Functional constipation （FC） is a clinically common functional bowel disorder characterized by a protracted course and associations with various chronic disorders and psychological abnormalities. Although not life-threatening， FC significantly impairs patients' quality of life. FC subtypes include slow-transit constipation （STC）， defecatory disorder （DD）， and normal-transit constipation （NTC）. The pathological mechanisms underlying FC have not been fully elucidated， and overall clinical efficacy remains unsatisfactory. Animal models of FC serve as essential tools for the study of disease mechanisms and the development of novel therapeutics. This article systematically reviews the current state of research on the animal models of FC and identifies that rodents， particularly rats and mice， are the most commonly used species. Dogs and pigs are also employed in complex intervention studies due to their physiological similarities to humans， though their use is limited by housing challenges and ethical considerations. Induction methods vary across different FC subtypes. STC models are primarily established with chemical agents such as loperamide or compound diphenoxylate. DD modeling often involves low-fiber diets combined with methylene blue injection or rectal narrowing. NTC modeling mainly relies on low-fiber dietary interventions. In addition， disease-syndrome combination models based on traditional Chinese medicine （TCM） theory have been developed， encompassing excess patterns such as heat accumulation， cold accumulation， and Qi stagnation， as well as deficiency patterns including Qi deficiency， blood deficiency， Yin deficiency， and Yang deficiency. These are achieved through an approach of disease model + syndrome induction， enabling the integration of mechanisms from both Western and TCM perspectives. Models are evaluated from two aspects： disease and syndrome manifestations （e.g.， colonic transit， secretory function， and TCM syndrome indicators such as mental state and body weight） and disease mechanisms （e.g.， enteric nervous system， interstitial cells of Cajal， smooth muscle cells， gut microbiota， and metabolites）. However， current research still faces challenges such as poor consistency in some models， non-specific interference in mechanism interpretation， insufficient studies on NTC， and lack of TCM tongue and pulse diagnosis in evaluation. Future efforts should focus on optimizing model stability and specificity to provide a more reliable experimental basis for investigating the pathological mechanisms of FC and developing therapeutic agents.

Objective:To assess the safety and efficacy of thiotepa, busulfan, and etoposide (TBE) conditioning followed by autologous hematopoietic stem-cell transplantation (TBE auto-HSCT) in primary central nervous system lymphoma (PCNSL) patients.Methods:Clinical data from 27 PCNSL patients who received TBE auto-HSCT at the Fifth Medical Center of PLA General Hospital between November 1, 2021, and April 30, 2024, were retrospectively analyzed.Results:Twenty-seven patients [16 males, 11 females; median age 57 (23–72) years] were included, with 12 (44.4%, 12/27) over 60. Twenty-five had newly diagnosed PCNSL and 2 were relapsed. Median time from diagnosis to transplantation was 6.9 (5.0–10.0) months. TBE auto-HSCT increased complete remission (CR) rate from 63.0 to 96.3% ( P= 0.005), and 9 of 10 patients in partial remission achieving CR post-transplant. Median follow-up was 24.5 months (range 2.0–36.0). Two-year progress-free and OS rates were (87.2±6.9) % and (88.6±6.2) %, respectively. Common grade 3 nonhematologic adverse events were diarrhea (18.5%, 5/27) and bacterial infections (14.8%, 4/27). One patient (64 years old) died from carbapenem-resistant Enterobacteriaceae infection within 2 months post-transplant, yielding a 100-day treatment-related mortality of 3.7% (1/27) . Conclusion:TBE-conditioned high-dose chemotherapy with auto-HSCT is effective, safe, and well-tolerated in PCNSL patients, including the elderly.

Objective To assess the effects of “dual low” scanning technology in conjunction with an individualized injection protocol in enhancing the quality of abdominal contrast-enhanced CT images. Methods A total of 200 patients who underwent abdominal contrast-enhanced CT examinations at the Hainan Western Central Hospital between January 2022 and January 2024 were selected for the study. Using a random number table, participants were randomly assigned to either a control group (n = 100, sub-hypertonic contrast agent + conventional tube voltage + individualized injection protocol) or an observation group (n = 100, isotonic contrast agent + tube voltage of 100 kV + individualized injection protocol). The study compared the impact of these two methodologies on the quality of abdominal contrast-enhanced CT images. Results During the arterial phase, the CT value of the abdominal aorta was significantly higher in the observation group than that in the control group (P < 0.05), suggesting that isotonic contrast agent and low tube voltage more effectively enhanced vascular signal. During the portal vein phase, the CT value was higher and the liver parenchymal noise was lower in the observation group those in the control group (P < 0.05), further validating the advantages of the “dual low” approach during the portal venous phase. The radiation dose was significantly lower in the observation group than that in the control group (P < 0.05), indicating that the “dual low” protocol effectively reduced radiation dose while enhancing patient safety. During the arterial phase, both the abdominal aorta noise and liver parenchymal noise were lower in the observation group than those in the control group (P < 0.05), demonstrating that the “dual low” strategy effectively reduced image noise and enhanced image clarity. The image quality scores were significantly higher in the observation group than in the control group (P < 0.05), indicating that high image quality could be achieved even at reduced radiation doses and contrast agent concentrations. Conclusion The “dual low” scanning technology, combined with an individualized injection protocol, not only effectively enhances the contrast of arteries and veins, reduces image noise, and improves the overall image quality, but also decreases radiation dose and enhances patient safety. Therefore, this technology is worth being widely promoted.

Objective:To investigate the active ingredients and targets of Compound Gastritis Mixture(CGM)in the treatment of chronic atrophic gastritis(CAG)by network pharmacology method,and to validate the potential mechanism combined with molecular docking technology and cellular experiments.Methods:The Traditional Chinese Medicine System Analysis Platform(TCMSP)and Swiss Target Prediction databases were used to select the herbal ingredients of CGM and the corresponding targets;the GeneCards and Online Mendelian Inheritance in Man(OMIM)database were used to screen the targets of CAG;the common targets of CGM and CAG were analyzed from the Venny2.1.0 platform;STRING online platform was used to construct protein-protein interaction(PPI)networks for common drug-disease targets and screen the core targets.Cytoscape 3.9.1 software was used to construct the drug-disease-target network and screen the drug core components;Gene Ontology(GO)fuctional,Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were used to analyze the common targets of CGM and CAG;and AutoDock analysis software was used to perform molecular docking analysis of predicted main components of the drugs and core targets.The gastric mucosal epithelial cells GES-1 were induced by lipopolysaccharide(LPS)to construct CAG cell model.The GES-1 cells were divided into blank group(10%serum complete medium),model group(10 mg·L-1 LPS),and different concentrations of CGM groups(50,100,200,400,800 and 1 600 g·L-1 CGM+10 mg·L-1 LPS),and cells were incubated for 12,24,and 48 h.The cell counting kit-8(CCK-8)assay was used to detect the proliferation activities of GES-1 cells.The GES-1 cells were divided into blank group(10%serum complete medium),model group(10 mg·L-1 LPS)and CGM group(1 600 g·L-1 CGM+10 mg·L-1 LPS).Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of interleukin(IL)-6,tumor necrosis factor(TNF),serine/threonine protein kinase 1(AKT1),IL-1β,and epidermal growth factor receptor(EGFR)mRNA in the cells in various groups.Results:A total of 198 ingredients of CGM were screened,and 128 common targets with CAG were identified.The main herbal ingredients of CGM in treatment of CAG were quercetin,kaempferol,and lluteolin,which mainly acted on the core targets of IL-6,TNF,AKT1,IL-1β,and EGFR.The GO function enrichment analysis results showed that the top 15 targets mainly focused on biological processes(BP)such as apoptosis,inflammatory response and cell proliferation,mainly included cellular components(CC)such as cytoplasm,cell surface and macromolecular complexes,and mainly exerted molecular functions(MF)such as proteins,enzymes and ubiquitin-protein ligases.A total of 158 pathways were obtained from KEGG signaling pathway enrichment analysis,mainly involved cancer-related pathways,TNF signaling pathways,viral infection,programmed cell death-ligand 1(PD-L1)/programmed cell death protein-1(PD-1)pathways,apoptosis,NOD-like receptor signaling pathways,Toll-like receptor signaling pathways,EGFR,and IL-17 signaling pathways.The binding energies of the core targets IL-6,TNF,IL-1β,AKT1,and EGFR with main herbal ingredients quercetin,kaempferol,and luteolin were<-5 kcal·mol-1.The CCK-8 assay results showed that compared with blank group,after 24 and 48 h of cell culture,the proliferation activities of the cells in model group were significantly decreased(P<0.01),and the inhibition of the proliferation activity was more obvious after 48 h;therefore,48 h was selected for the modeling time;compared with model group,the proliferation activities of cells in 800 and 1 600g·L-1 GCM groups were significantly decreased(P<0.01),and the promotion of cell proliferation activity was more obvious in 1 600g·L-1 GCM group,so the intervening concentration of this drug was selected for the subsequent experiments.The RT-qPCR method results showed that compared with blank group,the expression levels of IL-6,TNF,IL-1β,AKT1,and EGFR mRNA in the cells in model group were significantly increased(P<0.01);compared with model group,the expression levels of IL-6,IL-1β,AKT1 and EGFR mRNA in the cells in CGM group were significantly decreased(P<0.01).Conclusion:CGM may play a role in the prevention and treatment of CAG through multiple ingredients such as quercetin,kaempferol and lignocerol,acting on the multiple target proteins such as IL-6,TNF,AKT1,IL-1β,and EGFR,as well as involving a variety of"inflammatory-cancer-related"pathways.

Objective:To investigate the association between social jetlag and depressive symptoms among college students, as well as its potential influencing factors.Methods:A cross-sectional study was conducted through an online questionnaire platform (Wenjuanxing) from March to April 2023, collecting data on social jetlag, depressive symptoms, and other factors from students at Shantou University. Social jetlag time was defined as the absolute difference between the midpoint of sleep time on weekends and weekdays, with a cutoff at the 75th percentile. The presence of social jetlag was defined as social jetlag time≥1 hour. Depressive symptoms were assessed using the Beck Depression Inventory (BDI), with a score of≥10 indicating the presence of depressive symptoms. Participants were divided into depressive symptom group (BDI≥10) and non-depressive symptom group (BDI<10). Linear regression and logistic regression models were used to analyze the relationship between social jetlag and depressive symptoms, with interaction terms and subgroup analyses to explore potential influencing factors.Results:A total of 1 323 college students were included. The social jetlag time (median 0.71 hour vs. 0.50 hour, Z=-3.36, P<0.001) and prevalence of social jetlag (37.64% vs. 30.57%, χ2=7.03, P=0.008) were both higher in the depressive symptom group than in the non-depressive symptom group. The linear regression model showed that each additional hour of social jetlag was associated with an increase of 0.67 points in BDI score (95% CI=0.16-1.18, β=0.06, P=0.010), after adjusting for age, gender, body mass index, being a medical student, smoking, drinking, caffeine intake, physical exercise, anxiety symptoms, insomnia symptoms, and sleep duration. The logistic regression model indicated that social jetlag was a risk factor for depressive symptoms (O R=1.34, 95% CI=1.02-1.76, P=0.036), which was moderated by physical exercise (interaction P=0.033). Among participants without physical exercise, social jetlag was associated with depressive symptoms ( OR=1.71, 95% CI=1.18-2.48, P=0.005), while no such association was found among those with physical exercise ( OR=0.97, 95% CI=0.64-1.47, P=0.892). Conclusion:Social jetlag may be associated with depressive symptoms in college students. This adverse relationship may be improved by enhancing physical exercise.

Objective:To assess the safety and efficacy of thiotepa, busulfan, and etoposide (TBE) conditioning followed by autologous hematopoietic stem-cell transplantation (TBE auto-HSCT) in primary central nervous system lymphoma (PCNSL) patients.Methods:Clinical data from 27 PCNSL patients who received TBE auto-HSCT at the Fifth Medical Center of PLA General Hospital between November 1, 2021, and April 30, 2024, were retrospectively analyzed.Results:Twenty-seven patients [16 males, 11 females; median age 57 (23–72) years] were included, with 12 (44.4%, 12/27) over 60. Twenty-five had newly diagnosed PCNSL and 2 were relapsed. Median time from diagnosis to transplantation was 6.9 (5.0–10.0) months. TBE auto-HSCT increased complete remission (CR) rate from 63.0 to 96.3% ( P= 0.005), and 9 of 10 patients in partial remission achieving CR post-transplant. Median follow-up was 24.5 months (range 2.0–36.0). Two-year progress-free and OS rates were (87.2±6.9) % and (88.6±6.2) %, respectively. Common grade 3 nonhematologic adverse events were diarrhea (18.5%, 5/27) and bacterial infections (14.8%, 4/27). One patient (64 years old) died from carbapenem-resistant Enterobacteriaceae infection within 2 months post-transplant, yielding a 100-day treatment-related mortality of 3.7% (1/27) . Conclusion:TBE-conditioned high-dose chemotherapy with auto-HSCT is effective, safe, and well-tolerated in PCNSL patients, including the elderly.

Objective:To investigate the association between social jetlag and depressive symptoms among college students, as well as its potential influencing factors.Methods:A cross-sectional study was conducted through an online questionnaire platform (Wenjuanxing) from March to April 2023, collecting data on social jetlag, depressive symptoms, and other factors from students at Shantou University. Social jetlag time was defined as the absolute difference between the midpoint of sleep time on weekends and weekdays, with a cutoff at the 75th percentile. The presence of social jetlag was defined as social jetlag time≥1 hour. Depressive symptoms were assessed using the Beck Depression Inventory (BDI), with a score of≥10 indicating the presence of depressive symptoms. Participants were divided into depressive symptom group (BDI≥10) and non-depressive symptom group (BDI<10). Linear regression and logistic regression models were used to analyze the relationship between social jetlag and depressive symptoms, with interaction terms and subgroup analyses to explore potential influencing factors.Results:A total of 1 323 college students were included. The social jetlag time (median 0.71 hour vs. 0.50 hour, Z=-3.36, P<0.001) and prevalence of social jetlag (37.64% vs. 30.57%, χ2=7.03, P=0.008) were both higher in the depressive symptom group than in the non-depressive symptom group. The linear regression model showed that each additional hour of social jetlag was associated with an increase of 0.67 points in BDI score (95% CI=0.16-1.18, β=0.06, P=0.010), after adjusting for age, gender, body mass index, being a medical student, smoking, drinking, caffeine intake, physical exercise, anxiety symptoms, insomnia symptoms, and sleep duration. The logistic regression model indicated that social jetlag was a risk factor for depressive symptoms (O R=1.34, 95% CI=1.02-1.76, P=0.036), which was moderated by physical exercise (interaction P=0.033). Among participants without physical exercise, social jetlag was associated with depressive symptoms ( OR=1.71, 95% CI=1.18-2.48, P=0.005), while no such association was found among those with physical exercise ( OR=0.97, 95% CI=0.64-1.47, P=0.892). Conclusion:Social jetlag may be associated with depressive symptoms in college students. This adverse relationship may be improved by enhancing physical exercise.

Objective:This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma.Methods:The clinical data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) .Results:Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group [20% (6/30) vs 13% (4/32), P=0.028]. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration ( P<0.001). After 1 month of antiresorptive (AR) drug application, the decrease in the serum β-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group (68% vs 59% vs 27%, P<0.001). The increase in serum procollagen type Ⅰ N-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group (34% vs 20% vs 11%, P<0.05). The level of intact parathyroid hormone in each group increased after AR drug treatment. None of the patients developed osteonecrosis of the jaw and renal adverse events, and no statistically significant differences in the overall response rate, complete remission and stringent complete remission rates were found among the groups ( P>0.05), and the median PFS and OS time were not reached ( P>0.05) . Conclusions:In the treatment of MBD, DENOS minimizes nephrotoxicity and has strong AR effect. Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.

Objective:To explore diagnostic value of magnetic resonance apparent diffusion coefficient(ADC)combined with dynamic enhanced magnetic resonance imaging(DCE-MRI)for parotid lymphoma of parotid gland.Methods:Clinical data of 74 patients with tumors of parotid gland who admitted to Hainan Western Central Hospital from September 2021 to September 2023 were selected to carry out retrospective analysis,and they were divided into malignant tumor group(15 cases)and benign tumor group(59 cases)according to the diagnosis of surgical pathology.And then,the benign tumor group was further divided into two subgroups according to the result of surgical pathology,which included pleomorphic adenoma group(35 cases)and"parotid lymphoma of parotid gland"group(24 cases).The differences in ADC values and DCE-MRI parameters(Ve,Kep,Ktrans)were compared between malignant tumors and benign tumors,and between pleomorphic adenoma and parotid lymphoma of parotid gland.The efficacies of ADC values and DCE-MRI parameters in diagnosing malignant tumors were analyzed by means of the receiver operating characteristics(ROC)curve.Results:The ADC value,Ve value and Kep of benign tumor group were respectively(1.17±0.41)×10-3 mm2/s,(0.46±0.15)and(1.56±0.57)min,which were significantly higher than those[0.86±0.19× 103mm2/s,0.35±0.08,and 0.80±0.27 min]of malignant tumor group(t=2.841,2.733,5.004,P＜0.05),respectively.Results of binary logistic regression analysis showed that ADC,Ve and Kep were respectively influence factors on benign and malignant parotid tumors(OR=0.045,0.001,0.004,P＜0.05).ROC curve analysis showed that the AUC values of single ADC,Ve,Kep,and the combination of them were respectively 0.726,0.715,0.903 and 0.915 in diagnosing benign and malignant parotid tumors.There was not significant difference in Ktrans value between pleomorphic adenoma group and"parotid lymphoma of parotid gland"group(P＞0.05).The ADC value and Ve value of"parotid lymphoma of parotid gland"group were lower than those of pleomorphic adenoma group,while Kep value of"parotid lymphoma of parotid gland"group was higher than that of pleomorphic adenoma group,and the differences of them between two groups were significant(t=4.568,4.897,4.805,P＜0.05),respectively.Binary logistic regression analysis showed that ADC,Ve and Kep were influential factors of occurring parotid lymphoma of parotid gland(OR=0.042,0.000,13.452,P＜0.05),respectively.ROC curve analysis showed that the AUC values of single ADC,Ve and Kep,and the combined diagnosis of them were respectively 0.742,0.784,0.763 and 0.959 for parotid lymphoma of parotid gland.Conclusion:Magnetic resonance ADC value and DCE-MRI parameter have favorable value in identifying benign and malignant parotid tumors,and in identifying and diagnosing parotid lymphoma of parotid gland and pleomorphic adenoma,and the combined diagnosis has higher diagnostic value.

Objective:This study aimed to evaluate the efficacy and safety of daratumumab as a maintenance treatment after autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with newly diagnosed multiple myeloma (NDMM) .Methods:The clinical data, hematological and renal response, and safety of 15 post-transplant patients with NDMM who had received daratumumab maintenance between May 1, 2022 and June 30, 2023 were retrospectively analyzed.Results:Fifteen patients (11 males and 4 females) with a median age of 58 (41-72) years were included. Thirteen patients did not receive daratumumab during induction therapy and auto-HSCT, 6 patients had renal impairment, and nine patients had high-risk cytogenetics. The median infusion of daratumumab was 12 (6-17) times, and the median duration of maintenance was 6 (1.5-12) months. The treatment efficacy was evaluated in all 15 patients, and daratumumab maintenance therapy increased the rate of stringent complete response from 40% to 60%. The renal response rate and median estimated glomerular filtration rate of six patients with RI-NDMM were also improved. During daratumumab maintenance therapy, the most common hematological grade 3 adverse event (AE) was lymphopenia [4 of 15 patients (26.67%) ], whereas the most common nonhematologic AEs were infusion-related reactions [7 of 15 patients (46.67%) ] and grade 3 pneumonia [5 of 15 patients (33.33%) ]. The five patients with pneumonia were daratumumab naive [5 of 13 patients (38.46%) ], with a median of 8 (6-10) infusions. Among them, the chest computed tomography of three patients showed interstitial infiltrates, and treatment with methylprednisolone was effective. With a median follow-up of 12 months, the 1-year overall survival rate was 93.33%, and only one patient died (which was not related to daratumumab treatment) .Conclusions:Daratumumab was safe and effective as a maintenance agent for post-auto-HSCT patients with NDMM, and AEs were controllable. The most common nonhematologic AE was grade 3 pneumonia, and a less dose-intense maintenance regimen for the first 8 weeks could reduce the incidence of pneumonia.