ( F=0.882, P=0.454), and the main effect of time was significant ( F=12.925, P<0.001) .Further simple effect analysis showed that the ADS score of rTMS+ CBT group was lower than that of baseline(14.48±5.70, 10.00±6.51) ( P=0.01) at 24th week.(2)Patients in the four groups were assessed with OCDs scale at baseline, 2nd week, 8th week, 12th week and 24th week, and the interaction of group×time was significant ( F=2.015, P=0.042). Further simple effect analysis showed that the OCDs scores of rTMS group and rTMS+ CBT group at each follow-up time node were lower than those at baseline period (all P<0.05). (3)Patients in the four groups were assessed with MoCA scale at baseline, 8th week, 12th week and 24th week, and the interaction of group×time was not significant ( F=1.660, P=0.106), and the main effect of group and the main effect of time were significant ( F=2.964, P=0.038; F=14.239, P<0.001). Further simple effect analysis showed that the score of MoCA scale in CBT group at the 24th week was higher than that at baseline (21.73±5.81, 24.60±3.98)( P=0.029), the score of MoCA scale in rTMS+ CBT group at the 24th week was higher than that at the 8th week (23.50±6.01, 25.95±2.87) ( P=0.006), and the score of MoCA scale in rTMS group at the 12th week was higher than that in control group (22.08±6.64, 26.64±2.46)( P=0.009). Conclusion:rTMS combined with CBT can be effective in improving alcohol craving and cognitive function in patients with alcohol dependence, and has a good long-term effect.

Objective:To evaluate the clinical value of the transcutaneous neuromodulation (TN) in improving gastrointestinal function after gastrointestinal tumor operation.Methods:From April 2019 to June 2020, at The Affiliated People′s Hospital of Ningbo University, 100 patients who underwent gastrointestinal tumor surgery were included. The 100 patients were randomly divided into treatment group(receiving TN treatment, 50 cases)and control group (receiving sham TN treatment, 50 cases). The clinical data of the two groups was compared to evaluate the recovery of gastrointestinal function, which included the time of first defecation, time of first flatus, time of first ambulation, time of resuming diet, the incidence of nausea and vomiting within 3 d after operation and pain score (0 to 10). Heart rate variability (HRV) was compared between two groups to analyze the possible mechanism of TN improving gastrointestinal function after gastrointestinal tumor surgery. Independent sample t test and Chi-square test were used for statistical analysis. Results:Among 100 patients, there were 63 male and 37 female patients, the age was (67.0±11.3) years old, ranged from 28 to 92 years old. Compared with the control group, the time of first defecation, first flatus, first ambulation and resuming diet of treatment group reduced by 31.0%, 39.8%, 38.0% and 32.4% ((72.1±3.0) h vs.(104.5±2.9) h, (49.4±5.7) h vs.(82.1±3.1) h, (3.1±0.7) d vs.(5.0±0.9) d, (4.8±0.9) d vs. (7.1±0.8) d)), respectively; the pain scores on the day 2 and day 3 after operation and incidence of nausea and vomiting within 3 d after operation decreased by 50.0%, 65.5%, 26.0%(1.5±0.6 vs. 3.0±0.7, 1.0±0.6 vs. 2.9±0.6, 16.0%, 8/50 vs. 42.0%, 21/50), respectively, and the differences were statistically significant ( t=54.28, 35.72, 11.67, 13.66, 12.00 and 14.90, χ2=8.21, all P<0.01). The results of HRV analysis showed that the high frequency on day 3 was higher than that on day 1 of treatment group, and the ratio of low frequency to high frequency after operation was lower than that before operation of treatment group (0.5±0.1 vs. 0.4±0.1, 1.2±0.7 vs. 1.9±1.0), and the differences were statistically significant( t=-4.81 and 4.26, both P<0.01), which indicated TN could enhance vagal activity. Conclusions:TN promote the recovery of gastrointestinal function after gastrointestinal tumor operation, and can be used as an adjuvant therapy to accelerate the recovery of gastrointestinal function after gastrointestinal tumor operation.

Epidemiological analysis describes and compares the characteristics of a certain number of people to make causal inferences. The formation of the study population is always the first step. In this paper, we first define the concepts of cross-sections at both individual level and population level and introduce the three assumptions needed in the measurements in observational studies, i. e. the true values of the attributes are stable with time, the attribute variables are independent and the individuals are independent during the measuring process. We also determine that the causal inference research should be unified based on the time of the occurrence or beginning of a postulated cause, or exposure, should be in. Then, based on the dual roles of the population cross-section with causal thinking, we propose that research designs can be classified into two types with different characteristics: history reconstruction research and future exploration research. Finally, we briefly analyze the research design framework and the relationship between estimated effects and different designs. The discussion of the formation of a study population from the perspective of causal thinking can make a foundation for the classification of causal inference research design with appropriate effect parameters, which needs to be further studied.