ObjectiveTo investigate the effects of Jianpi Qinghua granules on blood glucose fluctuations in patients with newly diagnosed overweight/obese type 2 diabetes mellitus （T2DM） and Qi-Yin deficiency syndrome from the perspective of skeletal muscle mass and function， while providing new insights for the treatment of diabetes. MethodsThis study employed a randomized， double-blind， placebo-controlled design. A total of 110 newly diagnosed overweight/obese T2DM patients meeting the inclusion criteria were randomly assigned to either the traditional Chinese medicine （TCM） group （54 cases） or the control group （56 cases）. Patients in the TCM group received Jianpi Qinghua Granules， while those in the control group received a placebo. Both groups underwent dietary and exercise guidance. After 12 weeks of intervention， blood glucose fluctuations were assessed using the following parameters： time in the target blood glucose range （TIR）， mean daily blood glucose （MBG）， standard deviation of mean daily blood glucose （SDBG）， mean amplitude of glycemic excursions （MAGE）， coefficient of variation of blood glucose （CV）， glycated hemoglobin （HbA1c） achievement rate， fasting plasma glucose （FPG）， and 2 hour postprandial glucose （2 hPG）. Skeletal muscle mass was measured by dual-energy X-ray absorptiometry （DXA）， while skeletal muscle function was evaluated using a handheld dynamometer for distal muscle strength and a 5-time sit-to-stand test for lower limb function. Additionally， pancreatic islet function and TCM syndrome scores were analyzed. ResultsNo significant differences were observed in baseline data between the two groups before intervention， ensuring comparability. After treatment， compared to the control group， the TCM group showed a significant increase in TIR （P<0.01）. While the SDBG and CV decreased， and MBG and MAGE increased in the TCM group， these differences were not statistically significant. Notably， the TCM group exhibited significant reductions in 2 hPG （P<0.01） and HbA1c （P<0.05）， though the decrease in FPG was not statistically significant. The HbA1c achievement rate in the TCM group was significantly higher than that in the control group （χ²=45.498， P<0.01）. In terms of skeletal muscle mass and function， the TCM group demonstrated a significant increase in handgrip strength （P<0.01） and a significant reduction in the 5-time sit-to-stand duration （P<0.05）. However， although body fat percentage increased， leading to a decrease in skeletal muscle mass and the ratio of skeletal muscle to fat， these changes were not statistically significant. For pancreatic islet function， the TCM group showed significant reductions in fasting insulin （FINS） and homeostasis model assessment of insulin resistance （HOMA-IR） （P<0.01）. Additionally， the TCM syndrome score in the TCM group was significantly reduced （P<0.01）. ConclusionJianpi Qinghua granules may reduce blood glucose fluctuations in newly diagnosed overweight/obese T2DM patients with Qi-Yin deficiency syndrome by enhancing skeletal muscle function， improving pancreatic islet function， and ameliorating related TCM syndromes.

ObjectiveTo explore the application of virtual reality biofeedback training combined with oral localization therapy in dysphagia after oral cancer surgery. MethodsFrom May, 2023 to July, 2024, 86 patients with dysphagia after oral cancer surgery in Zhejiang Provincial People's Hospital were randomly divided into control group (n = 43) and experimental group (n = 43). The control group received conventional swallowing function training, while the experimental group added virtual reality biofeedback training combined with oral positioning therapy, for four weeks. The Standardized Swallowing Function Assessment Scale (SSA), Functional Oral Intake Scale (FOIS) and M.D.Anderson Dysphagia Inventory (MDADI) were used for evaluation before intervention, and two weeks, four weeks and eight weeks after intervention. ResultsFor scores of SSA , the main effects of group (F = 150.190, P < 0.001, η²_p = 0.641) and time (F = 230.870, P < 0.001, η²_p = 0.733), as well as the interaction effect (F = 16.910, P < 0.001, η²_p = 0.168) were all significant. For scores of FOIS, the main effects of group (F = 59.601, P < 0.001, η²_p = 0.415) and time (F = 89.464, P < 0.001, η²_p = 0.516), as well as the interaction effect (F = 7.990, P < 0.001, η²_p = 0.087) were all significant. For scores of MDADI, the main effects of group (F = 33.133, P < 0.001, η²_p = 0.283) and time (F = 49.650, P < 0.001, η²_p = 0.371), as well as the interaction effect (F = 3.224, P = 0.023, η²_p = 0.037) were all significant. ConclusionVirtual reality biofeedback training combined with oral localization therapy could improve the swallowing function, oral feeding ability and overall quality of life of patients with dysphagia after oral cancer surgery.

Objective To develop an active monitoring model for adverse drug events(ADEs)related to antimicrobial use in children based on the China hospital pharmacovigilance system(CHPS).Methods Trigger items for the active monitoring model were initially drafted through a review of relevant literature,adverse reaction databases,and drug label warnings,and subsequently refined using the Delphi method.A retrospective analysis was performed on pediatric inpatients who received antibiotics at Anning First People's Hospital between January 1 and December 31,2024.The detection rate and positive predictive value(PPV)of the active monitoring model were calculated and compared with spontaneous ADE reports from the same period.Risk factors for ADEs were further analyzed using logistic regression.Results 25 trigger items were established for the active monitoring model.Among 1,784 cases,233 ADEs were identified,yielding a detection rate of 13.06%(233/1,784).The spontaneous reporting rate of adverse events during the same period was 1.85%(33/1,784).The difference between the two was statistically significant(P<0.001).There were 727 positive trigger events,with 299 cases of ADE detected,resulting in an overall PPV of 41.13%(299/727).Logistic regression revealed that antibiotic use exceeding 3 days(OR=1.454,95%CI:1.012-2.088)was significantly associated with ADE occurrence.Conclusion Compared with conventional spontaneous reporting,the active monitoring model can significantly improve the detection rate of ADEs of pediatric antimicrobial drugs and achieve active and real-time monitoring of drug adverse events.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

OBJECTIVE: To accurately measure human energy metabolism with high temporal resolution, a respiratory gas analysis system was designed using a breath-by-breath approach. METHODS: Firstly, indirect calorimetry was employed in respiratory gas analysis to measure the respiratory flow and concentration signals in real-time. Secondly, oxygen consumption QO2 and carbon dioxide production QCO2 were calculated through respiratory characteristic alignment and respiratory signal segmentation. Finally, metabolic indexes were calculated according to the Weir formula. Furthermore, a controlled trial was formulated for validation comparisons with the MGC ULTIMA SYSTEM PFX CARDIO2. RESULTS: The results indicate that the data points of metabolic indexes measured by this system all fall within the confidence interval when compared with those of the MGC. CONCLUSION The system has high consistency with the MGC measurement results. Thus, the system can accurately measure metabolism in real-time and provide data support for clinical nutrition assessment and therapy.
Humans ; Energy Metabolism ; Breath Tests/instrumentation* ; Calorimetry, Indirect/instrumentation* ; Equipment Design

As the brain's resident immune cells, microglia perform crucial functions such as phagocytosis, neuronal network maintenance, and injury restoration by adopting various phenotypes. Dynamic imaging of these phenotypes is essential for accessing brain diseases and therapeutic responses. Although numerous probes are available for imaging pro-inflammatory microglia, no PET tracers have been developed specifically to visualize anti-inflammatory microglia. In this study, we present an ¹⁸F-labeled PET tracer (QTFT) that targets the P2Y₁₂, a receptor highly expressed on anti-inflammatory microglia. [¹⁸F]QTFT exhibited high binding affinity to the P2Y₁₂ (14.43 nmol/L) and superior blood-brain barrier permeability compared to other candidates. Micro-PET imaging in IL-4-induced neuroinflammation models showed higher [¹⁸F]QTFT uptake in lesions compared to the contralateral normal brain tissues. Importantly, this specific uptake could be blocked by QTFT or a P2Y₁₂ antagonist. Furthermore, [¹⁸F]QTFT visualized brain lesions in mouse models of epilepsy, glioma, and aging by targeting the aberrantly expressed P2Y₁₂ in anti-inflammatory microglia. In a pilot clinical study, [¹⁸F]QTFT successfully located epileptic foci, showing enhanced radioactive signals in a patient with epilepsy. Collectively, these studies suggest that [¹⁸F]QTFT could serve as a valuable diagnostic tool for imaging various brain disorders by targeting P2Y₁₂ overexpressed in anti-inflammatory microglia.

Alzheimer's disease (AD), characterized by β-amyloid (Aβ) aggregation and neuroinflammation, remains a formidable clinical challenge. Herein, we present an innovative nose-to-brain delivery platform utilizing lactoferrin (Lf)-functionalized lipid nanoparticles (LNPs) co-encapsulating α-mangostin (α-M) and β-site APP cleaving enzyme 1 (BACE1) siRNA (siB). This dual-modal therapeutic system synergistically combines the neuroprotective and microglia-reprogramming capabilities of α-M with the transcriptional silencing of BACE1 via siB, thereby simultaneously inhibiting Aβ production and enhancing its clearance. Fabricated via a microfluidic approach, the LNPs exhibited uniform particle size distribution, great encapsulation efficiency, and robust colloidal stability. Upon intranasal administration, Lf-functionalization enabled superior brain-targeting efficacy through receptor-mediated transcytosis. In vitro studies demonstrated that α-M reversed Aβ-induced low-density lipoprotein receptor downregulation, promoting microglial phagocytosis and autophagic degradation of Aβ, while siB effectively suppressed BACE1 expression, abrogating Aβ synthesis. In vivo investigations in APP/PS1 transgenic mice revealed remarkable cognitive recovery, substantial Aβ plaque reduction, and alleviation of neuroinflammation and oxidative stress. This intricately designed LNP system, exploiting a non-invasive and efficient nose-to-brain delivery route, provides a biocompatible, synergistic, and transformative therapeutic strategy for the multifaceted management of AD.

Objective To explore the role of the brief visuospatial memory test-revised(BVMT-R)in predicting the clinical conversion to psychosis in subjects with clinical high-risk for psychosis(CHR-P).Methods A total of 217 CHR subjects were recruited and assessed using BVMT-R at baseline.Participants were followed up for three years to determine whether they converted to psychosis.The relationship between BVMT-R total score and CHR-P conversion probability was analyzed using generalized additive model,and the cutoff values of BVMT-R total score for predicting CHR-P conversion were calculated by maximally selected rank statistics.Then,the total BVMT-R score was stratified into different intervals based on the cutoff values obtained as previously described.Finally,the positive likelihood ratios and the conversion rates at different time points were calculated for each interval.Results A total of 168 subjects with CHR-P completed the 3-year follow-up assessment.According to the results of the generalized additive model,the relationship between the BVMT-R total score and CHR-P conversion probability exhibited the characteristics of a piecewise function model.The cutoff values identified using the maximally selected rank statistics method were 18 and 29,which divided the BVMT-R total scores into three intervals:0-18,19-29,and 30-36.The positive likelihood ratios of the three intervals for predicting CHR-P psychosis conversion were significantly different(all P<0.01).All three intervals had significantly different rates of psychosis conversion at different follow-up time points(all P<0.01).Conclusion The total BVMT-R score can be divided into three intervals,each associated with a distinct positive likelihood ratio for predicting psychosis conversion in CHR-P individuals.Accordingly,the BVMT-R total score may serve as a preliminary indicator for estimating the probability of psychosis conversion in the CHR-P population.

Granulomatous vasculitis is a kind of necrotizing granulomatous vasculitis with the prominent feature of detectable anti-neutrophil cytoplasmic antibodies in serum, which often involves the respiratory tract and kidneys, and the onset of symptoms in the digestive tract is rare, and we now report a rare case of granulomatous vasculitis in which the gastrointestinal tract was involved as the first symptom in order to improve the clinician's understanding of this disease.

Objective:To evaluate the role of leucine-rich repeat kinase 2 (LRRK2) in the spinal dorsal horn in diabetic neuropathic pain (DNP) and to determine whether the mechanism involved nuclear factor kappa B (NF-κB) signaling pathway in rats.Methods:SPF healthy male Sprague-Dawley rats, aged 8 weeks, weighing 205-238 g, were fed a high-sugar and high-fat diet and received intraperitoneal injection of streptozotocin to induce a type 2 diabetes mellitus model. Successful DNP model was defined as the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) being below 85% of the baseline in type 2 diabetes mellitus rats. Thirty-six rats with DNP were allocated into 3 groups ( n=12 each) using a random number table method: DNP group, MLi-2 (LRRK2 inhibitor) group, and MLi-2+ phorbol 12-myristate 13-acetate (PMA) (NF-κB activator) group. MLi-2 1 mg/kg was intrathecally injected at L 5-6 in MLi-2 group. In MLi-2+ PMA group, MLi-2 1 mg/kg was intrathecally injected, and 1 h later PMA 20 μg/10 μl was intrathecally injected. In group DNP, the equal volume of 5% dimethyl sulfoxide was intrathecally injected. Twelve healthy rats were randomly selected and served as control group (C group). The animals were fed a standard diet, normal saline 2 ml was intraperitoneally injected, and the equal volume of 5% dimethyl sulfoxide was intrathecally injected in group C. Intrathecal injection was performed once a day for 7 consecutive days. The MWT and TWL were measured at 1, 3, 5 and 7 days after intrathecal injection, and the motor nerve conduction velocity (MNCV) was measured using neuroelectrophysiological techniques. The L 4-6 segments of the spinal cord were collected, and histopathological changes were observed through HE staining. The co-localization of leucine-rich repeat kinase 2 (LRRK2) in the spinal dorsal horn with the microglial activation marker ionized calcium-binding adaptor molecule-1 (Iba-1) was observed by immunofluorescence staining. The L 4-6 segments of the spinal dorsal horn were harvested for determination of the level of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 (using enzyme-linked immunosorbent assay) and expression of LRRK2, Iba-1, nuclear factor kappa B (NF-κB) p65 and phosphorylated NF-κB p65 (p-NF-κB p65) (by Western blot). Results:Compared to C group, the TWL was significantly shortened, the MNCV was decreased, the percentage of cells co-expressing LRRK2 and Iba-1 in the spinal dorsal horn was increased, the contents of TNF-α, IL-1β and IL-6 were increased, the expression of LRRK2 and Iba-1 was up-regulated, the ratio of p-NF-κB p65/NF-κB p65 was increased ( P<0.05), and histological examination revealed nuclear shrinkage and inflammatory cell infiltration in the spinal dorsal horn tissue in DNP group. Compared with DNP group, the MWT was significantly increased, the TWL was prolonged, the MNCV was elevated, the percentage of cells co-expressing LRRK2 and Iba-1 was decreased, the contents of TNF-α, IL-1β and IL-6 were decreased, the expression of LRRK2 and Iba-1 was down-regulated, the ratio of p-NF-κB p65/NF-κB p65 was decreased ( P<0.05), and pathological changes of the spinal dorsal horn tissue were significantly attenuated in MLi-2 group. Compared to MLi-2 group, the MWT was significantly decreased, the TWL was shortened, the MNCV was decreased, the percentage of cells co-expressing LRRK2 and Iba-1 was increased, the contents of TNF-α, IL-1β and IL-6 were increased, the expression of Iba-1 was up-regulated, and the ratio of p-NF-κB p65/NF-κB p65 was increased in MLi-2+ PMA group ( P<0.05). Conclusions:LRRK2 in spinal dorsal horn may be involved in the maintenance of DNP by promoting the inflammatory response mediated by microglial activation, and the mechanism may be related to the activation of NF-κB signaling pathway in rats.