Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Objective A serum proteomic approach was used to explore the targets of action of Peitu Qingxin Granules(composed of Rhizoma Atractylodis Macrocephalae,Forsythiae Fructus,Imperatae Rhizoma,Pseudostellariae Radix,etc.)in the treatment of atopic dermatitis.Methods Five patients with atopic dermatitis were selected and treated with Peitu Qingxin Granules for 12 weeks,and five healthy volunteers were used as controls.The clinical core evaluation indexes of atopic dermatitis patients after treatment,including Eczema Area and Severity Index/Scoring Atopic Dermatitis(EASI/SCORAD),Pruritus Score,Patient-Oriented Eczema Measure(POEM),and quality of life index,were assessed.Serum samples were examined using data-independent acquisition-mass spectrometry(DIA-MS)technology,and serum differential proteins between atopic dermatitis patients and healthy people,as well as serum differential proteins in atopic dermatitis patients before and after treatment with Peitu Qingxin Granules were screened according to P＜0.05 and Fold Change>1.2.GO function enrichment analysis and KEGG pathway enrichment analysis were performed on the differential proteins.Results(1)Compared with the pre-treatment period,the clinical core evaluation indexes of patients with atopic dermatitis,including the EASI/SCORAD,Pruritus Score,POEM,and quality-of-life index,were significantly improved after treatment,and the differences were all statistically significant(P＜0.05,P＜0.01).(2)A total of 28 differential proteins were analyzed in the healthy control group and atopic dermatitis group,of which 12 proteins expressions were increased and 16 proteins were decreased,including ALAD(δ-aminolevulinic acid dehydrogenase),LTA4H(leukotriene A-4 hydrolase),CA1(carbonic anhydrase 1),F11(coagulation factor XI),and LCP1(lymphocyte cytoplasmic protein 1),etc..The main signaling pathways involved are PI3K-AKT signaling pathway,lipids and atherosclerosis,ECM-receptor interaction,platelet activation,NF-κB signaling pathway,and neutrophil extracellular trap formation.(3)A total of 12 different proteins were analyzed in atopic dermatitis patients before and after treatment with Peitu Qingxin Granules,of which 8 proteins were increased and 4 proteins were decreased,including ALAD,FGA(fibrinogen α-chain),IGHV3-64D,and IGHV3-38.They were mainly involved in signaling pathways such as lipids and atherosclerosis,complement pathway,Staphylococcus aureus infection,NF-κB signaling pathway,fluid shear stress and atherosclerosis.(4)The expressions of three protein targets including ALAD,FGA and IGHV3-64D,were significantly down-regulated in patients with atopic dermatitis and significantly up-regulated after treatment with Peitu Qingxin Granules.Conclusion The differentially expressed proteins ALAD,FGA and IGHV3-64D may be the action targets of Peitu Qingxin Granules in the treatment of atopic dermatitis,which lays the foundation for further experimental validation.

Objective To explore the related factors for the unilateral flap and bilateral flap by changing the origi-nal operation plan in the extraction of maxillary impacted mesiodens.Methods 81 patients with impacted mesio-dens in the middle of the maxillary were retrospectively analyzed.The primary outcome variables were planned sur-gery (unilateral flap) and unplanned surgery (bilateral flap) .The secondary outcome variables consisted of opera-tion time and postoperative swelling.The predictive variables were as follows:the differential value of the shortest distance from the supernumerary tooth to the labial and palatal bone plates, which was divided into≥1.5 mm group and<1.5 mm group; the ratio of the distance from the adjacent tooth apex to the nasal floor, compared to the length of the supernumerary teeth, was recorded as≥1 and< 1.A statistical software SPSS 20 was used to com-plete the statistical analysis.Results When the differential value was less than 1.5 mm, the possibility of un-planned surgery increased, and the probability of planned surgery was 0.085 times than that of unplanned surgery.With age growing each 1-year, the probability of planned surgery gradually decreased, HR=0.745.The postopera-tive swelling of the palatal approach was only 0.374 times than that of the labial approach.With age increasing, the operation time increased gradually, B=1.213.The ratio of the distance from the adjacent tooth apex to the na-sal floor to the length of the supernumerary teeth did not affect the change of the surgical plan during the operation.Conclusion The shortest distance difference between the supernumerary teeth and the labial and palatal bone plates can be used as a reference for the selection of surgical approach for the extraction of maxillary impacted me-siodens.

Objective:To investigate the risk factors of pleural effusion after spinal separation surgery for patients with spinal metastatic tumors.Methods:A total of 427 patients with spinal metastatic tumors from January 2014 to January 2022 in the Second Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed. There were 252 males and 175 females, with an average age of 59±12 years (range, 15-87 years). All patients underwent separation surgery. Based on the chest CT within 1 month after surgery, the volume of pleural effusion was measured individually by reconstruction software. Pleural effusion was defined as small volume (0-500 ml), moderate volume (500-1 000 ml), and large volume (above 1 000 ml). Baseline data and perioperative clinical outcomes were compared between the groups, and indicators with statistically significant differences were included in a binary logistic regression analysis to determine the independent risk factors for the development of pleural effusion after isolation of spinal metastatic cancer. Receiver operating characteristic (ROC) curves were conducted to calculate the area under the curve (AUC) for each independent risk factor.Results:All patients successfully completed the operation. Among the 427 patients, there were 35 cases of large pleural effusion, 42 cases of moderate pleural effusion, and 350 cases of small pleural effusion. There were significant differences in tumor size (χ 2=9.485, P=0.013), intraoperative blood loss ( Z=-2.503, P=0.011), blood transfusion ( Z=-2.983, P=0.003), preoperative total protein ( Z=2.681, P=0.007), preoperative albumin ( Z=1.720, P= 0.085), postoperative hemoglobin ( t=2.950, P=0.008), postoperative total protein ( Z=4.192, P<0.001), and postoperative albumin ( t=2.268, P=0.032) in the large pleural effusion group versus the small and moderate pleural effusion group. Logistic regression analysis showed that decreased preoperative albumin ( OR=0.89, P=0.045) and metastases located in the thoracic spine ( OR=4.01, P=0.039) were independent risk factors for the occurrence of large pleural effusion after separation surgery. The ROC curve showed that the AUC and 95% CI for preoperative albumin, lesion location, and the combined model were 0.637 (0.54, 0.74), 0.421 (0.36, 0.48), and 0.883 (0.81, 0.92). The combined predictive model showed good predictive value. Conclusion:The volume of pleural effusion can be measured individually and quantitatively based on chest CT. Decreased preoperative albumin and metastases located in the thoracic spine are independent risk factors for the occurrence of large pleural effusion after separation surgery. The combined prediction of the two factors has better predictive efficacy.

Objective    To explore the safety and feasibility of uni-portal video-assisted thoracic surgery (VATS) for the treatment of bronchopulmonary sequestration (BPS). Methods    The clinical data of BPS patients with surgical resection in Shanghai Pulmonary Hospital from February 2010 to June 2021 were reviewed. The patients were divided into a VATS group and a thoracotomy group according to the operation method. The operation time, intraoperative blood loss, hospital stay and postoperative complication rate were compared between the two groups. The VATS group was subdivided into a uni-portal VATS group and a multi-portal VATS group for subgroup analysis. Results    Finally 131 patients were enrolled, including 62 males and 69 females with an average age of 39.3±13.2 years. There were 103 patients in the VATS group and 28 patients in the thoracotomy group. A total of 104 patients were diagnosed with left lower BPS, 26 with right lower BPS and 1 with bilateral lower BPS. The main symptom was cough (88 patients, 67.2%). There were 119 patients diagnosed by thoracic enhanced CT before operation. Compared with the thoracotomy group, the operation time was not statistically different (P=0.717), but the blood loss was less, the rate of postoperative complication was lower and hospital stay was shorter in the VATS group (P<0.05). The rate of conversion to open surgery in the uni-portal VATS group and multi-portal VATS group was 11.8% and 13.5%, respectively. Meanwhile, patients in the uni-portal VATS group had shorter operation time and postoperative hospital stay, less blood loss and lower postoperative complication rate than those in the multi-portal VATS group (P<0.05). Conclusion     In order to improve the rate of diagnosis, the lung enhanced CT scan should be selected as an optimal noninvasive method in adult suspected patients (especially those with solid cystic and solid lesions in the lower lobe). Uni-portal VATS is a safe and feasible method for BPS which can be widely promoted.

Objective To explore the impact of Suzi Jiangqi decoction(SJD)on the inflammatory state of patients with chronic obstructive pulmonary disease(COPD)through the regulation of the mitogen-activated protein kinase(MAPK)signaling pathway.Methods A total of 70 patients with stable COPD,treated from April 2023 to April 2024 at the Department of Traditional Chinese Medicine and Department of Respiratory outpatient clinic of Affiliated Jinhua Hospital,School of Medicine Zhejiang University were selected and randomly divided into observation group and control group,with 35 cases in each group.The control group received tiotropium bromide powder inhalation combined with budesonide/formoterol powder inhalation treatment,while the observation group was given SJD in addition to treatment of control group.After 12 weeks of treatment,the therapeutic effects were evaluated by assessing lung function,airway mucus hypersecretion,levels of interleukin(IL)-17,IL-6,and tumor necrosis factor(TNF)-α,CT quantitative parameters of the lung,as well as the expression levels of IL-17,p38MAPK,nuclear factor kappa-B(NF-κB)and C-X-C motif chemokine ligand 8(CXCL8)mRNA in sputum.Results Following treatment,there was a significant improvement in lung function indicators such as first second expiratory volume/forced vital capacity％,cough score,sputum difficulty score,sputum quality score,and sputum volume score for patients in both groups,with more pronounced improvements observed in observation group(P＜0.05).The levels of serum cytokines IL-17,IL-6 and TNF-αdecreased in both groups after treatment,with observation group showing a more significant reduction(P＜0.05).Additionally,the percentage ratio of low attenuation area to lung area(LAA％),emphysema index of lung CT in observation group significantly decreased after treatment(P＜0.05).Similarly,the expression levels of IL-17,p38MAPK,NF-κB and CXCL8 mRNA in sputum were also significantly reduced after treatment in observation group(P＜0.05).Conclusion SJD may improve lung function and inflammatory status in COPD patients by regulating the MAPK signaling pathway mediated by IL-17,demonstrating a positive therapeutic effect on the treatment of COPD.

BACKGROUND: Lung cancer is a disease with a high incidence rate in Yunnan province, yet there is a paucity of large-scale studies on its clinical epidemiology. This research aims to investigate the epidemiological characteristics of patients who underwent lung cancer surgery at Yunnan Cancer Hospital over the past decade, thereby providing a theoretical basis for the prevention and treatment of lung cancer. METHODS: Clinical data were collected from 15,967 patients who underwent lung cancer surgery at Yunnan Cancer Hospital between 2013 and 2022. A statistical analysis was conducted on the patients' general data, surgical information, pathological types of lung cancer, and other clinical epidemiological characteristics. RESULTS: Among the 15,967 cases of lung cancer, 46.3% were male and 53.7% were female, with the male-to-female ratio ranging from 0.68 to 1.61:1. The median age was 56 years (interquartile range: 49-63), and 37.0% of the patients were in the age group of 50-59 years. Since 2017, there has been an annual increase in the proportion of patients under the age of 60 years. The smoking status of the patients showed that 28.1% were smokers and 71.9% were non-smokers. Qujing city accounted for 41.4% and Kunming city for 23.2% of the cases in Yunnan province, with 29.6% of patients originating from Xuanwei and Fuyuan areas of Qujing city. The distribution of affected lung lobes was as follows: right upper lobe 28.2%, right middle lobe 6.3%, right lower lobe 20.1%, left upper lobe 22.7%, and left lower lobe 16.4%. The use of thoracoscopic surgery increased from 30.8% to 96.3%, with single-port thoracoscopic surgery comprising 61.3%. Lobectomy was performed in 64.2% of cases, wedge resection in 17.2%, and segmentectomy in 12.2%. The proportion of lobectomy decreased from 83.1% to 46.1%. The proportion of patients in stages 0-I increased from 43.5% to 82.8%, while stages II-IV decreased from 56.5% to 17.2%. Adenocarcinoma increased from 75.6% to 88.3%, and squamous cell carcinoma decreased from 21.5% to 8.6%. Among adenocarcinoma patients, 60.9% were female. Among sguamous cell carcinoma patients, 90.6% were male. The peak age for adenocarcinoma was 50-59 years, and for squamous cell carcinoma, it was 60-69 years. The smoking rate was higher among squamous cell carcinoma patients (65.9%) compared to adenocarcinoma patients (22.3%). Adenocarcinoma patients had a higher proportion in stages 0-I (76.3%), while squamous cell carcinoma patients were more prevalent in stages II-III (64.1%). CONCLUSIONS The findings indicate an increasing proportion of female patients with adenocarcinoma, a younger age of onset, a higher proportion of non-smoking lung cancer patients, and an increased proportion of stages 0-I lung cancer. These trends may reflect the epidemiological characteristics of patients undergoing lung cancer surgery in Yunnan and surrounding areas over the past decade.
Humans ; Female ; Male ; Lung Neoplasms/pathology* ; Middle Aged ; China/epidemiology* ; Aged ; Adult ; Aged, 80 and over

[This corrects the article DOI: 10.1016/j.apsb.2021.08.015.].

Objective To establish a quantitative polymerase chain reaction(PCR)method for the analysis of human-derived SRY DNA in mouse tissues,and to study the tissue distribution of human umbilical cord mesenchymal stem cells(HUCMSCs)in immunodeficient NOG mice after a single intravenous injection.Methods We established a quantitative PCR method for the analysis of human SRY DNA in mouse tissues,and validated the standard curve,linear range,accuracy,precision,and stability.Thirty-six NOG mice(18 male,18 female)were administered 3.5×107 HUCMSCs/kg by single intravenous injection.Six mice were then anesthetized and dissected after blood collection(EDTA anticoagulation)at 6,12,24,and 72 h,and at 1 and 2 weeks,respectively.DNA was extracted from lung,kidney,heart,liver,brain,spinal cord,stomach,small intestine,fat,skin,spleen,testis,uterus,and ovary tissues,and the distribution of HUCMSCs in each tissue was determined by the validated quantitative PCR method for detecting the human-derived SRY gene in mouse tissues.In addition,18 NOG mice(9 male,9 female)were divided into control(n = 6)and treatment groups(n = 12)injected intravenously with 0.9%sodium chloride and 3.5×107 cells/kg,respectively.Acute toxic reactions were observed during the administration period,and four animals were dissected at 72 h and at 2 and 4 weeks after administration to observe the gross organs.Mitochondrial protein expression was detected in paraffin sections of lung tissues by immunohistochemistry to analyze the colonization of HUCMSCs in lung tissues.Results The established RT-qPCR method for human-derived SRY DNA in mouse tissues met the validation criteria for each index.After a single intravenous injection in NOG mice,HUCMSCs were mainly distributed in the lungs and blood within 1 week after administration,with higher concentrations in lung tissues than in blood.The concentrations of HUCMSCs in lung tissue and blood remained relatively stable within 6～24 h and 6～72 h,respectively,and then decreased over time.The distribution of HUCMSCs in other tissues was not measured at all sampling points.The colonization result showed that HUCMSCs were detected in lungs 72 h after intravenous injection,but not at 2 and 4 weeks.No obvious acute toxicity was observed in NOG mice after single intravenous administration of HUCMSCs.Conclusions The above method for analyzing the distribution of HUCMSCs in mouse tissue is reliable and feasible.HUCMSCs were mainly distributed in lung and blood in NOG mice within 1 week after a single intravenous injection,and mainly colonized lung tissue at 72 h.A single intravenous administration of HUCMSCs has a good safety profile.

OBJECTIVE: To explore the clinical characteristics and genetic basis for three children with Congenital chlorine diarrhea (CCD). METHODS: Three children with CCD who attended the Affiliated Children's Hospital of Capital Pediatric Institute from June 2014 to August 2020 were selected as the research subjects. Peripheral blood samples of the three children and their parents were collected for genetic testing. And the results were verified by Sanger sequencing. RESULTS: The clinical manifestations of the three children have included recurrent diarrhea, with various degrees of hypochloremia, hypokalemia and refractory metabolic alkalosis. Genetic testing revealed that the three children have all carried variants of the SLC26A3 gene, including homozygous c.1631T>A (p.I544N) variants, c.2063_1G>T and c.1039G>A (p.A347T) compound heterozygous variants, and c.270_271insAA(p.G91kfs*3) and c.2063_1G>T compound heterozygous variants. Sanger sequencing confirmed that all of the variants were inherited from their parents. CONCLUSION The variants of the SLC26A3 gene probably underlay the CCD in these children. Above finding has enriched the spectrum of SLC26A3 gene variants.
Humans ; Child ; Chlorine ; Genetic Testing ; Hypokalemia/genetics* ; Homozygote ; Diarrhea/genetics* ; Mutation