OBJECTIVE To study the safety of Shuangshu decoction in rats and its efficacy in improving functional dyspepsia （FD） in rats. METHODS In safety test， 40 rats were divided into blank control group， Shuangshu decoction low-dose， medium- dose and high-dose groups [108， 216， 324 g/（kg·d）， calculated by raw medicine， the same applies below]； they were given relevant medicine intragastrically， for continuous 14 days. The mortality and toxic reactions of rats were recorded， and the organ indexes of the liver， kidney， spleen， lung and heart of rats were calculated； the pathological morphological changes in the liver， kidney， spleen， lung， heart， stomach， duodenum， and colon were observed to evaluate the acute toxicity of Shuangshu decoction. Another 40 rats were grouped and administered in the same way for 30 consecutive days. The mortality and toxic reactions of the rats were recorded， and the corresponding organ indexes were calculated. The pathological morphological changes in the corresponding organs were observed， and blood routine and serum biochemical indicators were measured， in order to assess the subacute toxicity of Shuangshu decoction. In pharmacodynamic experiments: 50 rats were divided into blank control group， model group， and Shuangshu decoction low-， medium-， and high-dose groups （9.45， 18.9， 37.8 g/kg）， with 10 rats in each group. Except for blank control group， rats in all other groups were used to establish the FD rat model by subcutaneous injection of loperamide （3.5 mg/kg）. Rats in each group were administered the corresponding drug solution/normal saline intragastrically， once a day， for 14 consecutive days. After the last medication， fecal moisture content， intestinal propulsion rate， gastric emptying rate and serum level of motilin were all detected， and interstitial cell of Cajal （ICC） ultrastructure of rats was observed in colon tissue. RESULTS The safety experiments showed that no death occurred in each dose group， and no significant difference was found in organ coefficient， routine blood and serum biological index， compared to blank control group （P＞0.05）； no abnormality was found in organ appearance and pathological sections. The results of the pharmacodynamic experiments showed that， compared with the blank control group， the fecal moisture content， gastric emptying rate， intestinal propulsion rate， and serum motilin levels in the model group were significantly decreased （P＜0.05）； in the colonic tissue， the mitochondria in the ICC exhibited severe swelling with the disappearance of cristae， and the endoplasmic reticulum was dilated. Compared with model group， the rats in Shuangshu decoction high-dose group showed significant increases in the above quantitative indicators （P＜ 0.05）； additionally， there was a large number of mitochondria in the ICC of the colonic tissue， with clear cristae and regular arrangement. CONCLUSIONS Shuangshu decoction is safe and has a beneficial improving effect on FD rats； its mechanism of action may be related to the regulation of gastrointestinal hormone expression to promote gastric emptying and intestinal propulsion， as well as the repair of mitochondrial structure in ICCs to restore gastrointestinal function.

Objective: To explore the network structure of eating behaviors with anxiety, depression and perceived stress in adolescents, so as to provide a basis for effective prevention and intervention of eating behavior problems and negative emotions in adolescents. Methods: Based on the Psychology and Behavior Investigation of Chinese Residents (2021) database, the study was conducted among 3 087 adolescents. Sakata Eating Behavior Scale Short From(EBS-SF) was used to investigate their eating behaviors. The Patient Health Questionnaire-9(PHQ-9), Generalized Anxiety Disorder Scale-7 Item(GAD-7), and Perceived Stress Questionnaire-3 Item (PSQ-3) were used to evaluate their depression, anxiety and perceived stress. Network analysis method was applied to construct a network of eating behaviors and negative emotional symptoms among adolescents, so as to evaluate the centrality, bridge strength, stability and accuracy of each item. Results: The total scores of eating behaviors, depression,anxiety and stress perception in adolescents were 17.41±4.53,6.95±6.08,4.86±5.03,9.34±3.80,respectively. The symptom with the highest intensity and expected impact was "I am only satisfied when I buy more food than I need", with a node intensity and expected impact value of 4.37. The nodes Depression and Anxiety were the most closely connected(weight=0.87). There were no statistically significant differences in the network structure( M =0.13,0.11) and network connection strength(female and male:4.16,4.06, s =0.10;urban and rural areas:4.08,4.07, s =0.01) between different sexes and residents ( P >0.05). Conclusion The negative impact of comorbidities such as anxiety, depression, perceived stress and eating behaviors among adolescents can be reduced through targeted prevention and intervention of core symptoms and bridging symptoms.

Anxiety disorder is a major symptom of autism spectrum disorder (ASD) with a comorbidity rate of ~40%. However, the neural mechanisms of the emergence of anxiety in ASD remain unclear. In our study, we found that hyperactivity of basolateral amygdala (BLA) pyramidal neurons (PNs) in Shank3 InsG3680 knock-in (InsG3680^+/+) mice is involved in the development of anxiety. Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs. Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680^+/+ mice. Further study found that the diminished control of the BLA by medial prefrontal cortex (mPFC) and optogenetic activation of the mPFC-BLA pathway also had a rescue effect, which increased the feedforward inhibition of the BLA. Taken together, our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680^+/+ mice.
Animals ; Prefrontal Cortex/metabolism* ; Basolateral Nuclear Complex/metabolism* ; Mice ; Anxiety/metabolism* ; Nerve Tissue Proteins/genetics* ; Male ; Gene Knock-In Techniques ; Pyramidal Cells/physiology* ; Mice, Transgenic ; Neural Pathways/physiopathology* ; Mice, Inbred C57BL ; Microfilament Proteins

Objective:To explore the experience and inner feeling of self-nutrition management in patients with nasopharyngeal carcinoma undergoing radiotherapy and chemotherapy based on health action process approach (HAPA) model as the theoretical foundation.Methods:This study was a qualitative sutdy. Using the purposive sampling method, the semi-structured interview was conducted on 15 nasopharyngeal carcinoma patients with radiotherapy and chemotherapy in Department of Tumor Center Area 2 in the Second Affiliated Hospital of University of South China. Colaizzi 7-step analysis method was used to analyze the original data.Results:According to the two stages of HAPA model, three themes were extracted, namely, positive cognition of self-nutrition management, difficulty in self-nutrition management and lack of self-nutrition management ability.Conclusions:Medical staff should analyze individual differences among patients, understand their subjective feelings, confusion and needs for self nutrition management, provide personalized nutrition education and support, improve their self nutrition management experience and enhance their self nutrition management abilities.

ObjectiveTo investigate the effect and possible mechanism of Shenfu Injection （参附注射液） on rat cardiomyocyte injury induced by isoproterenol from the perspective of regulating the high mobility group protein B1 （HMGB1）/ Toll-like receptor 4 （TLR4）/nuclear factor κB （NF-κB） pathway through the deacetylation modification of silent information regulator 1 （SIRT1）. MethodsThe optimal concentration and intervention duration of isoproterenol hydrochloride and the optimal intervention concentration of Shenfu Injection were screened out by CCK-8 method. Logarithmically growing H9c2 rat cardiomyocytes were taken at 5×10⁴ cells/well and divided into normal group， model group， Shenfu Injection group， and SIRT1 inhibitor group， with 3 replicates in each group.Except for the normal group， the cells in the other groups were induced by isoproterenol hydrochloride to establish a chronic heart failure cell model. After modeling， the Shenfu Injection group was given Shenfu Injection at the optimal intervention concentration， and the SIRT1 inhibitor group was given 1 μmol/L of SIRT1 inhibitor EX-527， for optimal intervention duration.CCK-8 assay was used to detect the cell activity and calculate the inhibitory rate. ELISA assay was used to detect the nicotinamide adenine dinucleotide oxidation state/ nicotinamide adenine dinucleotide reduction state （NAD+/NADH） in cardiomyocytes. Immunofluorescence was used to detect the immunofluorescence localization of HMGB1 and SIRT1 in cardiomyocytes. Western blotting was used to detect the protein expression of acetylated HMGB1 in cardiomyocytes， HMGB1 in the nucleus and cytoplasm， and SIRT1， TLR4， myeloid differentiation factor 88 （MYD88） and NF-κB p65 in cardiomyocytes. RT-qPCR was used to detect the mRNA expression of SIRT1， HMGB1， TLR4， MYD88 and NF-κB p65 in cardiomyocytes. ResultsThe optimal intervention concentration of isoproterenol hydrochloride was 300 μmol/L， and the intervention duration was 48 hours； 8% was the optimal intervention concentration of Shenfu Injection. Compared to those in the normal group， the cell activity， NAD+/NADH value， nuclear HMGB1 protein expression， cardiomyocyte SIRT1 protein and mRNA expression in the model group decreased， while the cell inhibition rate， cardiomyocyte acetylated HMGB1 and cytoplasmic HMGB1 protein expression， cardiomyocyte TLR4， MYD88， NF-κB p65 protein and mRNA expression all increased （P＜0.05）； fluorescence localization showed that the content of HMGB1 in cardiomyocytes in the model group increased and was localized in both the nucleus and cytoplasm.Compared to the model group and the SIRT1 inhibitor group， the Shenfu Injection group showed significant improvements in all the above indicators （P＜0.05）； fluorescence localization showed that the SIRT1 content increased in the Shenfu injection group， while the HMGB1 content decreased， and was mainly located in the nucleus. ConclusionShenfu Injection can improve myocardial cell damage by increasing SIRT1 expression to reduce the acetylation level of HMGB1， regulating the HMGB1/TLR4/NF-κB pathway and inhibiting the nuclear translocation of HMGB1.

Objective To establish a method for the simultaneous determination of DOX·HCl and LND. Methods HPLC was performed on Agilent 5 HC-C₁₈（2） （4.6 mm × 250 mm, 5 µm） column. The mobile phase was methanol-0.1% TFA aqueous solution, and the gradient elution procedure were: 0 to 3 min, 65% methanol; 3 to 7 min, 65%→90% methanol; 7 to 13 min, 90% methanol; 13 to 15 min, 90%→65% methanol; 15 to 20 min, 65% methanol. The collection time was 20 min, the balance time was 3 min, the UV detection wavelengths were 205 nm and 253 nm. The flow rate was 1.0 ml/min and the column temperature was 35℃. The amount of inlet was 10 µl. Results The method was highly specific, and both DOX·HCl and LND exhibited good linearity in the concentration range of 1-40 µg/ml and 6-240 µg/ml, respectively. The two compounds’ precision, stability, and recovery satisfied the requirements of the method. Conclusion This study established a HPLC method that was suitable for the simultaneous detection of DOX·HCl and LND. This method’s high level of specificity, accuracy, and reliability .

Background and purpose:Radical surgery after neoadjuvant immunotherapy combined with chemotherapy(nICT)in patients with locally advanced esophageal squamous cell carcinoma(LAESCC)has good efficacy and safety,and it can improve the patients'pathological complete remission(pCR)rate,main pathologic response(MPR)rate and R0 resection rate.The prognosis of patients with pCR/MPR after nICT is significantly better compared with patients without pCR.The prognosis of patients achieving pCR/MPR after neoadjuvant therapy has been demonstrated to be significantly better than that of patients with non-pCR/MPR.Therefore,finding predictive factors of pCR/MPR is beneficial for us to screen out the advantageous populations for combination therapy.The aim of this study was to investigate the value of clinical data of patients with LAESCC before and after nICT in predicting the degree of remission of different pathologies after radical surgery following neoadjuvant treatment and to observe the safety of the treatment.Methods:Data of patients with locally LAESCC who underwent radical surgery after nICT from January 2019 to June 2023 at the Affiliated Hospital of Chuanbei Medical College were collected.The clinical data of all patients as well as some blood,inflammation and nutritional indexes of patients before and after neoadjuvant therapy were collected,and the patients were grouped according to the different degrees of pathological remission after neoadjuvant therapy.Data were analyzed by multi-group comparative analysis of variance(ANOVA)and LSD-t post-hoc test.We explored the factors that had an influence on the different degrees of pathological remission,and collected and recorded the patients'adverse reactions during neoadjuvant therapy as well as their eventual surgeries.Results:Data of 62 patients with LAESCC treated with nICT who underwent radical surgery were collected.Only one patient showed grade 4 myelosuppression during neoadjuvant therapy,and the rest of the patients had adverse reactions≤grade 2.The R0 resection rate of the surgery was 98.39%.The present study was compared with the previous studies of LAESCC treated with neoadjuvant chemotherapy followed by radical surgery performed in Affiliated Hospital of Chuanbei Medical College.Compared with the previous studies conducted in our center,no significant difference was observed in terms of operation time,intraoperative bleeding,postoperative hospitalization time and surgical complications.The postoperative pathologic results showed that the pCR rate was 22.58%(14/62),and the MPR rate was 40.32%(25/62).According to the different tumor regression grade(TRG)after surgery,patients were divided into 3 groups of TRG1,TRG2 and TRG3-4,and differences in the platelet distribution width(PDW)before neoadjuvant therapy and the preoperative neutrophil-to-lymphocyte ratio(NLR)after neoadjuvant therapy were statistically significant among the 3 groups(P＜0.05).Further intra-group two-by-two comparisons of PDW before neoadjuvant therapy and NLR before surgery after neoadjuvant therapy were performed for the three groups of patients,respectively,and it was found that the PDW and NLR in the TRG2 group were lower compared with the TRG3-4 group,and the differences were statistically significant(P＜0.05).Conclusion:Radical surgery after nICT treatment in patients with LAESCC can have high R0 resection rate,pCR rate,MPR rate and reliable safety,and the lower PDW of patients before neoadjuvant therapy and the lower NLR of patients before surgery after neoadjuvant therapy predict better pathological remission efficacy.

Hyperbranched polymers (HBPs) have drawn great interest in the biomedical field on account of their special morphology, low viscosity, self-regulation, and facile preparation methods. Moreover, their large intramolecular cavities, high biocompatibility, biodegradability, and targeting properties render them very suitable for anti-tumor drug delivery. Recently, exploiting the specific characteristics of the tumor microenvironment, a range of multifunctional HBPs responsive to the tumor microenvironment have emerged. By further introducing various types of drugs through physical embedding or chemical coupling, the resulting HBPs based delivery systems have played a crucial part in improving drug stability, increasing effective drug concentration, decreasing drug toxicity and side effects, and enhancing anti-tumor effect. Here, based on different types of tumor microenvironment stimulation signals such as pH, redox, temperature, etc., we systematically review the preparation and response mechanism of HBPs, summarize the latest advances in drug delivery applications, and analyze the challenges and future research directions for such nanomaterials in biomedical clinical applications.

ObjectiveTo study the modeling characteristics of primary dysmenorrhea models in animals and to provide references for the standardization of the primary dysmenorrhea animal models. MethodThe research articles on animal models of primary dysmenorrhea were retrieved to establish a database. The types of experimental animals， modeling methods， modeling cycle， drug dosage， drug injection methods， high-frequency detection indicators， positive drug types， etc.， were summarized and analyzed. ResultA total of 171 research articles that met the criteria were included. The animals for primary dysmenorrhea model induction were mainly SD rats， Wistar rats， and Kunming mice. Most of them were prepared by combining estradiol and oxytocin with the modeling cycle of 9 d≤t≤12 d. In terms of drug dosage for rats， estradiol benzoate was 0.5 mg·d^-1 on the 1st and 10th days and 0.2 mg·d^-1 on the 2^nd to 9^th days， while oxytocin at 2 U·d^-1 was the most common. In terms of drug dosage for mice， diethylstilbestrol at 2 mg·kg^-1·d^-1 and oxytocin at 20 U·kg^-1·d^-1 were the most common. In terms of injection methods， oxytocin was mainly administered by intraperitoneal injection and estradiol （estradiol benzoate and diethylstilbestrol） by subcutaneous injection. The detection indicators were mainly behavioral indicators of the writhing assay or the related biochemical indicators in the uterus or serum by enzyme-linked immunosorbent assay. The positive western medicines were dominated by ibuprofen and Chinese medicines by Tongjingbao. ConclusionAlthough primary dysmenorrhea animal models have become a hot topic， the existing reviews are not comprehensive， and the modeling standards and traditional Chinese medicine （TCM） syndrome evaluation are inadequate. By summarizing and analyzing the big data of the animal models， this study proposed some specific views to provide guidance and references for establishing the standard and ideal animal models of primary dysmenorrhea， so as to carry out research on this disease.