Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Background and objective Lung adenocarcinoma(LUAD)is a highly morbid and fatal cancer.De-spite advancements in modern medical treatment,the 5-year survival rate of patients remains suboptimal.Our previous study revealed that zinc finger SWIM-type containing 1(ZSWIM1),a novel protein,promotes the proliferation,migration,and inva-sion of LUAD cells.The aim of this study is to investigate the impact ofE3 ubiquitin ligase tripartite motif protein 21(TRIM21)on ZSWIM1-mediated cell proliferation and migration.Methods The interaction and co-localization between TRIM21 and ZSWIM1 were verified using co-immunoprecipitation(Co-IP)and immunofluorescence(IF).The effects of TRIM21 and ZSWIM1 on the proliferation and migration of LUAD cells were assessed through MTT and Transwell assays,respectively.Western blot(WB)analysis was conducted to evaluate the impact of TRIM21 and ZSWIM1 on the expression of epithelial-mesenchymal transition(EMT)markers in LUAD cells.The influence of TRIM21 on the ubiquitination of ZSWIM1 was exam-ined using Co-IP combined with WB.Results TRIM21 was found to interact and co-localize with ZSWIM1.Overexpression of TRIM21 inhibited the proliferation and migration of LUAD cells.Overexpression of TRIM21 reduced the promoting effect of ZSWIM1 on the proliferation,migration,and invasion of lung adenocarcinoma cells,and reversed the impact of ZSWIM1 on the expression of E-cadherin and Vimentin.Conversely,knockdown of TRIM21 further enhanced the promoting effect of ZSWIM1 on the proliferation and migration of LUAD cells.Mechanistically,we observed that overexpression of TRIM21 significantly en-hanced the ubiquitination level of ZSWIM1,leading to a decrease in ZSWIM1 protein expression.Conclusion TRIM21 binds to and promotes the ubiquitination of ZSWIM1,resulting in reduced protein expression of ZSWIM1,which leads to the inhibition of ZSWIM1-mediated promotion of proliferation,migration,and invasion in LUAD cells.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Acute lung injury (ALI), as a common clinical emergency, is pulmonary edema and diffuse lung infiltration caused by inflammation. The lack of non-invasive alert strategy, resulting in failure to carry out preventive treatment, means high mortality and poor prognosis. Stimulator of interferon genes (STING) is a key molecular biomarker of innate immunity in response to inflammation, but there is still a lack of STING-targeted strategy. In this study, a novel STING-targeted PET tracer, [¹⁸F]FBTA, was labeled with high radiochemical yield (79.7 ± 4.3%) and molar activity (32.5 ± 2.9 GBq/μmol). We confirmed that [¹⁸F]FBTA has a strong STING binding affinity (K_d = 26.86 ± 6.79 nmol/L) and can be used for PET imaging in ALI mice to alert early lung inflammation and to assess the efficacy of drug therapy. Our STING-targeted strategy also reveals that [¹⁸F]FBTA can trace ALI before reaching the computed tomography (CT) diagnostic criteria, and demonstrates its better specificity and distribution than [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG).

Fear memories are temporarily suppressed after repeated retrieval, a phenomenon known as memory extinction.How to reduce or even eliminate fear memory is the key to the treatment of fear related diseases such as post-traumatic stress disorder(PTSD). A single extinction training based on Pavlov's fear regulation task could only inhibit the expression of conditioned fear memory traces, but it could not eliminate the acquired conditioned fear memory. However, according to the reconsolidation theory based on memory, the retrieval-extinction paradigm has a more lasting effect on the erasure and rewriting of fear memory, and can effectively prevent the return of fear memory. Studies have shown that extraction-regression is closely related to a variety of neurotransmitter receptors such as glutamate receptor(GluR), dopamine receptor(DAR), L-type voltage-gated calcium channels(LVGCs) and cannabinoid. Moreover, its effect is closely related with factors such as retrieval-extinction memory stage. At present, most of the researches on extracted boundary conditions only stay at the level of behavior, with little understanding and exploration on the level of molecular mechanism. From the perspective of molecular neurobiology, with different stages of memory and different types of receptors and molecular mechanisms, this research reviewed the mechanisms of retrieval-extinction in recent years.It provided valuable signaling pathways, molecular targets and research directions for the treatment of fear-related diseases such as PTSD.

Although mesenchymal stem cell-derived exosomes (MSC-exos) have been shown to have therapeutic effects in experimental periodontitis, their drawbacks, such as low yield and limited efficacy, have hampered their clinical application. These drawbacks can be largely reduced by replacing the traditional 2D culture system with a 3D system. However, the potential function of MSC-exos produced by 3D culture (3D-exos) in periodontitis remains elusive. This study showed that compared with MSC-exos generated via 2D culture (2D-exos), 3D-exos showed enhanced anti-inflammatory effects in a ligature-induced model of periodontitis by restoring the reactive T helper 17 (Th17) cell/Treg balance in inflamed periodontal tissues. Mechanistically, 3D-exos exhibited greater enrichment of miR-1246, which can suppress the expression of Nfat5, a key factor that mediates Th17 cell polarization in a sequence-dependent manner. Furthermore, we found that recovery of the Th17 cell/Treg balance in the inflamed periodontium by the local injection of 3D-exos attenuated experimental colitis. Our study not only showed that by restoring the Th17 cell/Treg balance through the miR-1246/Nfat5 axis, the 3D culture system improved the function of MSC-exos in the treatment of periodontitis, but also it provided a basis for treating inflammatory bowel disease (IBD) by restoring immune responses in the inflamed periodontium.
Colitis ; Exosomes ; Humans ; Periodontitis/therapy* ; Periodontium ; T-Lymphocytes, Regulatory ; Th17 Cells

This study aimed to evaluate the efficacy of Chinese herbal medicine (CHM) in patients with severe/critical coronavirus disease 2019 (COVID-19). In this retrospective study, data were collected from 662 patients with severe/critical COVID-19 who were admitted to a designated hospital to treat patients with severe COVID-19 in Wuhan before March 20, 2020. All patients were divided into an exposed group (CHM users) and a control group (non-users). After propensity score matching in a 1:1 ratio, 156 CHM users were matched by propensity score to 156 non-users. No significant differences in seven baseline clinical variables were found between the two groups of patients. All-cause mortality was reported in 13 CHM users who died and 36 non-users who died. After multivariate adjustment, the mortality risk of CHM users was reduced by 82.2% (odds ratio 0.178, 95% CI 0.076-0.418; P < 0.001) compared with the non-users. Secondly, age (odds ratio 1.053, 95% CI 1.023-1.084; P < 0.001) and the proportion of severe/critical patients (odds ratio 0.063, 95% CI 0.028-0.143; P < 0.001) were the risk factors of mortality. These results show that the use of CHM may reduce the mortality of patients with severe/critical COVID-19.
Age Factors ; Aged ; COVID-19/therapy* ; China ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Odds Ratio ; Propensity Score ; Retrospective Studies ; Survival Rate

Objective:To evaluate the efficacy and safety of budesonide viscous suspension (BVS) in preventing extensive esophageal stenosis after endoscopic submucosal dissection(ESD).Methods:Data of 62 cases of early esophageal neoplasms or precancerous lesions receiving ESD whose postoperative mucosal defects were more than half the circumference of the esophageal lumen at Fujian Provincial Hospital from October 2014 to December 2018 were retrospectively studied. The patients were divided into the BVS group who received BVS therapy (n=24) and the control group who received no intervention (n=38). The incidence of postoperative stenosis, the number of bougie dilation procedures and complications were compared between the two groups. Risk factors for postoperative stricture were analyzed by logistic regression.Results:The incidence of postoperative stenosis [16.7% (4/24) VS 47.3% (18/38), P=0.005], the number of bougie dilation procedures (1.50±0.58 VS 2.70±1.09, P=0.039) in the BVS group were significantly lower than those in the control group. No serious adverse events such as perforation or massive hemorrhage related to BVS were observed in the BVS group. Multivariate logistic regression analysis showed circumferential extension ≥3/4 ( OR=37.970, 95% CI: 6.338-227.482) and non-intervention with BVS( OR=20.962, 95% CI: 3.374-130.243) were the independent risk factors for esophageal stricture after ESD. Conclusion:Administration of BVS is an effective and safe method to reduce the incidence of stenosis and the number of bougie dilation procedures for extensive esophageal stenosis after ESD.

Objective To explore the diagnostic value of pink sign of iodine staining for early esophageal carcinoma. Methods Data of 312 lesions of 306 patients with suspected early esophageal carcinoma who received iodine staining from November 2015 to October 2017 were analyzed retrospectively. Lesions were divided into positive pink sign group and negative pink sign group according to the result of iodine staining. The relationship between pink sign and pathology were analyzed. Lesions recorded onset time of pink sign were divided into 4 groups by the onset time of pink sign, 0-30 s,>30-60 s,>60-90 s and>90-120 s, the diagnostic value of which was assessed with the receiver operating characteristic ( ROC) curve. Results Among the 312 lesions, 208 were identified positive pink sign, including 28 of inflammation or low-grade intraepithelial neoplasia ( LGIN ) , 180 of high-grade intraepithelial neoplasia ( HGIN ) or carcinoma, and 104 lesions were identified negative pink sign, including 69 of inflammation or LGIN, 35 of HGIN or carcinoma. The sensitivity, specificity and accuracy of positive pink sign in the diagnosis of HGIN and early esophageal carcinoma was 83. 7％, 71. 1％ and 79. 8％, respectively. Multivariate analysis showed a significant association between the onset time of pink sign and histopathology ( P=0. 000, OR=0. 016, 95％CI=0. 042-0. 324) . The onset time of pink sign was recorded in 89 lesions in the positive group. The area under ROC curve of the onset time of pink sign was 0. 899, and the optimal cut-off value was 60 s, which indicated the good validity of the test with the sensitivity, specificity and accuracy of 92. 8％, 84. 2％and 91. 0％, respectively. Conclusion The pink sign of iodine staining for diagnosis of early esophageal carcinoma shows a high consistance rate, especially that appears within 60 s.

Objective To investigate whether human RhoA is modified by SUMO. Methods Overlap extension PCR and double digestion technique were used to construct the eukaryotic expression vector pcDNA3-3flag-RhoA, which was identified by sequencing. The plasmid was transfected into HEK293T cells and its expression was detected by Western blotting. Immunofluorescence assay was used to detect whether RhoA is co-localized with SUMO. Co-Immunoprecipitation was used to detect whether RhoA is modified by SUMO. Results The recombinant plasmid pcDNA3-3flag-RhoA was successfully constructed and verified. Western blotting showed that the recombinant plasmid pcDNA3-3flag-RhoA expressed abundant fusion protein in HEK293T cells. Immunofluorescence showed that RhoA was co-localized with SUMO2/3 but not with SUMO1. Co-immunoprecipitation verified that RhoA was modified by SUMO2/3 but not SUMO1. Conclusion Human RhoA is modified by SUMO2/3 and probably participates in the regulation of axon regrowth after nervous system injury.