Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons and the accumulation of Lewy bodies, leading to motor and nonmotor symptoms. While both genetic and environmental factors contribute to PD, recent studies highlight the crucial role of lipid metabolism disturbances in disease progression. Altered lipid homeostasis promotes protein aggregation and oxidative stress, with significant changes in lipid classes such as sphingolipids and glycerolipids observed in patients with PD. These disturbances are involved in key pathological processes, such as α-synuclein aggregation, organelle dysfunction, lipid-mediated neuroinflammation, and impaired lipid homeostasis. This review examines the relationship between lipid species and PD progression, focusing on the physiological roles of lipids in the central nervous system. It explores the mechanistic links between lipid metabolism and PD pathology, along with lipid-related genetic risk factors. Furthermore, this review discusses lipid-targeting therapeutic strategies to mitigate PD progression, emphasizing the potential of lipid modulation for effective treatment development.
Humans ; Parkinson Disease/metabolism* ; Lipid Metabolism/physiology* ; Animals ; Oxidative Stress/physiology* ; alpha-Synuclein/metabolism*

BACKGROUND: Parkinson's disease (PD) is a leading cause of death and disability worldwide, and is associated with a significant Global Burden of Disease (GBD). We analyzed the trends in PD incidence, mortality, and disability-adjusted life year (DALY) burden in China, and compared them with global data. METHODS: Estimates and 95% uncertainty intervals (UIs) for incidence, mortality, DALYs, years lived with disability (YLDs), and years of life lost (YLLs) for PD were extracted from the GBD, Injuries, and Risk Factors Study 2021. We describe the epidemiology of PD at global and Chinese levels, analyze trends in incidence and mortality from 1990 to 2021 by joinpoint regression models, and decompose PD burden according to population size, age structure, and epidemiological changes. RESULTS: GBD 2021 estimated 508,378 (95% UI: 430,499-592,748) incident cases of PD, 92,035 (95% UI: 75,908-108,133) deaths, and 2,159,514 (95% UI: 1,826,196-2,521,344) DALYs in China, with the higher age-standardized rate (ASR) in incidence, mortality and DALYs than the global levels. The DALY burden of PD in China increased slightly from 1990 to 2021, consistent with the global upward trend. Joinpoint regression analysis indicated that the ASR of incidence in China increased faster than the global average, while the ASR of mortality decreased, with the fastest decline in 2004-2014. Decomposition analysis revealed that men and the middle sociodemographic index (SDI) quintile (32.82%) were responsible for the most significant DALYs, whose changes were primarily driven by population growth and aging. CONCLUSIONS The burden of PD showed an overall increasing trend from 1990 to 2021, which was primarily driven by population growth and aging. This study highlights the significant challenges in controlling and managing PD, including the increase in cases and gender differences, which may provide guidance for comprehensive strategies to address the changing profiles of PD in China.
Humans ; Parkinson Disease/mortality* ; China/epidemiology* ; Global Burden of Disease ; Male ; Incidence ; Female ; Disability-Adjusted Life Years ; Middle Aged ; Aged ; Adult ; Quality-Adjusted Life Years ; Aged, 80 and over ; Cost of Illness ; Adolescent ; Pattern Analysis, Machine

Objective To establish the fingerprints of QiangliDingxuan tablets(QLDX),determine their pharmacody-namic indexes of vasodilation and study the spectrum-effect relationships between the chemical components of QLDX and the property of vasodilation.Methods The rate of vascular relaxation was used as an index to evaluate the extent to which QLDX relaxed isolated superior mesenteric artery ring.The Grey correlation degree and partial least square regression(PLSR)were used to analyze"spectrum-effect"correlations before components with greater contribution to drug efficacy were screened out.Results There were 21 common peaks in the HPLC fingerprint of QLDX,and the similarity exceeded 0.88.A comparison with the chromatogram of the reference substance revealed 14 characteristic peaks.Vasodilative experiments showed that all the 10 batches of samples had vasodilatory effects.The correlation between the 21 chromato-graphic peaks was greater than 0.73.PLSR showed that 11 components were positively correlated with the vasodilatory effect.Six known compounds included parishin A,parishin C,5-hydroxymethylfurfural,luteolin,Linarin and ligustrazine.Conclusion The vasodilatory effect of QLDX results from the combined action of multiple components.Parishin A,parishin C,5-hydroxymethylfurfural,luteolin,Linarin and ligustrazine are positively correlated with this effect,which may be the main pharmacodynamic substance basis of vascular relaxation.

Purpose: The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti–programmed cell death-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT. Materials and Methods: This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child-Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles. Results: During a median follow-up of 11.23 months (range, 3.07 to 34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The 2-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively. Conclusion Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.

BACKGROUND: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines. METHODS: Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT + CD4 + and TIGIT + CD8 + T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose. RESULTS: Compared to that in HCs, the frequency of TIGIT + CD8 + T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT + CD8 + T cells also increased. A decrease in the ratio of both T naïve (T N ) and central memory (T CM ) cells among TIGIT + CD8 + T cells and an increase in the ratio of the effector memory (T EM ) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT + CD8 + T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT + CD8 + T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT + CD8 + T cells in PLWH were significantly weaker than those of TIGIT - CD8 + T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT + CD8 + T cells and TIGIT - CD8 + T cells was insignificant at 4W and 12W, except at 0W. CONCLUSIONS TIGIT expression on CD8 + T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8 + T cells, thereby enhancing the effectiveness of vaccination.
Humans ; Antibodies, Viral ; CD8-Positive T-Lymphocytes ; COVID-19/complications* ; COVID-19 Vaccines/immunology* ; HIV Infections/complications* ; Receptors, Immunologic ; SARS-CoV-2

Objective: To investigate the specificity of endogenous metabolic profile in plasma of patients with occupational acute methyl acetate poisoning using non-targeted metabolomics. Methods: A total of six patients with occupational acute methyl acetate poisoning were selected as the poisoning group, while 10 healthy workers without occupational exposure history of chemical hazards in the same industry were selected as the control group using the judgment sampling method. Metabolites in patient plasma of the two groups were detected using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry, and non-targeted metabolomics analysis was performed. Principal component analysis and partial least squares discriminant analysis were used to identify differential metabolites and analyze their metabolic pathways. Results: There were significant differences in metabolite profiles in patient plasma between poisoning group and control group. A total of 195 differentially expressed metabolites were screened in plasma of patients in poisoning group, including 119 upregulated and 76 downregulated metabolites. Lipid substances (lipids and lipid-like molecules) accounted for the highest proportion (21.5%). The differential metabolites of poisoning group were related to folate biosynthesis, amino acid metabolism, pyrimidine metabolism, sphingolipid biosynthesis and other metabolic pathways in plasma compared with the control group (all P<0.05). Conclusion: Occupational acute methyl acetate poisoning affects metabolism of the body. The folic acid biosynthesis, amino acid and lipid metabolism and other pathways may be involved in the occurrence and development of poisoning.

Objective:To explore whether deep learning could apply to recognize the recurrent laryngeal nerve in the video of unilateral axillary approach endoscopic thyroidectomy.Methods:Videos of endoscopic thyroidectomy via unilateral axillary approach in Peking Union Medical College Hospital from Jul. 1st, 2020 to May. 1st, 2021 were collected. Videos containing the recurrent laryngeal nerve were selected, and the outline of recurrent laryngeal nerve were marked by two senior thyroid surgeons and staffs. Data were divided into training set and test set in a ratio of 5:1, and classified into high, medium and low recognition group according to difficulty of recognizing the outline of the nerve. The neuron network was based on PSPNet combined with Resnet50. All data were analyzed by R (ver. 4.0.2) .Results:A total of 38 videos including 35,501 frames of pictures were included in this study. 29, 704 frames of 32 videos were in our training set and 5797 frames of 6 videos were in the test set. When the intersection over union (IOU) threshold is 0.1, the sensitivity and precision is 100.0%/92.1%, 95.8%/80.2% and 81.0%/80.6% in high, medium and low recognition group respectively. When the IOU threshold is 0.5, the sensitivity and precision is 92.6%/85.3%, 71.7%/60.5% and 38.1%/37.9% in high, medium and low recognition group respectively, indicating that neuron network could located the outline of recurrent laryngeal nerve in high and medium recognition group. False negatives were often due to small targets and unclear boundaries.Conclusion:Recurrent laryngeal nerve recognition based on deep learning is feasible and has potential application value in endoscopic thyroidectomy, which may help surgeons reduce the risk of accidental injury of recurrent laryngeal nerve and improve the safety of thyroidectomy.

Objective:To investigate the feasibility and efficacy of three mini-incision double eyelid blepharoplasty with concurrent reposition of orbital fat pad to correct sunken upper eyelids.Methods:The data of patients who underwent orbital fat reposition to correct upper eyelid depression during the period from January 2018 to April 2021 in the Medical Plastic and Cosmetic Center of Beijing Tongren Hospital affiliated to Capital Medical University were retrospectively analyzed. During the operation, the central mass of orbital fat and its lateral extension were fully dissociated, and then transferred and fixed inward through three mini-incisions. Postoperative follow-up was performed to observe the improvement of the double eyelid shape and upper eyelid depression, and the patient satisfaction was recorded.Results:A total of 72 patients (140 eyes) were included in this study, including 1 male and 71 females, with an average age of 28 years (19-40 years old), 122 eyes with mild upper eyelid depression and 18 eyes with moderate upper eyelid depression before operation. Postoperative follow-up was 6-24 months, with an average of 11 months. The curvature of the double eyelid after operation was smooth and basically symmetrical. Among the 122 eyes with mild upper eyelid depression before operation, 118 eyes were completely corrected after operation, and 4 eyes were not improved. Of the 18 eyes, 3 eyes were completely corrected after operation, and 15 eyes still had mild upper lid depression. The overall satisfaction rate was 93.1% (67/72), the rate of double eyelid failure was 3.6% (5/140), and no other serious complications were found.Conclusions:Three mini-incision double eyelid blepharoplasty simultaneously with orbital fat reposition can effectively correct mild and moderate sunken upper eyelid deformity. The postoperative double eyelid shape is stable with high satisfaction rate.

Objective:To explore whether deep learning could apply to recognize the recurrent laryngeal nerve (RLN) in videos of endoscopic thyroidectomy (ETE) via breast approach.Methods:Videos of ETE via breast approach in Peking Union Medical College Hospital from Feb. 2020 to Aug. 2021 were collected. Videos containing RLN were selected, and the outline of RLN was marked by two thyroid surgeons. Then data were divided into a training set and a test set in a ratio of 5:1 and classified into the high and low difficulty group according to a senior thyroid surgeon’s opinion. Those pictures were input to D-LinkNet model. Precision, sensitivity and mean dice index was calculated.Results:A total of 46 videos including 153, 520 frames of pictures were included in this study. 131,039 frames of 39 videos were in the training set and 22,481 frames of 7 videos were in the test set. When the intersection over union threshold was 0.1, the sensitivity and precision was 92.9%/72.8% and 47.6%/54.9% in high and low recognition group, respectively. When the intersection over union threshold was 0.5, the sensitivity and precision turned to 85.8%/67.2% and 37.6%/43.5% in high and low difficulty group, respectively. Mean Dice index was 0.781 and 0.663 in high and low difficulty group, respectively.Conclusions:RLN recognition based on deep learning is feasible and has potential application value in ETE, which may help surgeons reduce the risk of accidental injury of RLN and improve the safety of thyroidectomy.

Objective:To investigate the feasibility and efficacy of three mini-incision double eyelid blepharoplasty with concurrent reposition of orbital fat pad to correct sunken upper eyelids.Methods:The data of patients who underwent orbital fat reposition to correct upper eyelid depression during the period from January 2018 to April 2021 in the Medical Plastic and Cosmetic Center of Beijing Tongren Hospital affiliated to Capital Medical University were retrospectively analyzed. During the operation, the central mass of orbital fat and its lateral extension were fully dissociated, and then transferred and fixed inward through three mini-incisions. Postoperative follow-up was performed to observe the improvement of the double eyelid shape and upper eyelid depression, and the patient satisfaction was recorded.Results:A total of 72 patients (140 eyes) were included in this study, including 1 male and 71 females, with an average age of 28 years (19-40 years old), 122 eyes with mild upper eyelid depression and 18 eyes with moderate upper eyelid depression before operation. Postoperative follow-up was 6-24 months, with an average of 11 months. The curvature of the double eyelid after operation was smooth and basically symmetrical. Among the 122 eyes with mild upper eyelid depression before operation, 118 eyes were completely corrected after operation, and 4 eyes were not improved. Of the 18 eyes, 3 eyes were completely corrected after operation, and 15 eyes still had mild upper lid depression. The overall satisfaction rate was 93.1% (67/72), the rate of double eyelid failure was 3.6% (5/140), and no other serious complications were found.Conclusions:Three mini-incision double eyelid blepharoplasty simultaneously with orbital fat reposition can effectively correct mild and moderate sunken upper eyelid deformity. The postoperative double eyelid shape is stable with high satisfaction rate.