ObjectiveTo evaluate the clinical efficacy of Fuzheng Huaji Formula （扶正化积方） for chronic hepatitis B to reduce the incidence of liver cirrhosis and hepatocellular carcinoma. MethodsA retrospective cohort study was conducted， collecting medical records of 118 patients with chronic hepatitis B and 234 patients with hepatitis B-related cirrhosis who visited the hospital between January 1， 2014， and December 31， 2018. The use of Fuzheng Huaji Formula was designated as the exposure factor. Patients receiving antiviral treatment for hepatitis B without concurrent Fuzheng Huaji Formula therapy were included in the western medicine group， while those receiving antiviral treatment combined with Fuzheng Huaji Formula for a cumulative treatment lasting longer than 3 months were included in the combined treatment group. The follow-up observation period was five years. Kaplan-Meier survival analysis was used to assess the cumulative incidence of cirrhosis in patients with chronic hepatitis B and the cumulative incidence of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis. Univariate and multivariate Cox regression analyses were employed to examine the factors influencing the occurrence of cirrhosis and hepatocellular carcinoma. ResultsAmong patients with chronic hepatitis B， there were 55 cases in the combined treatment group and 63 cases in the western medicine group； among patients with hepatitis B-related cirrhosis， there were 110 cases in the combined treatment group and 124 cases in the western medicine group. Five-year follow-up outcomes for chronic hepatitis B patients showed that the cumulative incidence of cirrhosis was 5.45% （3/55） in the combined treatment group and 17.46% （11/63） in the western medicine group， with a statistically significant difference between groups （Z = 2.003， P = 0.045）. Five-year follow-up outcomes for hepatitis B-related cirrhosis patients showed that the cumulative incidence of hepatocellular carcinoma was 8.18% （9/110） in the combined treatment group and 22.58% （28/124） in the western medicine group， also showing a statistically significant difference （Z = 3.007， P = 0.003）. Univariate and multivariate Cox regression analyses indicated that treatment with Fuzheng Huaji Formula is an independent protective factor in preventing the progression of chronic hepatitis B to cirrhosis and the progression of hepatitis B-related cirrhosis to hepatocellular carcinoma （P＜0.05）. ConclusionCombining Fuzheng Huaji Formula with antiviral therapy for hepatitis B can effectively intervene in the disease progression of chronic hepatitis B， reducing the incidence of cirrhosis and hepatocellular carcinoma.

Objective:To investigate the management of granulation tissue during surgery for infected congenital preauricular fistula and to assess the surgical outcomes. Methods:To summarize the surgical methods and the treatment of granulation methods in 140 cases of congenital preauricular fistula during the period of infection treated in our department from January 2018 to September 2022. The study divided patients into an observation group （79 patients） undergoing fistulectomy without granulation treatment, and a control group （61 patients） where fistulectomy and granulation resection were performed concurrently.. After six months of follow-up, the wound healing, recurrence rates, and the aesthetic assessment of granulation healing were evaluated using the Stony Brook Scar Evaluation Scale（SBSES）. Results:The two surgical approaches were applied to a total of 140 patients with infected congenital preauricular fistula. There was no statistical difference in wound healing and recurrence rates between the observation group and the control group. However, the observation group exhibited smaller scars. Conclusion:In cases of infected congenital preauricular fistula, surgical removal without excising granulation tissue is feasible, leading to effective healing and lesser scar formation.
Humans ; Cicatrix ; Wound Healing ; Craniofacial Abnormalities ; Fistula/surgery* ; Treatment Outcome

Objective To analyze the current status and latent profiles on the decision fatigue of nurses. Methods A total of 812 nurses from four public tertiary hospitals in Guangdong Province were selected as the research subjects using the convenience sampling method. The Decisional Fatigue Scale, the Nursing Work Environment Scale, the Nurses Job Stress Scale, and the Chinese version of 10-item Connor-Davidson Resilience Scale were used to assess the level of decision fatigue, work environment, job stress level, and resilience among nurses. The characteristics of latent profiles on the decision fatigue of nurses were analyzed, and multinomial logistic regression was used to analyze the influencing factors of latent profiles on the decision fatigue of nurses. Results The median and 25th and 75th percentiles of the scores of the decision fatigue of nurses were 10.0 (9.0, 15.0). The average scores for work environment, job stress, and resilience were (107.9±24.0), (86.1±23.8), and (23.6 ± 8.3), respectively. The result of latent profile analysis showed that the decision fatigue of nurses could be classified into three types: low fatigue-energetic, medium fatigue-avoidant and high fatigue-burnout, accounting for 15.0%, 59.6%, and 25.4%, respectively. The results of multinomial logistic regression showed that the risk of being classified as medium fatigue-avoidant was higher among practice nurse than nurse (P<0.05). Nurse with a monthly income of 5 000 to 10 000 yuan had higher risk of being classified as medium fatigue-avoidant than those with >10 000 yuan (P<0.05). And nurse with poorer work environment scores had higher risk of being classified as medium fatigue-avoidant than those with higher scores (P<0.01). Nurse with higher score on job stress and lower score on resilience had higher risk of being classified as medium fatigue-avoidant and high fatigue-burnout, than those with lower score of job stress and higher score on resilience (all P<0.01). Conclusion There is a heterogeneity in the decision fatigue of nurses, which can be categorized into three categories: low fatigue-energetic, medium fatigue-avoidant and high fatigue-burnout. The influencing factors of latent profile on the decision fatigue of nurses are job title, individual monthly income, work environment, job stress, and resilience.

OBJECTIVE To investigate the effect and mechanism of action of KRT8 small interfering RNA(si-KRT8)in exosomes derived from patient serum with hypopharyngeal carcinoma on chemosensitivity to 5-fluorouracil(5-FU)in human pharyngeal squamous cell carcinoma FaDu cell line.METHODS The cancerous tissues of hypopharyngeal cancer patients and The serum,cancerous tissues and paracancerous tissues of drug-resistant patients after treatment were collected.A 5-FU-resistant cell line of FaDu(FaDu/R)was constructed for subsequent experiments.Exosomes were isolated from patient serum by ultrafast gradient centrifugation,identified using transmission electron microscopy and Western blot(WB)techniques.si-KRT8 was encapsulated into exosomes(Exosome@si-KRT8)using electroporation technology and subsequently used to treat cells.Real-time fluorescence quantitative PCR(RT-qPCR)and WB were used to detect the expression levels of KRT8 in different tissues,exosomes after electroporation of si-KRT8,and FaDu cells,respectively.Cell counting kit-8(CCK-8),terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay,migration invasion technique and WB were used to detect the effects of Exosome@si-KRT8 on viability,apoptosis,and epithelial-mesenchymal transition of FaDu/R cells.RESULTS The expression level of KRT8 in drug-resistant tissues of hypopharyngeal carcinoma and FaDu/R cells was elevated compared with that in paraneoplastic tissues,cancer tissues and normal FaDu cells(t=15.79,P＜0.01).Isolated patient serum exosomes showed a double membrane structure and expressed both CD63 and TSG101 proteins,and KRT8 expression in exosomes was decreased after electro-transfection with si-KRT8(t=6.70,P＜0.01).Exosome@si-KRT8 inhibited KRT8 protein expression levels in FaDu/R cells(t=123.50,P＜0.01).Compared with the 5-FU group and the 5-FU+Exosome group,Exosome@si-KRT8 was able to inhibit the viability of FaDu/R cells(t=17.07,P＜0.01),promote the level of apoptosis in FaDu/R cells,and inhibit the expression of drug-resistance-associated proteins in FaDu/R cells(P-gp:t=103.20,MDR1:t=238.60,P＜0.01),and Exosome@si-KRT8 was able to suppress the expression of metastasis of FaDu/R cells(t=42.30,t=122.00,P＜0.01)and promoted the expression of E-cadherin while inhibiting the expression level of N-cadherin(t=130.80,t=83.90,P＜0.01).CONCLUSION Serum-derived exosome encapsulation of si-KRT8 enhances chemosensitivity of hypopharyngeal carcinoma cells and its mechanism of action may be related to inhibition of epithelial-mesenchymal transition.

Objective:To evaluate the role of activation of vesicular glutamate transporter 2 (VGLUT2) neurons in vagal nodose ganglion in dexmedetomidine-caused bradycardia in mice.Methods:Ninety-six SPF healthy male VGLUT2-cre mice, aged 10 weeks, weighing 20-25 g, were divided into 6 groups ( n=16 each) by the random number table method: normal saline control group (NS group), dexmedetomidine group (Dex group), viral control + chemogenetic control + dexmedetomidine group (eGFP-NS+ Dex group), viral transfection + chemogenetic control + dexmedetomidine group (hM4Di-NS+ Dex group), viral control + chemogenetic inhibition + dexmedetomidine group (eGFP-CNO+ Dex group) and viral transfection + chemogenetic inhibition + dexmedetomidine group (hM4Di-CNO+ Dex group). Dexmedetomidine 100 μg/kg was intraperitoneally injected in Dex group. The equal volume of normal saline was intraperitoneally injected in NS group. AAV2/9-hSyn-DIO-hM4Di-eGFP was injected in the right nodose ganglion in hM4Di-NS+ Dex group and hM4Di-CNO+ Dex group, and AAV2/9-hSyn-DIO-eGFP was injected in the right nodose ganglion in eGFP-NS+ Dex group and eGFP-CNO+ Dex group, allowing the virus expression for 21 days. On the 22nd day after virus injection, clozapine-n-oxide (CNO) 5 mg/kg was intraperitoneally injected in hM4Di-CNO+ Dex group and eGFP-CNO+ Dex group, the equal volume of normal saline was intraperitoneally injected in hM4Di-NS+ Dex group and eGFP-NS+ Dex group, 1 h later the efficacy of CNO reached the peak, and then dexmedetomidine 100 μg/kg was intraperitoneally injected. The respiratory rate, heart rate, SpO 2 and discharge frequency of the right vagal nodose ganglion were synchronously measured by multi-channel electrophysiology in vivo. The expression of phosphorylated extracellular signal-regulated kinase (pERK) and VGLUT2 and co-expression of pERK and VGLUT2 in the right vagal nodose ganglion were detected by immunofluorescence assay. Results:Compared with NS group, the percentage of heart rate variation and neuron firing frequency after administration were significantly increased, and pERK expression was up-regulated in the other five groups ( P<0.05). Compared with Dex group, the percentage of heart rate variation and neuron firing frequency after administration were significantly decreased, and pERK expression was down-regulated in hM4Di-CNO+ Dex group, and no significant change was found in the parameters mentioned above in hM4Di-NS+ Dex group, eGFP-NS+ Dex group and eGFP-CNO+ Dex group ( P>0.05). Compared with hM4Di-CNO+ Dex group, the percentage of heart rate variation and neuron firing frequency after administration were significantly increased, and pERK expression was up-regulated in eGFP-CNO+ Dex group ( P<0.05). There was no significant difference in the percentage of respiratory variation and SpO 2 among the six groups ( P>0.05). The expression of VGLUT2-positive neurons was abundant in nodose ganglia, and the co-expression rate of pERK and VGLUT2 was nearly 90%. The co-expression rate of pERK and VGLUT2 decreased to about 30% after inhibition of VGLUT2 neurons in ganglion. Conclusions:The mechanism by which dexmedetomidine causes bradycardia is associated with activation of VGLUT2 neurons in vagal nodose ganglia in mice.

ObjectiveIn recent years， with the sharp decline of wild resources in Arisaematis Rhizoma and Pinelliae Rhizoma and the immaturity of medicinal cultivation technology， their adulterants have appeared frequently in the market， and the main identifying characteristics have mostly disappeared in the circulation of medicinal materials. Therefore， there is an urgent need to establish a molecular identification method that can quickly and effectively identify the specificity of Arisaematis Rhizoma and Pinelliae Rhizoma. MethodAfter comparison of the rbcL sequences of Arisaematis Rhizoma，Pinelliae Rhizoma， and their adulterants， the specific enzyme cleavage sites Hae Ⅲ and Dra Ⅰ of Arisaematis Rhizoma and Pinelliae Rhizoma， respectively， were selected and identified by polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP）. The main system conditions of PCR-RFLP reaction were established and optimized， and their durability and the ability to detect genuine， adulterants， and mixed counterfeits were investigated. ResultThe PCR-RFLP identification method of Arisaematis Rhizoma and Pinelliae Rhizoma was established. After specific primer amplification， Arisaematis Rhizoma and Pinelliae Rhizoma could be digested by Hae Ⅲ and Dra Ⅰ-restricted endonucleases respectively， at annealing temperature of 54 ℃， the number of cycles of 35， and the amount of DNA template of 3-30 ng， producing two fragments or small cut fragments with a single band between 100-250 bp， whereas the mixed counterfeits were not cleaved and both showed a band at 250 bp. The method is highly accurate in identifying adulterants and mixed counterfeits of Arisaematis Rhizoma or Pinelliae Rhizoma. ConclusionThe PCR-RFLP method developed in this study allows for the rapid identification of Arisaematis Rhizoma and Pinelliae Rhizoma.

There is an accumulating body of evidence implicating the muscarinic acetylcholine receptor 4 (M₄) in schizophrenia and dementia with Lewy bodies, however, a clinically validated M₄ positron emission tomography (PET) radioligand is currently lacking. As such, the aim of this study was to develop a suitable M₄ PET ligand that allows the non-invasive visualization of M₄ in the brain. Structure-activity relationship studies of pyrazol-4-yl-pyridine derivates led to the discovery of target compound 12 - a subtype-selective positive allosteric modulator (PAM). The radiofluorinated analogue, [¹⁸F] 12, was synthesized in 28 ± 10% radiochemical yield, >37 GBq/μmol and an excellent radiochemical purity >99%. Initial in vitro autoradiograms on rodent brain sections were performed in the absence of carbachol and showed moderate specificity as well as a low selectivity of [¹⁸F] 12 for the M₄-rich striatum. However, in the presence of carbachol, a significant increase in tracer binding was observed in the rat striatum, which was reduced by >60% under blocking conditions, thus indicating that orthosteric ligand interaction is required for efficient binding of [¹⁸F] 12 to the allosteric site. Remarkably, however, the presence of carbachol was not required for high specific binding in the non-human primate (NHP) and human striatum, and did not further improve the specificity and selectivity of [¹⁸F] 12 in higher species. These results pointed towards significant species-differences and paved the way for a preliminary PET study in NHP, where peak brain uptake of [¹⁸F] 12 was found in the putamen and temporal cortex. In conclusion, we report on the identification and preclinical development of the first radiofluorinated M₄ PET radioligand with promising attributes. The availability of a clinically validated M₄ PET radioligand harbors potential to facilitate drug development and provide a useful diagnostic tool for non-invasive imaging.

Abstract: With the development of molecular biology, non-coding sRNA has been found to play an important regulatory role in gene expression and protein activity, affecting various biological pathways including mosquito resistance against insecticides. Understanding the molecular regulatory mechanisms of drug resistance is essential for controlling mosquitoes, , of which metabolic resistance being the most critical mechanism, mainly referring to the high expression of metabolic detoxification enzyme-related genes (especially the cytochrome P450 enzyme system) in mosquitoes. On the basis of verification of insecticide resistance-related genes, further research on the correlation between sRNA and mosquito resistance-related genes provides new ideas and directions for further exploring the mechanism of mosquito resistance. The study of mosquito metabolic resistance mechanism is of great significance for the control of vector mosquitoes, drug resistance monitoring and novel insecticide development. This article reviews the progress of research on the resistance genes, sRNAs biosynthesis, genes involved in regulating mosquito metabolic detoxification enzymes and their applications.

Objective: To investigate the mediating role of psychological resilience in the relationship between family intimacy and adaptability and experiential avoidance among undergraduate nursing students (hereafter referred as nursing undergraduates). Methods: A total of 725 nursing undergraduates from six colleges in Guangdong Province were selected as the research subjects using convenience sampling method. The Acceptance Action Questionnaire-2nd Edition, Conner-Davidson Resilience Scale and Family Intimacy and Adaptability Scale were used to evaluate the experiential avoidance, psychological resilience, and family intimacy and adaptability, respectively. Results: The mean scores of experiential avoidance, psychological resilience and family intimacy and adaptability among nursing undergraduates were (23.4±7.7), (58.8±8.9) and (99.7±20.3), respectively. The results of the mediation analysis indicated that the total effect of family intimacy and adaptability on experiential avoidance was -0.16 (P<0.01), with a direct effect of -0.05 (P>0.05). Psychological resilience played a significant mediating role in the relationship between family intimacy and adaptability and experiential avoidance among nursing undergraduates (P<0.01). The standardized mediation effect was -0.11, accounting for 68.8% of the total effect. Conclusion: Resilience plays a mediating role between family intimacy and adaptability and experiential avoidance among nursing undergraduates.

Objective:To investigate the inhibitory effect and killing mechanism of Bcl-2 BH4 selective inhibitor BDA-366 on NK/T cell lymphoma (NK/TCL) .Methods:Human NK cell leukemia cell line YT and human NK/TCL cell line NK92 cells were treated with 0, 0.05, 0.10, 0.20, 0.30, 0.40, 0.50 μmol/L BDA-366. CCK-8 assay was used to calculate the half inhibitory concentration (IC 50) value of BDA-366 on these cells. The apoptosis levels of cells in control group and IC 50 BDA-366 treated group were detected by flow cytometry. Western blotting was used to detect the expression levels of apoptosis-related proteins in cells of control group and 1/2 IC 50, IC 50, 2× IC 50 BDA-366 treated groups. TMRE and Fluo-3 fluorescent probe were used to detect mitochondrial membrane potential of control group and IC 50 BDA-366 treated group, and the intracellular Ca 2+ concentration of control group, IC 50, 2× IC 50 BDA-366 treated groups. NOD-SCID mice in control group and 10 mg/kg BDA-366 intraperitoneal injection group were weighed and HE staining was performed to evaluate the toxicity of BDA-366 in vivo. Results:The IC 50 of BDA-366 for YT and NK92 cells were 0.065 and 0.086 μmol/L respectively. The apoptosis rates of YT cells in the control group and 0.065 μmol/L BDA-366 group were (6.62±1.59) % and (34.60±3.06) % respectively. The apoptosis rates of NK92 cells in the control group and 0.086 μmol/L BDA-366 group were (5.57±0.88) % and (29.18±0.90) % respectively, both with statistically significant differences ( t=14.05, P<0.001; t=32.58, P<0.001). The relative expression of Bax in NK92 cells of the control group, 0.043, 0.086 and 0.172 μmol/L BDA-366 groups were 0.85±0.00, 1.26±0.04, 1.51±0.18, 1.15±0.10 ( F=20.70, P<0.001), the relative expression of Bax in BDA-366 groups were higher than that in the control group (all P<0.05). The fluorescence intensity of TMRE of YT cells in the control group and 0.065 μmol/L BDA-366 group were 8 372.00±330.47 and 6 419.67±311.34, and that of NK92 cells in the control group and 0.086 μmol/L BDA-366 group were 9 169.00±535.72 and 7 311.67±295.52 respectively, and there were statistically significant differences ( t=7.45, P=0.002; t=5.26, P=0.006). In YT cells, the intracellular Ca 2+ concentrations of 0.065 and 0.130 μmol/L BDA-366 groups were significantly higher than that of the control group (5 791.67±220.45, 6 729.33±585.39, 4 874.67±112.61, F=19.16, P=0.003) ( P=0.039; P=0.002). In NK92 cells, the intracellular Ca 2+ concentrations of 0.086 and 0.172 μmol/L BDA-366 groups were significantly higher than that of the control group (4 553.67±17.62, 4 740.33±254.50, 4 185.67±17.67, F=10.96, P=0.010) ( P=0.039; P=0.007). There was no statistically significant difference in body weight change on day 12 compared with day 0 of NOD-SCID mice between BDA-366 group and control group [ (3.18±0.01) g vs. (2.73±0.58) g, t=0.60, P=0.570], and HE staining showed no abnormal morphology of heart, liver, spleen, lung and kidney in BDA-366 group. Conclusion:BDA-366 promotes NK/TCL cells apoptosis in vitro, but does not cause weight loss and morphological changes of organs by HE staining in vivo. The inhibitory effect of BDA-366 on NK/TCL cells may be achieved by increasing Bax expression, inducing Ca 2+ release and reducing mitochondrial membrane potential.