To improve the targeted therapeutic effect of magnolol (Mag) on neuroblastoma, Mag-loaded mitochondria-targeting immunoliposomes modified by datuximab (aGD2) and triphenylphosphine (TPP) (Mag/aGD2-T-ILN) were prepared, and their physicochemical properties, targeting characteristics and anti-tumor activity were evaluated. Physico-chemical properties showed that the surface of Mag/aGD2-T-ILN was smooth and spherical, with good dispersibility. The particle sizes, PDI and Zeta potentials of Mag/aGD2-T-ILN were measured to be (136.5 ± 5.1) nm, 0.184 ± 0.010 and (27.5 ± 3.6) mV, respectively. Mag/aGD2-T-ILN could release the drug continuously and slowly, and maintain good stability at 4 ℃. Cytotoxicity test exhibited that the IC50 of 2-ME/aGD2-T-ILN was (4.07 ± 0.48) µmol/L, and compared with free Mag, the toxicity of Mag/aGD2-T-ILN to SH-SY5Y cells increased by 6.4 times. Cellular binding and uptake assays suggested that Rho-aGD2-T-ILN could specifically target GD2-positive tumor cells and then further reach their mitochondria. Therapeutic efficacy indicated that Mag/aGD2-T-ILN could better suppress the growth of SH-SY5Y tumor cells in the body with lower toxicity and less side-effects. The results demonstrated that the Mag/aGD2-T-ILN nanoparticles system could achieve intracellular endocytosis through specific binding of antibodies and antigens between the carrier and the surface of tumor cells and electrostatic interaction, then effectively delivered and released the drugs into mitochondria by crossing the mitochondrial phospholipid membrane through TPP, and thus achieving mitochondria-targeting therapy of Mag/aGD2-T-ILN. Through the construction of this active targeting delivery system, the clinical application value of datuximab and Mag is improved, providing a novel approach for the clinical treatment of neuroblastoma.

The nucleus accumbens (NAc) plays an important role in various emotional and motivational behaviors that rely on heightened wakefulness. However, the neural mechanisms underlying the relationship between arousal and emotion regulation in NAc remain unclear. Here, we investigated the roles of a specific subset of inhibitory corticotropin-releasing hormone neurons in the NAc (NAc^CRH) in regulating arousal and emotional behaviors in mice. We found an increased activity of NAc^CRH neurons during wakefulness and rewarding stimulation. Activation of NAc^CRH neurons converts NREM or REM sleep to wakefulness, while inhibition of these neurons attenuates wakefulness. Remarkably, activation of NAc^CRH neurons induces a place preference response (PPR) and decreased basal anxiety level, whereas their inactivation induces a place aversion response and anxious state. NAc^CRH neurons are identified as the major NAc projection neurons to the bed nucleus of the stria terminalis (BNST). Furthermore, activation of the NAc^CRH-BNST pathway similarly induced wakefulness and positive emotional behaviors. Taken together, we identified a basal forebrain CRH pathway that promotes the arousal associated with positive affective states.
Animals ; Septal Nuclei/metabolism* ; Nucleus Accumbens/physiology* ; Corticotropin-Releasing Hormone/metabolism* ; Wakefulness/physiology* ; Neurons/metabolism* ; Male ; Mice ; Mice, Inbred C57BL ; Neural Pathways/physiology* ; Anxiety/physiopathology* ; Reward

Objective To explore the application of sensory integration training and Beckman mouth muscle training in children with language delay.Methods A total of 120 children with language delay who were admitted to Nanjing Tongren Hospital and Southeast University Affiliated Zhongda Hospital from March 2018 to March 2023 were selected as research objects.They were divided into control group and observation group according to a random number table,with 60 cases in each group.The control group received Beckman mouth muscle training,and the observation group received sensory integration training and Beckman mouth muscle training.The Gesell Developmental Schedule(Gesell)scores,sign-significant relation(S-S)scores,and Beckman mouth motor assessment scale scores were compared between the two groups before and after training.Results The scores of major motor activity,individual social behavior,language,adaptive behavior,and gross and fine motor activity were increased after training in both groups,and these scores in the observation group were significantly higher than those in the control group(all P<0.05).The DQ values of language comprehension,language expression,and operational capacity were increased after training in both groups,and these values in the observation group were significantly higher than those in the control group(all P<0.05).The tongue,cheek and lip movement scores were increased after training in both groups,and these scores in the observation group were significantly higher than those in the control group(all P<0.05).Conclusion Sensory integration training and Beckman mouth muscle training can effectively improve language development and mouth motor function,and promote language comprehension,language expression,and operational capacity in children with language delay.

Primary intrahepatic stones (PIS) is a refractory disease with a high incidence rate in southwest China, and some patients still require surgery again or even more times after initial treatment. Many studies in recent years have shown that some specific flora can colonize in the intrahepatic bile duct, leading to chronic infection and inflammation of the biliary system, and these specific types of flora, called "stone-causing flora", can produce metabolites such as β-glucuronidase and play an important role in the formation of pigmented stones. This article analyzes the role of stone-causing flora in the pathogenesis of PIS, so as to provide more treatment options for PIS patients.

OBJECTIVE：To investi gate the potential mechanism of couplet medicine of Cuscutae Semen-Lycii Fructus in the treatment of premature ovarian failure. METHODS ：Main active components and related targets of couplet medicine of Cuscutae Semen-Lycii Fructus in the treatment of premature ovarian failure were obtained from TCMSP ，GeneCards and OMIM database. The intersection genes between them were screened using Venn online tool. Cytoscape 3.7.0 software was adopted to establish the active ingredients-target network and the PPI network. GO and KEGG pathway enrichment analysis on intersection genes were carried out by DAVID database. Finally ，an active component-target-key pathway network was constructed. RESULTS ：Totally 42 active components ，231 and 1 913 targets for active components and disease were obtained from couplet medicine of Cuscutae Semen-Lycii Fructus. The components with high node degree included quercetin ，kaempferol，β-sitosterol，isorhamnetin，glycitein， stigmasterol and sesamin ，etc. There were 149 intersection genes between the active component targets and premature ovarian failure targets. PPI network contained 149 nodes and 2 970 edges，with an average node degree of 39.9 and an average medium of 0.005 4. The results of GO analysis showed that molecule function of the above-mentioned genes mainly involved protein binding ， enzyme binding ，etc. Biological process mainly included that positive regulatio n of transcription from RNA polymerase Ⅱ promoter，positive regulation of transcription DNA-templated ， Cell components mainly included nucleus ，cytoplasm，etc. Signaling pathway mainly involved cancer signaling pathway ， hepatitis B signling pathway ，PI3K/AKT signaling pathway ， MAPK signaling pathway ， etc. The results of active 617693370@qq.com component-target-key pathway network showed that active components of Cuscutae Semen and Lycii Fructus were flavonoids and alcohols ；key target included AKT 1，TP53， VEGFA，IL6，TNF，etc. Signaling pathway mainly involved cancer signaling pathway ，hepatitis B signaling pathway ，PI3K/AKT signaling pathway ，MAPK signaling pathway ，etc. CONCLUSIONS ：Through PI 3K/AKT signaling pathway and MAPK signaling pathway，the active components of couplet medicine of Cuscutae Semen-Lycii Fructus may act on AKT 1，TP53 and other targets ， and then play a therapeutic role on premature ovarian failure. The Potential active components stigmasterol ，sesamin and potential targets IL 6，TNF were found.

Vitamins are classified as either fat-soluble (vitamins A, D, E, K) or water-soluble (vitamins B and vitamin C). Traditional methods of immunoassay have only been developed for vitamins D,B6, B9 and B12. However, they cannot distinguish between vitamin subtypes such as D2, D3 and associated epi isomers (which has higher leveks in infants),giving false positive or negative results. Mass spectrometry has become a gold standard method for small molecule analysis in biological samples with its advantages in speed,resolution,sensitivity and specificity. It is widely used in clinical research and diagnosis and provides an efficient method for simultaneous detection of multivitamins in one injection using one low volume sample collection.

OBJECTIVE:To evaluate the effectiveness and safety of repaglinide combined with metformin versus glimepiride combined with metformin in the treatment of type 2 diabetes mellitus (T2DM),and to provide evidence-based reference for the clinic. METHODS:Retrieved from CJFD, VIP, Wanfang database, PubMed, Embase, Medline and Cochrane Library, randomized controlled trials (RCTs) about therapeutic efficacy (HbA1c, FPG, 2 hPG) and safety (the incidence of ADR,hypoglycemia and gastrointestinal reaction)of repaglinide combined with metformin(trial group)versus glimepiride combined with metformin(control group)in the treatment of T2DM were collected. Meta-analysis was performed by using Rev Man 5.2 statistical software after data extraction and quality evaluation with Cochrane systematic evaluation manual. RESULTS:A total of 12 RCTs were included,involving 957 patients. Results of Meta-analysis showed that the decrease of 2 hPG in trial group was significantly better than control group,with statistical significance [MD=-0.70,95％CI(-1.02,-0.38),P<0.001]. There was no statistical significance in the decrease of HbA1c [MD=0.00,95％CI(-0.24,0.25),P=0.98] or FPG [MD=0.10,95％CI(-0.17,0.36),P=0.47],the incidence of ADR [OR=0.54,95％CI(0.28,1.06),P=0.07],hypoglycemia [OR=0.52,95％CI(0.13,2.06),P=0.35] or gastrointestinal reactions [OR=0.60,95％CI(0.15,2.41),P=0.47] between 2 groups. CONCLUSIONS:Repaglinide combined with metformin is better than glimepiride combined with metformin in reducing 2 hPG,but both of them have similar safety.

OBJECTIVE To analyze disease-related clinical features and therapeutic effects of basal cell adenoma in head and neck. METHODS Clinical data of 9 patients with pathologically diagnosed basal cell adenoma in head and neck between Mar 2007 and Jan 2016 in our department were analyzed retrospectively. The ratio of male 3 to female 6 was 1:2. The median age of the patients was 48.9 years old(22 to 65 years). 5 cases affected parotid gland, 1 occurred in left maxillary sinus and infratemporal fossa, 1 involved nasopharyngeal and pterygopalatine fossa, 1 originated from nasal vestibule and 1 derived from nasal septum. RESULTS 8 of the patients underwent surgical treatment, while one patient with tumor involving the left maxillary sinus and infratemporal fossa was given a transnasal surgery for concurrent rhinosinusitis and subsequently confirmed by pathology. The postoperative follow-up period was between 1 and 10 years. One patient with tumor affecting infratemporal fossa recurred 1.5 years after surgery, while the rest shown no signs of recurrence and complication. CONCLUSION Basal cell adenoma in head and neck is a rare kind of disease. Clinical features and imaging helped to differenced basal cell adenoma in head and neck from other diagnoses, but definite diagnosis relies on the pathological tests.Surgery may provide good effects and prognosis on patients with basal cell adenoma.

Objective To investigate the effects of Dermatophagoides pteronyssinus ( Der p) on the expression of TLR4 and IL-4 in P815 mast cells and to further analyze the immunoregulatory effects of 1,25-(OH)2D3 on Der p treated P815 mast cells.Methods Different concentrations of Der p and 1,25-( OH) 2 D3 were used alone or in combination to stimulate P815 mast cells.The supernatants of the stimulated cell culture were analyzed by enzyme-linked immunosorbent assay ( ELISA) for the detection of IL-4.The stimulated cells were collected and analyzed by real-time PCR and Western blot assays for the detection of TLR4atmRNAandproteinlevels,respectively.Results (1)TLR4expressionwasdetectedinP815 cells.The expression of TLR4 was enhanced in P815 cells treated with various concentrations of Der p.A significant dose-dependent up-regulation of TLR4 was observed in P815 cells after incubation with Der p for 36 h.(2) Der p promoted the release of IL-4 in P815 cells (P<0.05).(3) No significant differences with the expression of TLR4 and IL-4 were observed among 1,25(OH)2D3 treatment groups as compared with the control group (P>0.05).(4) 10-8 mol/L of 1,25(OH)2D3 promoted the Der p-induced expression of TLR4 in P815 cells (P<0.01).However, 1,25(OH)2D3 inhibited the release of IL-4 in a dose-dependent manner(P<0.05orP<0.01).Conclusion (1)Derpcouldpromotetheinflammationandallergicreac-tion through up-regulating TLR4 and IL-4 in mast cells.(2) The possible mechanism for the inhibitory of 1, 25(OH)2D3 on Der p-induced immune responses was due to the suppression of Th2-type immune responses through inhibiting the synthesis and secretion of IL-4 in mast cells.

Objective:To evaluate the efficacy and safety of palonosetron in preventing chemotherapy-induced vomiting. Meth-ods:A multi-center, randomized, double-blind, and self-cross-over positively controlled clinical trial design was used. All patients were randomized into two groups, as follows:Regiment A (61 cases) and Regiment B (64 cases). Regimen A with palonosetron hydrochlo-ride injection (test agent) was used in the treatment cycle A, whereas granisetron hydrochloride injection (control drug) was used in the cycle B. Treatments were randomly administered on the patients of the two groups. Regimen B was on the contrary, the control drug was used in the cycle A, and the test agent was used in the treatment cycle B. All patients treated with the test agent were classified as the test group, whereas those treated with the control drug were classified as the control group. Complete control rate and adverse reac-tion of acute and delayed vomiting in the two groups during the two cycles of chemotherapy regimen were compared. Results: In Group One, the complete control rate of delayed vomiting was significantly higher in the palonosetron administration cycles than in the granisetron cycles (76.92%vs. 55.38%, P=0.0110). In the same group, the frequency of vomiting was significantly less in palonosetron cycles than in the granisetron cycles during day 1 to day 5 (1.32±3.42 vs. 1.94±3.03, P=0.0096). The incidences of adverse effects were low in both groups. No grades 3 and 4 adverse effects were observed. Conclusion: Palonosetron showed efficacy in preventing the acute and delayed chemotherapy-induced vomiting. The drug is superior to granisetron, specifically in delaying vomiting in Group One. Palonosetron hydrochloride showed slight adverse effects. Hence, this drug can be used in clinic.