INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

As one of the chronic diseases with high incidence in contemporary society, cervical spondylosis has increasing patient groups who gradually present a low age, and it seriously affects social and public health. Although modern medicine has made great progress in the pathological research and clinical treatment of cervical spondylosis, patients still face gastrointestinal side effects of nonsteroidal anti-inflammatory drugs(NSAIDs), neck pain, limited mobility, upper limb numbness, and other symptoms after conservative or surgical treatment. In the theory of traditional Chinese medicine(TCM), cervical spondylosis belongs to the categories of "Bi syndrome" "stiff neck" "stiff Bi", etc. With the change of the times, the change of lifestyle, and the application of western medicine treatment, the etiology and pathogenesis of TCM in cervical spondylosis also show new characteristics. In terms of etiology and pathogenesis, it involves the invasion of wind, cold, and dampness, long-term strain, liver and kidney deficiency, Qi and blood stasis, which are associated with factors such as cervical degeneration, muscle tension and spasm, intervertebral disc herniation, and nerve root compression in modern medicine. In terms of the evolution of pathogenesis, in the early stage, wind, cold, and dampness, were more common in Xuanfu, resulting in unfavorable muscles and bones, poor flow of Qi and blood, and cervical spondylosis and radiculopathy. Medium-term phlegm stasis and internal knots, sluggish muscles and veins, and long-term weathering and fire are more likely to occur in the vertebral artery and sympathetic radiculopathy. In the later stage, the positive Qi is depleted; the true Yin is damaged, and the viscera Qi and blood are deficient, which is most common in cervical myelopathy. The strategy of treating cervical spondylosis with TCM classic formulas applies Gegen Decoction, Wutou Decoction, Qianghuo Shengshi Decoction, Mahuang Jiazhu Decoction to patients with wind, cold, and dampness. Patients with phlegm dampness and blood stasis are treated with Huoxue Xiaoling Dan, Jinlingzi Powder, Siwu Decoction, Banxia Baizhu Tianma Decoction, Shuanghe Decoction, etc. For those patients with liver, spleen, and kidney deficiency, Huangqi Guizhi Wuwu Decoction, Tianma Gouteng Decoction, Guishao Dihuang Pills, Shenling Baizhu Powder, and Lizhong Decoction are used to invigorate the spleen, nourish Qi and blood, and tonify liver and kidney. In clinical practice, the authors advocate a safe and effective treatment plan of classic formulas based on deficiency and excess, the integration of formulas and syndromes, and the combination of modern research results, so as to relieve symptoms, reduce recurrence, and reduce medical burden.
Humans ; Spondylosis/drug therapy* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Cervical Vertebrae/pathology*

Sepsis is a life-threatening clinical syndrome and one of the most challenging health problems in the world. Pathologically, sepsis and septic shock are caused by a dysregulated host immune response to infection, which can eventually lead to multiple organ failure and even death. As an adaptor transporter between the endoplasmic reticulum and Golgi apparatus, stimulator of interferon response cGAMP interactor 1 (STING1, also known as STING or TMEM173) has been found to play a vital role at the intersection of innate immunity, inflammation, autophagy, and cell death in response to invading microbial pathogens or endogenous host damage. There is ample evidence that impaired STING1, through its immune and non-immune functions, is involved in the pathological process of sepsis. In this review, we discuss the regulation and function of the STING1 pathway in sepsis and highlight it as a suitable drug target for the treatment of lethal infection.
Autophagy ; Humans ; Immunity, Innate ; Multiple Organ Failure ; Sepsis ; Shock, Septic

Objective: To estimate the incidence of HIV-1 infection in men who have sex with men (MSM) in key areas of China through HIV-1 limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA), analyze the deviation from the actual results and identify influencing factors, and provided reference for improving the accuracy of estimation results. Methods: Based on the principle of the cohort randomized study design, 20 cities were selected in China based on population size and the number of HIV-positive MSM. The sample size was estimated to be 700 according to the HIV-1 infection rate in MSM. MSM mobile phone app. was used to establish a detection appointment and questionnaire system, and the baseline cross-sectional survey was conducted from April to November 2019. LAg-Avidity EIA was used to identify the recent infected samples. The incidence of HIV-1 infection was calculated and then adjusted based on the estimation formula designed by WHO. The influencing factors were identified by analyzing the sample collection and detection processes. Results: Among the 10 650 blood samples from the participants, 799 were HIV-positive in initial screening, in which 198 samples (24.78%) missed during confirmation test. Only 621 samples were received by the laboratory. After excluding misreported samples, 520 samples were qualified for testing. A total of 155 samples were eventually determined as recent infection through LAg-Avidity EIA; Based on the estimation formula , the incidence of HIV-1 infection in MSM in 20 cities was 4.06% (95%CI:3.27%-4.85%), it increased to 5.53% (95%CI: 4.45%-6.60%)after the adjusting for sample missing rate. When the sample missing rate and misreporting rate were both adjusted, the incidence of HIV-1 infection in the MSM increased to 5.66% (95%CI:4.67%-6.65%). The actual incidence of HIV-1 infection in MSM in the 20 cities might be between 4.06% and 5.66%. Conclusions: Sample missing and misreporting might cause the deviation of the estimation of HIV-1 infection incidence. It is important to ensure the sample source and the quality of sample collection and detection to reduce the deviation in the estimation of HIV-1 infection incidence.
Cross-Sectional Studies ; HIV Infections/epidemiology* ; HIV-1 ; Homosexuality, Male ; Humans ; Immunoenzyme Techniques ; Incidence ; Male ; Sexual and Gender Minorities

Objective: To analyze the clinical characteristics of Wilson's disease (WD) with onset of acute liver failure (ALF) in children. Methods: Clinical data of 19 children diagnosed with WD presented with ALF in Xi'an Children's Hospital from January 2016 to April 2021 were retrospectively analyzed, including general condition, clinical manifestation, laboratory examination, and gene detection. The children were divided into the death group and survival group according to the clinical outcome. The children who had hepatic WD with non-ALF onset during the same period were selected as the control. The general conditions and laboratory indexes were compared between death group and survival group, ALF group and non-ALF group. T-test, Mann Whitney U test or χ² test were used to compare the differences between the two groups. Results: Of the 19 WD children with ALF onset, 10 were females and 9 were males. The age of admission was (10.1±2.6) years and time to onset of first visit was 9 (4, 15) days. Among the WD children with ALF onset, 4 children were lost to follow-up, 5 cases death (death group) and 10 cases survived (survival group). The ceruloplasmin in the death group was higher than that in the survival group (0.078 (0.055, 0.105) vs. 0.033 (0.027, 0.058) g/L, Z=-2.33, P=0.020). There were 95 children who had hepatic WD with non-ALF onset. The WD patients with ALF onset were older at admission (9.9 (8.0, 11.1) vs. 5.4 (3.7, 6.9) years, Z=-5.25, P<0.001), had higher ceruloplasmin (0.060 (0.030, 0.078) vs. 0.024 (0.006, 0.060) g/L, Z=-3.11, P=0.002), 24 h urinary copper (674 (205, 1 803) vs. 149 (108, 206) μg, Z=-4.25, P<0.001), and positive rate of K-F ring [17/19 vs. 7%(7/95), χ²=50.17, P<0.001] while shorter onset time at initial visit (0.3 (0.1, 0.5) vs. 1.0 (0.7, 6.0) months, Z=-4.28, P<0.001). There was no gender difference between the two groups [9/19 vs. 61%(58/95), χ²=1.22, P=0.269]. Of the 19 WD children with ALF onset, 13 had the ATP7B gene tested, and 15 reported variants were detected. The main variations were c.2333G>T (p. Arg778Leu), c.2621C>T (p. Ala874Val) and c.2975C>T (p. Pro992Leu). The allele frequencies were 6/26(23%), 4/26(15%) and 3/26(12%), respectively. Conclusions: Children of WD onset with ALF are school-aged and above. They have an acute onset, a short course of the disease, and poor prognosis. The positive rate of K-F ring, ceruloplasmin and urinary copper are higher than those of the hepatic WD children with non-ALF onset.
Ceruloplasmin/metabolism* ; Child ; Copper/metabolism* ; Female ; Hepatolenticular Degeneration/genetics* ; Humans ; Liver Failure, Acute/therapy* ; Male ; Retrospective Studies

Objective:To explore the effect of different extracts of Thlaspi Herba on the gut microbiota of hyperuricemia mice， and to reveal the substance basis and mechanism of its hypouricemic activity. Method:Eighty-eight male Kunming mice were divided into 11 groups， including blank group， model group， allopurinol group， high and low dose groups of petroleum ether extract， high and low dose groups of ethyl acetate extract， high and low dose groups of n-butanol extract， high and low dose groups of total flavonoids extract. Mice in the blank group were given 0.5% sodium carboxymethylcellulose by gavage， and the other groups were given oteracil potassium （500 mg·kg^-1） by gavage to duplicate the hyperuricemia model. After modeling for several hours， the blank group and the model group were given distilled water by gavage， while mice in the allopurinol group were given allopurinol suspension （50 mg·kg^-1）， and mice in each treatment group were given high and low doses of corresponding extract （5， 2.5 g·kg^-1）. The serum uric acid （SUA） level and xanthine oxidase （XOD） activity were measured after 14 days. Fresh feces were collected for 16S rDNA sequencing. Result:Compared with the blank group， SUA level and XOD activity of model group were significantly increased （P<0.05）. Compared with the model group， SUA level and XOD activity of the allopurinol group were significantly decreased （P<0.01）. After intervention， SUA level were significantly decreased （P<0.05， P<0.01）， except for high dose and low dose groups of petroleum ether extract and low dose group of total flavonoids extract， XOD activity was significantly inhibited in low dose group of petroleum ether extract， high dose group of total flavonoids extract， and high and low dose groups of n-butanol extract （P<0.05， P<0.01）. The high dose group of total flavonoids extract was the most significant. The results of flora sequencing showed that α diversity and abundance of the model group changed significantly， and Bacteroidetes， Firmicutes and Lactobacillaceae were significantly correlated with XOD activity. After intervention， the operational taxonomic unit （OTU）， ACE， Chao1 and Shannon indexes of the high and low dose groups of total flavonoids extract were significantly increased （P<0.05， P<0.01）. Relative abundance of Bacteroidetes in low dose group of ethyl acetate extract， high dose group of total flavonoids extract， and high and low dose groups of n-butanol extract was significantly decreased （P<0.01）， and the relative abundance of Firmicutes was significantly increased （P<0.01）. The relative abundance of Lactobacillaceae in low dose group of n-butanol extract and high dose group of total flavonoids extract was significantly increased （P<0.01）. Conclusion:The effective part of Thlaspi Herba for reducing uric acid is mainly flavonoids， the improvement of SUA level and XOD activity by affecting gut microbiota such as Lactobacillaceae， Bacteroidetes and Firmicutes， may be one of its mechanisms.

Objectives: To investigate the prevalence and associated risk factors of tinnitus in Sichuan and Chongqing. Methods: We designed a tinnitus epidemiological questionnaire. The multi-stage stratified cluster random sampling methods was applied to obtain study subjects in six areas (Nanchong, Jiangjin, Fengdu, Yunyang, Suining and Ya'an), which were selected for epidemiological investigation. Home visit completion of epidemiological questionnaires was conducted. The trained investigators guided the respondents to fill in the tinnitus epidemiological questionnaires, and the epidemiological status of six areas on prevalence and risk factor was investigated. SPSS 22.0 software was used for statistical analysis. Results: Sampling population were 10 289, in which 9 273 were valid questionnaires. There were 4 281 males and 4 992 females, with an average age of 47.3 years, among which 34.83% (3 230/9 273) had tinnitus. 3.99% (370/9 273) were diagnosed with bothersome tinnitus. In a multivariable logistic regression mod, the following factors were associated with onsetting of tinnitus: sleep disorder [Odds Ratio(OR)=3.74] and noise exposure(OR=1.99). The risk of disease was lowest in the age of 30-40 years old, while the risk of disease was higher for people under 30 and over 40. In another multivariable logistic regression mode, the following factors were associated with having bothersome tinnitus: older people were more likely to suffer from tinnitus, sleep disorders (OR=4.68) and noise exposure (OR=1.56). Conclusions: The prevalence of tinnitus in Sichuan and Chongqing is about 34.83%, but most of the tinnitus is short-lived and has low loudness, which will not affect the patients. Only a small number of patients with tinnitus (3.99%) persist and affect their health and need treatment. The occurrence and exacerbation of tinnitus may be related to sleep, age, and noise exposure.
Adult ; Aged ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Surveys and Questionnaires ; Tinnitus/epidemiology*

Objective:To investigate the etiology, prognosis and prognostic factors of pediatric acute liver failure(PALF), in order to provide the basis for clinical treatment of PALF.Methods:The clinical data of children with PALF hospitalized at Hunan Children′s Hospital from May 2008 to May 2018 were collected, and the causes and prognosis were analyzed.According to the prognosis, the patients were divided into the death group and the survival group, whose biochemical indexes were then compared.After that, the statistical analysis of different data were carried out by using t-test, Wilcoxon test and χ2 test separately. Results:In 120 PALF cases, there were 68 males and 52 females, and there were 36 infants, 34 toddlers, 22 preschoolers and 28 school-age children.Twenty cases (16.7%) were caused by sepsis, 19 cases (15.8%) by genetic metabolic diseases, 18 cases (15.0%) by poisoning, 12 cases (10.0%) by viral infection, 6 cases (5.0%) by drugs, 1 case (0.8%) by bile polyp, and 1 case (0.8%) by tumor disease.Besides, the etiology of 43 cases (35.9%) was unknown.Among the cases with known etiologies, genetic metabolic and infectious diseases were the main cause of disease in infants, toddler patients were mostly caused by infectious diseases and drug/toxicants, and drug/toxicants and hereditary metabolic diseases were the dominant cause of disease in school-age children and preschoolers.Mortality rate of children with PALF was 50.0%.Among them, the mortality of Epstein-Barr virus-associated hemophagocytic syndrome, sepsis, Citrin deficiency and Tyrosinemia was higher than that of other diseases.Compared with the survival group, the total bilirubin (TB)[159.00(73.05, 274.00) μmol/L vs.62.75(2.65, 221.75)μmol/L], direct bilirubin(DB)[83.00(41.43, 160.00) μmol/L vs.38.74(10.98, 128.75) μmol/L], prothrombin time (PT)[39.60(24.93, 62.60) s vs.24.65(21.43, 29.83) s], international standardized ratio (INR)[3.40(2.30, 6.74) vs.2.09(1.85, 2.84)], and blood ammonia (NH 3) levels [109.50(85.25, 149.75) μmol/L vs.80.00(60.25, 102.75) μmol/L] in the death group were significantly increased, and the diffe-rences were statistically significant(all P<0.05); while the levels of albumin[(28.72±5.88) g/L vs.(33.69±4.96) g/L], alanine aminotransferase (ALT) [586.50(223.25, 1 082.00) U/L vs.1 434.00(615.00, 3 334.50) U/L]and aspartate aminotransferase (AST) [827.50(545.00, 2 024.00) U/L vs.1 663.50(821.00, 4 886.75) U/L]in the death group were significantly decreased, and the differences were statistically significant(all P<0.05). However, the blood glucose and cholesterol levels in both groups had no statistically significant difference. Conclusion:The mortality of children with PALF is high, and different age groups have different etiologies.The increase of TB, DB, PT, INR, NH3 and the ratio of hepatic encephalopathy, and the decrease of albumin, AST and ALT suggest poor prognosis.

OBJECTIVE: To investigate the efficacy of bone marrow mesenchymal stem cells (BMMSC) on children with refractory graft-versus-host disease (GVHD) and to judge the efficacy of BMMSC by dynamically monitoring the changes of cytokines in children with GVHD before and after infusion of BMMSC, so as to provide a theoretical basis for clarifying the mechanism of BMMSC. METHODS: 17 children with refractory aGVHD including 7 of grade II, 6 cases of grade III and 4 cases of grade IV after allo-HSCT were enrolled. All the children with aGVHD, who received routine immunosuppressive therapy, but the state of disease not improved, were treated with immunosuppressive drugs combined with BMMSC infusion. Study endpoints included safety of BMMSC infusion, response to BMMSC, and overall response of aGVHD. The serum levels of IL-2α, IL-6, IL-10, IL-8 and TNF-α in aGVHD patients were measured by chemiluminescence before infusion of BMMSCs and Day 7, Day 14 after infusion of BMMSCs. RESULTS: The cumulative median dose of BMMSCs was 5.5 (3.4-11.1) × 10/kg for average of 3.7 times, and the median time of 16.5 (4-95) days for the first infusion of MSCs. In 17 cases of refractory GVHD, 14 responded to treatment, whereas 3 patients failed. The total effective rate was 82.4% and no adverse reactions occurred. Of the 14 survived cases (82.4%), the median follow-up time was 944 (559-1245) days from the first infusion of MSCs. The levels of TNF-α in children with grade II, III and IV GVHD before treatment were 9.5±4.3 pg/ml, 16.3±10.9 pg/ml and 35.8±21.2 pg/ml respectively. The difference between grade II and IV, III and IV was statistically significant (P<0.05). Compared with the ineffective group of BMMSC infusion, the serum TNF-αlevel in the BMMSCs treatment effective group was 10.8±5.6 pg/ml vs 40.6±14.8 pg/ml (t=-3.901, P<0.05) before treatment. In the effective group of BMMSCs infusion, IL-10 20±17.4 pg/ml of day 14 was significantly higher than that 7.3±3.1 pg/ml before the treatment (t=-2.850, P<0.05), while , the serum levels of IL-2α, IL-6, IL-8, TNF-α were not statistically significantly different (P＞0.05). CONCLUSION The infusion of BMMSC is safe and effective in the treatment of refractory GVHD in children. TNF-αlevel relates with the severity of GVHD. BMMSC may play an anti-GVHD role by up regulating the level of cytokine IL-10 in vivo.

OBJECTIVE：To provide refere nce f or the quality control and evaluation of rice-wine processed Coptidis Rhizoma decoction piece. METHODS ：Taking 17 batches of rice-wine processed Coptidis Rhizoma decoction piece from different manufacturers as samples ，HPLC method was adopted to determine the contents of 4 kinds of alkaloids as epiberberine ，coptisine， palmatine and berberine. The compound weights of epiberberine ，berberine，palmatine and berberine were calculated by the subjective and objective combination weighting method （AHP combined with variation coefficient ）. Then the quality evaluation method was used to evaluate the quality of decoction pieces combined with the appearance of decoction pieces and the contents of 4 alkaloids. The percent mass constant was calculated and the grade of rice-wine processed Coptidis Rhizoma decoction piece was classified. RESULTS ：According to the results of content determination of 4 kinds of alkaloids ，among 17 batches of samples ，a total of 13 batches of samples met the requirements of 2015 edition of Chinese Pharmacopoeia （part Ⅳ）. Mass constants of 13 batches of qualified samples were 10.03-26.96，and the percent mass constants were 37.20％-100％. If the percent mass constant ≥ 80％ of the sample was listed as the first-class product ，the sample with the percent mass constant between 50％-＜80％ was classified as the second-class product ，and the rest was listed as the third-class product ，therefore the quality constant of first-class product was ≥21.57，that of second-class product was 13.48-＜21.57，and that of third-class product was ＜13.48. According to the grading standard ，3 batches of 13 batches of qualified samples are classified as first-class products ，6 batches are classified as second-class products ，4 batches are classified as third-class products. CONCLUSIONS ：The established subjective and objective combination weighting method and quality constant method can more scientifically and reasonably classify rice-wine processed Coptidis Rhizoma decoction piece.