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

OBJECTIVES: To investigate the relationship between the polygenic risks for various psychiatric disorders and clinical and neuropsychological characteristics in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Using a cross-sectional design, 285 children with ADHD and 107 healthy controls were assessed using the Child Behavior Checklist, the Behavior Rating Inventory of Executive Function for parents, the Wechsler Intelligence Scale for Children, Fourth Edition, and the Cambridge Neuropsychological Test Automated Battery. Blood samples were collected for genetic data. Polygenic risk scores (PRSs) for various psychiatric disorders were calculated using the PRSice-2 software. RESULTS: Compared with the healthy controls, the children with ADHD displayed significantly higher PRSs for ADHD, major depressive disorder, anxiety disorder, and obsessive-compulsive disorder (P<0.05). In terms of daily-life executive function, ADHD-related PRS was significantly correlated with the working memory factor; panic disorder-related PRS was significantly correlated with the initiation factor; bipolar disorder-related PRS was significantly correlated with the shift factor; schizophrenia-related PRS was significantly correlated with the inhibition, emotional control, initiation, working memory, planning, organization, and monitoring factors (P<0.05). The PRS related to anxiety disorders was negatively correlated with total IQ and processing speed index (P<0.05). The PRS related to obsessive-compulsive disorder was negatively correlated with the processing speed index and positively correlated with the stop-signal reaction time index of the stop-signal task (P<0.05). CONCLUSIONS PRSs for various psychiatric disorders are closely correlated with the behavioral and cognitive characteristics in children with ADHD, which provides more insights into the heterogeneity of ADHD.
Humans ; Attention Deficit Disorder with Hyperactivity/genetics* ; Child ; Male ; Female ; Cross-Sectional Studies ; Neuropsychological Tests ; Multifactorial Inheritance ; Adolescent ; Mental Disorders/etiology* ; Executive Function ; Genetic Risk Score

The PA-PB1 interface of the influenza polymerase is an attractive site for antiviral drug design. In this study, we designed and synthesized a mini-library of indazole-containing compounds based on rational structure-based design to target the PB1-binding interface on PA. Biological evaluation of these compounds through a viral yield reduction assay revealed that compounds 27 and 31 both had a low micromolar range of the half maximal effective concentration (EC₅₀) values against A/WSN/33 (H1N1) (8.03 μmol/L for 27; 14.6 μmol/L for 31), while the most potent candidate 24 had an EC₅₀ value of 690 nM. Compound 24 was effective against different influenza strains including a pandemic H1N1 strain and an influenza B strain. Mechanistic studies confirmed that compound 24 bound PA with a K _d which equals to 1.88 μmol/L and disrupted the binding of PB1 to PA. The compound also decreased the lung viral titre in mice. In summary, we have identified a potent anti-influenza candidate with potency comparable to existing drugs and is effective against different viral strains. The therapeutic options for influenza infection have been limited by the occurrence of antiviral resistance, owing to the high mutation rate of viral proteins targeted by available drugs. To alleviate the public health burden of this issue, novel anti-influenza drugs are desired. In this study, we present our discovery of a novel class of indazole-containing compounds which exhibited favourable potency against both influenza A and B viruses. The EC₅₀ of the most potent compounds were within low micromolar to nanomolar concentrations. Furthermore, we show that the mouse lung viral titre decreased due to treatment with compound 24. Thus our findings identify promising candidates for further development of anti-influenza drugs suitable for clinical use.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

OBJECTIVE To explore the effects of levosimendan on cardiac function， hemodynamics and prognosis of patients with septic shock complicated with myocardial depression， and evaluate the safety of levosimendan. METHODS Patients with septic shock complicated with myocardial depression who were admitted to the Department of Critical Care Medicine of Chongqing University Three Gorges Hospital from April 2021 to August 2023， underwent adequate fluid resuscitation， had a mean arterial pressure （MAP） ≥65 mmHg， and received pulse indicator continuous cardiac output （PiCCO） monitoring were enrolled. The patients were randomly divided into dobutamine group and levosimendan group according to a random number table， with 20 patients in each group. Both groups received intravenous infusion of Norepinephrine bitartrate injection at a dose of 0.1-2.0 μg/（kg·min）. On this basis， the dobutamine group additionally received intravenous infusion of Dobutamine hydrochloride injection at a dose of 5- 10 μg/（kg·min） for 3 to 7 days， while the levosimendan group additionally received intravenous infusion of Levosimendan injection at a dose of 0.1-0.2 μg/（kg·min） for 24 hours. Heart rate （HR） and hemodynamic parameters [systolic blood pressure， diastolic blood pressure， MAP， central venous pressure （CVP）]， PiCCO monitoring parameters [cardiac function index （CFI）， cardiac index （CI）， stroke volume index （SVI）， extravascular lung water index， global end-diastolic volume index， pulmonary vascular permeability index （PVPI）， global ejection fraction （GEF）， systemic vascular resistance index， left ventricular contractility index]， and prognosis indicators [death within 3 days after administration， mechanical ventilation time，intensive care unit （ICU） stay time， 28-day mortality rate] were compared between the two groups before treatment and at 24 and 72 hours after treatment. Adverse reactions were E-mail：recorded for both groups. RESULTS Compared with before treatment in the same group， CFI， CI and GEF at 24 hours after treatment， CI and GEF at 72 hours after treatment in the dobutamine group， as well as SVI at 24 hours after treatment and SVI and GEF at 72 hours after treatment in the levosimendan group were significantly increased； PVPI at 72 hours after treatment in the dobutamine group was significantly decreased （P＜0.05）. Compared with the dobutamine group during the same period， patients in the levosimendan group had significantly lower HR and significantly higher CVP at 24 hours after treatment （P＜0.05）. Within 3 days after administration， there were no deaths in either group； there were no statistically significant differences in mechanical ventilation time， ICU stay time， 28-day mortality rate， or the incidence of adverse reactions between the two groups （P＞0.05）. CONCLUSIONS For patients with septic shock complicated with myocardial depression who have undergone adequate fluid resuscitation and have a MAP of ≥65 mmHg， levosimendan is comparable to dobutamine in improving cardiac function and hemodynamic parameters， without affecting patients’ prognosis or increasing the risk of adverse reactions such as hypotension.

Objective:To compare the short-term effect of the arthroscopic reconstruction of anterior cruciate ligament (ACL) by femoral tunnel positioning through the tendon incision (TI) technique and anteromedial (AM) technique.Methods:Between December 2015 and March 2017, 176 patients with ACL injuries underwent arthroscopic ACL reconstruction at the First Affiliated Hospital of USTC were analyzed. According to the method of localization of femoral tunnel, they were divided into two groups: TI group (localization of femoral tunnel by TI for reconstruction of ACL) and AM group (localization of femoral tunnel by AM for reconstruction of ACL). There were 87 patients in the TI group (63 males and 24 females) with an age of 32.8±9.4 years (range, 19-51 years) and a body mass index (BMI) of 24.8±6.3 kg/m 2 (range, 18.1-31.7 kg/m 2), including 9 obese patients (BMI>28 kg/m 2). There were 89 patients in the AM group (59 males and 30 females) with an age of 36.7±13.0 years (range, 17-56 years) and a BMI of 25.7±5.8 kg/m 2 (range, 18.9-31.6 kg/m 2), including 11 obese patients. To evaluate whether the drill was in contact with the articular surface of the medial condyle of the femur, whether the anterior angle of the medial meniscus was damaged, the sagittal and coronal angles of the femoral tunnel and the total length of the femoral tunnel. The anterior drawer test, Lachmann test, pivot shift test, knee flexion angle (KFA), Lysholm score, International Knee Documentation Committee (IKDC) score and the incidence of postoperative complications were compared between the two groups. At the same time, the time of taking out tendon, operation time, hospital stay and recovery time were compared between two groups of obese people. Results:In the TI group, the guide pin could reach all areas of the medial wall of the lateral femoral condyle from the inferior cartilage edge to the top of the intercondylar fossa, the drill bit had no contact with the medial femoral condyle (MFC), and the anterior angle of the medial meniscus was not damaged. In AM Group, 3 cases of MFC and 1 case of anterior horn of medial meniscus were injured in order to get the best position of femoral tunnel. The angle of femoral tunnel in sagittal plane (50.2°±3.2°) and coronal plane (46.1°±5.8°) in experimental group was notably larger than that in control group (45.6°±5.4°, 38.3°±4.7°), the difference was statistically significant ( P<0.05). However, there was no significant difference in the length of femoral tunnel between the two groups (38.2±3.2 mm and 37.7±2.5 mm, P>0.05). All patients were followed up for an average of 8.3±2.1 (range, 3-12) months. The positive rates of anterior drawer test, Lachmann test and pivot shift test were not significantly different between the two groups at 3, 6, 9 and 12 months after operation ( P>0.05). The KFA, Lysholm and IKDC scores in both groups were significantly increased after operation ( P<0.05), but there was no significant difference of above indexes between the two groups ( P>0.05). The overall complication rate in AM group (14.6%, 13/89) was significantly higher than that in TI group (6.9%, 6/87), the difference was statistically significant ( P<0.05). Additionally, the tendon harvesting (15.0±0.2 min vs. 26.0±0.2 min, P<0.05) and operation time (2.0±0.3 h vs. 3.0±0.4 h, P<0.05) were significantly shortened among obese patients in experimental group compared with those in control group. Conclusion:The TI technique demonstrates comparable effectiveness to the AM technique in ACL reconstruction through femoral tunnel positioning, with the added advantage of safer femoral tunnel localization. This approach minimizes the risk of iatrogenic injuries to the articular cartilage of the medial condyle of the femur and the anterior horn of the medial meniscus. Furthermore, the TI technique reduces tendon removal time, particularly beneficial for obese patients.

Aim To investigate the role of metabolites of eicosapentaenoic acid (EPA) in promoting the transdifferentiation of pancreatic α cells to β cells. Methods Male C57BL/6J mice were injected intraperitoneally with 60 mg/kg streptozocin (STZ) for five consecutive days to establish a type 1 diabetes (T1DM) mouse model. After two weeks, they were randomly divided into model groups and 97% EPA diet intervention group, 75% fish oil (50% EPA +25% DHA) diet intervention group, and random blood glucose was detected every week; after the model expired, the regeneration of pancreatic β cells in mouse pancreas was observed by immunofluorescence staining. The islets of mice (obtained by crossing GCG

BACKGROUND:Lycium barbarum polysaccharide has many biological activities and has been found to have potential effects on promoting wound healing. OBJECTIVE:To investigate the mechanism of lycium barbarum polysaccharide in tumor necrosis factor-α-mediated keratinocyte apoptosis and its effect on the healing of burn wounds. METHODS:(1)In vitro experiment:Keratinocytes were divided into four groups:cells were cultured in the α-MEM medium(complete medium)containing 15%fetal bovine serum and 1%glutamine in normal group,cultured in the complete medium containing lycium barbarum polysaccharide in positive control group,cultured in the complete medium containing tumor necrosis factor-α in model group,and cultured in the complete medium containing lycium barbarum polysaccharide and tumor necrosis factor-α in experimental group.After 24 hours of culture,cell proliferation was detected using cell counting kit-8 assay;Cleaved caspase-8,TNF R1,FADD,and LC3 were detected using western blot.Then an autophagy inhibitor group(the complete medium containing 3-methyladenine)and an autophagy inhibitor+lycium barbarum polysaccharide group(the complete medium containing lycium barbarum polysaccharide,tumor necrosis factor-α,and 3-methyladenine)were set up.After 24 hours of culture,keratinocyte apoptosis was detected by flow cytometry.(2)In vivo experiment:Six Sprague-Dawley rats were randomly divided into a control group and an experimental group,with three rats in each group.Four deep Ⅱ degree burn wounds with a diameter of 2 cm were made on the back of each rat.At 24 hours after modeling,mice in the control and experimental groups were coated with normal saline and lycium barbarum polysaccharide solution,respectively,once a day.Wound healing was observed regularly after treatment.Samples were taken 28 days after treatment and the pathologic pattern of the wound was observed. RESULTS AND CONCLUSION:(1)In vitro experiment:Addition of lycium barbarum polysaccharide alone did not affect cell proliferation and apoptosis and the expression of apoptotic and autophagic proteins in keratinocytes.After the addition of tumor necrosis factor α,the proliferation of keratinocytes was inhibited,the apoptotic rate increased,and the expression of apoptotic and autophagic proteins was elevated,while lycium barbarum polysaccharide could antagonize the above effects of tumor necrosis factor-α.Lycium barbarum polysaccharide combined with autophagy inhibitors further reduced the apoptotic rate of keratinocytes.(2)In vivo experiment:The wound healing rate of rats in the experimental group was higher than that of the control group at 12,16,20,24,and 28 days after treatment(P＜0.05,P＜0.01).Hematoxylin-eosin staining results at 28 days after treatment showed an intact and well-defined epidermis of the wound in the experimental group compared with the control group.To conclude,lycium barbarum polysaccharide protects the integrity of skin epidermal tissue and promotes wound healing by inhibiting autophagy and apoptosis of keratinocytes.

Objective:To compare the postoperative tunnel enlargement and clinical outcomes of anterior cruciate ligament (ACL) reconstruction using the all-inside technique with the traditional outside-in graft introduction technique.Methods:A retrospective analysis was conducted on 47 patients with ACL injuries who were admitted to the First Hospital of the University of Science and Technology of China between December 2021 and July 2022. The patients were categorized into two groups based on the surgical approach used for ACL reconstruction. There were 25 cases in the all-inside group, 18 males and 7 females, aged 27.72±7.33 years, 17 cases on the left side and 8 cases on the right side; 22 cases in the traditional group, 11 males and 11 females, aged 27.82±7.12 years, 11 cases on the left side and 11 cases on the right side. Clinical parameters including the length of hospital stay, surgical duration, pain levels assessed via the visual analogue scale (VAS), Lysholm score, International Knee Documentation Committee (IKDC) score, and Tegner score were recorded and compared between the two groups. Additionally, femoral and tibial tunnel enlargement was evaluated using postoperative CT scans conducted one year after surgery.Results:All patients were followed up for 15.64±2.04 months (range, 12-21 months). The mean operation time was 178.60±42.90 min in the all-inside group and 133.60±28.77 min in the traditional group, indicating a statistically significant longer operation time in the all-inside group ( P<0.05). On postoperative days 1 and 15, the VAS scores were lower in the all-inside group (7.08±1.29 and 5.56±1.33 points) compared to the conventional group (7.96±1.29 and 6.32±1.13 points), with a statistically significant difference ( P<0.05). However, the differences in VAS scores between the two groups at postoperative months 1, 6, and 12 were not statistically significant ( P>0.05). The preoperative Lysholm, IKDC, and Tegner scores in the all-inside group and the conventional group were 34.00±18.63, 36.24±15.01, 1.20±1.12 points and 36.18±13.64, 38.23±14.94, 1.55±1.14 points, respectively, and at 6 months after surgery, respectively were 72.60±13.95, 74.12±12.03, 3.56±1.05 points, and 68.41±10.80, 66.59±17.93, 3.23±1.15 points, and at 12 months postoperatively were 92.32±5.23, 81.40±7.24, 5.28±1.62 points and 91.27±6.32, 82.18±7.26, 4.96±1.25 points. Both groups improved at 6 months postoperatively compared with preoperatively ( P<0.05), and further improved at 12 months postoperatively compared with 6 months postoperatively ( P<0.05), but the differences in each functional score between the two groups were not statistically significant at all time points ( P>0.05). At 1 year postoperatively, the values of femoral and tibial tunnel enlargement in the all-inside group (1.78±1.03 mm, 1.18±0.97 mm) were smaller than those in the conventional group (2.30±1.33 mm, 1.83±1.00 mm), and the differences were statistically significant ( P<0.05). The difference between the femoral side tunnel enlargement and tibial side enlargement in the traditional group was not statistically significant ( P>0.05), while the femoral side enlargement in the all-inside group was significantly larger than the tibial side ( P<0.05). The difference in Lysholm, IKDC and Tegner scores between grade 0 and grade 1 tunnel enlargement on the femoral side and tibial side was not statistically significant ( P>0.05). Conclusion:The short-term clinical outcomes following ACL reconstruction using the all-inside technique versus the traditional tunnel technique were comparable. However, early postoperative pain was less severe with the all-inside technique, and tunnel enlargement was smaller. The degree of bone tunnel enlargement did not significantly impact early clinical outcomes.