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:To explore the experience and learning curve of single-line suspension suction rod-assisted hybrid cavity-building thyroid surgery via the oral vestibular approach.Methods:Clinical data of 138 patients undergoing single-line suspension suction rod-assisted hybrid cavity-building thyroid surgery via oral vestibular approach from Sep. 2019 to Dec. 2021 in the Department of Thyroid and Breast Surgery of Affiliated Hospital of North Sichuan Medical College were retrospectively analyzed. The cumulative sum (CUSUM) method and best-fit curve analysis were used to compare the differences in each index such as operative time, intraoperative bleeding, number of lymph nodes cleared in the central region and postoperative related complications at various stages of the learning curve.Results:All 138 patients underwent single-line suspension rod-assisted hybrid cavity-building thyroid surgery via the oral vestibular approach, and one patient was converted to open surgery due to large intraoperative bleeding in the mass. There were 14 males and 124 females, mean age (36.07±8.49) years (20-55 years), thyroid tumor size (7.74±6.49) mm (2.4-50mm), 5 cases underwent Subtotal thyroidectomy, 129 cases underwent Unilateral lobectomy + lymph node dissection in the middle region, and 4 cases total thyroidectomy + central zone lymph node dissection. The number of surgical cases corresponding to the apex of the CUSUM learning curve was 45, and the learning curve was divided into two stages: the learning improvement stage (1-45 cases) and the mastery stage (46-138 cases). The operative time, intraoperative bleeding, postoperative hospital stay, and chin numbness were all lower in the proficiency period than in the learning and training period ( P<0.05), and the number of lymph nodes cleared in the central region was larger than that in the learning and improvement stage ( P<0.05), while the differences in other indexes between the two stages were not statistically significant ( P>0.05) . Conclusion:The single-line suspension suction rod-assisted hybrid cavity-building thyroid surgery via the oral vestibular approach has clinical application value and is worth promoting, and the number of surgical cases to be accumulated to master this technique is 45.

Objective:To investigate the feasibility and safety of single-position robotic assisted laparoscopic anterograde bilateral inguinal lymphadenectomy for penile cancer.Methods:The clinical data of 6 patients with penile cancer admitted to our hospital from January 2019 to January 2020 were retrospectively analyzed. The mean age was (52.0±8.6)years old. The pathology was primary focal squamous cell carcinoma, with 2 cases of high differentiation, and 4 cases of medium differentiation. All the 6 patients underwent single-position robotic assisted laparoscopic anterograde bilateral inguinal lymphadenectomy. Preoperative physical and imaging examinations indicated bilateral inguinal lymph node enlargement, and no distant metastasis was found in all of the 6 patients. The supine position was taken, with the head low and feet high about 15°, the legs straight and separated as far as possible in the shape of "Chinese eight" . The da Vinci robotic patient cart was placed between legs of the patient, after inserting the trocars. The external boundary of bilateral inguinal lymph node dissection was the line between the anterior superior iliac spine and 20 cm lower, the inner boundary was the pubic tubercle and its 15cm medial lower measurement, and the line between the inner boundary and the external lower edge was the lower boundary.Results:All the 6 operations were successfully completed without transfer to open surgery. Both sides of the inguinal lymph nodes were dissected at the same time. The space establishment and trocar insertion were performed simultaneously. There was no need for mobile robotic arm system during the operation. The average operative time was (105.0±20.5) min, and the amount of intraoperative blood loss was less than 50ml, the average hospital stay was(7±3) days. An average of(15.0±2.5) lymph nodes were dissected on each side. Intraoperative freezing suggested single positive lymph nodein 2 patients and no positive lymph node in 4 patients. There was no skin necrosis, 1 case of delayed wound healing, and 2 cases of lymphatic leakage. All patients were cured by conservative treatment. The 6 patients were followed up for 12-14 months, and there was no recurrence or metastasis.Conclusions:Single-position robotic assisted laparoscopic anterograde bilateral inguinal lymphadenectomy can achieve the expected surgical outcome, and has fewer perioperative complications. The surgery is safe and effective.

Objective: To investigate the clinical value of dual-phase arterial spin-labeled perfusion imaging(3D-ASL) in the evaluation of collateral circulation compensation in patients with severe cerebrovascular stenosis. Methods: From December 2017 to August 2018, 73 patients with severe cerebral artery stenosis confirmed by MRA in Linfen Central Hospital were collected and studied.The two-phase superconducting magnetic resonance imaging was performed[Post Label Delay(PLD): 1 525ms, 2 525ms] three-dimensional quasli continuous arterial spin labeling(3D-PCASL) imaging.Bilateral phase cerebral blood flow(CBF) was measured on the affected side and mirror side respectively.The CBF values of the affected side and mirror side were compared and analyzed, and the abnormal perfusion cases were compared and analyzed. Results: In 73 patients with severe cerebrovascular stenosis, the CBF values of the bilateral affected side[CBF 1 525ms(18.33±6.42)mL·100g^-1·min^-1, CBF 2 525ms(34.81±11.68)mL·100g^-1·min^-1] were lower than those of the mirror side[CBF 1 525ms(41.25±16.84)mL·100g^-1·min^-1, CBF 2 525ms(47.74±14.90)mL·100g^-1·min^-1], the differences were statistically significant(Z=-9.348, -7.476, all P<0.001). The ratio of abnormal perfusion in PLD=2525ms group[CBF(34.81±11.68)mL·100g^-1·min^-1]was higher than that in PLD=1 525ms group[CBF(18.33±6.42)mL·100g^-1·min^-1], the difference was statistically significant(Z=-9.196, P<0.001). The percentage of abnormal perfusion in PLD group of 2 525ms(56.2%) was lower than that in PLD group of 1 525ms(94.5%), the difference was statistically significant(χ²=5.393, P=0.02). Conclusion Dual-phase ASL(PLD=1 525ms, 2 525ms) combined with ASL can more accurately evaluate the compensations of fast collateral circulation and slow collateral circulation, and provide individualized treatment.

Objective:To explore the correlations of moderate to severe leukoaraiosis (LA) with hemorrhagic transformation (HT) and prognoses of patients with acute ischemic stroke after intravenous thrombolysis.Methods:Clinical data of 144 patients with acute ischemic stroke who underwent intravenous thrombolysis in our hospital from August 2017 to November 2018 were retrospectively collected. Van Swieten scale (vSS) was used to determine the leukoaraiosis degrees in these patients based on CT findings of the head before treatment. According to the CT results of head re-examination within 24 h of treatment, HT appearance of the patients was judged. The prognoses of these patients were evaluated according to modified Rankin scale (mRS) scores 90 d after discharge. Multivariate Logistic regression analysis was performed to determine the independent risk factors for HT and prognoses of patients with acute ischemic stroke after intravenous thrombolysis.Results:Among 144 patients, 23 patients (15.97%) had HT and 121 (84.03%) had non-HT; 61 patients (42.36%) were with poor prognosis and 83 (57.64%) were with good prognosis. As compared with patients in the non-HT group, patients in the HT group had significantly higher proportion of patients with moderate to severe LA, D-dimer level and urine specific gravity ( P<0.05). Multivariate Logistic regression analysis showed that moderate to severe LA ( OR=0.281, 95%CI: 0.105-0.753, P=0.012) and D-dimer ( OR=1.654, 95%CI: 1.100-2.489, P=0.016) were independent risk factors for HT. As compared with the patients in the good prognosis group, the patients in the poor prognosis group had significantly advanced age, statistically higher baseline NIHSS scores and proportion of patients with HT and positive urine sugar, significantly higher levels of random blood glucose and D-dimer, significantly higher plasma fibrinogen content, significantly higher international normalized ratio, and significantly longer plasma prothrombin time before treatment ( P<0.05). The TOAST etiological types of patients between good prognosis group and poor prognosis group were significantly different ( P<0.05). Multivariate Logistic regression analysis showed that baseline NIHSS scores ( OR=1.395, 95%CI: 1.213-1.605, P=0.000) and white blood cell count ( OR=1.292, 95%CI: 1.040-1.606, P=0.021) were independent risk factors for poor prognosis. Conclusions:Acute ischemic stroke patients with moderate to severe LA and high D-dimer are prone to HT after intravenous thrombolysis. Acute ischemic stroke patients with higher baseline NIHSS scores and peripheral white blood cell count are prone to have poor prognosis.

OBJECTIVE： To investigate the substance basis and mechanism of Xiaochaihu decoction in treatment of sepsis， and to provide reference for clinical application and R&D of the decoction. METHODS： Based on TCM integrative pharmacology platform （TCMIP）， chemical component analysis of Xiaochaihu decoction， disease target prediction， gene function and pathway enrichment analysis were all performed. The multi-dimensional network relationship of “TCM-chemical components-core targets-key pathways” was established， and the mechanism of Xiaochaihu decoction in treatment of sepsis was investigated. RESULTS： A total of 224 predicted chemical ingredients of Xiaochaihu decoction （including saikoside， ginsenoside， glycyrrhizin， etc.） interacted with 118 key targets about sepsis， including PF4， MYD88， TLR4， CD14， NOS3， etc. Its anti-sepsis mechanism involved nervous system， endocrine system， immune response and energy metabolism， etc. CONCLUSIONS： Based on “neuronal- endocrine-immune-metabolism”， Xiaochaihu decoction achieved its role in regulating sepsis by multi-level， multi-channel and multi-channel. This research may reveal the potential mechanism of Xiaochaihu decoction for sepsis， and the prescription provide theoretical basis for further experimental research of pharmacodynamic substance basis and mechanism of action．

Objective To study the clinical value of whole －body magnetic resonance diffusion weighted imaging(WB－DWI) in evaluating the chemotherapy response for lung cancer,thus to provide evidence for optimizing clinical imaging examination. Methods From October 2017 to May 2018,60 patients with lung cancer confirmed by histopathology in Linfen Central Hospital were selected. The patients underwent DWI examinations before chemotherapy and after two cycles of chemotherapy. The change of tumor size,distant metastasis and apparent diffusion coefficient (ADC) value were compared before and after chemotherapy. The correlation between the change rate of ADC value and the shrinkage rate of tumor size in the effective group was analyzed. Results Of 60 cases,1 case had new cerebral metastases after chemotherapy. There were statistically significant differences in ADC value [(1. 12 ± 0.33) ×10 －3mm2/svs.(1.56±0.40) ×10 －3mm2/s]andtumorsize[(4.63±2.75)cmvs.(2.28±1.45)cm] between before and after chemotherapy in the effective group(t= －3. 954,4. 711,all P＜0. 01). There was correlation between the change of ADC value and tumor size(r=0. 34,P＜0. 05). Conclusion WB－DWI can not only detect the change of tumor size and distant metastasis quickly and effectively,but also can observe the microscopic changes of tumor cells by measuring ADC value. So it can predict the early therapeutic response of the tumor and make effective evaluation for the staging and chemotherapy response of lung cancer.

Objective To investigate the influence of moderate to severe leukoaraiosis (LA) in prognoses of acute ischemic stroke patients after endovascular treatment.Methods From January 2017 to December 2018, 60 patients with acute ischemic stroke due to anterior circulation large vessel occlusion underwent endovascular treatment and obtained complete vessel recanalization in our hospital were evaluated for degrees of LA severity according to head CT scan and van Swieten scale (2-4 scores were defined as moderate-severe LA). According to modified Rankin scale (mRS) scores 90 d after treatment, the patients were divided into poor prognosis group and good prognosis group. Univariate analysis was used to compare the differences of influencing factors of the two groups. Multivariate Logistic regression analysis was further used to explore the influence of moderate to moderate-severe LA in poor prognosis of patients after endovascular treatment.Results Of the 60 patients, 18 did not have LA, 19 had mild LA, and 23 had moderate-severe LA; 32 had poor prognosis and 28 had good prognosis. Univariate analysis showed that the patients from the poor prognosis group had significantly higher proportion of moderate-severe LA (59. 4％ [19/32]vs. 14.3％ [4/28]), significantly higher baseline National Institutes of Health Stroke Scale (NIHSS) scores ([23.4±10.1]vs. [14.7±7.0]), significantly higher baseline diastolic blood pressure ([87.5±18.9] mmHgvs. [78.3±15.1] mmHg), significantly higherproportion of patients with hypertension history (68.8％ [22/32]vs. 42.9％ [12/28]), and statistically older age ([70.6±9.4] yearsvs. [61.3±12.5] years) than the patients from the good prognosis group (P<0.05). On multivariable Logistic regression analysis, the presence of moderate-severe LA (OR=5.032, 95％CI: 1.026-24.679,P=0.046) and baseline NIHSS scores were independent risk factors for poor prognosis of patients after endovascular treatment.Conclusion Patients with acute ischemic stroke accompanied with moderate-severe LA are more likely to have poor prognosis after endovascular treatment.

OBJECTIVE:To provide reference for clinical application and related new drug R&D of the couplet medicines of Platycodon grandiflorum-Glycyrrhiza uralensis. METHODS:All set prescription preparations containing P. grandiflorum-G. uralensis in Ministry of Public Health Drug Standard·TCM Set Prescription Preparation were collected;data mining and analysis for the syndrome and treatment rules of these prescriptions were performed by using TCM Inheritance System V 2.5. RESULTS:There were a total of 315 set prescription preparations containing couplet medicine of P. grandiflorum-G. uralensis , 89 main syndromes and 88 main diseases. Among of them,high frequency major syndrome were exterior syndrome attacked by wind-heat and exterior syndrome tightened by wind-cold,and dominating medicine combination were respectively Yinqiao powder and Xingsu powder. High frequency main diseases were common cold and cough. Core medicine combination in the treatment of common cold included Yinqiao powder, Xingsu powder,Huoxiang zhengqi powder and Chaihu zhijie decoction,etc. Core medicine combination in the treatment of cough included Xingsu powder,Zhisou powder,Tongxuan lifei pills and Qingjin huatan decoction,etc. CONCLUSIONS:The study confirms the syndrome and treatment rules of set prescription preparations containing couplet medicines of P. grandiflorum-G. uralensis , and could provide evidence for clinical application of the couplet medicines of P. grandiflorum-G. uralensis and new drug R&D.

Objective To evaluate the application value of whole exome sequencing (WES) in diagnosis of NDDs (neuro-developmental disorders) children.Metheod WES was used for the diagnosis of 35 unexplained NDD children, which admitted to the outpatient and ward of Children′s hospital affiliated to Capital institute of pediatric from November 2015 to November 2016.These children′s clinical data was collected detailedly.Using bioinformatics software tools combining with patient′s phenotype, the candidate genetic/genomic variants of these patients were identified from WES data.The final pathogenicity of genetic/genomic variants was interpreted according to the guideline of the American College of Medical Genetics and Genomics (ACMG), meanwhile, the variants validation and co-separation analysis in the parents and their family members were performed by Sanger sequencing, real time-PCR and multiplex ligation-dependent probe amplification (MLPA).Results 14 pathogenic single nucleotide variants (SNVs) and three pathogenic copy number variations (CNVs) were detected in the 35 NDD children, the detection rate in this study is 48.6%.Among the 14 pathogenic SNVs, 11 of them are the definite NDD-related genes according to OMIM database (such as CHARGE syndrome, Wiedemann-Steiner syndrome, Cockayne syndrome, etc.), and six of them are de novo (6/11, 54.6%).Three pathogenic CNVs were identified from WES data, including two microduplications and one microdeletion.Meanwhile, a female child carrying a frame shift mutation in MECP2 was found and the germline mosaicism with low-frequency mutation of this site (8.4%) was confirmed by his father's sperm.Conclusions The diagnosis rate of WES in NDDs children is 48.6% in our small-sample study.In addition to pathogenic/likely pathogenic SNVs, CNVs can be detected successfully from WES data, which effectively improved the diagnosis yield in NDDs children.