ObjectiveTo investigate the potential mechanism of the Jianpi Yishen Huatan Formula （健脾益肾化痰方，JPYSHF） in treating squamous cell lung cancer through the LncRNA ALAL-1/USP4/HDAC2 signaling pathway. MethodsForty Sprague-Dawley （SD） rats were randomly divided into a control group and high-， medium-， and low-dose JPYSHF group with 10 rats in each group. Rats in the JPYSHF groups were administered JPYSHF concentrated liquid at doses of 45， 30， and 15 g/（kg·d） via intragastric gavage， respectively， while the control group received 10 ml/（kg·d） of normal saline， once daily for 10 consecutive days before preparation of drug containing serum. Human lung squamous carcinoma SK-MES-1 cells were divided into a control group and low-， medium-， and high-dose JPYSHF-medicated serum groups. The control group was cultured with 10% saline-containing serum， while the JPYSHF groups were cultured with 10% low-， medium-， or high-dose medicated serum. After 48 hours of incubation， flow cytometry was used to detect apoptosis rates， and a cell scratch assay was performed to evaluate migration areas at 0 h and 24 h to calculate migration rate. Additional SK-MES-1 cells were divided into control serum， JPYSHF-medicated serum （low-， medium-， high-） dose， LncRNA-silenced group （transfected with ALAL-1 siRNA）， USP4-inhibited group （treated with 35 μmol/L PR-619， a deubiquitinase inhibitor）， and HDAC2-inhibited group （treated with 60 μmol/L Vorinostat）. After 24 and 48 hours of culture， cell viability was assessed using the CCK-8 assay； LncRNA ALAL-1， USP4， and HDAC2 mRNA levels were quantified by qPCR after 24 hours； USP4 and HDAC2 protein levels were measured by Western Blot after 48 hours. ResultsCompared with the control serum group， the total apoptosis rate of cells in middle- and high-JPYSHF-medicated serum group significantly increased， and the cell migration rate of cells in the low-， middle- and high-JPYSHF-medicated serum group significantly decreased （P＜0.05 or P＜0.01）. The cell migration rate of the low-， medium- and high-JPYSHF-medicated serum groups decreased with the increase of concentration in a concentration-dependent manner （P＜0.05 or P＜0.01）. Compared with the control serum group at the same time， the cell viability at 24 h and 48 h significantly decreased in all groups （P＜0.05 or P＜0.01）. Compared with the low-JPYSHF-medicated serum group at the same time， the cell viability at 24 h and 48 h also decreased in the high-JPYSHF-medicated serum group and the LncRNA silencing group （P＜0.05）. Compared with the control serum group， the expression of USP4 and HDAC2 mRNA reduced in the low- and medium-dose JPYSHF-medicated serum groups and the USP4 inhibitor group， and the expression of LncRNA ALAL-1， USP4 and HDAC2 mRNA reduced in the high-dose JPYSHF-medicated serum group and LncRNA-silencing group， and HDAC2 mRNA expression reduced in the HDAC2 inhibitor group. USP4 and HDAC2 protein levels were reduced in cells of all groups except for USP4 protein level in HDAC2 inhibitor group （P＜0.05 or P＜0.01）. ConclusionJPYSHF-medicated serum inhibits proliferation and promotes apoptosis of human lung squamous carcinoma cells， and its mechanism of action may be related to its inhibition of the LncRNA ALAL-1/USP4/HDAC2 pathway， with best effect at a high concentration.

Sepsis is a life-threatening organ dysfunction caused by infection. Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway plays a key role in the regulation of inflammatory response， oxidative stress and apoptosis. Some traditional Chinese medicine monomers， such as flavonoids （such as taxifolin）， alkaloids （such as sinomenine）， and stilbenes （such as piceatannol） can exert anti-inflammatory， anti-oxidation， and inhibition of apoptosis by regulating the JAK/ STAT signaling pathway， which is helpful to improve sepsis. Traditional Chinese medicine compounds （such as Zuojinfang） and traditional Chinese medicine injections （such as Astragalus injection， Xuebijing injection） can also inhibit inflammation， protect organ function， and reduce sepsis-related damage by regulating JAK/STAT signaling pathway. Although traditional Chinese medicine has shown great potential in the prevention and treatment of sepsis， the current research mainly focuses on in vitro and animal models， and more relative clinical researches need to be conducted.

Objective To investigate the application value of spectral computed tomography venography(CTV)in the display and staging of deep venous thrombosis(DVT)in the lower extremity.Methods Eighty-two patients with CTV were selected and ran-domly divided into group A(42 patients)and group B(40 patients).Group A:tube voltage 120 kVp.Group B:gemstone spectral ima-ging(GSI)mode,reconstruction of 50 keV and iodine(water)maps.The CT and standard deviation(SD)values of the veins were measured,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were calculated in 120 kVp images of group A and in 50 keV images of group B.Two observers scored the image quality of the 2 groups subjectively,and Kappa test was used to examine the con-sistency.Based on the duration from the occurrence of clinical symptoms,the DVTs were classified.The CT values and iodine con-centration(IC)of DVT were measured in the 120 kVp images of group A and in the iodine(water)maps of group B,respectively.The receiver operating characteristic(ROC)curve was drawn to compare the effectiveness of CT values and IC in diagnosing DVT staging.Results CT values,SNR,and CNR of veins in group B were higher than those in group A(P<0.05).The subjective scores of the two groups were consistent(Kappa=0.926-0.955,P<0.05).The score for the display of veins and thrombus clarity in group B was 5(4,5),which was better than the score of 4(3,4)in group A(P<0.05).The efficiency of IC in diagnosing DVT staging[area under the curve(AUC)=0.973]was better than that of CT values(AUC=0.891).Conclusion The spectral CTV can improve the contrast of lower extremity deep veins and the clarity of thrombus,and can provide more objective indicators for the diagnosis of thrombus staging,which is conducive to accurate clinical diagnosis and treatment.

Purpose To explore the feasibility of using virtual non-contrast images derived from spectral CT for pulmonary angiography(CTPA)to replace true non-contrast scan of chest,in order to reduce radiation dose.Materials and Methods Fifty-six patients undergoing CTPA examination in the First Affiliated Hospital of Dalian Medical University were prospectively enrolled.All patients underwent both conventional chest CT and spectral CTPA scan.On both virtual unenhanced images and true unenhanced images,CT values and standard deviation values of the pulmonary parenchyma in the level of thoracic aorta,main pulmonary artery,erector spine,as well as pulmonary apex,tracheal carina,and lung base were measured.Signal noise ratio and contrast noise ratio of thoracic aorta and pulmonary artery were calculated.The image quality and iodine residue of the two groups was evaluated.The consistency of subjective scores was also assessed.Dose length product,CT dose index volume and contrast agent dosage were recorded.The CT value,signal noise ratio,contrast noise ratio,radiation dose and subjective score of each region of interest in true unenhanced and virtual unenhanced images were compared.Results The inter-observer subjective scores were consistent(Kappa=0.984-0.992,P＜0.05).The subjective scores of the chest true unenhanced and virtual unenhanced images were 4.75±0.65 and 4.65±0.49,respectively,with no statistical difference(t=0.630,P=0.437).There was no significant difference in CT values of thoracic aorta,pulmonary artery and lung tissues between true unenhanced and virtual unenhanced images(P＞0.05).There was no significant difference in signal noise ratio and contrast noise ratio between pulmonary artery and thoracic aorta(P＞0.05).Replacing conventional chest scan with virtual unenhanced images of CTPA reduced the radiation dose by approximately 55％,reducing from(7.27±1.74)mSv to(3.26±0.84)mSv.Conclusion It is feasible to use CTPA virtual non-contrast images to replace conventional unenhanced CT chest imaging for lung disease screening,since it can significantly reduce the radiation dose to patients.

Objective To investigate the application value of energy spectral CT low energy(keV)targeted reconstruction tech-niques combined with adaptive statistical iterative reconstruction-Veo(ASIR-V)algorithm in lower extremity computed tomography venography(CTV).Methods Forty patients with lower extremity CTV examination were retrospectively selected.Gemstone spec-tral imaging(GSI)mode was used with a transient tube voltage of 80 kVp/140 kVp and tube current in GSI Assist mode.Group A(conventional group):70 keV combined with 40％ASIR-V mono-energy images,conventional display field of view(DFOV)inclu-ding both lower extremity.Group B(low keV group):50 keV combined with 50％ASIR-V mono-energy images,DFOV as in group A.Group C(low keV targeted reconstruction group):50 keV combined with 50％to 80％ASIR-V mono-energy images(10％interval,called as groups C1-C4),targeted reconstruction(small DFOV,covered one lower extremity with left and right femurs as the center).The CT and standard deviation(SD)values of the bilateral lower extremity veins were measured on each axial image and the signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were calculated.Two observers scored the venous images and the sharpness of embolus display subjectively using a 5-point scale and Kappa test was used to examine the consistency.Results In terms of vein dis-play,the score of groups B and C was better than that of group A(P＜0.05).In terms of embolus display sharpness,the scores of large and small embolus in group C increased with the increase of ASIR-V percentage initially and then gradually decreased(P＜0.05).The scores in group C2 were the highest which were superior to the scores of group B and group A(P＜0.05).The CT values of each venous segment in groups B and C were higher than those in group A(P＜0.05).In groups C1 to C4,with the increasing weight of ASIR-V,the SNR and CNR increased gradually(P＜0.05),but slightly lower than those in group B(P＜0.05).Conclusion 50 keV targeted reconstruction techniques combined with 60％ASIR-V algorithm significantly improves the contrast of lower extremity veins and the embolus display sharpness,providing more accurate clinical imaging information.

Purpose: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. Materials and Methods: Seventy-five patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and preoperative and postoperative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients. Results: The tumor-informed fixed assay had a higher preoperative positive rate than the tumor-agnostic assay (73.3% vs. 57.3%). The preoperative ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined postoperative ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR], 20.74; 95% confidence interval [CI], 7.19 to 59.83; p < 0.001), which was an independent predictor by multivariable analysis (HR, 28.57; 95% CI, 7.10 to 114.9; p < 0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest preoperative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in postoperative landmark (HR, 26.34; 95% CI, 6.01 to 115.57; p < 0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04; 95% CI, 0.94 to 9.89; p=0.052). Conclusion Our study confirmed the prognostic value of the ctDNA positivity at postoperative day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.

Background and purpose:Colorectal cancer(CRC)is one of the common malignancies,but the mechanism by which it develops resistance to drug remains unclear.The tumor microenvironment(TME),especially cancer-associated fibroblast(CAF),plays an important role in the occurrence,development and drug resistance of tumors.This study aimed to investigate the effect of inflammatory cancer-associated fibroblasts(iCAF)on drug resistance in CRC cells and its possible mechanism.Methods:The primary CAFs were collected from CRC patients underwent surgery in Putuo Hospital,Shanghai University of Traditional Chinese Medicine from Aug.2022 to Sep.2022,and the primary cells were sorted according to the surface marker of CAF[approved by the Ethics Committee of Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine:PTEC-A-2023-5(S)-1],platelet derived growth factor receptor alpha(PDGFRA),to screen iCAF.Human intestinal fibroblast(HIF)and iCAF cells were cultured using serum-free medium to obtain conditioned medium.According to the treatment method,colon cancer cells were divided into control group(no treatment),experimental group 1(treated with HIF-CM)and experimental group 2(treated with iCAF-CM).We observed the changes in the survival rate and apoptotic rate of CRC cells,the changes in protein and mRNA levels and the effect on the Wnt/β-catenin signaling pathway after stimulation with HIF-CM or iCAF-CM.Results:After iCAFs stimulation,the half inhibition concentration(IC50)of CRC cells was higher compared with the control group and HIF-CM group(P＜0.05).Compared with the control group and HIF-CM group,the apoptotic rate of tumor cells in iCAF-CM group decreased significantly,the expression of caspase-3 was decreased,and the expressions of Bcl-2,Bcl-xL and survivin were increased(P＜0.05).The Wnt/β-catenin signaling pathway was activated in the iCAF-CM group.Conclusion:iCAFs can mediate drug resistance in CRC cells,and the mechanism is related to the activation of Wnt/β-catenin signaling pathway.

Objective:To study the prevalence and epidemiological characteristics of adult thyroid nodules in Wuhan City, and to analyze the influencing factors of thyroid nodules, so as to provide basis for prevention and treatment of adult thyroid nodules in Wuhan City.Methods:From 2019 to 2021, two communities or towns were selected from each of the 13 districts in Wuhan City using multi-stage cluster random sampling method. One hundred permanent residents over the age of 16 were selected from each community or town according to the inclusion and exclusion criteria (age and sex ratio balanced), for questionnaire survey, physical examination, urinary iodine test and thyroid ultrasound examination. The influencing factors of thyroid nodules was analyzed using logistic regession and Spearman correlation.Results:A total of 2 578 adults were investigated, including 1 168 men and 1 410 women. The age was (41.79 ± 13.01) years. The prevalence of thyroid nodules was 35.49% (915/2 578). The prevalence of single nodules was 19.16% (494/2 578), which was higher than that of multiple nodules [16.33% (421/2 578), χ 2 = 2 577.00, P < 0.001]. Multivariate logistic regression analysis showed that female ( OR = 2.033, 95% CI: 1.631 - 2.535), older ( OR = 1.404, 95% CI: 1.290 - 1.528), history of thyroid disease ( OR = 1.351, 95% CI: 1.211 - 1.506) and diabetes ( OR = 1.449, 95% CI: 1.083 - 1.938) were independent risk factors for adult thyroid nodules ( P < 0.05). The median urinary iodine of residents in Wuhan City was 185.32 μg/L, at an appropriate level of iodine nutrition, there was no correlation between urinary iodine and thyroid nodules ( r = 0.02, P = 0.391). Conclusions:The prevalence of thyroid nodules of adults in Wuhan City is high. Women, older, a history of thyroid diseases and diabetes are all risk factors for thyroid nodules. No correlation is found between urinary iodine level and thyroid nodules.

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

Objective:To evaluate the clinical value of lymph node dissection (LND) for intrahepatic cholangiocarcinoma (ICC) after surgical resection.Methods:A retrospective study was conducted on the clinical data of 156 patients who underwent surgery for ICC in Eastern Hepatobiliary Surgery Hospital of Naval Military Medical University from November 2010 to December 2017, including 94 males and 62 females, aged (60.0±9.5) years. Curative surgery was performed in 114 cases. Of 64 cases were in stage Ⅰ according to American Joint Committee on Cancer (AJCC), including 38 cases of non-lymph node dissection (NLND) and 26 cases of LND; 21 cases were in AJCC stage Ⅱ, including 11 cases of NLND and 10 cases of LND; 22 cases were in AJCC stage Ⅲb, including 14 cases of LND and 8 cases of lymph node resection (LNR); 5 cases were in AJCC stage Ⅲa, 2 cases were in AJCC stage Ⅳ. Univariate and multivariate Cox regression analysis were used for the risk factors of ICC prognosis. The log-rank test compared the survival rates of the two groups.Results:Cox multivariate analysis indicated that lymph node metastasis was independent risk factors for prognosis in patients with ICC ( HR=1.96, 95% CI: 1.09-3.55, P=0.026). A total of 114 patients were included in the curative surgery group. The 1-, 3-, and 5-year overall survival (OS) rates of the negative lymph node group ( n=91) were 65.9%, 47.3% and 35.6%, respectively, which were significantly better than those of the positive lymph node group ( n=23) who had 1-, 3-, 5-year OS rates of 56.5%, 17.7% and 0, respectively (χ 2=8.11, P=0.004 ). In stage Ⅰ and Ⅱ patients, there were no significant differences in 1-, 3-, 5-year OS rates between the NLND group and the LND group (both P>0.05 ). In stage Ⅲb patients, the LND group had 1-, 3-, 5-year OS rates of 71.4%, 29.8% and 0, respectively, significantly better than those of the LNR group who had 1-, 3-, 5-year OS rates of 37.5%, 0 and 0, respectively (χ 2=6.45, P=0.011). Conclusions:Lymph node metastasis is an independent risk factor affecting the prognosis of ICC. Lymph node dissection should be performed cautiously in ICC with AJCC stage Ⅰ and Ⅱ, while routine lymph node dissection is recommended in ICC with AJCC stage Ⅲb.