Objective To establish a model of radiation-induced myocardial fibrosis in mice, and study the effect of TGF-β/SMAD pathway on radiation-induced myocardial fibrosis in mice and the protective effect of pirfenidone capsules (PFD) on radiation-induced myocardial fibrosis. Methods Male C57BL/6J mice were randomly divided into control group, irradiation group, and drug intervention groups (low-dose PFD + irradiation group and high-dose PFD + irradiation group). After radiation exposure, the control group and the irradiation group were given sodium carboxymethyl cellulose by gavage, while the low-dose PFD + irradiation group and the high-dose PFD + irradiation group were given PFD at 150 and 300 mg/kg daily by gavage for 12 consecutive weeks, respectively. The body weights of mice were measured and recorded weekly. The pathological changes of heart tissues in mice were observed by H&E and Masson’s trichrome staining. The expression levels of TGF-β, SMAD2, and SMAD3 mRNAs in mouse heart tissues were detected by RT-PCR. The expression levels of TGF-β, SMAD2, and SMAD3 proteins in mouse heart tissues were detected by Western blot. The expression levels of CK and CK-MB in mouse heart tissues were detected by blood biochemical tests. Results H&E and Masson’s trichrome staining showed severe myocardial fibrosis in the irradiation group compared with the control group. Compared with the irradiation group, the two groups with drug intervention showed reduced heart disease and myocardial fibrosis. RT-PCR and Western blot showed that the expression levels of TGF-β, SMAD2, and SMAD3 were up-regulated in the irradiation group compared with the other three groups (P < 0.05). The expression levels of TGF-β, SMAD2, and SMAD3 were down-regulated in the two groups treated with PFD compared with the irradiation group (P < 0.05). The expression levels of CK and CK-MB in mouse heart tissues were down-regulated in the two groups treated with PFD compared to irradiation group (P < 0.05). Conclusion Radiation has long-term effects on normal heart tissue, causing myocardial damage and promoting myocardial fibrosis. The up-regulation of TGF-β/SMAD pathway is related to the formation of radiation-induced myocardial fibrosis. PFD can mitigate the progression of myocardial fibrosis and protect heart tissue by down-regulating TGF-β/SMAD pathway.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Objective To evaluate the value of pre-ascent 6-minute walking test performed at a high altitude in predicting the incidence of acute mountain sickness(AMS)induced by rapid ascent to a very high altitude.Methods After baseline information was collected,participants completed the 6-minute walking test at a high altitude of 2 900 m.Then,they rapidly ascended to a very high altitude of 5 000 m.The Lake Louise score was recorded to assess AMS.Results The AMS group showed a shorter pre-ascent 6-minute walking distance(6MWD)at the high altitude than the non-AMS group[480.00(450.00,521.75)m vs.546.00(516.50,568.50)m,P=0.006].No difference was observed regarding the pre-ascent heart rate or peripheral oxygen saturation(both P>0.05).The pre-ascent 6MWD at the high altitude was negatively correlated with the Lake Louise score assessed after rapid ascent to the very high altitude(r=-0.497,P=0.012).Logistic regression analysis confirmed that the pre-ascent 6MWD at the high altitude was associated with the risk of AMS induced by rapid ascent to the very high altitude(OR=0.971,95% CI=0.947-0.996,P=0.022).The results indicated that the pre-ascent 6MWD demonstrated ideal prediction performance(area under receiver operating characteristic curve=0.846,P=0.006).Conclusion The pre-ascent 6MWD recorded at the high altitude is a convenient and reliable predictor of the AMS induced by rapid ascent to the very high altitude.
Humans ; Altitude Sickness/diagnosis* ; Male ; Adult ; Female ; Young Adult ; Middle Aged ; Acute Disease ; Walk Test ; Walking ; Altitude ; Exercise Test

Objective:To compare the chemical composition of decoction and granules of Sangju Decoction; To provide a method for quality evaluation of Sangju Decoction.Methods:HPLC was used to establish fingerprints, and a comprehensive comparative study was conducted on the traditional decoction and formula granules of Sangju Decoction from four aspects: chemical composition type, fingerprint similarity, chemical pattern recognition analysis, and representative index component content.Results:The fingerprint similarity of the 10 batches of traditional decoction was >0.988. 35 peaks were identified and 12 peaks were identified as common peaks (neochlorogenic acid for peak 7, chlorogenic acid for peak 10, cryptochlorogenic acid for peak 11, 1,3-dicaffeoylquinic acid for peak 13, rutin for peak 17, lenoside A for peak 19, lignan for peak 20, isochlorogenic acid B for peak 24, ammonium glycyrrhizate for peak 25). The fingerprint similarity of the formulation pellets was >0.983, and 29 characteristic peaks were identified. Compared with the traditional decoction, some batches of the granules lacked peaks 14, 26, 27, 30, 32 and 34, and clustering analysis (CA), principal component analysis (PCA), and orthogonal partial least squares discriminant analysis (OPLS-DA) could distinguish between the two. The contents of the 10 index components neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, 1,3-dicaffeoylquinic acid, forsythia ester glycoside A, grass glycosides, isochlorogenic acid B, 3,5-O-dicaffeoylquinic acid, forsythia glycosides, monkshood glycosides in the traditional soup were higher than that in the granules, and the contents of rutin and ammonium glycyrrhizate in the granules were higher than that in traditional decoction.Conclusions:The content and composition of traditional decoction and formula granules of Sangju Decoction are significantly different. The combination of fingerprinting and chemical pattern identification effectively can effectively evaluate the difference between traditional decoction and formula granules of Sangju Decoction, which can lay a foundation for the quality control and rational clinical application of formula granules of Sangju Decoction.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective:To investigate the ultrasonographic features of medullary thyroid carcinomas (MTCs) of different sizes and supply valid information for separating MTCs from papillary thyroid carcinomas (PTCs).Methods:There were 87 patients with MTC and 220 patients with PTC detected by ultrasonography and confirmed by pathology at Tianjin Medical University Cancer Institute and Hospital from June 2018 to March 2022. Nodules were divided into the large nodule group (the maximum diameter of the tumor was＞1 cm) and the small nodule group (the maximum diameter of the tumor was ≤1 cm). There were 97 cases in the small nodule group, including 28 cases of MTC and 69 cases of PTC. There were 210 cases in the large nodule group, including 59 cases of MTC and 151 cases of PTC. After stratification by thyroid nodules, ultrasonographic features of thyroid nodules and metastatic lymph nodes, preoperative serum calcitonin (CT) and carcinoembryonic antigen (CEA) levels were compared between MTC and PTC patients.Results:In the small nodule group, the proportion of MTCs exhibiting hypoecho, smooth margins, and having blood flow signals was higher than that of PTCs, with statistically significant differences (all P＜0.05). In the large nodule group, the proportion of MTCs showing cystic solidity, hypoecho, smooth margins, blood flow, and the type Ⅳvascular distribution was higher than PTCs, and the difference of calcification type between them was also statistically significant (all P＜0.05). In contrast, the differences in the number of lesions and aspect ratio between MTCs and PTCs were not statistically significant regardless of nodule size (all P＞0.05). In the small nodule group,6 metastatic lymph nodes of medullary thyroid carcinoma (LNM-MTC) and 11 metastatic lymph nodes of papillary thyroid carcinoma (LNM-PTC) were correctly diagnosed by ultrasound, respectively. The diagnostic compliance rate of ultrasound was 78.6% (22/28) and 78.3% (54/69), respectively, with no statistically significant difference ( P=0.973). In the large nodule group, 28 LNM-MTC and 11 LNM-PTC were correctly diagnosed by ultrasound, respectively. The diagnostic compliance of ultrasound was 88.1% (52/59) and 73.5% (111/151), respectively, which was statistically significant ( P=0.022). Among them, 82.1% of LNM-MTC and 56.6% of LNM-PTC showed abnormal blood flow signals, with a statistically significant difference ( P=0.016). There were significant differences in preoperative serum CT and CEA levels of different sizes of MTCs (all P＜0.05). Conclusions:Different sizes of MTCs require diverse demonstrative criteria. Abnormal blood flow signal is of great significance in the diagnosis of LNM-MTC. Within the absence of ultrasonic characteristics, preoperative serum CT test can provide confidence for the diagnosis of MTC.

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.

Objective:To investigate the ultrasonographic features of medullary thyroid carcinomas (MTCs) of different sizes and supply valid information for separating MTCs from papillary thyroid carcinomas (PTCs).Methods:There were 87 patients with MTC and 220 patients with PTC detected by ultrasonography and confirmed by pathology at Tianjin Medical University Cancer Institute and Hospital from June 2018 to March 2022. Nodules were divided into the large nodule group (the maximum diameter of the tumor was＞1 cm) and the small nodule group (the maximum diameter of the tumor was ≤1 cm). There were 97 cases in the small nodule group, including 28 cases of MTC and 69 cases of PTC. There were 210 cases in the large nodule group, including 59 cases of MTC and 151 cases of PTC. After stratification by thyroid nodules, ultrasonographic features of thyroid nodules and metastatic lymph nodes, preoperative serum calcitonin (CT) and carcinoembryonic antigen (CEA) levels were compared between MTC and PTC patients.Results:In the small nodule group, the proportion of MTCs exhibiting hypoecho, smooth margins, and having blood flow signals was higher than that of PTCs, with statistically significant differences (all P＜0.05). In the large nodule group, the proportion of MTCs showing cystic solidity, hypoecho, smooth margins, blood flow, and the type Ⅳvascular distribution was higher than PTCs, and the difference of calcification type between them was also statistically significant (all P＜0.05). In contrast, the differences in the number of lesions and aspect ratio between MTCs and PTCs were not statistically significant regardless of nodule size (all P＞0.05). In the small nodule group,6 metastatic lymph nodes of medullary thyroid carcinoma (LNM-MTC) and 11 metastatic lymph nodes of papillary thyroid carcinoma (LNM-PTC) were correctly diagnosed by ultrasound, respectively. The diagnostic compliance rate of ultrasound was 78.6% (22/28) and 78.3% (54/69), respectively, with no statistically significant difference ( P=0.973). In the large nodule group, 28 LNM-MTC and 11 LNM-PTC were correctly diagnosed by ultrasound, respectively. The diagnostic compliance of ultrasound was 88.1% (52/59) and 73.5% (111/151), respectively, which was statistically significant ( P=0.022). Among them, 82.1% of LNM-MTC and 56.6% of LNM-PTC showed abnormal blood flow signals, with a statistically significant difference ( P=0.016). There were significant differences in preoperative serum CT and CEA levels of different sizes of MTCs (all P＜0.05). Conclusions:Different sizes of MTCs require diverse demonstrative criteria. Abnormal blood flow signal is of great significance in the diagnosis of LNM-MTC. Within the absence of ultrasonic characteristics, preoperative serum CT test can provide confidence for the diagnosis of MTC.

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.

Objective:To investigate the influence of curative-intent resection with textbook outcomes of liver surgery (TOLS) on long-term prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 824 patients with GBC in the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, who were admitted to 15 medical centers from January 2014 to January 2021, were collected. There were 285 males and 539 females, aged (62±11)years. According to the evalua-tion criteria of TOLS, patients were divided into those who achieved TOLS and those who did not achieve TOLS. Measurement data with normal distribution were represented as Mean± SD, and com-parison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data were conduc-ted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX stepwise regression model with backward Wald method was used for univariate and multivariate analyses. Results:(1) Achievement of TOLS. Of the 824 patients undergoing curative-intent resection for GBC, there were 510 cases achieving TOLS and 314 cases not achieving TOLS. (2) Follow-up. Of the 824 patients undergoing curative-intent resection for GBC, after excluding 112 deaths within 90 days after discharge, 712 cases were included for the survival analysis. The median follow-up time, median overall survival time and 5-year overall survival rate of the 510 patients achieving TOLS were 22.1(11.4,30.1)months, 47.6(30.6,64.6)months and 47.5%. The median follow-up time, median overall survival time and 5-year overall survival rate of the 202 patients not achieving TOLS were 14.0(6.8,25.5)months, 24.3(20.0,28.6)months and 21.0%. There was a significant difference in overall survival between patients achieving TOLS and patients not achieving TOLS ( χ2=58.491, P<0.05). (3) Analysis of factors influencing prognosis of patients. Results of multivariate analysis showed that TOLS, carcinoembryonic antigen (CEA), CA19-9, poorly differentiation of tumor, T2 stage of eighth edition of American Joint Committee on Cancer (AJCC) staging, T3 and T4 stage of eighth edition of AJCC staging, N1 stage of the eighth edition of AJCC staging, N2 stage of the eighth edition of AJCC staging, adjuvant therapy were independent factors influencing overall survival time of patients undergoing curative-intent resection for GBC ( hazard ratio=0.452, 1.479, 1.373, 1.612, 1.455, 1.481, 1.835, 1.978, 0.538, 95% c onfidence interval as 0.352-0.581, 1.141-1.964, 1.052-1.791, 1.259-2.063, 1.102-1.920, 1.022-2.147, 1.380-2.441, 1.342-2.915, 0.382-0.758, P<0.05). Conclusion:Patients under-going curative-intent resection for GBC with TOLS can achieve better long-term prognosis.