Pain is one of the common non-motor symptoms in patients with Parkinson disease and is characterized by early onset， a high incidence rate， and diverse types of discomfort， which seriously affects the quality of life of patients. Based on the related concepts of pain in Parkinson disease and the current status of research in China， this article reviews the commonly used non-pharmaceutical interventions for alleviating pain in patients and their mechanisms， in order to provide a basis for developing pain management regimens.
Parkinson Disease ; Pain

A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8⁺ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

Objective To discuss the morphological characteristics of three types of clinically rare cerebral aneurysms and arterial bifurcations.Methods A total of 17 patients with clinically rare cerebral aneurysms,including anterior cerebral artery-pericallosal artery aneurysms(ACA-PA aneurysms,n=8),internal carotid artery-anterior choroidal artery bifurcation aneurysms(ICA-AChA aneurysms,n=5)and vertebral artery-posterior inferior cerebellar artery bifurcation aneurysms(VA-PICA aneurysms,n=4),who received treatment in the Shijiazhuang People's Hospital between January 2017 and April 2020 were enrolled in this study.The clinical baseline data were recorded,and the morphological parameters of the aneurysms were determined.The bifurcation angle,small lateral angle and large lateral angle were defined as φ1,φ2 and φ3,respectively.D1,S1 and T1 represented the diameter,cross-sectional area and tortuosity of the main blood vessel,respectively.D2,S2 and T2 were defined as the corresponding parameters of the branch vessel forming small lateral angle with the main vessel.D3,S3 and T3 were the corresponding morphological parameters of the contralateral branch vessel.Results All of the ICA-AChA and VA-PICA bifurcation aneurysms were type D aneurysms and oriented towards the small lateral angle.Six ACA-PA bifurcation aneurysms were type C aneurysm,and 5 of them were oriented toward the small lateral angle.The S2 and φ2 of the ACA-PA and ICA-AChA bifurcations harboring aneurysms were significantly smaller than S3 and φ3(P＜0.05),while T2 was remarkably largerthan T3(P＜0.05).The VA-PICA bifurcations also showed a similar manifestations.Conclusion These three types of clinically rare cerebral aneurysms are mostly oriented towards the small lateral angle,and the diameter and cross-section area of the branch forming small lateral angle with parent artery were smaller than those of the contralateral branch vessel,while the tortuosity was greater than that of the contralateral branch.

Objective:To investigate the relationship between lifestyle factors and stroke in the elderly.Methods:Data were obtained from a natural cohort of the Multimodal Intervention to Delay Dementia and Disability in Rural China(MIND-China)study.A total of 5 009 participants aged 60 years and above were enrolled, of whom 954(19.05%)had experienced a stroke.Logistic regression analyses were conducted to assess the association between five lifestyle factors(smoking, drinking, physical exercise, social activity and sleep quality)and the incidence of stroke.Results:In model 1, after adjusting for age, sex and education, only social activity( OR=0.783, 95% CI: 0.668-0.917)and good sleep quality( OR=0.731, 95% CI: 0.621-0.860)emerged as protective factors against stroke(both P<0.05).No statistically significant associations were found between other lifestyle factors and stroke.Analysis of a variety of healthy lifestyle practice combinations showed that having 3( OR=0.639, 95% CI: 0.433-0.944), 4( OR=0.620, 95% CI: 0.409-0.941)and 5( OR=0.397, 95% CI: 0.197-0.799)healthy lifestyle practices were protective factors against stroke(all P<0.05).In model 2, after adjusting for age, sex, education, body mass index, diabetes, hyperlipidemia, hypertension, and the APOE genotype, the results were consistent with those of Model 1. Conclusions:Lifestyle factors are significantly associated with the risk of stroke in the elderly population.The healthier lifestyle practices are adopted, the lower the risk of stroke will be.

Objective To investigate the efficacy and safety of Yushi Huayu Zhixue prescription (Huayu prescription) combined with levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of adenomyosis (AM). Methods A prospective,randomized,double-blind,placebo-controlled trial was designed and 102 patients with AM admitted to the outpatient department of International Peace Maternal & Child Health Hospital and The First Affiliated Hospital of Naval Medical University (Second Military Medical University) from Dec. 2019 to Dec. 2022 were enrolled. The patients were randomly divided into Huayu prescription group and placebo group for double-blind clinical trial. The Huayu prescription group was treated with Huayu prescription 1 month after LNG-IUS placement,while the placebo group was treated with placebo 1 month after LNG-IUS placement,and both Huayu prescription and placebo were taken for 3 months. A total of 95 patients completed the follow-up,including 47 in the Huayu prescription group and 48 in the placebo group;and 7 were shed,with a shedding rate of 6.86％. The pictorial blood loss assessment chart (PBAC) score,uterine spotting days,visual analogue scale (VAS) score,uterine volume,serum carbohydrate antigen 125 (CA125) level and traditional Chinese medicine (TCM) syndrome quantitative score were compared between the 2 groups,and the safety was evaluated. Results After 3 months of treatment,compared with the placebo group,the PBAC score,spotting days,uterine volume,serum CA125 level and TCM syndrome quantitative score of patients in the Huayu prescription group were all decreased (all P<0.05),but there was no significant difference in the VAS score of dysmenorrhea (P>0.05). During the follow-up,no patients in the Huayu prescription group but 2 patients in the placebo group received surgical treatment (including 1 case of laparoscopic hysterectomy and 1 case of laparoscopic adenomyomectomy),and there was no significant difference in the surgical rate between the 2 groups (P>0.05). Meanwhile,no obvious adverse reactions were found in both groups. Conclusion Huayu prescription can significantly improve the spotting of patients with AM,promote uterine volume reduction,reduce serum CA125 level,and significantly improve the TCM syndrome of AM. It is suggest that AM patients should take Huayu prescription after placing LNG-IUS,so as to reduce the adverse reactions of LNG-IUS.

Purpose: Higher neutrophil-lymphocyte ratio (NLRs) indicate a pro-inflammatory state and are associated with poor survival. Conversely, higher albumin-globulin ratio (AGRs) may be associated with improved prognosis. We aimed to investigate the association between NLR and AGR and prognosis and survival in patients with breast cancer. Methods: This retrospective study included all patients with stage I–III breast cancer between 2011 and 2017 in Singapore General Hospital and National Cancer Center Singapore.Multivariate logistic regression analysis of NLR, AGR, age, stage, grade, and subtype was performed. Survival data between groups were compared using Cox regression analysis and log-rank tests. Results: A total of 1,188 patients were included, of whom 323 received neoadjuvant chemotherapy (NACT) and 865 underwent upfront surgery. In patients who underwent NACT, a higher AGR was significantly associated with a higher pCR rate (cut-off > 1.28; odds ratio [OR], 2.03; 95% confidence interval [CI], 1.13–3.74; p = 0.020), better DFS (cut off > 1.55; hazard ratio [HR], 0.37; 95% CI, 0.16–0.85; p = 0.019), and better CSS (cut off > 1.46; HR, 0.39; 95% CI, 0.17–0.92; p = 0.031). Higher NLR was significantly associated with worse DFS (cut off > 4.09; HR, 1.77; 95% CI, 1.07–2.91; p = 0.026) and worse CSS (cut off > 4.09; HR, 1.98; 95% CI, 1.11–3.53; p = 0.021). In patients who underwent upfront surgery, higher AGR correlated with significantly better OS (cut off > 1.17; HR, 0.54; 95% CI, 0.36–0.82; p = 0.004) and higher NLR correlated with worse OS (cut off > 2.38; HR, 1.63; 95% CI, 1.09–2.44; p = 0.018). Conclusion NLR and AGR are useful in predicting the response to NACT as well as prognosis of patients with breast cancer. Further studies are needed to explore their value in clinical decision making.

As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.

Objective:To observe the effect of lung distension stabilization formula combined with Liu Zi Jue exercise on the rehabilitation of patients with lung and kidney deficiency syndrome in stable phase of chronic obstructive pulmonary disease (COPD).Methods:Randomized controlled trial. A total of 179 patients with lung and kidney deficiency syndrome in stable COPD (admitted from April 2019 to April 2022) were enrolled in this study. The patients were randomly divided into western medicine conventional treatment group, combined treatment group and Liu Zi Jue group by random number table method. All the patients in the group received conventional western medicine treatment, and 59 patients in the Liu Zi Jue group received Liu Zi Jue treatment. Combined treatment group to take Liu Zi Jue + Lung distension stabilization formula. Data observation: clinical curative effect and TCM syndrome and total integral change before and after the treatment level of interleukin 8 (IL-8), pulmonary function index changes, COPD patients self-assessment scale (CAT) score, st George's hospital respiratory questionnaire (SGRQ) scores change were observed.Results:The total response rate was 66.67% (40/60) in the conventional treatment group, 83.05% (49/59) in the Liu Zi Jue group and 96.67% (58/60) in the combined treatment group. The total response rate in the combined treatment group was significantly higher than that in the conventional treatment group and the Liu Zi Jue group ( Z=3.76, P<0.01). The Liu Zi Jue group was significantly higher than the conventional western medicine group ( χ2=4.24, P=0.040). After treatment, the symptom score of combined treatment group was significantly lower than that of Liu Zi Jue group and conventional treatment group ( F=14.87, P<0.01), and that of Liu Zi Jue group was significantly lower than that of conventional treatment group ( t=5.87, P<0.01). The scores of CAT and SGRQ were significantly lower than those in the Liu Zi Jue group and conventional treatment group ( F values were 76.72 and 312.36, P<0.01), and those in Liu Zi Jue group were significantly lower than that of the conventional treatment group ( t=4.97, P<0.01). After treatment, the serum IL-8 level of the combined treatment group was significantly lower than that of the Liu Zi Jue group and the conventional treatment group ( F=154.64, P<0.01), and the Liu Zi Jue group was significantly lower than that of the conventional treatment group ( t=11.35, P<0.01). FVC [(2.93±0.60) L vs. (2.49±0.65) L, (2.25±0.63) L, F=20.62], FEV1 [(2.20±0.42) L vs. (1.88±0.41) L, (1.72±0.40) L, F=21.30] and FEV1% [(42.34±4.86) % vs. (38.85±5.00) %, (36.95±4.91) %, F=18.49] were significantly higher than those in the Liu Zi Jue group and conventional treatment group ( P<0.01). The Liu Zi Jue group was higher than that of the conventional treatment group ( t values were 3.76, 2.87, 5.15, P<0.01). Conclusion:Lung distension stabilization formula combined with Liu Zi Jue exercisecan promote the rehabilitation of COPD patients with lung and kidney deficiency syndrome in stable phase, improve the curative effect of patients, improve lung function, relieve symptoms, and improve the quality of life.

Objective:To analyze the diagnostic and prognostic value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma (ENKTCL) based on PET-CT staging.Methods:Clinical data of 186 patients who received bone marrow biopsy and bone marrow aspiration in Fujian Medical University Union Hospital from 2013 to 2021 were retrospectively analyzed. All patients were divided into bone marrow biopsy + bone marrow aspiration group ( n=186) and PET-CT + bone marrow biopsy group ( n=139). The sensitivity, specificity, positive and negative predictive values were compared between two groups. The data were analyzed and plotted. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:In the whole cohort, 45 patients were positive for bone marrow biopsy, and 30 of them were positive for bone marrow aspiration. A total of 141 patients who were negative for bone marrow biopsy also achieved negative results for bone marrow aspiration. A total of 139 patients completed PET-CT staging and bone marrow biopsy. And 30 patients were diagnosed with positive bone marrow by PET-CT, in which 22 of them were confirmed positive by bone marrow biopsy. Among 109 patients diagnosed with negative bone marrow by PET-CT, 5 of them were confirmed positive by bone marrow biopsy. All these cases were classified as stage Ⅳ due to distant metastases. PET-CT had a diagnostic sensitivity of 81.5%, a specificity of 92.9%, a positive predictive value of 73.3%, and a negative predictive value of 95.4%. Among early stage (Ⅰ-Ⅱ stage) patients diagnosed with PET-CT, all of them were negative for bone marrow biopsy (the negative predictive value was 100%). In stage Ⅳ patients ( n=55), the 1-year overall survival of patients with bone marrow involvement by bone marrow biopsy or PET-CT ( n=35) compared with their counterparts with the involvement of other organs ( n=20) was 28.7% vs.42.0% ( P=0.13), and 1-year progression free survival rates was 23.2% vs. 23.3% in ( P=0.94). Conclusions:Routine bone marrow biopsy does not change the original staging of patients with early stage ENKTCL based on PET-CT staging. Advanced stage patients with positive bone marrow biopsy tend to obtain worse prognosis, indicating that bone marrow biopsy still has certain value.

Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). This targeted liposome is prepared through a mature preparation process, and indoleamine-2,3-dioxygenase (IDO) inhibitor NLG919 was encapsulated into it. Moreover, mediated by the enhanced permeability and retention effect (EPR effect) and AUNP-12, NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues. At the same time, the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12, thus realizing the precise block of PD-1 signal pathway, and restoring the activity of T cells. The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.