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.

Combined radiomics nomogram of different machine learning models for preoperative distinguishing intraspinal schwannomas and meningiomas: a multicenter and comparative study.

AIMS: The objective of our study was to establish and verify a novel combined model based on multiparameter magnetic resonance imaging (MRI) radiomics and clinical features to distinguish intraspinal schwannomas from meningiomas. MATERIALS AND METHODS: This research analyzed the preoperative magnetic resonance (MR) images and clinical characteristics of 209 patients with intraspinal tumors who received tumor resection at three institutions. 159 individuals from institutions 1 and 2 were randomly assigned into a training group (n=111) and a test group (n=48) in a 7-3 ratio. A nomogram was constructed using the training cohort and was internally and externally verified in the test cohort and an independent validation cohort (n=50). Model performance was assessed utilizing the area under the curve (AUC) of receiver operating characteristics (ROC), decision curve analysis (DCA), and calibration curves. RESULTS: The nomogram exhibited superior predictive efficacy in distinguishing between spinal schwannomas and meningiomas when compared to both the radiomics model and the clinical model. The nomogram yielded AUCs of 0.994, 0.962, and 0.949 in the training, test, and external validation cohorts, respectively, indicating its exceptional differentiating ability. The DCAs demonstrated that the nomogram yielded the best net benefit. The calibration curves indicated that the nomogram got good agreement between the predicted and the actual observation. CONCLUSION: This research suggests that the nomogram incorporating clinical and radiomic features may be an effective auxiliary tool for distinguishing between intraspinal schwannomas and meningiomas, and has important clinical significance for clinical decision-making and prognosis prediction.

[Clinical pathway in Chinese county for lung cancer diagnosis and treatment (2023 edition)].

Lung cancer (LC) is the leading cause of death among patients with cancer both in worldwide and China. China accounts for 11.4% of the total number of cancer cases and 18.0% of the total number of cancer deaths in the world. Standardizing the diagnosis and treatment of LC is a key measure to improve the survival rate of LC patients and reduce the mortality rate. However, county hospitals generally face the problem of inaccessibility to advanced diagnostic and treatment technologies. Therefore, when developing quality control standards and clinical diagnosis and treatment specifications, it is necessary to combine the actual situation of county hospitals and formulate specific recommendations. The recommendations of treatment measures also need to consider the approval status of indications and whether it is included in the National Reimbursement Drug List (NRDL), to ensure the access to medicines. In order to solve the above problems, based on existing guidelines at home and abroad and the clinical work characteristics of county hospitals, the first clinical pathway in Chinese county for LC diagnosis and treatment (2023 edition) was compiled. This pathway elaborated on the imaging diagnosis, pathological diagnosis, molecular testing, and precision medicine based on histological-pathological types, tumor-node-metastasis (TNM) classification, and molecular classification, developed different diagnosis and treatment processes for different types of LC patients. Simultaneously, according to the actual work situation of county hospitals, the diagnosis and treatment recommendations in clinical scenarios are divided into basic strategies and optional strategies for elaboration. The basic strategies are the standards that county hospitals must meet, while the optional strategies provide more choices for hospitals, which are convenient for county doctors to put into clinical practice. All the recommended diagnostic and treatment plans strictly refer to existing guidelines and consensus, ensuring the scientificity.

[Developing pathology guidelines and consensus: methods and considerations].

Pathological diagnosis is vital in medicine. Developing and implementing high-quality pathology guidelines and consensus can enhance disease diagnosis accuracy and reduce unnecessary misdiagnosis and missed diagnoses. This article will cover the current status of pathology guidelines and consensus, methods for high-quality development, and the distinctions between them. Additionally, it will provide thoughts and suggestions for promoting their development in China.

[The association between body mass index and in-hospital major adverse cardiovascular and cerebral events in patients with acute coronary syndrome].

Objective: To assess the association between body mass index (BMI) and major adverse cardiovascular and cerebrovascular events (MACCE) among patients with acute coronary syndrome (ACS). Methods: This was a multicenter prospective cohort study, which was based on the Improving Care for Cardiovascular Disease in China (CCC) project. The hospitalized patients with ACS aged between 18 and 80 years, registered in CCC project from November 1, 2014 to December 31, 2019 were included. The included patients were categorized into four groups based on their BMI at the time of admission: underweight (BMI<18.5 kg/m2), normal weight (BMI between 18.5 and 24.9 kg/m2), overweight (BMI between 25.0 and 29.9 kg/m2), and obese (BMI≥30.0 kg/m2). Multivariate logistic regression models was used to analyze the relationship between BMI and the risk of in-hospital MACCE. Results: A total of 71 681 ACS inpatients were included in the study. The age was (63.4±14.7) years, and 26.5% (18 979/71 681) were female. And the incidence of MACCE for the underweight, normal weight, overweight, and obese groups were 14.9% (322/2 154), 9.5% (3 997/41 960), 7.9% (1 908/24 140) and 7.0% (240/3 427), respectively (P<0.001). Multivariate logistic regression analysis showed a higher incidence of MACCE in the underweight group compared to the normal weight group (OR=1.30, 95%CI 1.13-1.49, P<0.001), while the overweight and obese groups exhibited no statistically significant difference in the incidence of MACCE compared to the normal weight group (both P>0.05). Conclusion: ACS patients with BMI below normal have a higher risk of in-hospital MACCE, suggesting that BMI may be an indicator for evaluating short-term prognosis in ACS patients.

Impaired function of skeletal stem cells derived from growth plates in ovariectomized mice.

INTRODUCTION: Mouse skeletal stem cells (mSSCs, CD45-Ter119-Tie2-CD51+Thy-6C3-CD105-CD200+population) are identified in growth plates (GP) and play important roles in bone regeneration. However, the role of mSSCs in osteoporosis remains unclear. MATERIALS AND METHODS: The GP were stained by HE staining, and the mSSC lineage was analyzed by flow cytometry at postnatal of 14 days and 30 days in wild-type mice. The mice (8 weeks) were either sham operated or ovariectomy (OVX) and then sacrificed at 2, 4 and 8 w. The GP were stained by Movat staining, and mSSC lineage was analyzed. Then, mSSCs were sorted by fluorescence-activated cell sorting (FACS); the clonal ability, chondrogenic differentiation and osteogenic differentiation were evaluated, and the changed genes were analyzed by RNA-seq. RESULTS: The percentage of mSSCs were decreased with the narrow GP. Heights of GP were decreased significantly in 8w-ovx mice compared with 8w-sham mice. We found the percentage of mSSCs were decreased in mice at 2w after ovx, but the cell numbers were not changed. Further, the percentage and cell numbers of mSSCs were not changed at 4w and 8w after ovx. Importantly, the clonal ability, chondrogenic differentiation and osteogenic differentiation of mSSCs were impaired at 8w after ovx. We found 114 genes were down-regulated in mSSCs, including skeletal developmental genes such as Col10a1, Col2a1, Mef2c, Sparc, Matn1, Scube2 and Dlx5. On the contrary, 526 genes were up-regulated, including pro-inflammatory genes such as Csf1, Nfkbla, Nfatc2, Nfkb1 and Nfkb2. CONCLUSION: Function of mSSCs was impaired by up-regulating pro-inflammatory genes in ovx-induced osteoporosis.

Impaired ascending aortic elasticity in fetuses with tetralogy of Fallot.

OBJECTIVES: Aortic wall stiffness has been reported in infants with tetralogy of Fallot (ToF) and may contribute to long-term aortic dilation even after corrective repair surgery. However, little is known about aortic elasticity in fetuses with ToF and the association with neonatal aortic dilation. The objectives of this study were to assess measures of elasticity of the ascending aorta (AAo) in fetuses with ToF and explore the association with neonatal aortic annular dilation in this population. METHODS: Seventy-six singleton fetuses with ToF and 76 control fetuses of singleton low-risk pregnancies were enroled into this prospective study. Fetal measures of AAo elasticity, including mean longitudinal strain (MLS), global circumferential strain (GCS) and fractional area change (FAC), were assessed by velocity vector imaging. The z-score of the aortic valve (AV) diameter at the level of the annulus, as a measure of aortic annular dilation, was determined in newborns. Logistic regression analysis was used to investigate the association between fetal measures of AAo elasticity and neonatal aortic annular dilation (defined as an AV annular z-score > 2) in cases with ToF identified prenatally. RESULTS: Median MLS, GCS and FAC in fetuses with ToF were lower than those in normal fetuses (7.52% vs 12.15% for MLS, 22.05% vs 29.73% for GCS and 34.2% vs 48.3% for FAC, all P < 0.001). Aortic annular dilation was present in 53/76 (69.7%) newborns with ToF. After adjustment for gestational age at fetal echocardiography and birth weight, fetal MLS, GCS and FAC were independently associated with aortic annular dilation neonatally, with odds ratios of 0.66, 0.78 and 0.82, respectively (P < 0.05). The best cut-off values of these prenatal measures of AAo elasticity for predicting neonatal aortic annular dilation in fetuses with ToF were 9.02% for MLS, 23.56% for GCS and 37.2% for FAC (P < 0.001), with areas under the receiver-operating-characteristics curves of 0.94, 0.91 and 0.93, respectively. CONCLUSION: Measures of AAo elasticity are decreased in fetuses with ToF. Impaired AAo elasticity in the fetal period is associated with aortic annular dilation postnatally. Additional research is needed to evaluate the relationship between the AAo elasticity injury pattern and degeneration of AAo elasticity under stress as well as the long-term outcome in this population. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Circ_0002111/miR-134-5p/FSTL1 signal axis regulates tumor progression and glycolytic metabolism in papillary thyroid carcinoma cells.

BACKGROUND: Circular RNAs (circRNAs) have essential roles in the malignant progression of papillary thyroid carcinoma (PTC). Circ_0002111 was reported to facilitate cell proliferation and invasion abilities in PTC. This study was performed to explore the regulatory mechanism of circ_0002111 in PTC progression. METHODS: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used for the level detection of circ_0002111, microRNA-134-5p (miR-134-5p) and Follistatin Like 1 (FSTL1). Cell proliferation was assessed by 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay, EdU assay and colony formation assay. Cell migration ability was determined by transwell assay. Glycolysis was analyzed by extracellular acidification rate (ECAR), oxygen consumption rate (OCR), glucose consumption and lactate production. The protein quantification was performed through western blot. Xenograft tumor assay was used for the functional analysis of circ_0002111 in vivo. The target interaction was confirmed by dual-luciferase reporter assay and RNA pull-down assay. RESULTS: The significant upregulation of circ_0002111 was detected in PTC samples and cells. PTC cell proliferation, migration and glycolytic metabolism were suppressed after circ_0002111 downregulation. PTC tumorigenesis in vivo was also inhibited by circ_0002111 knockdown. In addition, circ_0002111 could target miR-134-5p and si-circ_0002111#1-induced inhibition of PTC progression was relieved by miR-134-5p expression downregulation. Furthermore, FSTL1 was a target gene for miR-134-5p and miR-134-5p served as a tumor repressor in PTC by targeting FSTL1. Moreover, circ_0002111 could increase the FSTL1 level via sponging miR-134-5p. CONCLUSION: All results indicated that circ_0002111 promoted the malignant behaviors of PTC cells partly by regulating the miR-134-5p/FSTL1 molecular network.

The 2021 SIIM-FISABIO-RSNA Machine Learning COVID-19 Challenge: Annotation and Standard Exam Classification of COVID-19 Chest Radiographs.

We describe the curation, annotation methodology, and characteristics of the dataset used in an artificial intelligence challenge for detection and localization of COVID-19 on chest radiographs. The chest radiographs were annotated by an international group of radiologists into four mutually exclusive categories, including "typical," "indeterminate," and "atypical appearance" for COVID-19, or "negative for pneumonia," adapted from previously published guidelines, and bounding boxes were placed on airspace opacities. This dataset and respective annotations are available to researchers for academic and noncommercial use.

[Influence of paper mixing pads thickness on the compressive strength of glass ionomer cement].

OBJECTIVE: To explore the influence of the thickness of mixed cardboard on the compressive strength of glass ionomer cement and the associated factors. METHODS: Three different types of glass ionomer cements were mixed on the top of 60, 40, 20 and 1 pieces of paper (P60, P40, P20 and P1), respectively. The compressive strength of the materials was tested after solidification, and the bubble rate was calculated with the assistance of scanning electron microscope. RESULTS: (1) Compressive strength: ① ChemFil Superior glass ionomer (CF): The average compressive strength of P1 group was the highest, which was significantly different from that of P40 and P60 groups (P values were 0.041 and 0.032 respectively); ② To Fuji IX GP glass ionomer (IX): The average compressive strength of P1 group was the highest, which was statistically different from that of P40 and P60 groups (P values were 0.042 and 0.038 respectively); ③ Glaslonomer FX-Ⅱ glass ionomer cement (FX): The average compressive strength of P1 group was the highest, which was statistically different from that of P20, P40 and P60 groups (P values were 0.031, 0.040 and 0.041 respectively), but there was no statistical difference among the other groups. All the three materials showed that the compressive strength of glass ions gradually increased with the decrease of the thickness of the blended paperboard, and the two materials had a highly linear negative correlation, the correlation coefficients of which were CF-0.927, IX-0.989, FX-0.892, respectively. (2) Scanning electron microscope: P1 group had the least bubbles among the three materials. CONCLUSION: It indicates that the thickness of mixed cardboard has a negative correlation with the compressive strength of glass ions. The thicker the mixed cardboard is, the greater the elasticity is. Excessive elasticity will accelerate the mixing speed when the grinding glass ions. Studies have shown that the faster the speed of artificial mixing is, the more bubbles is produced.The thicker ther mixed cardboard is, the more bubblesn are generated by glass ionomer cement, and the higher the compressive strength is. Using one piece of paper board to mix glass ionomer cement has the least bubbles and can obtain higher compressive strength.

[Clinical and molecular genetic analysis of Angelman syndrome with oculocutaneous albinism type 2: A case report and literature review].

To summarize the clinical diagnosis and treatment process and genetic test results and characteristics of one child with Angelman syndrome (AS) complicated with oculocutaneous albinism type 2 (OCA2), and to review the literature. "Angelman syndrome" "P gene" and "Oculocutaneous albinism type 2" were used as keywords to search at CNKI, Wanfang, and PubMed databases (from creation to December 2019). Then all the patients were analyzed. The patient in this study was a girl aged 1 year. After birth, she was found to present as white body, yellow hair, and nystagmus. She could raise her head at the age of 2 months and turn over at the age of 7 months. The head circumference was 42 cm and she could not sit alone or speak at present. Trio-based exome sequencing revealed that the patient carried a homozygous mutation of c.168del (p.Gln58ArgfsTer44) in the P gene, and her father was heterozygous and her mother was wild-type. The detection of copy number variation showed deletion on the maternal chromosome at 15q11.2-13.1 region (P gene located in this region) in the patient. Until December 2019, a total of 4 cases in the 4 literature had been reported. Adding our case here, the 5 cases were summarized and found that all the cases showed white skin, golden hair, and shallow iris after birth. Comprehensive developmental delay was found around 6 months of age after birth, and the language remained undeveloped in 2 cases till follow-up into childhood. Seizures occurred in 4 patients. Two cases had ataxia. All the 5 cases had acquired microcephaly. Two cases had a family history of albinism. Electroencephalogram monitoring was completed in 3 cases and the results were abnormal. Genetic tests showed that all the 5 cases had deletion on maternal chromosome at 15q11-13 region. Four cases carried mutation of P gene on paternal chromosome. And 1 case was clinically diagnosed as OCA2 without P gene test. AS combined with OCA2 is relatively rare. OCA2 is easily diagnosed based on the obvious clinical manifestations after birth. When combined with clinical manifestations such as neurodevelopmental delay, it might indicate the possibility of AS that is hardly diagnosed clinically at an early stage. Genetic tests can reveal the cross-genetic phenomenon of AS and OCA2 and the complex of them can be eventually diagnosed.

[Read-through circular RNA rt-circ-HS promotes hypoxia inducible factor 1α expression and renal carcinoma cell proliferation, migration and invasiveness].

OBJECTIVE: To identify and characterize read-through RNAs and read-through circular RNAs (rt-circ-HS) derived from transcriptional read-through hypoxia inducible factor 1α (HIF1α) and small nuclear RNA activating complex polypeptide 1 (SNAPC1) the two adjacent genes located on chromosome 14q23, in renal carcinoma cells and renal carcinoma tissues, and to study the effects of rt-circ-HS on biological behavior of renal carcinoma cells and on regulation of HIF1α. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing were used to examine expression of read-through RNAs HIF1α-SNAPC1 and rt-circ-HS in different tumor cells. Tissue microarrays of 437 different types of renal cell carcinoma (RCC) were constructed, and chromogenic in situ hybridization (ISH) was used to investigate expression of rt-circ-HS in different RCC types. Small interference RNA (siRNA) and artificial overexpression plasmids were designed to examine the effects of rt-circ-HS on 786-O and A498 renal carcinoma cell proliferation, migration and invasiveness by cell counting kit 8 (CCK8), EdU incorporation and Transwell cell migration and invasion assays. RT-PCR and Western blot were used to exa-mine expression of HIF1α and SNAPC1 RNA and proteins after interference of rt-circ-HS with siRNA, respectively. The binding of rt-circ-HS with microRNA 539 (miR-539), and miR-539 with HIF1α 3' untranslated region (3' UTR), and the effects of these interactions were investigated by dual luciferase reporter gene assays. RESULTS: We discovered a novel 1 144 nt rt-circ-HS, which was derived from read-through RNA HIF1α-SNAPC1 and consisted of HIF1α exon 2-6 and SNAPC1 exon 2-4. Expression of rt-circ-HS was significantly upregulated in 786-O renal carcinoma cells. ISH showed that the overall positive expression rate of rt-circ-HS in RCC tissue samples was 67.5% (295/437), and the expression was different in different types of RCCs. Mechanistically, rt-circ-HS promoted renal carcinoma cell proliferation, migration and invasiveness by functioning as a competitive endogenous inhibitor of miR-539, which we found to be a potent post-transcriptional suppressor of HIF1α, thus promoting expression of HIF1α. CONCLUSION: The novel rt-circ-HS is highly expressed in different types of RCCs and acts as a competitive endogenous inhibitor of miR-539 to promote expression of its parental gene HIF1α and thus the proliferation, migration and invasion of renal cancer cells.

[Efficacy of CT-guided partial radiofrequency ablation of bilateral responsible cranial nerves in the treatment of Meige syndrome].

Objective: To evaluate the efficacy of CT-guided partial radiofrequency ablation of bilateral responsible cranial nerves in the treatment of Meige syndrome. Methods: The Clinical data of 56 patients with Meige syndrome in the Department of Pain Medicine, Affiliated Hospital of Jiaxing University from June 2019 to January 2023 were retrospectively analyzed [19 males and 37 females, aged 42-76 (58.6±8.3) years], including 51 cases of blepharospasm, 3 cases of oromandibular dystonia and 2 cases of blepharospasm concomitant with oromandibular dystonia. CT-guided partial radiofrequency ablation of bilateral responsible cranial nerves was performed on different types of Meige syndrome. And the efficacy and complications of the technique were observed. Results: Fifty-one patients with blepharospasm Meige syndrome underwent CT-guided radiofrequency of facial nerve through bilateral stylomastoid foramen punctures, the symptoms of blepharospasm disappeared completely, leaving bilateral mild and moderate facial paralysis symptoms. Three patients with oral-mandibular dystonia underwent CT-guided radiofrequency therapy by bilateral foramen ovale puncture of mandibular branches of trigeminal nerve, masticatory muscle spasm disappeared, the patients had no difficulty opening the mouth, and the skin numbness in bilateral mandibular nerve innervation area was left. Two cases of Meige syndrome with blepharospasm concomitant with oromandibular dystonia were treated by radiofrequency of facial nerve and mandibular branch of trigeminal nerve, and all symptoms disappeared. The patients were followed up for 1-44 months after the operation, and the symptoms of mild and moderate facial paralysis disappeared at (3.2±0.8) months after the operation, but the numbness did not disappear. Three patients with blepharospasm recurred at the 14, 18 and 22 months after the operation, respectively, while the rest cases did not recur. Conclusions: According to different types of Meige syndrome, CT-guided partial radiofrequency ablation of responsible cranial nerves can effectively treat the corresponding type of Meige syndrome. The complications are only mild and moderate facial paralysis which can be recovered, and/or skin numbness in the mandibular region.

[Clinical characteristics and their influences on the survival of leptomeningeal metastasis derived from lung adenocarcinoma harboring epithelial growth factor receptor mutation].

Objective: To analyze the clinical characteristics of leptomeningeal metastasis (LM) patients from epithelial growth factor receptor (EGFR)-mutated lung adenocarcinoma, and their impacts on the survival of the patients. Methods: From July 2018 to July 2022, the clinicopathological data of 81 patients diagnosed as EGFR-mutated lung adenocarcinoma LM by cytopathology who admitted to the Department of Oncology of Xiangya Hospital of Central South University were retrospectively analyzed, including 33 males and 48 females. The age ranged from 31 to 76 years, with a median age of 54 years. All the 81 patients were followed up, with a median follow-up of 21.0 months (95%CI: 12.5 to 29.5 months). The Kaplan Meier method was used to draw survival curve. Cox proportional hazards regression model was used to analyze the impact of the factors on the survival of patients. Results: Among the 81 patients, the interval between the initial diagnosis of lung cancer and the pathological diagnosis of LM in cerebrospinal fluid (CSF) was 0-108 months, with a median interval of 14 months. Fifty-two patients (64.2%) used the third-generation epithelial growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs), while 17 patients (21.0%) used EGFR-TKIs in combination with other drugs, and 12 patients (14.8%) were treated with best supportive care (BSC). Sixty patients (74.1%) had a Kanofsky performance status (KPS) score of less than 60 points, and 71 patients (87.7%) had brain parenchymal metastasis and/or spinal metastasis. Twenty-two patients (27.2%) used pemetrexed through intrathecal CSF, and 17 patients (21.0%) used pemetrexed through the Ommaya sac to the CSF of the ventricle. The incidence of adverse event related to the administration of pemetrexed through CSF was 64.1% (25/39), mainly manifested as myelosuppression, including 22 patients of leukocyte reduction, 25 patients of hemoglobin reduction, and 14 patients of platelet reduction. The median post-leptomeningeal metastasis overall survival (pLM-OS) in 81 patients was 11.0 (95%CI: 7.7-14.3) months. KPS score≥60 points (HR=0.407, 95%CI: 0.170-0.973, P=0.043), CSF cytology negative after treatment (vs persistent positive, HR=0.351, 95%CI: 0.155-0.792, P=0.012), intraventricular administration of pemetrexed (vs non intraventricular administration of pemetrexed, HR=0.319, 95%CI: 0.137-0.745, P=0.008) and the treatment with third-generation EGFR-TKIs after LM (vs EGFR-TKIs in combination with other drugs, HR=0.486, 95%CI: 0.237-0.998, P=0.049) were a factor affecting pLM-OS of patients. Conclusions: Brain parenchyma, or/and spine are the most sites where the LM patients concurrently metastasize. KPS score≥60 points and CSF cytology negative after treatment, intraventricular administration of pemetrexed and the treatment with third-generation EGFR-TKIs are indictors affecting pLM-OS of the patients.

[The predictive value of melanin-concentrating hormone combined with other related biomarkers in cerebrospinal fluid in preoperative cognitive dysfunction of elderly patients].

Objective: To explore the predictive value of cerebrospinal fluid melanin-concentrating hormone (MCH) combined with other related biomarkers in preoperative cognitive dysfunction of elderly patients. Methods: A total of 80 patients who underwent elective hip or knee replacement under intravertebral anesthesia in Chifeng Municipal Hospital, Inner Mongolia, from March to November 2022 were prospectively included, with 32 males and 48 females, and aged 65-85 (70.7±5.2) years old. According to the evaluation results of the Montreal Cognitive Assessment (MoCA), patients were divided into the preoperative cognitive dysfunction (n=23) and control (n=57) groups. The levels of MCH, amyloid-ß 40 (Aß40), amyloid-ß 42 (Aß42), and phosphorylated tau protein (p-tau) in cerebrospinal fluid were determined by enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of each biomarker separately or in combination for preoperative cognitive dysfunction. Spearman's rank correlation analysis was utilized to test the correlation between the level of each biomarker and MoCA scores. Results: The levels of MCH, Aß40, Aß42, p-tau, and Aß42/p-tau in the preoperative cognitive dysfunction group were (35.53±5.94) µg/L, (39.21±9.18) ng/L, (221.83±43.17) ng/L, (42.64±9.74) ng/L, and 5.53±1.92, and the levels of these biomarkers in the control group were (28.74±4.90) µg/L, (36.37±7.87) ng/L, (280.23±45.67) ng/L, (35.00±9.27) ng/L, and 8.62±2.78, respectively. Compared with the control group, the levels of cerebrospinal fluid MCH and p-tau in the preoperative cognitive dysfunction group were significantly increased (all P<0.01), and the levels of Aß42 and Aß42/p-tau were significantly decreased (all P<0.001). MCH and Aß42/p-tau provided higher predictive values. The area under the curve (AUC) of MCH and Aß42/p-tau were 0.807 (95%CI: 0.703-0.911) and 0.842 (95%CI: 0.741-0.943), the sensitivity were 78.3% and 87.0%, and the specificity were 75.4% and 94.7%. MCH combined with Aß42/p-tau have the higher AUC of 0.915 (95%CI: 0.837-0.992), the sensitivity (87.0%) and specificity (86.0%) were both high, which had a higher predictive value. The levels of cerebrospinal fluid MCH and p-tau were negatively correlated with MoCA score (r=-0.467, -0.321, all P<0.01), and the levels of Aß42 and Aß42/p-tau were positively correlated with MoCA score (r=0.480, 0.520, all P<0.001). Conclusion: The increase in cerebrospinal fluid MCH levels is associated with preoperative cognitive dysfunction in elderly patients. MCH combined with Aß42/p-tau has the greatest predictive value.

[Association between serum potassium levels and all-cause mortality in patients with acute heart failure].

Objective: To investigate the relationship between different serum potassium levels at admission and discharge and all-cause mortality in patients with acute heart failure (HF). Methods: A total of 2 621 patients with acute HF who were hospitalized in the Heart Failure Center of Fuwai Hospital from October 2008 to October 2017 were analyzed. Patients were divided into three groups according to the different serum potassium levels at admission: hypokalemia with serum potassium<3.5 mmol/L (n=329), normokalemia with 3.5-5.5 mmol/L (n=2 270), and hyperkalemia with serum potassium>5.5 mmol/L (n=22). Clinical data such as patient history, comorbidities, clinical examination and drug use were collected, and systematic outpatient review or telephone follow-up was performed after patients were discharged from the hospital until January 2020. The primary outcome was all-cause death at 90 days, 2 years, and 5 years of follow-up. We compared the clinical characteristics of patients with different serum potassium levels at admission and discharge, and used a multivariate Cox proportional hazards regression model to analyze the association between serum potassium levels at admission and discharge and all-cause mortality. Results: The age of all patients was (58.0±15.3) years old, and 1 877 patients (71.6%) were male. There were 329 (12.6%) and 22 (0.8%) patients with hypokalemia and hyperkalemia at admission, and 38 (1.4%) and 18 (0.7%) at discharge, respectively. The serum potassium levels of all patients were (4.01±0.50) and (4.25±0.44) mmol/L at admission and discharge, respectively. The follow-up time[M(Q1,Q3)] of this study was 2.63(1.00,4.42)years, and a total of 1 076 all-cause deaths were recorded at the last follow-up. Compared with patients with normokalemia at discharge, discharged patients with hypokalemia and hyperkalemia were followed up for 90 days (90.3% vs 76.3% vs 38.9%), 2 years (73.8% vs 60.5% vs 33.3%) and 5 years (63.4% vs 44.7% vs 22.2%), respectively, and the difference of which in cumulative survival rates were statistically significant (all P values<0.001). The multivariate-adjusted Cox regression analysis showed that hypokalemia (HR=0.979, 95%CI: 0.812-1.179, P=0.820) and hyperkalemia (HR=1.368, 95%CI: 0.805-2.325, P=0.247) at admission were not associated with all-cause mortality risk, however, hypokalemia (HR=1.668, 95%CI: 1.081-2.574, P=0.021) and hyperkalemia (HR=3.787, 95%CI: 2.264-6.336, P<0.001) at discharge were associated with increased all-cause mortality risk. Conclusions: Both hypokalemia and hyperkalemia at discharge in hospitalized patients with acute HF were associated with increased short-and long-term all-cause mortality, and serum potassium levels should be closely monitored.

[Advances in clinical significance and detection methods research of high density lipoprotein subfractions].

High density lipoprotein (HDL) is an important biochemical index of clinical cardiovascular disease. Many new studies have demonstrated abnormalities of plasma HDL subfractions in patients with this disease,and their clinical significance is greater than the overall abnormalities of HDL. Therefore,the HDL subfraction as an important factor in cardiovascular disease has attracted extensive research and attention. This article summarizes current research on HDL subfractions,their measurements and their relationships with atherosclerosis and coronary artery disease.

[Safety of delayed vaccination with the national immunization program vaccines in children aged 0-6 years from 2019 to 2021 in Xuhui District, Shanghai City in China].

Objective: To understand the incidence of delayed vaccination with the national immunization program vaccines among children aged 0-6 years in Xuhui District, Shanghai, and to evaluate the safety of delayed vaccination. Methods: A stratified random sampling was used to obtain six vaccination clinics in Xuhui District, Shanghai. The vaccination records of children 0-6 years from these six vaccination clinics were collected from the Shanghai Immunization Program Information Management System. Adverse events following immunization (AEFI) data were collected from the China Information System for Disease Control and Prevention. Descriptive epidemiology was used to analyze the data. Children were divided into the timely vaccination group and delayed vaccination group according whether they were delayed in vaccination (received one month or more after the recommended age among children aged ≤1 year; received three months or more after the recommended age among children aged >1 year). The safety of four vaccination methods-individual vaccination, simultaneous vaccination, routine vaccination and combined vaccination-were further compared. Differences between groups were compared using chi-square test. Results: From 2019 to 2021, six vaccination clinics in Xuhui District administered 124 031 doses of the national immunization program vaccines among children aged 0-6 years, and delayed vaccinations accounted for 25.99% (32 234/124 031) of these doses. In 2020, the delayed vaccination rate during the first-level COVID-19 public health emergency response period in Shanghai was significantly higher than that in the same period in 2019 (34.70% vs. 24.19%, χ2=136.23, P<0.05). The delayed vaccination rate during the COVID-19 vaccination campaign in 2021 was significantly higher than that in the same period in 2019 (25.27% vs. 22.55%, χ2=82.80, P<0.05). From 2019 to 2021, a total of 475 cases of AEFI were reported in six vaccination clinics, with a reported incidence of 382.97 per 100 000 doses, including 421 cases of common adverse reaction (88.63%, 339.43 per 100 000 doses), 51 cases of rare adverse reaction (10.74%, 41.12 per 100 000 doses) and 3 cases of coincidences (0.63%, 2.42 per 100 000 doses). The reported incidence of AEFI among delayed vaccinations was significantly lower than that among timely vaccinations (291.62 per 100 000 doses vs. 415.05 per 100 000 doses). The incidence of AEFI for the four delayed vaccination methods (individual vaccination, simultaneous vaccination, routine vaccination and combined vaccination) was lower than that for timely vaccination. There were significant differences between the groups except for the routine vaccination group (χ2=9.82, P<0.05; χ2=5.46, P<0.05; χ2=2.97, P>0.05; χ2=11.89, P<0.05). Conclusions: In Xuhui District of Shanghai, 25.99% of doses of the national immunization program vaccines administered to children 0-6 years were delayed. Delayed vaccination does not increase the risk of AEFI compared with timely vaccination.

[Association between serum lysophosphatidylcholine level and elderly health index in older people from longevity areas of Guangxi Province].

Objective: To investigate the relationship between serum lysophosphatidylcholine (LPC) level and the health index of the elderly. Methods: A total of 251 subjects were selected from the 2016 baseline survey of the Yongfu Longevity Cohort in Guangxi Province among whom 66, 63 and 122 were in the young and middle-aged group (≤59 years old), the young group (60-89 years old) and the longevity group (≥90 years old), respectively. Demographic data were collected and related indicators of height, weight, blood pressure and lipid metabolism were measured. The cognitive and physical functions of the elderly were assessed by the results of the simple mental state scale and the daily living activity scale to construct the health index of the elderly. The serum levels of LPC16∶0, LPC18∶0, LPC18∶1 and LPC18∶2 were determined by liquid chromatography-tandem mass spectrometry, and the differences among different ages and health status groups were compared. The logistic regression model was used to analyze the relationship between the serum LPC level and the health index of the elderly. Results: With the increase in age, the proportion of female subjects increased, and the rate of smoking and drinking decreased. BMI, TC, TG, LDL-C, diastolic blood pressure, and the four LPCs levels decreased with the increase of age, and systolic blood pressure levels increased with the increase of age (all P values<0.05). There was no significant difference in HDL-C levels among age groups (P>0.05). With the decline of health status in the elderly, serum levels of LPC16∶0, LPC18∶0, LPC18∶1 and LPC18∶2 showed a downward trend (all P values<0.001). After adjusting for age and gender, only LPC18∶0 was associated with the health status in old age [OR (95%CI): 0.48 (0.25-0.92)]. For every 1 standard deviation (16.87 nmol/L) increase in serum LPC18∶0 concentration, the risk of poor health status in old age decreased by 52%. Conclusion: Serum LPC18∶0 was associated with the health status in old age independent of age and sex.

[Research progress on main disease-related factors of healthy life expectancy].

International research on healthy life expectancy (HALE) focuses on inequality of socioeconomic status and individual natural attributes. With the acceleration of population ageing and the increase in average life expectancy, the extension of unhealthy life expectancy and the increase of social and economic burden caused by diseases have gradually attracted the attention of countries around the world. Therefore, the evaluation of disease factors affecting HALE is a meaningful direction in the future. This study introduces the development process and commonly used measurement methods of HALE. According to the definition of health from the Global Burden of Disease Study and World Health Organization, physical and mental diseases such as cardiovascular and cerebrovascular diseases, chronic respiratory diseases, diabetes, malignant tumors and depression were selected to summarize the impact of these diseases and pre-disease states on HALE. It is expected to provide a theoretical basis for the formulation of relevant public health policies and the improvement of quality of life in China.