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.

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.

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.

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.

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.

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

ObjectiveTo clarify the differences in the efficacy and mechanism of different processed products of Atractylodes chinensis rhizoma by the pharmacodynamics and metabolomics studies of raw， bran-fried and rice water-processed products on rats with spleen deficiency. MethodSixty male SD rats were randomly divided into blank group， model group， raw product group（3.75 g·kg^-1）， bran-fried product group（3.75 g·kg^-1）， rice water-processed product group（3.75 g·kg^-1） and Shenling Baizhusan group（6.7 g·kg^-1）， with 10 rats in each group. The method of excessive fatigue+improper diet was used to establish a spleen deficiency model in rats. After the end of modeling， except for the blank and model groups， each dosing group was given the corresponding drug suspension， the immune organ coefficients of each group of rats were examined， the levels of interleukin-6（IL-6）， tumor necrosis factor-α（TNF-α）， immunoglobulin G（IgG）， amylase（AMS）， motilin（MTL）， gastrin（GAS）， Na⁺-K⁺-adenosine triphosphatase（ATPase）， aquaporin 2（AQP2）， AQP3 and AQP8 in rats were measured by enzyme-linked immunosorbent assay（ELISA）. Ultra high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS） combined with orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to search for biomarkers in the plasma samples of spleen-deficient rats by using two criteria［P<0.05 and variable importance in the projection（VIP） value>1］， and to compare the different modulatory effects of the three decoction pieces on the splenic-deficient biomarkers， and metabolic pathway analysis was conducted through the Kyoto Encyclopedia of Genes and Genomes（KEGG） database. ResultCompared with the blank group， the thymus index and spleen index of rats in the model group were significantly decreased（P<0.05）， the levels of IL-6， TNF-α， IgG and AQP2 were significantly increased（P<0.05）， the levels of AMS， GAS， MTL， AQP3， AQP8 and Na⁺-K⁺-ATPase were significantly decreased（P<0.05）. Compared with the model group， raw products， bran-fried products and rice water-processed products all increased thymus index and spleen index（P<0.05）， decreased IL-6， TNF-α， IgG and AQP2 levels（P<0.05）， and increased AMS， GAS， MTL， AQP3， AQP8 and Na⁺-K⁺-ATPase levels to different degrees. A total of 176 differential metabolites were screened in the model group compared with the blank group， of which 75， 72 and 84 biomarkers were called back by the raw products， bran-fried products and rice water-processed products， respectively（P<0.05， P<0.01）. Raw products of A. chinensis rhizoma mainly affected glycine， serine and threonine metabolism. Bran-fried products mainly affected alanine， aspartate and glutamate metabolism， D-arginine and D-ornithine metabolism. Rice water-processed products mainly affected glycine， serine and threonine metabolism， alanine， aspartate and glutamate metabolism， citrate cycle， thiamine metabolism， D-arginine and D-ornithine metabolism. ConclusionRaw products， bran-fried products and rice water-processed products of A. chinensis rhizoma all have good spleen strengthening effects， among which the effects of bran-fried products and rice water-processed products were stronger. Meanwhile， raw products has the strongest dryness， followed by bran-fried products， and the weakest dryness of rice water-processed products. The three decoction pieces are able to significantly modulate metabolic abnormalities in spleen-deficient rats， and the mechanism may be related to amino acid metabolism such as glycine， serine and threonine metabolism as well as alanine， aspartate and glutamate metabolism.

Aim To explore the effects of Lycium berry seed oil on Nrf2/ARE pathway and oxidative damage in testis of subacute aging rats. Methods Fifty out of 60 male SD rats, aged 8 weeks, were subcutaneously injected with 125 mg • kg"D-galactosidase in the neck for 8 weeks to establish a subacute senescent rat model. The presence of senescent cells was observed using P-galactosidase ((3-gal), while testicular morphology was examined using HE staining. Serum levels of testosterone (testosterone, T), follicle-stimulating hormone ( follicle stimulating hormone, FSH ) , luteinizing hormone ( luteinizing hormone, LH ) , superoxide dis-mutase ( superoxide dismutase, SOD ) , glutathione ( glutathione, GSH) and malondialdehyde ( malondial-dehyde, MDA) were measured through ELISA, and the expressions of factors related to aging, oxidative damage, and the Nrf2/ARE pathway were assessed via immunohistochemical analysis and Western blotting. Results After successfully identifying the model, the morphology of the testis was improved and the intervention of Lycium seed oil led to a down-regulation in the expression of [3-gal and -yH2AX. The serum levels of SOD, GSH, T, and FSH increased while MDA and LH decreased (P 0. 05) . Additionally, there was an up-regulated expression of Nrf2, GCLC, NQOl, and SOD2 proteins in testicular tissue ( P 0. 05 ) and nuclear expression of Nrf2 in sertoli cells. Conclusion Lycium barbarum seed oil may reduce oxidative damage in testes of subacute senescent rats by activating the Nrf2/ARE signaling pathway.