Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

Objective To analyze the characteristics of real-world adverse drug events(ADEs)of trabectedin based on the FDA Adverse Event Reporting System(FAERS)database in order to provide references for clinical drug safety management.Methods A total of 1 349 trabectedin-related reports were extracted from the FAERS database from Q1 2007 to Q4 2024.Using the MedDRA coding classification system for system organ class(SOC)and preferred term(PT),signal detection was performed through 4 proportional imbalance methods,including reporting odds ratio(ROR)and proportional reporting ratio(PRR).Subgroup analyses by gender,age,and temporal trends were also conducted.Results Hematological and lymphatic system disorders and hepatobiliary system disorders were the primary SOCs involved.High-frequency PTs included neutropenia(123 cases)and anemia(117 cases).Eight potential ADEs that have not been listed in the drug product instruction were identified.The median onset time of ADEs was 21 d,showing an early failure pattern,with differences observed by gender(females more prone to hematological toxicity)and age(elderly more susceptible to febrile neutropenia).Conclusion Trabectedin requires close attention to hematological toxicity,hepatotoxicity,and newly identified multi-system potential risks.Clinically,monitoring should be strengthened based on time windows and population characteristics to optimize drug regimens.Countermeasure It is recommended to strengthen the full cycle monitoring of anti-tumor drugs,standardize the reporting of adverse reactions,and establish a multi-departmental collaborative research platform.

Objective:To construct patient-derived xenograft (PDX) models from head and neck squamous cell carcinoma (HNSCC) patients, to explore the effect of immune reconstitution timing on the PDX modeling and immune microenvironment in humanized immune system mice (huHSC-NCG-hIL15), and to provide a reliable animal model for research on the mechanisms of head and neck squamous carcinoma and for studies on immune therapy drug interventions.Methods:This study enrolled 28 HNSCC patients (25 laryngeal carcinomas, 3 hypopharyngeal carcinomas). PDX models were established in Balb/c nude (nu) mice, NSG mice, and humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Fresh HNSCC samples were transplanted into Balb/c nu and NSG mice to generate PDX models, with subsequent analysis of success-associated factors. One successfully established PDX tumor was subsequently implanted into humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Tumor transplantation was performed at distinct immune reconstruction timepoints (2 vs. 7 weeks post-reconstitution), and tumor growth patterns were monitored. Flow cytometry and multiplex immunohistochemical staining were utilized to characterize immunological profiles in peripheral lymphoid organs and tumor microenvironments. Hematoxylin-eosin (HE) staining was employed to assess histomorphological concordance between primary patient tumors and PDX model tissues. Results:HNSCC PDX models were successfully established. NSG mice exhibited a higher and more stable tumor take rate compared to Balb/c nu mice (pilot study: 4/10 vs. 3/10 cases; mean take rate 60%-80% vs. 20%-60 %). The PDX success rate in NSG mice was 46.4% (13/28). In the huHSC-NCG-hIL15 mice model with immune reconstitution at 7 weeks, tumors grew significantly faster, and the PDX modeling process was shorter (617 mm3 at day 70 in 7-week cohort vs.280 mm3 in 2-week cohort). Flow cytometry analysis of the immune microenvironment showed that at 7 weeks of immune reconstitution, the proportions of B cells in the spleen and tumor tissues(2-week vs. 7-week: spleen 16.2% vs. 61.7%, tumor 26.0% vs. 38.8%) and myeloid cells in the spleen (2-week vs. 7-week: spleen 47.2% vs. 88.1 %) were significantly higher, while mice at 2 weeks post-reconstitution showed a higher proportion of T cells (2-week vs. 7-week: spleen 13.2% vs. 9.3%, tumor 4.8% vs. 2.5%). HE results demonstrated that the tumor tissues in PDX models maintained a high degree of morphological similarity to the primary tumors in both NSG and huHSC-NCG-hIL15 mouse models. Conclusion:The HNSCC PDX modeling protocol demonstrates operational feasibility and high reproducibility, establishing this model as a robust platform for mechanistic and immunotherapeutic studies.

Immunotherapy for cancer,as an emerging treatment modality,has made significant strides in recent years and has become a crucial therapeutic approach following surgery,radiotherapy,chemotherapy,and targeted therapy.In particular,the clinical utilization of immune checkpoint inhibitors(ICIs)has not only enhanced the survival rates of patients with refractory or recurrent tumors but has also significantly optimized the overall strategy for cancer treatment.However,as the population undergoing cancer immunotherapy continues to grow,this expansion not only yields clinical benefits but also precipitates a range of specific adverse reactions known as immune-related adverse events(irAEs).Pleural effusion is a common and severe complication in cancer patients,significantly affecting both their quality of life and treatment outcomes.Typically,tumor-related pleural effusion is often due to pleural metastasis,with malignant pleural effusion(MPE)characterized by rapid growth,being difficult to control,and tendency for recurrence.With the approval of new drugs and the expansion of indications for existing medications,the number of cancer patients receiving ICIs treatment is increasing,bringing ICIs-related pleural effusion into focus.While ICIs treatment-related pleural effusion is relatively rare in clinical practice,it is closely linked to treatment choices of patients and prognosis.Unlike MPE,the pathogenesis of ICIs treatment-related pleural effusion is more complex,not only involving non-specific immune activation leading to autoimmune inflammatory reactions but also potentially related to nodular pleural granulomatous reactions,eosinophilic chronic pleurisy,and tumor-infiltrating lymphocytes.In terms of diagnosis,ICIs treatment-related pleural effusion is typically diagnosed through exclusion,requiring the exclusion of other causes such as tumor progression,radiotherapy,and chemotherapy-induced pleural effusion,adding complexity and difficulty to the diagnostic process.Treatment for ICIs treatment-related pleural effusion often involves glucocorticoids,tocilizumab,or infliximab,aiming to alleviate symptoms and improve prognosis by suppressing excessive immune reactions.Preventing the occurrence of ICIs treatment-related pleural effusion is equally crucial,necessitating comprehensive patient assessment before ICIs administration and continuous monitoring during treatment to promptly detect and manage potential adverse reactions.Through this comprehensive management approach,the impact of ICIs treatment-related pleural effusion on patient quality of life and treatment outcomes can be minimized,optimizing overall treatment results.This review aimed to explore the pathogenesis,histological features,clinical manifestations,diagnostic methods and treatment strategies of ICIs treatment-related pleural effusion,and delve into the characteristics of ICIs treatment-related pleural effusion,in order to enhance understanding of this complication and provide a reference for clinical practice.

Objective:To explore the clinical application value of ultrasound detection of endometrial blood flow perfusion in evaluating the pregnancy outcomes of frozen-thawed embryo transfer (FET) cycles.Methods:A case-control study of 226 patients underwent preimplantation genetic testing (PGT) in the Department of Reproductive Medicine of Chengdu Women's and Children's Central Hospital was conducted. Patients enrolled from December 2021 to August 2024 underwent three-dimensional ultrasound endometrial receptivity testing on the day before FET. According to the pregnancy outcomes, they were divided into clinical pregnancy group ( n=155) and non-pregnancy group ( n=71). The general characteristics and endometrial receptivity parameters were compared between the two groups. Binary logistic regression was used to analyze the factors affecting pregnancy. Results:There was no significant difference in age, proportion of primary infertility, anti-Müllerian hormone, and antral follicle count between the two groups (all P>0.05). The duration of infertility in the clinical pregnancy group [(2.79±2.45) years] was significantly lower than that in the non-pregnancy group [(3.44±1.68) years, P=0.046], the basal luteinizing hormone (LH) level in clinical pregnancy group [(4.37±3.02) U/L] was higher than that in the non-pregnancy group [(3.59±2.02) U/L, P=0.047]. On the day before embryo transfer, the single-plane endometrial blood flow branch in the pregnancy group (4.83±1.57) was more than that in the non-pregnancy group (3.44±1.51), the difference was statistically significant ( P=0.001). The clinical pregnancy group had significantly different endometrial morphology types A [5.2% (8/155)], B [25.8% (40/155)], and C [69.0% (107/155)] compared with the non-pregnancy group [16.9% (12/71), 33.8% (24/71), 49.3% (35/71), P=0.003], respectively, the number of peristalsis waves in the clinical pregnancy group [1(0, 2)] was less than that in the non-pregnancy group [1(0, 4), P=0.046]. There were no significant differences in endometrial thickness, peristaltic wave classification, endometrial volume, endometrial and subendometrial blood flow pulse index/resistance index between the two groups (all P>0.05). Binary logistic regression analysis showed that the endometrial blood flow branch, endometrial peristalsis and basal LH level were independent factors affecting the pregnancy outcome of patients underwent PGT during FET cycle ( OR=1.855, 95% CI: 1.478-2.327, P=0.001; OR=0.813, 95% CI: 0.667-0.990, P=0.040; OR=1.163, 95% CI: 1.000-1.351, P=0.049). Among them, the area under the receiver operating characteristic curve of endometrial blood flow branches for the prediction of PGT-FET pregnancy outcome was 0.725, P=0.001. Conclusion:Endometrial blood flow branch, which represents the intensity of blood perfusion, has a good clinical value in evaluating the pregnancy outcome during FET cycle.

Objective:To explore the clinical application value of ultrasound detection of endometrial blood flow perfusion in evaluating the pregnancy outcomes of frozen-thawed embryo transfer (FET) cycles.Methods:A case-control study of 226 patients underwent preimplantation genetic testing (PGT) in the Department of Reproductive Medicine of Chengdu Women's and Children's Central Hospital was conducted. Patients enrolled from December 2021 to August 2024 underwent three-dimensional ultrasound endometrial receptivity testing on the day before FET. According to the pregnancy outcomes, they were divided into clinical pregnancy group ( n=155) and non-pregnancy group ( n=71). The general characteristics and endometrial receptivity parameters were compared between the two groups. Binary logistic regression was used to analyze the factors affecting pregnancy. Results:There was no significant difference in age, proportion of primary infertility, anti-Müllerian hormone, and antral follicle count between the two groups (all P>0.05). The duration of infertility in the clinical pregnancy group [(2.79±2.45) years] was significantly lower than that in the non-pregnancy group [(3.44±1.68) years, P=0.046], the basal luteinizing hormone (LH) level in clinical pregnancy group [(4.37±3.02) U/L] was higher than that in the non-pregnancy group [(3.59±2.02) U/L, P=0.047]. On the day before embryo transfer, the single-plane endometrial blood flow branch in the pregnancy group (4.83±1.57) was more than that in the non-pregnancy group (3.44±1.51), the difference was statistically significant ( P=0.001). The clinical pregnancy group had significantly different endometrial morphology types A [5.2% (8/155)], B [25.8% (40/155)], and C [69.0% (107/155)] compared with the non-pregnancy group [16.9% (12/71), 33.8% (24/71), 49.3% (35/71), P=0.003], respectively, the number of peristalsis waves in the clinical pregnancy group [1(0, 2)] was less than that in the non-pregnancy group [1(0, 4), P=0.046]. There were no significant differences in endometrial thickness, peristaltic wave classification, endometrial volume, endometrial and subendometrial blood flow pulse index/resistance index between the two groups (all P>0.05). Binary logistic regression analysis showed that the endometrial blood flow branch, endometrial peristalsis and basal LH level were independent factors affecting the pregnancy outcome of patients underwent PGT during FET cycle ( OR=1.855, 95% CI: 1.478-2.327, P=0.001; OR=0.813, 95% CI: 0.667-0.990, P=0.040; OR=1.163, 95% CI: 1.000-1.351, P=0.049). Among them, the area under the receiver operating characteristic curve of endometrial blood flow branches for the prediction of PGT-FET pregnancy outcome was 0.725, P=0.001. Conclusion:Endometrial blood flow branch, which represents the intensity of blood perfusion, has a good clinical value in evaluating the pregnancy outcome during FET cycle.

Immunotherapy for cancer,as an emerging treatment modality,has made significant strides in recent years and has become a crucial therapeutic approach following surgery,radiotherapy,chemotherapy,and targeted therapy.In particular,the clinical utilization of immune checkpoint inhibitors(ICIs)has not only enhanced the survival rates of patients with refractory or recurrent tumors but has also significantly optimized the overall strategy for cancer treatment.However,as the population undergoing cancer immunotherapy continues to grow,this expansion not only yields clinical benefits but also precipitates a range of specific adverse reactions known as immune-related adverse events(irAEs).Pleural effusion is a common and severe complication in cancer patients,significantly affecting both their quality of life and treatment outcomes.Typically,tumor-related pleural effusion is often due to pleural metastasis,with malignant pleural effusion(MPE)characterized by rapid growth,being difficult to control,and tendency for recurrence.With the approval of new drugs and the expansion of indications for existing medications,the number of cancer patients receiving ICIs treatment is increasing,bringing ICIs-related pleural effusion into focus.While ICIs treatment-related pleural effusion is relatively rare in clinical practice,it is closely linked to treatment choices of patients and prognosis.Unlike MPE,the pathogenesis of ICIs treatment-related pleural effusion is more complex,not only involving non-specific immune activation leading to autoimmune inflammatory reactions but also potentially related to nodular pleural granulomatous reactions,eosinophilic chronic pleurisy,and tumor-infiltrating lymphocytes.In terms of diagnosis,ICIs treatment-related pleural effusion is typically diagnosed through exclusion,requiring the exclusion of other causes such as tumor progression,radiotherapy,and chemotherapy-induced pleural effusion,adding complexity and difficulty to the diagnostic process.Treatment for ICIs treatment-related pleural effusion often involves glucocorticoids,tocilizumab,or infliximab,aiming to alleviate symptoms and improve prognosis by suppressing excessive immune reactions.Preventing the occurrence of ICIs treatment-related pleural effusion is equally crucial,necessitating comprehensive patient assessment before ICIs administration and continuous monitoring during treatment to promptly detect and manage potential adverse reactions.Through this comprehensive management approach,the impact of ICIs treatment-related pleural effusion on patient quality of life and treatment outcomes can be minimized,optimizing overall treatment results.This review aimed to explore the pathogenesis,histological features,clinical manifestations,diagnostic methods and treatment strategies of ICIs treatment-related pleural effusion,and delve into the characteristics of ICIs treatment-related pleural effusion,in order to enhance understanding of this complication and provide a reference for clinical practice.

Objective:To construct patient-derived xenograft (PDX) models from head and neck squamous cell carcinoma (HNSCC) patients, to explore the effect of immune reconstitution timing on the PDX modeling and immune microenvironment in humanized immune system mice (huHSC-NCG-hIL15), and to provide a reliable animal model for research on the mechanisms of head and neck squamous carcinoma and for studies on immune therapy drug interventions.Methods:This study enrolled 28 HNSCC patients (25 laryngeal carcinomas, 3 hypopharyngeal carcinomas). PDX models were established in Balb/c nude (nu) mice, NSG mice, and humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Fresh HNSCC samples were transplanted into Balb/c nu and NSG mice to generate PDX models, with subsequent analysis of success-associated factors. One successfully established PDX tumor was subsequently implanted into humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Tumor transplantation was performed at distinct immune reconstruction timepoints (2 vs. 7 weeks post-reconstitution), and tumor growth patterns were monitored. Flow cytometry and multiplex immunohistochemical staining were utilized to characterize immunological profiles in peripheral lymphoid organs and tumor microenvironments. Hematoxylin-eosin (HE) staining was employed to assess histomorphological concordance between primary patient tumors and PDX model tissues. Results:HNSCC PDX models were successfully established. NSG mice exhibited a higher and more stable tumor take rate compared to Balb/c nu mice (pilot study: 4/10 vs. 3/10 cases; mean take rate 60%-80% vs. 20%-60 %). The PDX success rate in NSG mice was 46.4% (13/28). In the huHSC-NCG-hIL15 mice model with immune reconstitution at 7 weeks, tumors grew significantly faster, and the PDX modeling process was shorter (617 mm3 at day 70 in 7-week cohort vs.280 mm3 in 2-week cohort). Flow cytometry analysis of the immune microenvironment showed that at 7 weeks of immune reconstitution, the proportions of B cells in the spleen and tumor tissues(2-week vs. 7-week: spleen 16.2% vs. 61.7%, tumor 26.0% vs. 38.8%) and myeloid cells in the spleen (2-week vs. 7-week: spleen 47.2% vs. 88.1 %) were significantly higher, while mice at 2 weeks post-reconstitution showed a higher proportion of T cells (2-week vs. 7-week: spleen 13.2% vs. 9.3%, tumor 4.8% vs. 2.5%). HE results demonstrated that the tumor tissues in PDX models maintained a high degree of morphological similarity to the primary tumors in both NSG and huHSC-NCG-hIL15 mouse models. Conclusion:The HNSCC PDX modeling protocol demonstrates operational feasibility and high reproducibility, establishing this model as a robust platform for mechanistic and immunotherapeutic studies.

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

Objective We tried to investigate the effects of human umbilical cord mesenchymal stem cell exosomes(hUCMSC-Exos)on the proliferation of human dermal papilla cells(HDPCs)and the mechanism of hUCMSC-Exos promoting hair growth.Methods HDPCs were isolated using two-step enzymatic method and cul-tured in vitro.Human umbilical cord mesenchymal stem cells(hUC-MSCs)were cultured.Cell culture supernatant was collected,and exosomes were isolated and extracted using high-speed centrifugation.Electron microscopy,particle size,and surface marker identification were performed on them.Dihydrotestosterone(DHT)induces HDPCs and establishment of an androgenic alopecia cell model.Co-culture hUCMSC-Exos with HDPCs,cell proliferation experiment(EdU)was used to detect the relative activity of induced HDPCs.Real-time qPCR was used to detect the expression level of alkaline phosphatase(ALP),and Western blot was used to detect β-catenin,Wnt10b,GSK-3β expression at the protein level.Results The obtained primary HDPCs,hUC-MSCs,and hUCMSC-Exos were all conformed to the characteristics of dermal papilla cells,mesenchymal stem cells,and exosomes.The num-ber of EdU positive cells significantly increased,and exosomes could effectively promote the proliferation of HDPCs(P<0.05),enhance the vitality of HDPCs and alleviate the damage caused by DHT(P<0.05).Real-time qPCR showed that exosomes could enhance the expression level of ALP gene(P<0.05)and hair follicle induction ability.Western Blot confirmation β-catenin,Wnt10b,GSK-3β were differences in expression at the protein level(P<0.05).Conclusions HUCMSC-Exos could promote DHT induced proliferation of HDPCs,enhance their hair follicle regeneration and repair ability,and its mechanism may be related to the activation of Wnt/β-catenin signaling pathway.