Objective To investigate the global burden of visceral leishmaniasis (VL) from 1990 to 2021 and predict the trends in the burden of VL from 2022 to 2035, so as to provide insights into global VL prevention and control. Methods The global age-standardized incidence, prevalence, mortality and disability-adjusted life years (DALYs) rates of VL and their 95% uncertainty intervals (UI) were captured from the Global Burden of Disease Study 2021 (GBD 2021) data resources. The trends in the global burden of VL were evaluated with average annual percent change (AAPC) and 95% confidence interval (CI) from 1990 to 2021, and gender-, age-, country-, geographical area- and socio-demographic index (SDI)-stratified burdens of VL were analyzed. The trends in the global burden of VL were projected with a Bayesian age-period-cohort (BAPC) model from 2022 to 2035, and the associations of age-standardized incidence, prevalence, mortality, and DALYs rates of VL with SDI levels were examined with a smoothing spline model. Results The global age-standardized incidence [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)], prevalence [AAPC = -0.06%, 95% CI: (-0.06%, -0.06%)], mortality [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)] and DALYs rates of VL [AAPC = -2.38%, 95% CI: (-2.44%, -2.33%)] all appeared a tendency towards a decline from 1990 to 2021, and the highest age-standardized incidence [2.55/10⁵, 95% UI: (1.49/10⁵, 4.07/10⁵)], prevalence [0.64/10⁵, 95% UI: (0.37/10⁵, 1.02/10⁵)], mortality [0.51/10⁵, 95% UI: (0, 1.80/10⁵)] and DALYs rates of VL [33.81/10⁵, 95% UI: (0.06/10⁵, 124.09/10⁵)] were seen in tropical Latin America in 2021. The global age-standardized incidence and prevalence of VL were both higher among men [0.57/10⁵, 95% UI: (0.45/10⁵, 0.72/10⁵); 0.14/10⁵, 95% UI: (0.11/10⁵, 0.18/10⁵)] than among women [0.27/10⁵, 95% UI: (0.21/10⁵, 0.33/10⁵); 0.06/10⁵, 95% UI: (0.05/10⁵, 0.08/10⁵)], and the highest mortality of VL was found among children under 5 years of age [0.24/10⁵, 95% UI: (0.08/10⁵, 0.66/10⁵)]. The age-standardized incidence (r = -0.483, P < 0.001), prevalence (r = -0.483, P < 0.001), mortality (r = -0.511, P < 0.001) and DALYs rates of VL (r = -0.514, P < 0.001) correlated negatively with SDI levels from 1990 to 2021. In addition, the global burden of VL was projected with the BAPC model to appear a tendency towards a decline from 2022 to 2035, and the age-standardized incidence, prevalence, mortality and DALYs rates were projected to be reduced to 0.11/10⁵, 0.03/10⁵, 0.02/10⁵ and 1.44/10⁵ in 2035, respectively. Conclusions Although the global burden of VL appeared an overall tendency towards a decline from 1990 to 2021, the burden of VL showed a tendency towards a rise in Central Asia and western sub-Saharan African areas. The age-standardized incidence and prevalence rates of VL were relatively higher among men, and the age-standardized mortality of VL was relatively higher among children under 5 years of age. The global burden of VL was projected to continue to decline from 2022 to 2035.

In the era of big data, neuroimaging and algorithmic analyses have propelled brain science research and brain mapping. Acupuncture, widely recognized as an effective surface stimulation therapy, has demonstrated therapeutic efficacy for various brain conditions such as stroke and depression. However, the mechanisms linking acupuncture to brain function and its modulatory effects on brain activity require systematic exploration. Additionally, there is an urgent need to scientifically reinterpret traditional meridian theory and enhance its clinical applicability. Therefore, we propose the initiative of constructing a "brain mapping atlas of meridian, collateral and body surface stimulation" to explore the patterns linking the therapeutic effects of stimulating the twelve meridians, eight extraordinary vessels, divergent channels, collateral channels, sinew channels, and skin regions to brain function. This initiative aims to provide a scientific interpretation of traditional Chinese medicine meridian theory and enhance its practical applicability. This paper begins by reviewing the current state of brain mapping. It then summarizes existing research on the relationship between acupuncture and the brain, highlighting the necessity of constructing this atlas. The paper further analyzes the methodologies and technical challenges involved. Finally, the potential applications of the brain mapping atlas of meridian, collateral and body surface stimulation, and its main significance in advancing traditional meridian theory to keep pace with the times are prospected.
Humans ; Acupuncture Therapy ; Meridians ; Big Data ; Brain/physiology* ; Brain Mapping

OBJECTIVE: To compare the protective effects of electroacupuncture (EA) and transcutaneous electrical acupoint stimulation (TEAS) during pregnancy on maternal immune activation (MIA)-induced adverse pregnancy outcomes, fetal developmental defects, and neuropsychological behavior abnormalities in offspring mice. METHODS: Eighty pregnant C57BL/6 mice were randomly divided into 5 groups: control, model, EA, TEAS, and sham-stimulation groups, 16 mice in each group. MIA models were replicated on the day 12.5 of pregnancy via tail intravenous injection with polyinosinic-polycytidylic acid. On the second day of modeling success, in the EA and TEAS groups, the interventions were delivered at bilateral "Zusanli" (ST36), with a frequency of 2 Hz, a current of 0.5 mA, and for 20 min each day in the pregnant mice; and the interventions lasted 6 days. Body mass and fertility indexes of pregnant mice, and the development indexes of offspring mice were recorded. Liquid phase suspension chip technology was used to detect the levels of cytokines and chemotactic factors in the serum of pregnant mice and and fetal brain of offspring mice. Flow cytometry was adopted to detect the proportion of the subgroups and subtypes of spleen T lymphocytes and macrophages in pregnant mice. Using the open field test, prepulse inhibition (PPI) test and Morris water maze, the spatial learning and memory were assessed in offspring mice. Immunofluorescence staining was used to detect microglial count in the medial prefrontal cortex (mPFC) in offspring mice. RESULTS: Compared with the control group, the model group showed a reduced body mass of pregnancy mice (P<0.01), smaller litter size and fewer live births (P<0.01, P<0.05), the increase in dead birth and the decrease in offspring survival rate (P<0.05, P<0.01). When compared with model group, in the EA group and the TEAS group, the body mass of pregnancy mice rose (P<0.05), litter size and live births increased (P<0.05, P<0.01), the dead birth was reduced and the offspring survival rate higher (P<0.05). In comparison with the control group, the model group showed the increase in the levels of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), γ-interferon (IFN-γ) in the serum of pregnant mice, and spleen M1 macrophage proportion (P<0.01, P<0.05), and the decrease in spleen M2 macrophages of pregnant mice (P<0.01); and the increase in MCP-1 and IL-6 in fetal brain of offspring mice (P<0.05). Compared with the model group, the EA group and the TEAS group showed the decrease in MCP-1, IL-6 and IFN-γ, and spleen M1 macrophage proportion (P<0.01, P<0.05), and the increase in spleen M2 macrophages of pregnant mice (P<0.01, P<0.05) ; and the decrease in MCP-1 and IL-6 in fetal brain of offspring mice (P<0.05). Compared with the control group, in the model group, the total movement distance, escape incubation were extended (P<0.05, P<0.01), the frequency of entering the central area and crossing the platform decreased, and the activity duration in central area was shortened (P<0.05, P<0.01), the average speed rose (P<0.05), PPI%, the percentage of target quadrant swimming time in the total time and that of target quadrant swimming distance in the total distance were reduced (P<0.05, P<0.01) in offspring mice. When compared with the model group, in the EA group and TEAS group, the total movement distance and escape incubation were shortened, the average speed was reduced (P<0.05), PPI% and the frequency of crossing the platform increased (P<0.05, P<0.01); the percentage of target quadrant swimming time in the total time and that of target quadrant swimming distance in the total distance rose (P<0.05, P<0.01) in the offspring mice. In the EA group, the frequency of entering the central area and the activity duration in central area were higher (P<0.05, P<0.01); and in the the TEAS group, the activity duration in central area were longer (P<0.05). When compared with the control group, in the model group, microglial count in mPFC was elevated in offspring mice (P<0.05). In comparison with the model group, the EA group and the TEAS group showed the decrease of microglial count in mPFC (P<0.05). CONCLUSION EA and TEAS at "Zusanli" (ST36) during pregnancy effectively improve in the pregnancy outcomes and fetal brain developmental abnormalities induced by infection, and attenuate neurodevelopmental defects and mental disorders of offspring mice through inhibiting inflammatory activation of microglia in mPFC.
Animals ; Female ; Pregnancy ; Electroacupuncture ; Acupuncture Points ; Mice ; Mice, Inbred C57BL ; Humans ; Male

Transarterial radioembolization (TARE) is a widely utilized therapeutic approach for hepatocellular carcinoma (HCC), however, the clinical implementation is constrained by the stringent preparation conditions of radioembolization agents. Herein, we incorporated the superstable homogeneous iodinated formulation technology (SHIFT), simultaneously utilizing an enhanced solvent form in a carbon dioxide supercritical fluid environment, to encapsulate radionuclides (such as ¹³¹I,¹⁷⁷Lu, or ¹⁸F) with lipiodol for the preparation of radiolipiodol. The resulting radiolipiodol exhibited exceptional stability and ultra-high labeling efficiency (≥99%) and displayed notable intratumoral radionuclide retention and in vivo stability more than 2 weeks following locoregional injection in subcutaneous tumors in mice and orthotopic liver tumors in rats and rabbits. Given these encouraging findings, ¹⁸F was authorized as a radiotracer in radiolipiodol for clinical trials in HCC patients, and showed a favorable tumor accumulation, with a tumor-to-liver uptake ratio of ≥50 and minimal radionuclide leakage, confirming the feasibility of SHIFT for TARE applications. In the context of transforming from preclinical to clinical screening, the preparation of radiolipiodol by SHIFT represents an innovative physical strategy for radionuclide encapsulation. Hence, this work offers a reliable and efficient approach for TARE in HCC, showing considerable promise for clinical application (ChiCTR2400087731).

Objective Depression,a most common psychiatric disease,is defined in Traditional Chinese Medicine(TCM)as Yu Syndrome,i.e.,depression disorder,or Baihe Disease,i.e.,lily bulb disease,a category of emotional disorders treated with lily-based TCM preparations.In TCM,depression is managed through syndrome differentiation and treatment,which is characterized by high efficacy and safety.However,there is no unified standard for the classification of depression syndromes,which leads to a disconnection between the analysis of patients'medication patterns and their actual syndromes and hinders the study of medication patterns specific to particular syndromes.Therefore,this study is focused on investigating the medication patterns of different sub-types of depression patients based on an objective classification system of depression.Methods We searched for and retrieved clinical literature on TCM formulas for depression from relevant databases,including China National Knowledge Infrastructure(CNKI),Wanfang Data,VIP Database,Sinomed,Web of Science,and PubMed.Information on patient symptoms and medication was standardized.Then,the symptoms and the medication frequency of depression patients were statistically analyzed.We used the K-means clustering method combined with implicit structural analysis to objectively categorize depression patients into sub-types.In addition,the main symptoms and core TCM formulas of each sub-type of depression patients were identified.On the basis of objective classification system,we also statistically analyzed the characteristics of herbs used on depression patients,including the 4 basic properties,the 5 flavors,the attributes,the therapeutic efficacy,and the co-occurrence patterns,which may help reveal the medication patterns.Results A total of 3 537 publications and 4 434 prescriptions were included in the analysis.By using the K-means algorithm and latent structure analysis methods,patients with depression were categorized into 9 sub-types,with Cluster 6 accounting for the largest proportion.The most common symptoms among depression patients were insomnia and a depressed mood.Medication frequency analysis showed that Radix Bupleuri(Chai Hu),Radix Paeoniae Alba(Bai Shao),Poria(Fu Ling),Rhizoma Chuanxiong(Chuan Xiong),and Radix Curcumae(Yu Jin)were the most commonly used TCM herbs.For the depression sub-types of Clusters 1,2,and 6,blood-activating and stasis-dissolving herbs were used most often.The depression sub-types of Clusters 3,4,5,8,and 9 were mainly treated with qi-regulating herbs,while the depression sub-type of Cluster 7 was treated with qi-supplementing herbs.Depression patients were mostly treated with herbs that were cold or warm in nature and had sweet,bitter,and pungent flavors.Moreover,treatments for Cluster 1 and Cluster 6 mainly targeted the spleen meridian,while those for Cluster 2,Cluster 3,Cluster 4 and Cluster 5 mainly targeted the heart meridian.The treatments for the other sub-types mainly targeted the liver meridian.The core TCM formulas for the 9 depression sub-types included Zishui Qinggan Decoction,Danzhi Xiaoyao Powder,Huanglian Wendan Tang,Chaihu Guizhi Tang,Modified Xiaoyao Powder,Qinggan Jieyu Tang,Xiaoyao Powder,Xuefu Zhuyu Decoction,and Bazhen Decoction.The most commonly used Chinese herbal medicinal formulas were Gan Cao-Chai Hu,Bai Shao-Chai Hu,and Chen Pi-Chai Hu.Conclusion Based on machine learning,this study reveals the scientific aspects of TCM typing and syndrome-based treatment.It clarifies the rationale for targeting different symptoms in depression treatment and provides theoretical support for clinicians to make medication prescriptions.It also presents a new perspective for investigating TCM medication patterns.

Objective To discuss the application of enhanced MRI-based radiomics nomogram in predicting the efficacy of initial transcatheter arterial chemoembolization(TACE)in patients with intermediate to advanced hepatocellular carcinoma(HCC).Methods A total of 195 patients with advanced HCC(CNLC Ⅱ b-Ⅲb),who received initial TACE at the Affiliated Fifth Hospital of Wenzhou Medical University(Center 1)from January 2019 to March 2024,at the Lishui Municipal People's Hospital(Center 2)from July 2021 to June 2023,and at the Rui'an Municipal People's Hospital(Center 3)from January 2022 to January 2024,were enrolled in this study.A total of 134 patients from Center 1 were randomly divided into a training set(n=94)and an internal validation set(n=40)at a 7∶3 ratio;and other 61 patients from Center 2 and Center 3 were selected as the external validation set.Based on the modified Response Evaluation Criteria in Solid Tumors(mRECIST)criteria,the early efficacy of the initial TACE procedure was evaluated.The patients were divided into an effective group and an ineffective group.The tumor contours were delineated on the arterial,portal,and equilibrium phase images of enhanced MRI,and the corresponding radiomics features were extracted.Based on reduced-dimensional features,the Logistic regression,support vector machine,lightweight gradient boosting machine,and multi-layer perceptron models were established.Univariate analysis and multivariate logistic regression analysis were used to screen independent predictive factors,and a nomogram was established in conjunction with the optimal radiomics score.The area under the receiver operating characteristic curve(AUC)was used to evaluate the performance of the model,and decision curve analysis was adopted to calculate the net benefits.Results After screening,9 key radiomics features were obtained.The lightweight gradient boosting machine model showed good prediction performance.The AUCs of the training set,internal validation set,and external validation set were 0.909,0.836 and 0.783 respectively,which was selected as the optimal radiomics model.The nomogram constructed based on AFP level,peritumoral enhancement,and optimal radiomics score could further improve its performance,with AUC values of 0.962,0.890 and 0.821 in the training set,internal validation set,and external validation set respectively.Decision curve analysis showed that this model could bring higher net benefits to patients.Conclusion The nomogram constructed based on the enhanced MRI-based radiomics combined with AFP level and peritumoral enhancement can effectively predict the efficacy of the initial TACE in patients with intermediate to advanced HCC.

OBJECTIVE To analyze the influential factors on trough concentration （cmin） and area under the drug concentration time curve （AUC） of voriconazole （VRZ） in pediatric patients with thalassemia undergoing hematopoietic stem cell transplantation （HSCT）. METHODS A total of 60 pediatric patients with thalassemia undergoing HSCT who used VRZ for prevention or treatment of invasive fungal infection were collected in our hospital from January 2021 to January 2024. The plasma concentration of VRZ was measured by high-performance liquid chromatography and the AUC was calculated. The factors affecting cmin and AUC of VRZ were analyzed using multiple linear regression. RESULTS A total of 120 cases of VRZ cmin in 60 pediatric patients was obtained and 27 cases of VRZ AUC in 26 pediatric patients were obtained. The median concentration of VRZ cmin was 0.31 mg/L； 46 cases had a cmin in 0.5-5 mg/L（ 38.33%）， 2 cases had a cmin＞5 mg/L（ 1.67%）， and 72 cases had a cmin＜0.5 mg/L. The median AUC of VRZ was 11.68 mg·h/L. The patient’s body weight， HSCT postoperative days， lymphocyte count， and combined use of phenytoin sodium， tacrolimus or cyclosporine had significant effects on VRZ cmin （P＜0.05）. Lymphocyte count and combined use of phenytoin sodium had significant effects on VRZ AUC （P＜0.05）. CONCLUSIONS The body weight， HSCT postoperative days， lymphocyte count， and combined use of phenytoin sodium， tacrolimus or cyclosporine are independent factors affecting VRZ cmin. Lymphocyte count and combined use of phenytoin sodium are independent factors affecting VRZ AUC.

【Objective】 To investigate the level of serum bone metabolism and biochemical markers and bone density of plasmapheresis donors, and to provide scientific basis for ensuring the health and safety of plasmapheresis donors in China. 【Methods】 A total of 437 plasmapheresis donors from Linwu plasmapheresis station in Hunan Province from July 1 to September 30, 2022 were recruited to determine the levels of total serum calcium, albumin, serum 25-hydroxyvitamin D (25OHD), serum type I procollagen N-terminal propeptide (P1NP), and collagen type 1 crosslinked carboxyl-terminal peptide (β-CTX). Dual-energy X-ray method was used to measure the bone density of the anteroposterior lumbar spine (L1-L4) and bilateral femoral neck bone density of plasmapheresis donors. Plasmapheresis donors were grouped according to the type of plasma donation (first-time and repeat plasmapheresis donors) and the total number of plasma donations to assess the differences in bone density and serum bone metabolism biochemical markers between groups. The dose-response relationship between the total number of plasmapheresis donations and biochemical indexes was analyzed by limiting cubic spline, and the influencing factors of different indexes were explored by multiple linear regression. 【Results】 A total of 437 plasmapheresis donors were included in this study, including 187 first-time plasmapheresis donors and 250 repeat plasmapheresis donors. There were no significant differences in bone density and prevalence of osteoporosis between first-time donors and repeat donors (P>0.05). There was also no significant difference in bone density levels between groups of total number of plasmapheresis donations. The levels of albumin and 25OHD decreased with the increase of the total number of plasma donations, while the serum P1NP level was positively correlated with the total number of plasma donations. The results of the restriction cubic spline showed that the total number of plasmapheresis donations had a nonlinear dose-response relationship with 25OH and P1NP (P<0.05). The results of multiple linear regression showed that the frequency of plasmapheresis donation was the influencing factor of 25OHD, and the total number of plasmapheresis donation was the influencing factor of P1NP. 【Conclusion】 Plasmapheresis donation does not affect the bone health of donors and increase the risk of osteoporosis due to the use of long-term anticoagulants, but it will increase the osteogenic activity of plasmapheresis donors. It is recommended that middle-aged and elderly plasmapheresis donors supplement vitamin D appropriately.

Mental disorders are characterized by disturbances in behavior,volition,emotion,and cognition and are considered emotional diseases in traditional Chinese medicine.Acupuncture is one of the most widely used complementary alternative therapies for the treatment of mental disorders.Recently,there has been growing interest in the use of the Tong Du Tiao Shen(Dredging Du meridian to regulate the spirit)as a primary treatment.However,a comprehensive summary of the establishment and related acupuncture methods of Tong Du Tiao Shen is lacking.This paper aims to address this gap by exploring the origin and development of Tong Du Tiao Shen,its application in treating mental disorders,and the modern biological mechanisms involved.Ultimately,this paper seeks to expand the clinical application of Tong Du Tiao Shen acupuncture and provide a scientific basis for future research in this field.

Objective:To analyze the efficacy and safety of FOLFOX-hepatic arterial infusion chemotherapy (HAIC) combined with targeted immunotherapy for initial unresectable hepatocellular carcinoma.Methods:A retrospective analysis was conducted on the data of initial unresectable hepatocellular carcinoma patients who visited Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from June 2022 to June 2023. A total of 51 patients were enrolled, including 47 males and 4 females, with the age of (56.1±10.7) years. All 51 patients received HAIC combined with immune targeted therapy. After each HAIC combined with immune targeted therapy, the efficacy was evaluated according to the modified response evaluation cirteria in solid tumor (mRECIST). Objective response rate and disease control rate were calculuted. The conversion surgery rate and adverse events during treatment were recorded. Follow up patients' disease progression and survival status, and meanwhile analyze prognosis.Results:According to mRECIST assessment, the number of patients with complete remission, partial remission, disease stability, and disease progression were 4 (7.8%), 27 (52.9%), 14 (27.4%), and 6 (11.8%), respectively. The disease remission rate was 60.8%(31/51), and the disease control rate was 88.2%(45/51). After HAIC combined with immune targeted therapy, 13 patients underwent liver cancer resection, with a surgical conversion rate of 25.5%(13/51). The median progression free survival of 51 patients was 14.2 months, and the median overall survival has not yet been reached. The progression free survival rates of 51 patients at 6 and 12 months were 90.2% and 64.7%, respectively, and the cumulative survival rates at 6 and 12 months were 100% and 86.3%, respectively. During the treatment period, all patients experienced various degrees of adverse reactions, 38(75.5%) patients were grade 1-2 adverse accidents, which could be relieved and controlled after corresponding treatment.Conclusion:FOLFOX-HAIC combined with targeted immunotherapy provides an effective and safe treatment option for unresectable hepatocellular carcinoma, offering surgical resection opportunities for unresectable hepatocellular carcinoma patients.