ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

Objective To compare the long-term survival outcomes of patients with T_1-2N₀M₀ duodenal neuroendocrine tumor (DNET) after endoscopic resection (ER) or surgical resection (SR). Methods Patients diagnosed with T_1-2N₀M₀ DNET between January 1, 2004, and December 31, 2015, were extracted from the SEER database. Kaplan-Meier survival curve and log-rank test were used to compare overall survival (OS) rate and cancer-specific survival (CSS) rate between patients undergoing ER or SR. Propensity score matching (PSM) was used to reduce grouping differences, and multivariate Cox regression was used to analyze factors affecting OS and CSS before and after PSM. Results A total of 656 patients were included, with 457 in ER group and 199 in SR group. Before PSM, there was no significant difference in the 5-year OS rate between the ER and SR groups (88.9% vs 89.6%), but there was a significant difference in the 5-year CSS rate (99.3% vs 96.9%, P＝0.017). Before PSM, multivariate Cox regression analysis showed advanced age was an independent risk factor for decreased OS (P＜0.001). After PSM, there was no significant difference between the ER group (n＝187) and SR group (n＝187) in 5-year OS rate (90.2% vs 88.9%) or CSS rate (98.9% vs 96.7%). After PSM, multivariate Cox regression also showed advanced age was an independent risk factor for decreased OS, while resection method was not an independent factor for OS or CSS. Conclusions There is no significant difference in OS or CSS after endoscopic treatment and surgical treatments for patients with T_1-2N₀M₀ DNET, and advanced age is an independent factor for OS.

Purpose: This study aimed to investigate the molecular characteristics associated with better prognosis in breast cancer. Methods: We performed targeted sequencing of 962 genes in 56 samples, categorizing them into long-term and short-term survival groups as well as chemotherapy-sensitive and chemotherapy-resistant groups for further analyses. Results: The results indicated that the tumor mutational burden values were significantly higher in the short-term survival and chemotherapy-resistant groups (p = 0.008 and p = 0.003, respectively). Somatic mutation analysis revealed that the mutation frequencies of BCL9L and WHSC1 were significantly lower in the long-term survival group than those in the short-term survival group (p = 0.029 and p = 0.024, respectively). CREB-regulated transcription coactivator 1 (CRTC1) mutations occurred significantly more frequently in the chemotherapy-resistant group (p = 0.027) and were associated with shorter progression-free survival (p = 0.036).Signature weighting analysis showed a significant increase in Signature.3, which is associated with homologous recombination repair deficiency in the chemotherapy-sensitive group (p = 0.045). Conversely, signatures related to effective DNA repair mechanisms, Signature.1 and Signature.15, were significantly reduced (p = 0.002 and p < 0.001, respectively). Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that gene mutations were significantly enriched in the JAK-STAT signaling pathway. Conclusion This study, through intergroup comparative analysis, found that immunotherapy (using programmed death 1/programmed death-ligand 1 inhibitors) may improve the prognosis of patients with short survival and chemotherapy resistance. Additionally, the study revealed that mutations in BCL9L and WHSC1 could serve as biomarkers for breast cancer prognosis, while CRTC1 mutations and Signature.3 could predict chemotherapy response. The study also found that the JAK-STAT pathway might be a potential therapeutic target for chemotherapy resistance. Therefore, this study identifies molecular characteristics that influence the prognosis of breast cancer patients, providing important theoretical insights for the development of personalized treatment strategies.

ObjectiveTo investigate the clinical efficacy and safety of state-target formula Angelica and Safflower spot removal essence in the treatment of melasma. MethodsA randomized，double-blind，placebo-controlled parallel-group trial was conducted，selecting patients with Qi stagnation and blood stasis type of melasma who visited the dermatology outpatient department of Beijing Hospital of Integrated Traditional Chinese and Western Medicine from September 2022 to February 2023. In accordance with the double-blind principle，a random number table was generated to randomly divide the patients into an experimental group （50 cases） and a control group （50 cases）. The experimental group applied the Angelica and Safflower spot removal essence topically，while the control group applied a placebo topically，with continuous treatment for 8 weeks and a follow-up of 1 month. Melasma Area and Severity Index （MASI），Physician Global Assessment （PGA），patient self-assessment scoring，VISIA detection and scoring were performed before medication and on the first day after stopping medication，and all adverse events were recorded. ResultsIn a study involving 100 patients，87 cases were included in the analysis. The experimental group consisted of 45 cases，with 5 dropouts，and the control group had 42 cases，with 8 dropouts. The baseline data of the patients in both groups were consistent，with no statistically significant differences. After treatment，the total effective rate of the experimental group was 75.56% （34/45），significantly higher than the control group's 2.38% （1/42），and the difference was statistically significant （χ²=48.38，P<0.01）. Compared with before treatment，after treatment，the MASI score，VISIA image spot，brown spot，and red area score of the experimental group patients were significantly reduced （P<0.05，P<0.01），while there was no statistically significant difference in the control group patients. Compared with the control group after treatment，the experimental group showed more significant improvement （P<0.05，P<0.01）. VISIA image analysis showed that after 8 weeks of treatment，the experimental group showed significant improvement in surface spots，deep spots，and red areas，while the control group remained unchanged or showed an increasing trend. 42.22% （19/45） of the experimental group had a PGA score of 3 or below，while 88.89% （40/45） had a PGA score of 4 or below. 80.95% （34/42） of the control group had a PGA score of 5 or above，and the difference between the two groups was statistically significant （χ²=38.26，P<0.01）. There was no statistically significant difference in the recurrence rate and adverse reaction rate within one month between the experimental group and the control group. ConclusionThe state-target formula Angelica and Safflower spot removal essence is clinically effective and safe in the treatment of melasma.

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

RNA splicing is an essential cellular process in which a series of protein-nucleic acid complexes cut and splice the products of gene transcription to generate mature RNA， and it plays an important role in maintaining the normal life activities of cells. Extensive studies have shown that proteins and nucleic acids associated with RNA splicing undergo the pathological changes such as aggregation in neurodegenerative diseases， and inadequate RNA splicing is observed in lesions. Genetic alterations within RNA splicing-related genes can cause neurodegenerative diseases. All these findings suggest that abnormalities in RNA splicing pathways may play a significant role in the pathogenesis of neurodegenerative diseases. This article reviews the research advances in the alterations of RNA splicing in common neurodegenerative diseases in terms of histopathology， biochemistry， and genetics， as well as related cell biology and animal models， in order to clarify their role in the pathogenesis of neurodegenerative diseases.
Alzheimer Disease ; Parkinson Disease

Objective:To investigate the effect of laparoscopic splenectomy and azygoportal disconnection (LSD) on liver synthesis and development of liver cirrhosis.Methods:This is a prospective case series study.The clinical data of liver cirrhotic patients with portal hypertension who received LSD at the Department of Hepatobiliary Surgery of Northern Jiangsu People′s Hospital Affiliated to Yangzhou University from September 2014 to January 2016 were included. This study analyzed the diameter of the portal vein, the velocity of portal blood flow, the routine blood parameters, the liver function, the synthetic proteins of liver (antithrombin Ⅲ (AT-Ⅲ), protein S, protein C), and the serum content of liver fibrotic markers(collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase). Repeated measures ANOVA was used for comparison between multiple groups, and least significance difference was used for post-hoc multiple comparison.Results:A total of 106 patients were included in the study, including 70 males and 36 females, aged (51.8±9.8) years(range: 28 to 75 years).Compared with the preoperative results, the diameter of portal vein and the velocity of portal vein decreased after surgery ( F=14.03, 12.15, respectively, both P<0.01). Compared with the preoperative results, the total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score and classification were improved ( F=17.96, 56.01, 66.63, 35.83, 33.49, and 27.50, respectively, all P<0.01), and the AT-Ⅲ, protein S, protein C,collagen type Ⅳ, procollagen type Ⅲ, laminin and hyaluronidase levels were also improved ( F=47.87, 36.26, 18.02, 2.79, 14.58, 44.35, and 14.38, respectively, all P<0.01). Compared with the preoperative period, the diameter of portal vein was reduced from the first week to the 24 th month after surgery ( t=5.45 to 9.39, all P<0.01). Compared with the preoperative period, the velocity of portal vein blood from the first week after surgery to the 24 th month after surgery was decreased ( t=4.02 to 8.43, all P<0.01). Compared with the preoperative period, routine blood parameters (white blood count, hemoglobin, platelet count), liver function (total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score), liver synthetic protein (AT-Ⅲ, protein S, protein C) and liver fibrotic markers (collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase) were improved to varying degrees at the 24th month after surgery ( t=-20.46 to 11.93, all P<0.01). Conclusion:Preliminary findings show that LSD can reduce portal vein pressure, restore blood cell number, and improve liver synthesis function and the degree of liver fibrosis in patients with portal hypertension in liver cirrhosis.

Objective:To investigate the effect of laparoscopic splenectomy and azygoportal disconnection (LSD) on liver synthesis and development of liver cirrhosis.Methods:This is a prospective case series study.The clinical data of liver cirrhotic patients with portal hypertension who received LSD at the Department of Hepatobiliary Surgery of Northern Jiangsu People′s Hospital Affiliated to Yangzhou University from September 2014 to January 2016 were included. This study analyzed the diameter of the portal vein, the velocity of portal blood flow, the routine blood parameters, the liver function, the synthetic proteins of liver (antithrombin Ⅲ (AT-Ⅲ), protein S, protein C), and the serum content of liver fibrotic markers(collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase). Repeated measures ANOVA was used for comparison between multiple groups, and least significance difference was used for post-hoc multiple comparison.Results:A total of 106 patients were included in the study, including 70 males and 36 females, aged (51.8±9.8) years(range: 28 to 75 years).Compared with the preoperative results, the diameter of portal vein and the velocity of portal vein decreased after surgery ( F=14.03, 12.15, respectively, both P<0.01). Compared with the preoperative results, the total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score and classification were improved ( F=17.96, 56.01, 66.63, 35.83, 33.49, and 27.50, respectively, all P<0.01), and the AT-Ⅲ, protein S, protein C,collagen type Ⅳ, procollagen type Ⅲ, laminin and hyaluronidase levels were also improved ( F=47.87, 36.26, 18.02, 2.79, 14.58, 44.35, and 14.38, respectively, all P<0.01). Compared with the preoperative period, the diameter of portal vein was reduced from the first week to the 24 th month after surgery ( t=5.45 to 9.39, all P<0.01). Compared with the preoperative period, the velocity of portal vein blood from the first week after surgery to the 24 th month after surgery was decreased ( t=4.02 to 8.43, all P<0.01). Compared with the preoperative period, routine blood parameters (white blood count, hemoglobin, platelet count), liver function (total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score), liver synthetic protein (AT-Ⅲ, protein S, protein C) and liver fibrotic markers (collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase) were improved to varying degrees at the 24th month after surgery ( t=-20.46 to 11.93, all P<0.01). Conclusion:Preliminary findings show that LSD can reduce portal vein pressure, restore blood cell number, and improve liver synthesis function and the degree of liver fibrosis in patients with portal hypertension in liver cirrhosis.

Purpose: This study aimed to investigate the molecular characteristics associated with better prognosis in breast cancer. Methods: We performed targeted sequencing of 962 genes in 56 samples, categorizing them into long-term and short-term survival groups as well as chemotherapy-sensitive and chemotherapy-resistant groups for further analyses. Results: The results indicated that the tumor mutational burden values were significantly higher in the short-term survival and chemotherapy-resistant groups (p = 0.008 and p = 0.003, respectively). Somatic mutation analysis revealed that the mutation frequencies of BCL9L and WHSC1 were significantly lower in the long-term survival group than those in the short-term survival group (p = 0.029 and p = 0.024, respectively). CREB-regulated transcription coactivator 1 (CRTC1) mutations occurred significantly more frequently in the chemotherapy-resistant group (p = 0.027) and were associated with shorter progression-free survival (p = 0.036).Signature weighting analysis showed a significant increase in Signature.3, which is associated with homologous recombination repair deficiency in the chemotherapy-sensitive group (p = 0.045). Conversely, signatures related to effective DNA repair mechanisms, Signature.1 and Signature.15, were significantly reduced (p = 0.002 and p < 0.001, respectively). Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that gene mutations were significantly enriched in the JAK-STAT signaling pathway. Conclusion This study, through intergroup comparative analysis, found that immunotherapy (using programmed death 1/programmed death-ligand 1 inhibitors) may improve the prognosis of patients with short survival and chemotherapy resistance. Additionally, the study revealed that mutations in BCL9L and WHSC1 could serve as biomarkers for breast cancer prognosis, while CRTC1 mutations and Signature.3 could predict chemotherapy response. The study also found that the JAK-STAT pathway might be a potential therapeutic target for chemotherapy resistance. Therefore, this study identifies molecular characteristics that influence the prognosis of breast cancer patients, providing important theoretical insights for the development of personalized treatment strategies.