Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.

[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].

Wound healing is a complex biochemical process. The use of herbal medicine in wound healing not only carries forward the wisdom of traditional medicine, with its anti-inflammatory and immune-regulating effects, but also reflects the direction of modern biopharmaceutical technology, such as its potential in developing new biomaterials like hydrogels. This article first outlines the inherent structural properties of healthy skin, along with the physiological characteristics related to chronic wounds in patients with diabetes and burns. Subsequently, the article delves into the latest advancements in clinical and experimental research on the impact of active constituents in herbal medicine on wound tissue regeneration, summarizing existing studies on the mechanisms of various herbal medicines in the healing of diabetic and burn wounds. Finally, the paper thoroughly examines the application and mechanisms of plant polysaccharide hydrogels containing active herbal compounds in chronic wound healing. The primary objective is to provide valuable resources for the clinical application and development of herbal medicine, thereby maximizing its therapeutic potential. It also represents the continuation of traditional medical wisdom, offering new possibilities for advancements in regenerative medicine and wound care.

OBJECTIVE: To explore the effects of different endotracheal tube cuff pressure management modes on cuff sealing and the pressure exerted on the tracheal wall. METHODS: A prospective self-controlled study was conducted. Eleven patients undergoing endotracheal intubation and mechanical ventilation with an automatic airway management system (AGs) admitted to the Second Medical Centre of the Chinese People's Liberation Army General Hospital from October 1, 2020, to April 1, 2022, were enrolled as the study subjects. Within 24 hours after the establishment of artificial airway and mechanical ventilation, four cuff pressure management modes were randomly applied to each patient for 24 hours in sequence: automatic cuff pressure management mode [modeI: the safe range of cuff pressure was set at 20-35 cmH₂O (1 cmH₂O≈0.098 kPa), and the CO₂ pressure above the endotracheal tube cuff was automatically detected by AGs every 5 minutes to determine the cuff sealing status, and the cuff pressure was automatically adjusted], constant cuff pressure (25 cmH₂O) management mode (mode II: the cuff pressure was monitored by AGs through a pressure sensor, and the cuff pressure was maintained at 25 cmH₂O via a pressure pump), constant cuff pressure (30 cmH₂O) management mode (mode III: the cuff pressure was monitored by AGs through a pressure sensor, and the cuff pressure was maintained at 30 cmH₂O via a pressure pump), and manual cuff pressure management mode (mode IV: the cuff pressure was manually measured by nurses every 6-8 hours using a cuff pressure gauge to keep the cuff pressure at 25-30 cmH₂O after inflation). The CO₂ pressure above the endotracheal tube cuff (at 60-minute intervals) and the cuff pressure changes (at 50-ms intervals) were recorded to compare the differences in number of cuff leaks [no leak was defined as CO₂ pressure = 0, small leak as 0 < CO₂ pressure < 2 mmHg (1 mmHg≈0.133 kPa), and large leak as CO₂ pressure ≥ 2 mmHg] and cuff pressure among modesI-IV. RESULTS: A total of 24 CO₂ pressure measurements were taken per patient across the four modes, resulting in a total of 264 detections for each mode. Regarding the cuff leak, the total number of leak and large leak in modeIwas significantly lower than that in modes II-IV [total leak: 30 cases (11.36%) vs. 81 cases (30.68%), 70 cases (26.52%), 103 cases (39.02%); large leak: 15 cases (5.68%) vs. 50 cases (18.94%), 48 cases (18.18%), 66 cases (25.00%), all P < 0.05]. There was no significant difference in the number of cuff leak between modes II and III, and mode IV had the most severe cuff leak. In terms of cuff pressure, since mode IV required blocking the cuff tube from the AGs tube and the AGs cuff pressure management module did not actually work, real-time monitoring of cuff pressure was not possible. Therefore, cuff pressure changes were only analyzed in modes I-III. Each of the 11 patients underwent 24-hour cuff pressure monitoring under modes I-III, with 19 008 000 monitoring times for each mode. The cuff pressure in mode I was between that in modes II and III [cmH₂O: 27.09 (26.10, 28.14) vs. 26.60 (25.92, 27.47), 31.01 (30.33, 31.88), both P < 0.01]. Moreover, the number of extreme values of cuff pressure > 50 cmH₂O in mode I was significantly lower than that in modes II and III [19 900 cases (0.105%) vs. 22 297 cases (0.117%), 27 618 cases (0.145%), both P < 0.05]. CONCLUSION Dynamically monitoring the CO₂ pressure above the cuff to guide the adjustment of endotracheal tube cuff pressure can achieve better cuff sealing with a relatively lower cuff pressure load.
Humans ; Intubation, Intratracheal/instrumentation* ; Pressure ; Prospective Studies ; Respiration, Artificial ; Male ; Airway Management/methods* ; Female ; Middle Aged

The bioactivity-guided isolation of potentially active natural products has been widely utilized in pharmaceutical discovery. In this study, by screening fungal extracts against coxsackievirus B3 (CVB3), three new aspochalasins, templichalasins A‒C (1‒3), along with six known aspochalasins (4‒9) were isolated from an active extract derived from the endophytic fungus Aspergillus templicola LHWf045. Compound 1 features a unique 5/6/5/7/5 pentacyclic ring system, while compounds 2 and 3 possess unusual 5/6/6/7 tetracyclic skeletons. Their structures were characterized through extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Additionally, we demonstrated that compound 4 can be readily converted into compounds 1‒3 under mild acidic conditions and proposed a plausible mechanism for this conversion. Bioactivity evaluation of compounds 1‒9 against CVB3 revealed the inhibitory effects of all compounds against the virus. Notably, compound 9 exhibited superior antiviral activity, surpassing the commercial drug ribavirin in selectivity index (SI) value.
Antiviral Agents/isolation & purification* ; Aspergillus/chemistry* ; Molecular Structure ; Enterovirus B, Human/drug effects* ; Endophytes/chemistry* ; Cytochalasins/isolation & purification* ; Drug Discovery ; Humans

Dental treatments for children and adolescents have unique clinical characteristics that differ from dental care for adults in terms of children's physiology, psychology, and behavior. These differences impose specific requirements on the application of local anesthesia in pediatric dental procedures. This article presents expert consensus on the principles of local anesthesia techniques in pediatric dental therapies, including the use of common anesthetic drugs and dosage control, safety and efficacy evaluation, and prevention and management of complications. The aim is to improve the safety and quality of pediatric dental treatments and offer guidance for clinical application by dentists.
Humans ; Child ; Anesthesia, Local/methods* ; Consensus ; Anesthesia, Dental/methods* ; Adolescent ; Anesthetics, Local/administration & dosage* ; Dental Care for Children

ObjectiveTo sum up the clinical features of 5α-reductase type 2 deficiency （5α-RD2） complicated by central precocious puberty （CPP）， and provide experience for clinicians. MethodsA retrospective review was conducted of child patients with 5α-RD2 followed up to puberty at a single tertiary pediatric center， in whom 6 cases developed CRP. Clinical characteristics and treatment history of them were analyzed. A literature review was also performed to investigate possible mechanisms underlying the co-occurrence of 5α-RD2 and CPP. ResultsThe median age at initial presentation was 5.55 years （IQR 3.50-7.20）. Common clinical features included micropenis and hypospadias. Median stretched penile length （SPL） was 2.25 cm （IQR 1.8-2.8）， with an SPL-SDS of -4.5 （IQR -3.1 to -5.8）. Median external masculinization score （EMS） and Prader scores were 8.5 （IQR 5.0-9.0） and 4.5 （IQR 3.0-5.0）， respectively. Pubertal onset occurred at a median age of 8.70 years （IQR 7.80-9.00）. Three patients were overweight or obese. Five had received 2.5% dihydrotestosterone （DHT） gel prior to pubertal onset， with a median cumulative dose of 205.5 mg/kg （IQR 72.0-660.3 mg/kg） with DHT gel therapy. Notably， one patient with normal body mass index （BMI） and no history of androgen or gonadotropin therapy also exhibited early pubertal onset at 8.4 years. ConclusionCPP in children with 5α-RD2 may be associated with prior dihydrotestosterone （DHT） gel therapy and elevated BMI； however， a potential intrinsic link to the underlying disorder cannot be excluded. Further studies are needed to elucidate the pathophysiological mechanisms.

Objective:To investigate the effect of Chinese Herbal Anti-Alopecia and Hair Growth Solution(CHAaHGS)on the hair growth through in vitro experiments on the human dermal papilla cells(HDPCs),in vivo experiments in the C57BL/6 mice,and human efficacy tests,and to clarify its potential mechanism.Methods:The HDPCs were divided into control group,CHAaHGS group,and minoxidil group.MTT method was used to detect the proliferation activities of HDPCs in various groups;enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of vascular endothelial growth factor(VEGF),hepatocyte growth factor(HGF),insulin-like growth factor-1(IGF-1),and transforming growth factor β1(TGF-β1)in the supernatant of HDPCs in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of VEGF,HGF,IGF-1,TGF-β1,and alkaline phosphatase(ALP)mRNA in the HDPCs in various groups;Western blotting method was used to detect the expression levels of β-catenin,dishevelled segment polarity protein 1(DVL1),glycogen synthase kinase 3β(GSK-3β),phosphorylated GSK-3β(p-GSK-3β),and wingless-type MMTV integration site family member 3a(Wnt3a)proteins in the HDPCs in various groups.A total of 18 mice were randomly divided into control group,CHAaHGS group,and minoxidil group,with 6 mice in each group.The mouse hair loss model was established using hair removal cream,and corresponding drug treatments were administered immediately after hair removal.The lengths and weights of newly grown hair on day 21 of the mice in various groups were detected;HE staining was used to observe the morphology of hair follicles in the dorsal depilated skin areas of the mice in various groups on day 7;ELISA method was used to detect the levels of VEGF,HGF,IGF-1,and TGF-β1 in the skin tissue of dorsal depilated areas of the mice in various groups.Sixty subjects were randomly divided into control group and CHAaHGS group,with 30 subjects in each group.The numbers of hair loss and hair densities of the subjects in various groups were detected at weeks 0,4,8,and 12.Results:The MTT assay results showed that compared with control group,the proliferation activity of the cells in 50 mg·L-1CHAaHGS group was significantly increased(P＜0.01).The ELISA assay results showed that compared with control group,the levels of VEGF,HGF,and IGF-1 in the cell supernatant of HDPCs in CHAaHGS group were significantly increased(P＜0.05 or P＜0.01),and the TGF-β1 level was significantly decreased(P＜0.01).The RT-qPCR results showed that compared with control group,the expression levels of VEGF,HGF,IGF-1,and ALP mRNA in the cells in CHAaHGS group were significantly increased(P＜0.05 or P＜0.01),and the TGF-β1 mRNA expression level was significantly decreased(P＜0.01).The Western blotting results showed that compared with control group,the expression levels of β-catenin,DVL1,p-GSK-3βand Wnt3a proteins in the cells in CHAaHGS group were significantly increased(P＜0.05 or P＜0.01),and the GSK-3β protein expression level was significantly decreased(P＜0.05).In animal experiments,on day 21,compared with control group,the length of newly grown hair of the mice in CHAaHGS group was significantly increased(P＜0.05),and the hair weight was significantly increased(P＜0.01).On day 7,the HE staining results showed that compared with control group,the hair follicle spacing of the mice in CHAaHGS group was significantly decreased(P＜0.05),and the number of hair follicles was significantly increased(P＜0.01);the ELISA assay results showed that compared with control group,the levels of VEGF,HGF,and IGF-1 in skin tissue of dorsal depilated area of the mice in CHAaHGS group were significantly increased(P＜0.05 or P＜0.01),and the TGF-β1 level was significantly decreased(P＜0.05).In human efficacy test,compared with control group,the number of hair loss of the subjects in CHAaHGS group was significantly decreased at week 12(P＜0.01),and the local hair density was increased(P＜0.05).Conclusion:CHAaHGS promotes hair growth,and the mechanism may be related to its ability to increase the proliferation activity of HDPCs,induce the secretion of VEGF,HGF,and IGF-1,and activate the Wnt/β-catenin signaling pathway.

When performing motorized flight missions,the pilots often receive strong vestibular stimulation and then induce the flight illusion,which produces great interference to the flight safety.Previous studies have suggested that vestibular stimulation has some effect on cognitive function.Through reviews of relevant literatures at home and abroad,this paper focuses on summarizing the influence of vestibular stimulation on spatial memory ability,attention,sensory perception,executive ability,spatial viewpoint selection and control ability,aiming to improve the understanding of the relationship between vestibular stimulation and cognitive function,to provide a reference for the future vestibular stimulation training.

Objective To investigate the efficacy of lacosamide combined with ketogenic diet in the treatment of pediatric epilepsy and its impacts on the levels of serum glial fibrillary acidic protein(GFAP)and specific protein of the central nervous system(S-100β).Methods A total of 64 chil-dren with epilepsy from July 2022 to April 2024 were selected and randomly divided into conventional group(n=32)receiving oral lacosamide tablets and combined group(n=32)receiving ketogenic di-et therapy based on the conventional group.The efficacy,cognitive function,and intelligence of chil-dren in both groups after treatment,as well as the levels of serum GFAP and S-100β,the frequency of seizures,and electroencephalogram(EEG)findings before and after treatment were evaluated.Results After treatment,the number of alpha waves,the Full-scale Intelligence Quotient(FIQ)of the Wechsler Intelligence Scale for Children,and the Montreal Cognitive Assessment(MoCA)scores increased in both groups,with a greater increase in the combined group compared to the conventional group,and the differences were statistically significant(P＜0.05).The levels of serum S-100β and GFAP,the frequency of seizures,and the number of cases with slow waves and epileptiform waves decreased after treatmen,and these indicators were lower in the combined group than in the conventional group,with sta-tistically significant differences(P＜0.05).The total effective rate was 90.63％in the combined group and 68.75％in the conventional group,with a statistically significant difference(P＜0.05).The incidence of adverse reactions was 12.50％in the combined group and 9.38％in the conventional group,with no statistically significant difference(P＞0.05).Conclusion Lacosamide combined with ketogenic diet shows good efficacy in the treatment of pediatric epilepsy,and the combined therapy improves neurological function by synergistically reducing the levels of GFAP/S-100β.