OBJECTIVE To investigate the effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparoscopic cholecystectomy. METHODS A total of 200 patients scheduled for laparoscopic cholecystectomy at Suzhou Ninth Hospital Affiliated to Soochow University from January 2023 to December 2024 were randomly assigned to control group （n＝100） and observation group （n＝100）. One minute before the initiation of anesthesia， patients in the control group received intravenous injections of Propofol emulsion injection， Sufentanil citrate injection， and Succinylcholine chloride injection. On this basis， patients in the observation group received an intravenous injection of Esketamine hydrochloride injection. The anxiety status of patients in both groups was compared， along with their general intraoperative conditions （including sufentanil dosage， duration of pneumoperitoneum， operative time， anesthesia time， and extubation time）， postoperative recovery， incidence of adverse reactions， and the need for dezocine rescue analgesia. Heart rate and mean arterial pressure， entropy index （state entropy and response entropy）， inflammatory marker levels [interleukin-6 （IL-6） and C-reactive protein （CRP）]， numerical rating scale （NRS） for pain intensity were compared between the two groups at different time points. RESULTS No significant differences were found between the two groups in pneumoperitoneum duration， operative time， anesthesia time，extubation time， incidence of postoperative dry mouth， entropy index or length of stay in the post-anesthesia care unit （P＞0.05）. Compared with the control group， the observation group showed significantly lower postoperative STAI-S scores， reduced intraoperative sufentanil consumption， decreased incidence of postoperative nausea， vomiting， and shivering， the need for dezocine rescue analgesia， as well as lower plasma IL-6 and CRP levels at 24 h after surgery， and NRS （P＜0.05）. The heart rate and mean arterial pressure of patients in the observation group at the start of surgery， end of surgery， and during extubation were all significantly higher than those in the control group （P＜0.05）. CONCLUSIONS Subanesthetic dose of esketamine can effectively alleviate postoperative anxiety， reduce intraoperative opioid consumption， suppress postoperative inflammatory response， relieve postoperative pain， and promote recovery in patients undergoing laparoscopic cholecystectomy.

OBJECTIVE To investigate the therapeutic effect and mechanism of Qiwei dongqingye powder （QDP） on bronchial asthma in mice. METHODS The mice were divided into blank group （normal saline）， model group （normal saline）， dexamethasone group （2 mg/kg）， and QDP low-， medium-， and high-dose groups （200， 400， 800 mg/kg）， with 14 mice in each group. Except for the blank group， mice in all other groups were given ovalbumin via intraperitoneal injection followed by aerosol inhalation to induce a bronchial asthma model. During the modeling process， mice in each group were administered corresponding drug solutions or normal saline intragastrically/intraperitoneally. After the last medication， the number of cells in the bronchoalveolar lavage fluid （BALF） of the mice was observed and counted； the pathological changes of the bronchus and lung tissue were observed； the levels of malondialdehyde （MDA）， nitric oxide （NO）， total superoxide dismutase （T-SOD）， and glutathione peroxidase （GSH-Px） in the lung tissue of the mice were determined， and the level of interleukin-17 （IL-17） in the BALF and serum was determined. Transcriptomics was employed to predict and validate the mechanism of action of QDP against bronchial asthma. RESULTS Compared with the model group， the total cell count， neutrophil count， lymphocyte count， and macrophage counts in the BALF of the QDP high-dose group were all significantly reduced （ P ＜0.05）； the levels of MDA and NO in the lung tissue， and the levels of IL-17 in the BALF and serum were all decreased significantly （ P ＜0.05）； the levels of T-SOD and GSH-Px were significantly increased （ P ＜0.05）； the arrangement of lung tissue cells tended to normalize， with reduced infiltration of inflammatory cells and decreased exfoliation of bronchial simple columnar epithelial cells. The transcriptomic results revealed that the differentially expressed genes were B-cell receptor signaling pathway， nuclear factor κB （NF-κB） signaling pathway， ferroptosis signaling pathway， and others. Further validation revealed that， compared with the model group， the expression levels of NF-κB p65 and chemokine ligand 20， as well as the phosphorylation level of NF-κB inhibitor protein α， were significantly decreased in the lung tissues of the mice in all QDP groups （ P ＜0.05）. Conversely， the protein expression of nuclear factor erythroid 2-related factor 2 （Nrf2） and heme oxygenase 1 （HO-1） were significantly increased （ P ＜0.05）. CONCLUSIONS QDP can effectively alleviate bronchial asthma by inhibiting the NF-κB signaling pathway， activating the Nrf2/HO-1 signaling pathway， regulating oxidative stress， and reducing inflammatory responses.

ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

Objective:To study the characteristics of thyroid-associated ophthalmopathy (TAO) clinical trials based on WHO International Clinical Trials Registry Platform (ICTRP).Methods:The WHO ICTRP database was searched from their inception to October 25, 2024.Data including the basic registration information, study type, study design, study stage, intervention measures and outcomes were extracted, and a descriptive analysis of the included trials was performed using bibliometric method.Results:A total of 288 trials were identified, the number of registrations for TAO interventional clinical trials was on the rise.Among them, 13 trials without key registration information, 93 without intervention, 2 with non-TAO subjects, 28 without control group, and 4 with duplicate study registration numbers or extension studies were excluded.Finally, 142 intervention trials were included in this study.The top three in registration numbers were China (44 trials), the United States (40 trials), and Europe (31 trials), and most of them were single-center studies (99 trials, accounting for 69.7%). For study design, 131 trials were randomized controlled trials, and 122 trials reported its masking method.Main stage of the trials was phase Ⅲ (31 trials, accounting for 21.8%). Drug treatments (121 trials, accounting for 85.2%) were the main intervention measures, and most of them were monoclonal antibody drugs (55 trials). Clinical activity score (81 trials) and exophthalmia (80 trials) were the commonly used outcome measures.Conclusions:The number of registrations for TAO interventional clinical trials is on the rise, with monoclonal antibody drugs as the main intervention measures.However, issues such as the limited registration number, uneven distribution of countries/regions, incomplete information, and low quality of study design remain to be addressed.Researchers should raise the awareness of registration and design of clinical trials, deepen international and interregional cooperation, improve the review and tracking mechanism of clinical trial registration platforms, and promote the high-quality development of TAO clinical trials.

Objective:To investigate the prognosis of postoperative adjuvant therapy for hepatocellular carcinoma after conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 103 patients with initially unresectable hepatocellular carcinoma (HCC) who were admitted to 11 medical centers in China, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from November 2019 to May 2023 were collected. There were 83 males and 20 females, aged (54±12)years. All 103 patients underwent conversion therapy of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) successfully followed by sequential hepatectomy, of which 72 patients undergoing postoperative adjuvant therapy were divided into the adjuvant therapy group, and 31 patients undergoing postoperative follow-up monitoring were divided into the follow-up monitoring group. Observation indicators: (1) follow-up and postoperative condi-tions; (2) analysis of factors influencing recurrence-free survival time of patients; (3) stratified ana-lysis. Comparison of count data between group was conducted using the chi-square test or Fisher exact probability. The R software was used to draw survival curves, and the Log-rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the Cox proportional hazard model. Results:(1) Follow-up and postoperative conditions. All 103 patients were followed up for 21.0(range, 1.9?47.2)months, with the median recurrence-free survival time of 28.7 months and the 1-, 2-, 3-year recurrence-free survival rates of 68.6%, 55.6%, 41.2%. The median overall survival time of 103 patients was unreached, and the 1-, 2-, 3-year overall survival rates were 90.9%, 82.1%, 69.6%, respectively. The median recurrence-free survival time was 33.1 months in patients of the adjuvant therapy group, with the 1-, 2-year recurrence-free survival rates as 77.2%, 61.5%. The median recurrence-free survival time was 11.1 months in patients of the follow-up monitoring group, with the 1-, 2-year recurrence-free survival rates as 46.6%, 40.8%. There was a significant difference in recurrence-free survival between the two groups of patients ( χ2=5.492, P<0.05). (2) Analysis of factors influencing recurrence-free survival time of patients. Results of multivariate analy-sis showed that pathologic complete response and postoperative adjuvant therapy were independent factors influencing recurrence-free survival time of HCC patients undergoing conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy ( hazard ratio=0.297, 0.492, 95% confidence interval as 0.137?0.647, 0.268?0.903, P<0.05). (3) Stratified analysis. Of the 71 patients with non-pathologic complete response, the median recurrence-free survival time of 48 patients in the adjuvant therapy group was 24.0 months, with the 1-, 2-year recurrence-free survival rates as 67.4%, 48.8%. The median recurrence-free survival time of 23 patients with non-pathological complete response in the follow-up monitoring group was 7.4 months, with the 1-, 2-year recurrence-free survival rates as 35.0%, 26.3%. There was a significant difference in recurrence-free survival between the 48 patients with non-pathologic complete response in the adjuvant therapy group and the 23 patients with non-pathologic complete response in the follow-up monitoring group ( χ2=5.241, P<0.05). Conclusion:For HCC patients with conversion therapy of TKIs and ICIs followed by sequential hepatectomy, postoperative adjuvant therapy, compared to postoperative follow-up monitoring, can prolong the recurrence-free survival time of patients, of whom cases with non-pathologic complete response can benefit from adjuvant therapy.

Purpose To explore the clinical value of real-time three-dimensional automatic left atrial quantification technology in evaluating left atrial volume and function in heart failure with preserved ejection fraction(HFpEF).Materials and Methods A total of 65 patients diagnosed as HFpEF at the Fourth Affiliated Hospital of Harbin Medical University from December 2021 to October 2023 were prospectively enrolled.The control group included 65 healthy subjects who underwent ultrasound examination during the same period and were matched with the HFpEF group in terms of age and gender.According to the New York Heart Association(NYHA)cardiac function classification,patients with NYHA grade Ⅰ+Ⅱ were classified into the HFpEF group A,and those with grade Ⅲ+Ⅳ into the HFpEF group B.Relevant clinical data,conventional ultrasound parameters and three-dimensional ultrasound parameters were recorded in both the HFpEF group and the control group.Left atrial volume parameters,longitudinal strain parameters and circumferential strain parameters were analyzed.The area under the receiver operating characteristic curve was used to compare the diagnostic efficacy of left atrial functional parameters for HFpEF.Results Compared with the control group,the HFpEF group exhibited significant abnormalities in cardiac structure and function.Specifically,left ventricular posterior wall thickness,interventricular septal thickness at end-diastole,and mean E/e′ were significantly increased(t=-5.127,-5.886,-16.670,all P<0.05),while the absolute value of left ventricular global longitudinal strain(LVGLS)and septal and lateral mitral annular e′ were significantly decreased(t=-17.092,40.279,45.412,all P<0.05).All left atrial volume parameters were significantly increased,whereas left atrial functional and strain parameters were significantly decreased(t=-13.632-6.912,all P<0.05).Compared with HFpEF group A,HFpEF group B showed lower left atrial total emptying fraction,left atrial expansion index,left atrial contraction strain and absolute value of LVGLS(t=2.062,3.545,-2.189,-2.586),as well as a higher left atrial minimum volume(t=-2.187),respectively(all P<0.05).Left atrial reservoir strain was negatively correlated with N-terminal pro-B-type natriuretic peptide and mean E/e′(r=-0.395,-0.626,both P<0.05),and positively correlated with the absolute value of LVGLS(r=0.602,P<0.05).The LASr and LAEI had high predictive value for HFpEF,with area under the curve of 0.898 and 0.817,cut-off values of 20.5%and 112%,sensitivities of 96.9%and 83.1%,specificities of 75.4%and 78.5%,and Youden indices of 0.723 and 0.616,respectively.Conclusion Real-time three-dimensional automatic left atrial quantification technology enables early and sensitive detection of left atrial dysfunction in HFpEF.Among the parameters derived,LASr(a strain parameter)and LAEI(a functional parameter)exhibit high diagnostic efficacy for HFpEF.

Hepatocellular carcinoma(HCC)is categorized into two major classes based on the heterogeneity of histological phenotypes:proliferative HCC and non-proliferative HCC.These classes exhibit distinct clinical,molecular and imaging characteristics.Within these two major categories,there exist multiple pathological subtypes,each demonstrating unique molecular and histological features that manifest differently in imaging findings.Additionally,the prognosis of these HCC pathological subtypes diverges from that of not-otherwise-specified HCC,and current clinical guidelines for their treatment remain unclear.This article aims to summarize the imaging manifestations and prognosis of the histopathological subtypes of HCC,so as to enhance identification and judgement of HCC subtypes,and to provide a theoretical basis for selecting appropriate therapeutic strategies.

Objective:To study the characteristics of thyroid-associated ophthalmopathy (TAO) clinical trials based on WHO International Clinical Trials Registry Platform (ICTRP).Methods:The WHO ICTRP database was searched from their inception to October 25, 2024.Data including the basic registration information, study type, study design, study stage, intervention measures and outcomes were extracted, and a descriptive analysis of the included trials was performed using bibliometric method.Results:A total of 288 trials were identified, the number of registrations for TAO interventional clinical trials was on the rise.Among them, 13 trials without key registration information, 93 without intervention, 2 with non-TAO subjects, 28 without control group, and 4 with duplicate study registration numbers or extension studies were excluded.Finally, 142 intervention trials were included in this study.The top three in registration numbers were China (44 trials), the United States (40 trials), and Europe (31 trials), and most of them were single-center studies (99 trials, accounting for 69.7%). For study design, 131 trials were randomized controlled trials, and 122 trials reported its masking method.Main stage of the trials was phase Ⅲ (31 trials, accounting for 21.8%). Drug treatments (121 trials, accounting for 85.2%) were the main intervention measures, and most of them were monoclonal antibody drugs (55 trials). Clinical activity score (81 trials) and exophthalmia (80 trials) were the commonly used outcome measures.Conclusions:The number of registrations for TAO interventional clinical trials is on the rise, with monoclonal antibody drugs as the main intervention measures.However, issues such as the limited registration number, uneven distribution of countries/regions, incomplete information, and low quality of study design remain to be addressed.Researchers should raise the awareness of registration and design of clinical trials, deepen international and interregional cooperation, improve the review and tracking mechanism of clinical trial registration platforms, and promote the high-quality development of TAO clinical trials.

Dose estimation of radiopharmaceutical therapy is essential for the accurate evaluation of its efficacy and safety, as well as for guiding subsequent clinical research. The dosimetry estimation process typically requires understanding of the in vivo spatial distribution and dynamic transportation of radionuclides, followed by calculation of the energy deposition in tumor target volume and organs at risk from ionizing radiation of varying types and energies released by accumulated radionuclides. This review focuses on advancements in the aforementioned research aspects and the relationship between internal radiation dose and biological effects. Furthermore, this review prospectively discusses future research directions, aiming to enhance comprehension of internal radiation dose estimation and provides theoretical frameworks and technical references for improving clinical evaluation accuracy in radiopharmaceutical therapy.