Tumor resistance to anti-mesothelin CAR-T cells caused by binding to shed mesothelin is overcome by targeting a juxtamembrane epitope.

Despite many clinical trials, CAR-T cells are not yet approved for human solid tumor therapy. One popular target is mesothelin (MSLN) which is highly expressed on the surface of about 30% of cancers including mesothelioma and cancers of the ovary, pancreas, and lung. MSLN is shed by proteases that cleave near the C terminus, leaving a short peptide attached to the cell. Most anti-MSLN antibodies bind to shed MSLN, which can prevent their binding to target cells. To overcome this limitation, we developed an antibody (15B6) that binds next to the membrane at the protease-sensitive region, does not bind to shed MSLN, and makes CAR-T cells that have much higher anti-tumor activity than a CAR-T that binds to shed MSLN. We have now humanized the Fv (h15B6), so the CAR-T can be used to treat patients and show that h15B6 CAR-T produces complete regressions in a hard-to-treat pancreatic cancer patient derived xenograft model, whereas CAR-T targeting a shed epitope (SS1) have no anti-tumor activity. In these pancreatic cancers, the h15B6 CAR-T replicates and replaces the cancer cells, whereas there are no CAR-T cells in the tumors receiving SS1 CAR-T. To determine the mechanism accounting for high activity, we used an OVCAR-8 intraperitoneal model to show that poorly active SS1-CAR-T cells are bound to shed MSLN, whereas highly active h15B6 CAR-T do not contain bound MSLN enabling them to bind to and kill cancer cells.

[Chinese expert guidance on overall application of lenvatinib in hepatocellular carcinoma].

Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4, 2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.

[Application of stereoscopic unequal S-plasty for reconstuction of the congenital hypoplastic ear lobe cleft associated with soft tissue deficiency].

Objective: To explore the ideal way of using the stereoscopic unequal S-plasty in reconstruction of the congenital hypoplastic ear lobe cleft with soft tissue deficiency. Methods: Data of 10 patients with the congenital hypoplastic ear lobe cleft associated with soft tissue deficiency who were treated using the stereoscopic unequal S-plasty in the plastic cosmetic surgery of Xuzhou Central Hospital from Aug 2018 to Aug 2022 were retrospectively analyzed. Six patients were male, 4 were female. Their ages ranged from 6 years to 19 years old, with a mean age of 13 years. Lobe deficiency size ranged from 0.8 cm×0.5 cm to 1.2 cm×1.0 cm. Results: The post-operation flaps had no venous congestion, infection or necrosises. During 3 to 12 months of follow-up, the technique made the shape of the ear lobe smoother. The incisions left inconspicuous scars. The result was satisfactory in terms of matching the contralateral normal ear lobe in shape and symmetry. Doctors and patients were satisfied with the results. Conclusions: The stereoscopic unequal S-plasty is an effective way to correct the the severe congenital ear lobe deformity. The good result,simple manipulation and short operation time are the advantages of this method.

[Pathological significance of plasma cell infiltration in diagnosing lymph node diseases].

Objective: To investigate the value of plasma cells for diagnosing lymph node diseases. Methods: Common lymphadenopathy (except plasma cell neoplasms) diagnosed from September 2012 to August 2022 were selected from the pathological records of Changhai Hospital, Shanghai, China. Morphological and immunohistochemical features were analyzed to examine the infiltration pattern, clonality, and IgG and IgG4 expression of plasma cells in these lymphadenopathies, and to summarize the differential diagnoses of plasma cell infiltration in common lymphadenopathies. Results: A total of 236 cases of lymphadenopathies with various degrees of plasma cell infiltration were included in the study. There were 58 cases of Castleman's disease, 55 cases of IgG4-related lymphadenopathy, 14 cases of syphilitic lymphadenitis, 2 cases of rheumatoid lymphadenitis, 18 cases of Rosai-Dorfman disease, 23 cases of Kimura's disease, 13 cases of dermal lymphadenitis and 53 cases of angioimmunoblastic T-cell lymphoma (AITL). The main features of these lymphadenopathies were lymph node enlargement with various degrees of plasm cell infiltration. A panel of immunohistochemical antibodies were used to examine the distribution of plasma cells and the expression of IgG and IgG4. The presence of lymph node architecture could help determine benign and malignant lesions. The preliminary classification of these lymphadenopathies was based on the infiltration features of plasma cells. The evaluation of IgG and IgG4 as a routine means could exclude the lymph nodes involvement of IgG4-related dieases (IgG4-RD), and whether it was accompanied by autoimmune diseases or multiple-organ diseases, which were of critical evidence for the differential diagnosis. For common lesions of lymphadenopathies, such as Castleman's disease, Kimura's disease, Rosai-Dorfman's disease and dermal lymphadenitis, the expression ratio of IgG4/IgG (>40%) as detected using immunhistochemistry and serum IgG4 levels should be considered as a standard for the possibility of IgG4-RD. The differential diagnosis of multicentric Castleman's diseases and IgG4-RD should be also considered. Conclusions: Infiltration of plasma cells and IgG4-positive plasma cells may be detected in some types of lymphadenopathies and lymphomas in clinicopathological daily practice, but not all of them are related to IgG4-RD. It should be emphasized that the characteristics of plasma cell infiltration and the ratio of IgG4/IgG (>40%) should be considered for further differential diagnosis and avoiding misclassification of lymphadenopathies.

[Efficacy and safety of transcatheter aortic valve replacement in the treatment of severe aortic stenosis].

Objective: To investigate the efficacy and safety of transcatheter aortic valve replacement (TAVR) in the treatment of severe aortic stenosis. Methods: The clinical data of patients with severe aortic stenosis who underwent TAVR at the People's Hospital of Xinjiang Uygur Autonomous Region between September 2016 and September 2022 were retrospectively analyzed. Changes in aortic transvalvular pressure gradients, valve orifice area, and activity tolerance of patients before and after the surgery were compared. Moreover, postoperative complications and follow-up results from 30 days to 6 years after the surgery were recorded. Results: A total of 76 patients were included in the study (50 males and 26 females), with an average age of (71.3±7.6) years, including 16 rheumatic valvular diseases, 60 senile degenerative diseases, 46 bicuspid valves and 30 tricuspid valves. The success rate of the operation was 96.1% (73/76). Compared with that before the operation, the mean aortic transvalvular pressure gradients decreased [(8.5±2.8) mmHg vs (68.5±19.2) mmHg (1 mmHg=0.133 kPa),P<0.001], but the valve orifice area increased [(1.91±0.31) cm2 vs (0.65±0.21) cm2, P<0.001]. Likewise, six-minute walking test (6MWT) showed that walking distance was longer after the surgery [(430±13) m vs (201±28) m, P<0.001]. There were 1 case of retroperitoneal hematoma, 1 case of stricture balloon dilatation after femoral artery suture concomitant with postoperative puncture site infection, 1 case of femoral artery surgical incision, 2 cases of valve-in-valve (ViV) and 5 cases of perivalvular leakage (4 cases were mild and 1 case was moderate) after the surgery, respectively. Moreover, acute left main artery occlusion during operation occurred in 1 case, ventricular rupture during operation occurred in 1 case and the patient was transferred to valve replacement surgery and finally dead, delayed coronary artery occlusion and death happened in 1 case, and all of the above-mentioned 3 cases were due to surgical failure. Postoperative pacemaker implantation due to third-degree atrioventricular block was performed in 5 cases. There were 1 case of pulmonary embolism, 1 case of transient right limb disorder, 1 case of gastrointestinal bleeding and 1 case of urethral bleeding after the surgery, respectively. The patients were followed up for (1.0±0.1) years (30 days to 6 years), and the results showed that 2 cases died, including 1 case died suddenly at home (the cause of death was unknown) and 1 case died of acute heart failure 8 months after the surgery. Chronic heart failure occurred repeatedly in 6 cases. The quality of life of other patients improved significantly. Conclusion: TAVR is effective and safe for patients with severe aortic stenosis.

[Prognostic factors for non-small cell lung cancer patients with central nervous system metastasis with positive driver genes].

Objective: To investigate the prognostic factors of patients with central nervous system (CNS) metastatic non-small cell lung cancer (NSCLC) with positive driver genes. Methods: The clinical data of 103 patients with CNS metastatic NSCLC admitted to Beijing Tongren Hospital from January 2016 to December 2020 were retrospectively analyzed, and the patients were divided into positive driver gene group (patients with driver genes mutation and receiving corresponding targeted therapy) and negative driver gene group. Cox univariate and multivariate regression analyses were performed to identify the factors affecting patients' prognosis, and the receiver operating characteristic curve (ROC) was used to compare the predictive ability of 4 scoring systems [recursive partitioning analysis (RPA) classes, diagnosis-specific graded prognostic assessment (DS-GPA) index, basic score for brain metastasesn (BS-BM) and (lung-molecular graded prognostic assessment (lung-mol GPA)]on patients' prognosis. Results: Among the 103 patients, 48 were males and 55 were females, and aged (64.6±9.7) years old. The median survival time of the 103 patients was 24.0 (95%CI: 20.0-28.0) months, the median survival time of the 59 patients in the positive driver gene group was 33.0 (95%CI: 23.4-42.6) months, the median survival time of the 44 patients in the negative driver gene group was 17.0 (95%CI: 14.4-19.6) months, and the difference was statistically significant (χ2=24.69, P<0.001). The results of Cox multivariate analysis showed that the negative driver genes (HR=3.788, 95%CI: 1.951-7.301, P=0.001), Karnofsky performance status (KPS) score<70 (HR=2.613, 95%CI: 1.185-5.761, P=0.017) and neutrophil-to-lymphocyte ratio (NLR)>3.22 (HR=2.714, 95%CI: 1.157-6.365, P=0.022) were independent risk factors affecting the prognosis of patients with CNS metastatic NSCLC. KPS score<70 (HR=3.719, 95%CI: 1.165-11.876, P=0.027) and no radiotherapy (HR=2.032, 95%CI: 1.033-11.364, P=0.041) were independent risk factors affecting the prognosis of patients with CNS metastatic NSCLC with positive driver genes. ROC curve analysis showed that the area under curve (AUC) value of lung-mol GPA was the highest among the 4 scoring systems (AUC=0.843, 95%CI: 0.731-0.956, P<0.001), and the AUC value of the lung-mol GPA combined scoring system (AUC=0.904, 95%CI: 0.816-0.991, P<0.001) was higher than lung-mol GPA. Conclusions: A low KPS score and no cranial radiation therapy are independent risk factors for the prognosis of patients with CNS metastatic NSCLC with positive driver genes; the lung-mol GPA joint scoring system is more conducive to the prognostic assessment of patients with CNS metastatic NSCLC with positive driver genes.

Radiomics nomogram in aiding preoperatively dilatation and curettage in differentiating type II and type I endometrial cancer.

AIM: To established a radiomics nomogram for improving the dilatation and curettage (D&C) result in differentiating type II from type I endometrial cancer (EC) preoperatively. MATERIAL AND METHODS: EC patients (n=875) were enrolled retrospectively and divided randomly into a training cohort (n=437) and a test cohort (n=438), according to the ratio of 1:1. Radiomics signatures were extracted and selected from apparent diffusion coefficient (ADC) maps. A multivariate logistic regression analysis was used to identify the independent clinical risk factors. An ADC based-radiomics nomogram was built by integrating the selected radiomics signatures and the independent clinical risk factors. Decision curve analysis (DCA) was conducted to determine the clinical usefulness of the radiomics nomogram. The net reclassification index (NRI) and total integrated discrimination index (IDI) were calculated to compare the discrimination performances between the radiomics nomogram and the D&C result. RESULTS: Receiver operating characteristic (ROC) curves showed that the clinical risk factors, the D&C, and the ADC based-radiomics nomogram yielded areas under the ROC curves (AUCs) of 0.70 (95% CI: 0.64-0.76), 0.85 (95% CI: 0.80-0.89), and 0.93 (95% CI: 0.90-0.96) in the training cohort and 0.64 (95% CI: 0.57-0.71), 0.82 (95% CI: 0.77-0.87) and 0.91 (95% CI: 0.87-0.95) in the test cohort, respectively. The DCA, NRI, and IDI demonstrated the clinically usefulness of the ADC based-radiomics nomogram. CONCLUSION: The ADC-based radiomics nomogram could be used to improve the D&C result in differentiating type II from type I EC preoperatively.

[Congenital factor X deficiency: a retrospective analysis of 11 cases].

Objective: To analyze the clinical characteristics, laboratory examination, diagnosis, treatment, and outcome of hereditary factor Ⅹ (FⅩ) deficiency. Methods: Clinical data of 11 patients with congenital FⅩ deficiency were retrospectively analyzed from July 2009 to February 2021. Results: There were 3 males and 8 females. Median age was 39 (5-55) years. The media duration of follow-up was 81.67 (1.87-142.73) months. Of the 11 patients, 10 had bleeding symptoms, 7 had ecchymosis or hemorrhage after skin bump, 7 had nosebleed, 6 had gingival hemorrhage, and 1 had muscle hematoma. Among the female patients, 6 had menorrhagia and 1 experienced bleeding after vaginal delivery. Family history of FⅩ deficiency was found in one case. Eight patients had a history of surgery, and four had postoperative bleeding. Laboratory findings were characterized by significantly prolonged activated partial thromboplastin time, prothrombin time, and decreased FⅩ activity (FⅩ∶C) . Four cases underwent gene mutation analysis and five new mutations were found. Four cases were treated with prothrombin complex concentrates (PCC) and seven cases with fresh frozen plasma (FFP) . One female patient had significantly reduced menstrual volume after PCC prophylactic therapy. One patient received FFP for prophylactic infusion with no bleeding during and after the operation. Conclusion: Most patients with congenital FⅩ deficiency had bleeding symptoms and there was no significant correlation between severity of bleeding symptoms and FⅩ∶C. Prophylaxis should be applied in patients with severe bleeding tendencies. Gene mutation test is significant for screening, diagnosis, and prognosis prediction of congenital FX deficiency.

[Splenectomy for the treatment of common variable immunodeficiency complicated with cytopenia: report of one case and literature review].

Objective: To improve the understanding of splenectomy for treating common variable immunodeficiency complicated with cytopenia. Methods: A case of common variable immunodeficiency complicated with cytopenia was reported, and the literature was reviewed. Results: The patient, female, 16 years old, was hospitalized for eight years due to thrombocytopenia; she manifested recurrent thrombocytopenia with leukopenia since adolescence. The patient was diagnosed with common variable immunodeficiency with repeated mild infections, splenomegaly, and significantly reduced plasma immunoglobulin levels. Additionally, splenectomy was performed with adequate immunoglobulin replacement therapy, and the pathology confirmed hypersplenism; her blood cell level returned to normal after surgery. Conclusions: Common variable immunodeficiency has various clinical manifestations and can be complicated with cytopenia. Under the premise of adequate immunoglobulin replacement therapy, splenectomy is a safe and effective treatment for common variable immunodeficiency in patients with recurrent cytopenia.

[Frequency characteristics of horizontal semicircular canals damage and the ultrastructure analysis of crista ampullaris in patients with Meniere's disease].

Objective: To investigate the frequency characteristics and the pathological characteristics of the horizontal crista ampullaris in patients with Meniere's disease,and to analyse its structural basis. Methods: Between March, 2019 and November, 2019, seventy-two patients diagnosed as Meniere's disease (27 males and 45 females, aged from 13 to 74 years, with a course of disease ranging from 4 months to 32 years)in Shandong Provincial ENT Hospital were included.Caloric test, sinusoidal harmonic acceleration test (SHA), video-head impulse test (v-HIT), Gadolinium-enhanced inner-ear 3D-FLAIR MRI and pure tone audiometry were conducted in the patients. The function of the horizontal semicircular canal in these patients were analysed as well as its relationship with the degree of endolymphatic hydrops,clinical stage and duration. Light microscopy and transmission electron microscopy were used to observe the ultrastructure of horizontal semicircular canal crista ampullaris from six patients with refractory Meniere's disease who underwent labyrinthectomy. The number of type Ⅰ and type Ⅱ vestibular hair cells, the common pathophysiological changes of horizontal semicircular canal crista ampullaris were investigated in these patients. Statistical analysis was performed using SPSS 19.0. Results: With the increase of detection frequency, the abnormal rate decreased gradually. The abnormal rate of caloric test was 69.4% (50/72), SHA 51.4% (37/72), V-HIT 36.1% (26/72), comparation of the positive rate among the three tests showed statistically significant differences(P<0.05).Neither caloric test nor SHA had correlation with the degree of hydrops(P>0.05), but v-HIT(r=0.434,P<0.01).There was correlation with clinical stage to SHA and v-HIT(r=0.338,0.462,P<0.01), except caloric test(P>0.05).No significant relation was found with caloric test, SHA, v-HIT and course of disease(P>0.05).Morphological observation found abnormal monolayer epithelialization of the horizontal semicircular canal crista ampullaris significantly decreased number of type Ⅱ hair cells compared with type Ⅰhair cells. Hair cells showed perinuclear vacuolization, cytoplasmic vacuoles, mitochondrial electron density increasement and loss of stereocilia. Conclusions: The horizontal semicircular canal damage in the patients with Meniere's disease has a frequency-dependent characteristic, mainly occurres in low frequency area. With progress of the disease, the high frequency area of ampulla will be impaired gradually, and it is related to the degree of endolymphatic hydrops and hearing level. Hair cell injury would be observed,the frequency characteristics may be more associated with the disorder of type Ⅱ hair cells.

[A prospective study of the effect and mechanism of autologous platelet-rich plasma combined with Meek microskin grafts in repairing the wounds of limbs in severely burned patients].

Objective: To observe the effect of autologous platelet-rich plasma (PRP) combined with Meek microskin grafts in repairing the wounds of limbs in severely burned patients, and to explore the mechanism. Methods: The prospective controlled research method was used. From September 2016 to January 2020, 16 patients aged 18-69 years, with extensive deep burns, including 9 males and 7 females, who met the selection criteria were admitted to the Department of Burns and Plastic Surgery of the 909th Hospital of the Joint Logistic Support Force of PLA. The bilateral limbs with similar injury in 8 patients were divided into Meek skin grafting+PRP group and Meek skin grafting alone group according to the random number table; in the other 8 patients, the limbs with severer injury were included in Meek skin grafting+PRP group, and the limbs on the other side were included in Meek skin grafting alone group. The wounds of affected limbs in the two groups were treated correspondingly. On post surgery day (PSD) 10, the survival and fusion of Meek microskin grafts were observed and the survival rate and fusion rate were calculated; the histological morphology and the angiogenesis of the basal tissue of Meek microskin graft were observed by hematoxylin-eosin staining and immunohistochemical staining, respectively, with the microvessels being counted. Data were statistically analyzed with paired sample t test. Results: On PSD 10, the wounds of affected limbs in Meek skin grafting+PRP group were dry, and most of the transplanted skin grafts were closely adhered to the basal tissue; while a small amount of exudate could be found in the wounds of affected limbs in Meek skin grafting alone group, and a small part of the transplanted microskin grafts fell off or poorly attached to the basal tissue. On PSD 10, the survival rate and the fusion rate of Meek microskin grafts in the wounds of affected limbs in Meek skin grafting+PRP group were (94±3)% and (86±4)%, which were significantly higher than (89±4)% and (79±4)% of Meek skin grafting alone group, respectively (t=3.633, 4.229, P<0.01). On PSD 10, the basal epidermis was closely connected with dermis of Meek microskin grafts in the wounds of affected limbs in Meek skin grafting+PRP group, with more inflammatory cell infiltration and active microvascular hyperplasia, while the basal epidermis was less closely connected with dermis of Meek microskin grafts in the wounds of affected limbs in Meek skin grafting alone group, with obvious degeneration of collagen fibers under the dermis, less inflammatory cell infiltration, and slightly poor microvascular hyperplasia. On PSD 10, the distribution of microvessels in basal tissue of Meek microskin grafts in the wounds of affected limbs in Meek skin grafting+PRP group were densely clustered, while the distribution of microvessels in Meek skin grafting alone group were scattered, sparse, and dotted. On PSD 10, the number of microvessels in basal tissue of Meek microskin grafts in the wounds of affected limbs in Meek skin grafting+PRP group was 36±6 in each 400-fold visual field, which was significantly more than 29±7 of Meek skin grafting alone group (t=2.671, P<0.05). Conclusions: Autologous PRP can effectively promote the survival rate and fusion rate of Meek microskin grafts in the wounds of limbs after escharectomy in severely burned patients by promoting angiogenesis at the base of Meek microskin grafts.

[Endovascular stenting for idiopathic intracranial hypertension with different types of venous sinus stenosis].

Objective: To evaluate the efficacy of endovascular stenting of various types of venous sinus stenosis in idiopathic intracranial hypertension (IIH). Method: Clinical, radiological, and manometric data before and after stenting in venous sinus stenosis were retrospectively analyzed in 99 IIH patients who were refractory to medical therapy or rapidly progressed between July 2004 to July 2019. The follow-up period was between 2.3 months to 11 years. Results: Our study enrolled 21 men (21.2%)and 78 women (78.8%) with average body mass index (BMI) 19.2-40.6(27.0±4.4) kg/m2 and median age 37 years. Before stent placement, the mean transverse sinus stenosis gradient was 1-59(26±8) mmHg. Patients with extrinsic stenosis were younger than those with intrinsic and mixed stenosis. In all cases, stenting was effective for papilledema. Fifty patients complained of headaches. Pulsatile tinnitus in twenty-eight patients completely alleviated after stenting. In one patient, replacement of stent did not improve symptoms, and a subsequent CSF diversion procedure was performed and effective. Conclusion: Irrespective of the type of stenosis, stenting of venous sinus stenosis is an effective treatment for IIH. Patients with persistent papilledema post-stenting and elevated transverse pressure pre-stenting should be followed closely as high risk of stenting failure may occur and further diversion procedure is needed.

The production of single cell protein from biogas slurry with high ammonia-nitrogen content by screened Nectaromyces rattus.

In this study, a novel method was proposed to obtain single cell protein (SCP) in yeast by using biogas slurry as culture medium. The results show that Nectaromyces rattus was the most efficient at producing SCP among the 7 different yeasts studied. Acetic acid was a better pH regulator than hydrochloric acid. After culture with the initial NH4+-N concentration 2,000 mg/L, C/N ratio 6:1, the initial pH 5.50 and rotation speed of 200 rpm, a total cell dry weight of 12.58 g/L with 35.96% protein content was obtained. Nineteen amino acids accounted for 46.85% of cell dry weight, and proline content was as high as 12.0% of the cell dry weight. However, sulfur-containing amino acids, including methionine and cystine, were deficient. Further research should focus on the high cell density culture to increase SCP production.

[Effectiveness of different screening strategies for cardiovascular diseases prevention in a community-based Chinese population: A decision-analytic Markov model].

OBJECTIVE: To evaluate the potential effectiveness of different screening strategies for cardiovascular diseases prevention in a community-based Chinese population from economically developed area of China. METHODS: Totally 202 179 adults aged 40 to 74 years without cardiovascular diseases at baseline (January 1, 2010) were enrolled from the Chinese electronic health records research in Yinzhou (CHERRY) study. Three scenarios were considered: the screening strategy based on risk charts recommended by the 2020 Chinese guideline on the primary prevention of cardiovascular diseases in Chinese adults aged 40-74 years (Strategy 1); the screening strategy based on the prediction for atherosclerotic cardiovascular disease risk in China (China-PAR) models recommended by the 2019 Guideline on the assessment and management of cardiovascular risk in China in Chinese adults aged 40-74 years (Strategy 2); and the screening strategy based on the China-PAR models in Chinese adults aged 50-74 years (Strategy 3). According to the guidelines, individuals who were classified into medium- or high-risk groups after cardiovascular risk assessment by the corresponding strategies would be introduced to lifestyle intervention, while high-risk population would take medication in addition. Markov model was used to simulate different screening scenarios for 10 years (cycles), using parameters mainly from the CHERRY study, as well as published data, Meta-analyses and systematic reviews for Chinese populations. The life year gained, quality-adjusted life year (QALY) gained, number of cardiovascular disease events/deaths could be prevented and number needed to be screened (NNS) were calculated to compare the effectiveness between the different strategies. One-way sensitivity analysis on uncertainty of cardiovascular disease incidence rate and probabilistic sensitivity analysis on uncertainty of distributions for the hazard ratios were conducted. RESULTS: Compared with non-screening strategy, QALYs gained were 1 433 [95% uncertainty interval (UI): 969-1 831], 1 401 (95%UI: 936-1 807), and 716 (95%UI: 265-1 111) for the Strategies 1, 2, and 3; and the NNS per QALY in the above strategies were 141 (95%UI: 110-209), 144 (95%UI: 112-216), and 198 (95%UI: 127-529), respectively. The Strategies 1 and 2 based on different guidelines showed similar effectiveness, while more benefits were found for screening using China-PAR models in adults aged 40-74 years than those aged 50-74 years. The results were consistent in the sensitivity analyses. CONCLUSION: Screening for cardiovascular diseases in Chinese adults aged above 40 years seems effective in coastal developed areas of China, and the different screening strategies based on risk charts by the 2020 Chinese guideline on the primary prevention of cardiovascular diseases or China-PAR models by the 2019 Guideline on the assessment and management of cardiovascular risk in China may have similar effectiveness.

Drug-eluting bead bronchial arterial chemoembolization vs. chemotherapy in treating advanced non-small cell lung cancer: comparison of treatment efficacy, safety and quality of life.

OBJECTIVE: This present study aimed to compare the treatment response, survival profile, quality of life (QoL), and safety between drug-eluting bead bronchial arterial chemoembolization (DEB-BACE) and chemotherapy in the treatment of advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Totally, 44 advanced NSCLC patients were analyzed retrospectively and were divided into DEB-BACE group (n=23) and chemotherapy group (n=21). Treatment response, European Organization for Research and Treatment of Cancer QoL Questionnaire-Core 30 (EORTC QLQ-C30), progression-free survival (PFS), overall survival (OS), and adverse events were assessed during the follow-up. RESULTS: At month (M) 2, M4 and M6 post initial treatment, objective response rate (ORR) was elevated (all p <0.05), and disease control rate (DCR) tended to be higher (without statistical significance) in DEB-BACE group compared with chemotherapy group. Regarding the QLQ-C30 item scores, the scores of physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning were increased, while the scores of nausea and vomiting, dyspnea, constipation were decreased in DEB-BACE group compared with chemotherapy group (all p <0.05). Based on survival profile, DEB-BACE group achieved better PFS and OS compared with chemotherapy group independent of TNM stage, which was also supported by further subgroup analysis and Cox's proportional hazard regression analysis (all p <0.05). Furthermore, two groups all exhibited mild and tolerable adverse events. CONCLUSIONS: DEB-BACE has the potential to be an additional treatment option with favorable therapeutic efficacy, improved QoL, and tolerable safety for advanced NSCLC patients.

Prognostic significance of palliative gastrectomy in incurable advanced gastric cancer: a retrospective cohort study and meta-analysis.

OBJECTIVE: There is controversy regarding the role of palliative gastrectomy in patients with incurable advanced gastric cancer requiring surgical intervention. The present retrospective cohort study and meta-analysis aimed to determine whether palliative gastrectomy plus chemotherapy can prolong the survival of patients with incurable advanced gastric cancer requiring surgical intervention. PATIENTS AND METHODS: The data from 153 patients diagnosed with incurable advanced gastric cancer requiring surgical intervention at our institute between January 2000 and December 2012 were retrospectively reviewed. We analyzed the value of palliative gastrectomy and identified the potential prognostic factors. We also conducted a meta-analysis of 10 studies to validate our results. RESULTS: Multivariate analysis indicated that palliative gastrectomy was a favorable independent prognostic factor for prolonged overall survival in incurable advanced gastric cancer patients requiring surgical intervention (p=0.029). The median survival of patients who underwent palliative gastrectomy plus chemotherapy was significantly longer than that of those who underwent non-resection surgery plus chemotherapy (12 months vs. 9 months, p=0.020). The patients in the non-resection surgery plus chemotherapy group exhibited significantly shorter overall survival than those in the D1+ lymphadenectomy group, D2 lymphadenectomy group, or distal gastrectomy group (p=0.021, p=0.007, and p=0.006, respectively). Our meta-analysis revealed that gastrectomy plus chemotherapy improved long-term survival in incurable advanced gastric cancer patients (hazard ratio (HR): 0.48; 95% confidence interval (CI): 0.35-0.67; p<0.001). CONCLUSIONS: Palliative gastrectomy plus chemotherapy may improve overall patient survival compared with non-resection operations plus chemotherapy in incurable advanced gastric cancer patients requiring surgical intervention.

LncRNA SNHG6 regulating Hedgehog signaling pathway and affecting the biological function of gallbladder carcinoma cells through targeting miR-26b-5p.

OBJECTIVE: Long-chain non-coding RNA (LncRNA) is abnormally expressed in various malignant tumors. In recent years, it has been found that the expression of LncRNA SNHG6 is upregulated in gallbladder carcinoma tissues, which participated in the occurrence and development of gallbladder carcinoma. However, the clinical value of SNHG6 in gallbladder cancer serum is not clear, and there are few studies regulating the biological function of gallbladder carcinoma cells. This study aimed to investigate LncRNA SNHG6 and miR-26b-5p in gallbladder carcinoma and its related mechanisms. PATIENTS AND METHODS: From February 2017 to February 2019, altogether 68 cases of gallbladder cancer patients admitted to the Yantai Yeda Hospital were collected as a study group, 70 healthy people as a control group. Gallbladder cancer cells and human colorectal mucosa cells were purchased. Sh-SNHG6, si-SNHG6, NC, miR-26b-5p-inhibitor, and miR-26b-5p-mimics were transfected into GBC-SD and NOZ cells. For the detection of SNHG6 and miR-26b-5p in samples we used qRT-PCR, WB was applied for the decreased protein expression of Gli1, Gli2, Shh, Smo, N-cadherin, vimentin, Snail, E-Cadherin, and Gli3 in cells. MTT assay was applied for the detection of cell proliferation, transwell assay for cell invasion, and flow cytometry assay for apoptosis. RESULTS: SNHG6 was highly expressed in gallbladder carcinoma, miR-26b-5p was downregulated, and the area under curve (AUC) of LncRNA SNHG6 and miR-26b-5p was more than 0.8. LncRNA SNHG6 and miR-26b-5p were related to age, sex, tumor invasion, differentiation degree, tumor location, and tumor-node-metastasis (TNM) staging of gallbladder cancer patients. Silencing of SNHG6 and upregulation of miR-26b-5p could promote cell apoptosis, inhibit cell growth, and epithelial-mesenchymal transition (ETM). Silencing of SNHG6 and upregulation of miR-26b-5p could inhibit Gli1, Gli2, Shh, Smo, N-cadherin, vimentin and Snail proteins, and promote upregulation of Gli3 and E-Cadherin expression. Dual-Luciferase report confirmed that SNHG6 and miR-26b-5p have targeted relationship. Rescue experiments showed that after co-transfecting sh-SNHG6+miR-26b-5p-mimics, and si-SNHG6+miR-26b-5p-inhibitor into GBC-SD and NOZ, the proliferation, invasion and apoptosis of cells were not different from those of miR-NC group without transfection sequence. CONCLUSIONS: Inhibition of LncRNA SNHG6 expression can upregulate miR-26b-5p mediated Hedgehog signaling pathway, affect epithelial-mesenchymal transition, proliferation and invasion of cells, so LncRNA SNHG6is hoped to be a latent therapeutic target for gallbladder carcinoma.

[Congenital factor â ¦ deficiency: a retrospective analysis of 43 cases].

Objective: To explore the pathogenesis, clinical characteristics, laboratory findings, diagnosis, treatment, and prognosis of congenital factor Ⅶ (FⅦ) deficiency. Methods: Clinical data of 43 patients with congenital FⅦ deficiency diagnosed from April 1999 to September 2019 were retrospectively analyzed. Results: There were 27 females and 16 males. Median age was 16 (1-70) years. Family history was found in 6 cases. There were 29 (67.4%) cases with bleeding symptoms, most common of which were mucocutaneous bleeding (13 cases, 30.2%) , oral bleeding (13 cases, 30.2%) , and epistaxis (9 cases, 20.9%) . Menorrhagia occurred in 11 cases (47.6% of female patients who were in fertile age) . Laboratory findings were characterized by significantly prolonged prothrombin time (PT) , normal partial thromboplastin time (APTT) , and decreased FⅦ activity (FⅦ∶C) . Ten cases received gene mutation analysis and 3 new mutations were found. Fourteen cases (32.6%) were treated with prothrombin complex concentrates (PCC) , 12 (27.9%) with fresh frozen plasma (FFP) , and 3 (7.0%) with human recombinant activated FⅦ (rFⅦa) . Twenty cases (46.5%) with no or mild bleeding symptoms did not receive any replacement therapy. Previous bleeding symptoms recurred in 5 patients (11.6%) , 8 females still had heavy menstrual bleeding, and 9 patients (20.9%) were lost to follow-up. Conclusion: Most patients with congenital FⅦ deficiency have mild or no bleeding symptoms, but have a tendency to excessive bleeding after surgery or trauma. There is no significant correlation between FⅦ∶C and severity of bleeding symptoms. Prophylaxis should be applied in patients with severe bleeding symptoms and rFⅦa is the first choice. Gene mutation test is significant for screening, diagnosis, and prognosis prediction of the disease.