Novel mechanisms driving renal tubulointerstitial fibrosis / 中国临床药理学与治疗学

Renal fibrosis, especially tubulointerstitial fibrosis, is the most common pathway of all chronic kidney diseases progressing to end-stage renal diseases. Several adaptive reactions occur in renal tubular epithelial cells after chronic injury, such as changes in glycolipid metabolism, unfolded protein response, autophagy and senescence, epithelial-to-mesenchymal transition and G2/M cell cycle arrest. Maladaptive repair mechanisms can induce tubulointerstitial fibrosis. This article will discuss the molecular mechanism of these adaptive responses of renal tubular epithelial cells driving renal tubulointerstitial fibrosis, and provide a basis for exploring new drug targets for renal tubulointerstitial fibrosis.

Establishment and genotype identification of hepatic stellate cell-specific Grk2 gene knockout mouse model / 中国药理学通报

Aim To establish a stable hepatic stellate cell ( HSC ) -specific G protein-coupled receptor kinase 2 ( GRK2 ) knockout mice and provide the important animal model for further studying the biological function of GRK2 in HSC. Methods The loxP-labeled Grk2 gene mouse (Grk2

Clinicopathological study of epithelioid and spindle cell rhabdomysarcoma with EWSR1/FUS-TFCP2 fusion / 中华病理学杂志

Objective: To investigate the clinicopathological and genetic features of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion. Methods: The clinical, morphological and immunohistochemical features of 14 cases of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion diagnosed from January 2019 to December 2022 in the Department of Pathology, Foshan Traditional Chinese Medicine Hospital, Foshan, China were retrospectively analyzed. The cases were all subject to FISH or next generation sequencing for analysis of molecular genetic features. The literature was reviewed. Results: There were 5 males and 9 females, with the age at presentation ranging from 6 to 36 years (mean, 22 years). Tumors occurred in the head and neck (9 cases), pelvic region (2 cases), bladder (one case), right humerus (one case), and the abdominal wall, humerus and pubic at the same time (one case). Presenting symptoms varied by location but often included pain or discomfort. Most of the patients showed aggressive radiographic features with soft tissue extension. The tumors had a median size of 6.6 cm (range, 2-23 cm). The tumors were poorly defined and irregularly shaped. Microscopic examination showed diffuse proliferation of spindle or epithelioid cells. While morphologically high-grade tumors displayed obvious cytological atypia, a high mitotic count and tumor necrosis, low-grade tumors grew in sheets and fascicles composed of spindle, epithelioid cells with moderate or abundant amounts of eosinophilic cytoplasm, without pronounced cytological atypia. The tumor cells expressed Desmin, MyoD1, and Myogenin, as well as ALK, EMA, and CKpan. EWSR1/FUS-TFCP2 gene fusion was detected in 14 cases with next generation sequencing and confirmed by FISH. Six cases had EWSR1-TFCP2 fusions and 8 cases showed FUS-TFCP2 fusions. Follow-up information was available in 13 patients, ranged from 5 to 37 months. At the end of follow-up period, 7 patients died of the disease. Six patients were alive:two cases had local recurrences and metastases, two cases of recurrences, one case of metastasis and one case without recurrences and metastasis. Conclusions: Epithelioid and spindle cell rhabdomysarcomas with EWSR1-TFCP2 or FUS-TFCP2 fusion show a very aggressive clinical course, and more commonly occur in the head and neck. Their genetic hallmark is the presence of EWSR1/FUS-TFCP2 fusions. Familiarity with its clinicopathological characteristics is helpful in avoiding misdiagnoses.

Mechanism on Banxia Xiexintang Inducing Ferroptosis in Gastric Cancer Cells Based on Nrf2/GPX4 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of Banxia Xiexintang （BXT） on the proliferation of human gastric cancer HGC-27， MKN-45， and AGS cells and its mechanism. MethodCell counting kit-8 （CCK-8） was used to detect the effects of different concentrations of BXT-containing serum （5%， 10%， and 20%） on the proliferation of HGC-27， MKN-45， and AGS cells. A mitochondrial membrane potential probe （TMRE） was used to detect the expression of mitochondrial membrane potential in cells. A kit was used to detect iron ion （Fe2+） content， lipid peroxide （LPO）， and superoxide dismutase （SOD） activity. Western blot was used to detect the protein expression levels of glycogen synthase3β （GSK3β）， phosphorylated GSK3β （p-GSK3β）， nuclear factor E2 related factor 2 （Nrf2）， and glutathione peroxidase 4 （GPX4）. The real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of member 11 of the cystine/glutamic acid reverse transporter solute vector family 7 （SLC7A11）， member 2 of the heavy chain solute vector family 3 （SLC3A2）， transferrin receptor 3 （TFRC）， and tumor protein （TP）53. ResultCCK-8 results showed that BXT and capecitabine could significantly reduce the survival rate of three kinds of gastric cancer cells after treatment with drug-containing serum for 24 h （P<0.01）. After 48 h of intervention with drug-containing serum， the survival rate of three kinds of gastric cancer cells was significantly decreased in both the capecitabine group and the BXT group compared with the blank group. The BXT group was dose-dependent， with 20% BXT having the most significant effect （P<0.01）. In terms of biochemical indicators of ferroptosis， compared with the blank group， BXT and capecitabine significantly decreased the expression of mitochondrial membrane potential （P<0.01） and SOD activity （P<0.01） and significantly increased the contents of LPO and Fe2+ （P<0.01）， so as to improve the sensitivity of gastric cancer cells to ferroptosis. In terms of the Nrf2/GPX4 pathway， compared with the blank group， the BXT group could reduce the protein expressions of p-GSK3β， Nrf2， and GPX4 （P<0.01） in gastric cancer cells and increase mRNA expressions of SLC7A11 and SLC3A2 （P<0.05）. It could also increase the protein expression of GSK3β （P<0.01） and mRNA expression of TP53 and TFRC （P<0.05， P<0.01） in gastric cancer cells. Inhibition of the Nrf2/GPX4 pathway induces ferroptosis in gastric cancer cells. Compared with the capecitabine group， the 20% BXT group showed a more obvious effect. ConclusionBanxia Xiexintang can induce ferroptosis in gastric cancer cells HGC-27， MKN-45， and AGS by inhibiting the Nrf2/GPX4 pathway.

Electroacupuncture improves motor function of rats with osteoarthritis by alleviating joint inflammation through the Wnt-7B/β-catenin signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of electroacupuncture on osteoarthritis in rats and explore the possible mechanism.@*METHODS@#Thirty SD rats were randomly divided into osteoarthritis model group, electro-acupuncture group and control group (n=10), and in the former two groups, early osteoarthritis was induced using a modified DMM surgical modeling method. After successful modeling, the rats in the electro-acupuncture group were treated with electro-acupuncture at bilateral "Housanli" and "Anterior knee point". Behavioral tests of the rats were performed and scored using the LequesneMG scale. Subchondral bone degeneration was observed in each group, and serum levels of IL-1β, ADAMTS-7, MMP-3 and COMP were measured using ELISA. The mRNA and protein expressions of IL-1β, Wnt-7B, β-catenin, ADAMTS-7, and MMP-3 in the cartilage tissue of the knee joints were detected using RT-PCR and Western blotting.@*RESULTS@#In behavioral tests, the rats in the model and electroacupuncture groups had significantly higher LequesneMG scores after modeling than those in the control group (P < 0.05). After 20 days of treatment, LequesneMG scores were significantly lowered in rats in the electroacupuncture as compared with the model rats (P < 0.05). Imaging examination revealed obvious subchondral bone damage in both the electroacupuncture group and the model group, but the damages were significantly milder with former group. Compared with the model rats, the rats receiving electroacupuncture had significantly lower serum levels of IL-1β, ADAMTS-7, MMP-3 and COMP (P < 0.05) with also lower expressions of IL-1β, Wnt-7B, β-catenin, ADAMTS-7 and MMP-3 in the cartilage tissues at both the mRNA and protein levels (P < 0.05).@*CONCLUSION@#Electroacupuncture can alleviate joint pain and improve subchondral bone damage in rats with osteoarthritis by reducing IL-1β levels in the joint cartilage tissue and serum to alleviate joint inflammation and by reducing such cytokines as ADAMTS-7 and MMP-3 via regulating the Wnt-7B/β-catenin signaling pathway.

Willingness of middle school students to engage in medicine and influencing factors during COVID-19 pandemic / 四川精神卫生

ObjectiveTo investigate the willingness of middle school students to engage in medicine and its influencing factors during COVID-19 pandemic in Lanzhou， so as to provide references for the early career planning education on middle school students. MethodsConvenient sampling method was used to choose 1 795 middle school students from 5 schools in Lanzhou from July 21 to July 31， 2022 for this study where an online questionnaire survey was distributed to collect data. A self-compiled questionnaire was used to gather the general information， assess the willingness to engage in medicine and seek the underlying reasons. The psychological resilience level of students was assessed using Resilience Scale for Adolescents. Then multivariate Logistic regression analysis was conducted to screen the factors associated with the willingness of middle school students to engage in medicine. ResultsAfter the local outbreak of COVID-19 in Lanzhou， 835 （46.52%） middle school students demonstrated their willingness to engage in medicine， and the top three reasons for their willingness were being affected by medical staff during the pandemic （75.69%）， having interests in medical sciences （67.31%）， and the potential increase of attention to national medical development after the epidemic （43.23%）. Logistical regression analysis showed that female gender （OR=1.438， P<0.01）， family members engaged in the medical and health industry （OR=1.574， P<0.01） and having a high psychological resilience score （OR=1.011， P<0.01） were related to the clear willingness to engage in medicine， while studying in senior middle school （OR=0.473， P<0.01） and excessive exposure （≥50%） to negative information during the epidemic （OR=0.797， P<0.05） were related to declining willingness to engage in medicine. ConclusionAfter the COVID-19 outbreak in Lanzhou， a large proportion of local middle school students show their willingness to engage in medicine， especially among those of female gender， having family members engaged in the medical and health industry and having high level of psychological resilience. Whereas students studying in senior middle school and with excessive exposure to negative information during the outbreak indicate low willingness to engage in medicine.

Clinical Observation of 32 Cases of Malignant Lymphoma Treated with Brentuximab Vedotin Combined with Chemotherapy / 肿瘤防治研究

Objective To retrospectively evaluate the clinical efficacy and safety of brentuximab vedotin(BV) combined with chemotherapy in the treatment of malignant lymphoma. Methods We collected the data of 32 lymphoma patients with CD30-positive status, including 14 cases of Hodgkin's lymphomas, 2 cases of diffuse large B-cell lymphomas, and 16 cases of mature T/NK cell lymphomas. Chemotherapy combined with BV was administered to all patients for a minimum of two cycles. The efficacy of the treatment was evaluated according to Lugano criteria every two cycles. Results Complete response rate and overall response rate after four cycles of treatment were 22% and 50%, respectively. Sixteen cases (50.0%) had grades 1 and 2 toxicity, and 16 cases (50.0%) had grade 3 toxicity or higher. The most common adverse events were neutropenia (50.0%), pneumonia (46.9%), and anemia (43.8%). The most common grade 3 or higher adverse events were pneumonia (18.8%) and febrile neutropenia (12.5%). Four patients discontinued brentuximab vedotin because of severe adverse events. Conclusion BV is effective in treating relapsed and refractory CD30- positive Hodgkin's lymphoma and peripheral T-cell lymphoma, and its overall safety is acceptable.

Comparison of two different methods of rapid expansion combined with maxillary protraction in the treatment of skeletal class Ⅲ malocclusion / 中华口腔医学杂志

Objective: To compare the effect of bone-anchored versus tooth-borne rapid palatal expansion (RPE) combined with maxillary protraction in the treatment of skeletal class Ⅲ patients with maxillary hypoplasia. Methods: Twenty-six skeletal class Ⅲ patients with maxillary hypoplasia in the late mixed or early permanent dentition were selected. All the patients underwent RPE combined with maxillary protraction in the Department of Orthodontics, Nanjing Stomatological Hospital, Medical School of Nanjing University from August 2020 to June 2022. The patients were divided into 2 groups. Thirteen patients were enrolled in the bone-anchored RPE group [4 males and 9 females, aged (10.2±1.7) years] and the others were in the tooth-borne RPE group [5 males and 8 females, aged (10.1±1.0) years]. Ten sagittal linear indices [Y-Is distance (the distance from the incisor edge of the maxillary incisor to the vertical reference axis), Y-Ms distance (the distance from the mesial contact point of the maxillary first molar to the vertical reference axis), the relative distance between the maxillary and mandibular molars, overjet, etc.], 6 vertical linear indices [PP-Ms distance (the distance changes from Ms to the palatal plane), etc.] and 8 angle indices [SN-MP angle (the upper external angle of the intersection of the sella-nasion plane and the mandibular plane), U1-SN angle (the lower internal angle of the intersection of the long axis of the maxillary central incisor and the sella-nasion plane), etc.] were measured on the cephalometric radiographs before and after the treatment. Six coronal indicators (the inclination of the left and right first maxillary molar, etc.) were measured on cone-beam CT images before and after the treatment. The proportion of skeletal and dental factors in the changes of overjet were calculated. The differences of the index changes between groups were compared. Results: After the treatment, the anterior crossbite were corrected in both groups, and classⅠor classⅡ molar relationship were attained. In bone-anchored group, the changes of Y-Is distance, Y-Ms distance and maxillary and mandibular molar relative distance were (3.23±0.70), (1.25±0.34) and (2.54±0.59) mm, respectively, significantly less than those in the tooth-borned group in which the corresponding changes were (4.96±0.97) mm (t=-5.92, P<0.001), (3.12±0.83) mm (t=-7.53, P<0.001) and (4.92±1.35) mm (t=-5.85, P<0.05), respectively. The change of overjet in the bone-anchored group was (4.45±1.25) mm, significantly less than that in the tooth-borned group (6.14±1.29) mm (t=-3.38, P<0.05). Skeletal and dental factors accounted for 80% and 20% of the overjet changes in the bone-anchored group, respectively. While in the tooth-borned group, skeletal and dental factors accounted for 62% and 38% of the overjet changes, respectively. The PP-Ms distance change in the bone-anchored group [(-1.62±0.25) mm] was significantly less than that in the tooth-borned group [(2.13±0.86) mm] (t=-15.15, P<0.001). The changes of SN-MP and U1-SN in the bone-anchored group were -0.95°±0.55° and 1.28°±1.30°, respectively, significantly less than those corresponding indices in the tooth-borned group (1.92°±0.95°, t=-9.43, P<0.001; 7.78°±1.94°, t=-10.04, P<0.001). In the bone-anchored group, the inclination changes of maxillary bilateral first molars in the left and right sides were 1.50°±0.17° and 1.54°±0.19°, significantly less than the corresponding indices in the tooth-borned group (2.26°±0.37°, t=6.47, P<0.001; 2.25°±0.35°, t=6.81, P<0.001). Conclusions: The bone-anchored RPE with maxillary protraction could reduce the adverse tooth compensation effect, including the protrusion of maxillary anterior incisors, the increase of overjet and mandibular plane angle, and the mesial movement, extrusion and buccal inclination of maxillary molars.

Clinical characteristics of acute occupational poisoning caused by carbon dioxide leakage from a cargo ship / 中华劳动卫生职业病杂志

Carbon dioxide is a simple asphyxial gas, with low concentrations having an excitatory effect on the respiratory center, while high concentrations have an inhibitory effect on the respiratory center. Simple carbon dioxide poisoning is rarely seen clinically. This article reviews and analyzes the treatment process of 9 cases of acute inhalation carbon dioxide poisoning in a cargo ship carbon dioxide leakage accident in May 2019, summarizes clinical treatment experience, and provides timely and effective treatment for acute pulmonary edema caused by acute inhalation carbon dioxide poisoning. In particular, the application of hormones has a good prognosis, improving clinicians' understanding of the disease.

Rapid determination of acetaminophen in plasma by LC-MS/MS / 中华劳动卫生职业病杂志

Objective: To establish a method for the rapid determination of acetaminophen (APAP) in human plasma by LC-MS/MS. Methods: The plasma samples were extracted by methanol and acetonitrile (1: 1) and purified directly. C(18) column was used for sample separation. The mobile phase were methanol (5 mmol/L ammonium acetate) and water (5 mmol/L ammonium acetate). Samples were analyzed by LC MS/MS with the electrospray ionization multi reaction monitoring (MRM) mode. Results: The calibration curves of APAP was linear in the concentration range of 0~10 mg/L, the correlation coefficient (r) was greater than 0.999 0. The relative standard deviation within and between batches was less than 10%. The recovery rate were 96.81%~101.7%. The detection limit of the method was 0.1 μg/L and the lower limit of quantification was 0.3 μg/L. Conclusion: This method has strong specificity, high sensitivity and reliable determination results. It is suitable for the rapid analysis of clinical plasma samples.

Clinicopathological features and prognosis of SMARCA4-deficient non-small cell lung carcinoma: an analysis of 127 cases / 中华病理学杂志

Objective: To investigate and elucidate the clinicopathological and prognostic characteristics of SMARCA4-deficient non-small cell lung cancer. Methods: The clinicopathological and prognostic data were collected in 127 patients with SMARCA4-deficient non-small cell lung cancer diagnosed in Shanghai Pulmonary Hospital, Shanghai, China from January 2020 to March 2022. The variation and expression of biomarkers related to treatment were retrospectively reviewed. Results: One hundred and twenty-seven patients were eligible for enrollment. Among them 120 patients (94.5%) were male and 7 cases (5.5%) were female, while the average age was 63 years (range 42-80 years). There were 41 cases (32.3%) of stage Ⅰ cancer, 23 cases (18.1%) of stage Ⅱ, 31 cases (24.4%) of stage Ⅲ and 32 cases (25.2%) of stage Ⅳ. SMARCA4 expression detected by immunohistochemistry was completely absent in 117 cases (92.1%) and partially absent in 10 cases (7.9%). PD-L1 immunohistochemical analyses were performed on 107 cases. PD-L1 was negative, weakly positive and strongly positive in 49.5% (53/107), 26.2% (28/107) and 24.3% (26/107) of the cases, respectively. Twenty-one cases showed gene alterations (21/104, 20.2%). The KRAS gene alternation (n=10) was most common. Mutant-type SMARCA4-deficient non-small cell lung cancer was more commonly detected in females, and was associated with positive lymph nodes and advanced clinical stage (P<0.01). Univariate survival analysis showed that advanced clinical stage was a poor prognosis factor, and vascular invasion was a poor predictor of progression-free survival in patients with surgical resection. Conclusions: SMARCA4-deficient non-small cell lung cancer is a rare tumor with poor prognosis, and often occurs in elderly male patients. However, SMARCA4-deficient non-small cell lung cancers with gene mutations are often seen in female patients. Vascular invasion is a prognostic factor for disease progression or recurrence in patients with resectable tumor. Early detection and access to treatment are important for improving patient survivals.

Analysis of the characteristics of viral infections in children with diarrhea in Beijing from 2018 to 2022 / 中华预防医学杂志

Objective: To explore the characteristics of viral infections in children with diarrhea in Beijing from 2018 to 2022. Methods: Real-time PCR and enzyme-linked immunosorbent assay were used to detect viral nucleic acid of Norovirus (NoV), Sappovirus (SaV), Astrovirus (AstV), Enteric Adenovirus (AdV) or antigen of Rotavirus (RV) in 748 stool samples collected from Beijing Capital Institute of Pediatrics from January 2018 to December 2021. Subsequently, the reverse transcription PCR or PCR method was used to amplify the target gene of the positive samples after the initial screening, followed by sequencing, genotyping and evolution analysis, so as to obtain the characteristics of these viruses. Phylogenetic analysis was performed using Mega 6.0. Results: From 2018 to 2021, the overall detection rate of the above five common viruses was 37.6%(281/748)in children under 5 years old in Beijing. NoV, Enteric AdV and RV were still the top three diarrhea-related viruses, followed by AstV and SaV, accounting for 41.6%, 29.2%, 27.8%, 8.9% and 7.5%, respectively. The detection rate of co-infections with two or three diarrhea-related viruses was 4.7% (35/748). From the perspective of annual distribution, the detection rate of Enteric AdV was the highest in 2021, while NoV was predominant in the other 4 years. From the perspective of genetic characteristics, NoV was predominant by GⅡ.4, and after the first detection of GⅡ.4[P16] in 2020, it occupied the first two gene groups together with GⅡ.4[P31]. Although the predominant RV was G9P[8], the rare epidemic strain G8P[8] was first detected in 2021. The predominant genotypes of Enteric AdV and AstV were Ad41 and HAstV-1. SaV was sporadic spread with a low detection rate. Conclusion: Among the diarrhea-related viruses infected children under 5 years of age in Beijing, the predominant strains of NoV and RV have changed and new sub-genotypes have been detected for the first time, while the predominant strains of AstV and Enteric AdV are relatively stable.

Clinical features and prognostic factors of elderly patients with mantle cell lymphoma / 中华血液学杂志

Objective: To examine the clinical characteristics and prognostic factors of elderly patients with mantle cell lymphoma (MCL) and the impact of nutrition and underlying diseases on the prognosis of elderly patients with MCL. Methods: retrospectively analyzed 255 elderly patients with MCL from 11 medical centers, including Peking University Third Hospital between January 2000 and February 2021. We analyzed clinical data, such as age, gender, Mantle Cell Lymphoma International Prognostic Index score, and treatment options, and performed univariate and multivariate prognostic analysis. We performed a comprehensive geriatric assessment on elderly MCL patients with medical records that included retraceable underlying disease and albumin levels, and we investigated the impact of basic nutrition and underlying disorders on MCL prognosis in the elderly. Results: There were 255 senior individuals among the 795 MCL patients. Elderly MCL was more common in males (78.4%), with a median age of 69 yr (ages 65-88), and the majority (88.6%) were identified at a late stage. The 3-yr overall survival (OS) rate was 42.0%, with a 21.2% progression-free survival (PFS) rate. The overall response rate (ORR) was 77.3%, with a 33.3% total remission rate. Elderly patients were more likely than younger patients to have persistent underlying illnesses, such as hypertension. Multivariate analysis revealed that variables related with poor PFS included age of ≥80 (P=0.021), Ann Arbor stage Ⅲ-Ⅳ (P=0.003), high LDH level (P=0.003), involvement of bone marrow (P=0.014). Age of ≥80 (P=0.001) and a high LDH level (P=0.003) were risk factors for OS. The complete geriatric assessment revealed that renal deficiency was associated with poorer OS (P=0.047) . Conclusions: Elderly MCL patients had greater comorbidities. Age, LDH, renal function, bone marrow involvement, and Ann Arbor stage are all independent risk factors for MCL in the elderly.

Prognostic Prediction Value and Biological Functions of Non-Apoptotic Regulated Cell Death Genes in Lung Adenocarcinoma / 中国医学科学杂志(英文版)

Objective To explore the potential biological functions and prognostic prediction values of non-apoptotic regulated cell death genes (NARCDs) in lung adenocarcinoma.Methods Transcriptome data of lung adenocarcinoma were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. We identified differentially expressed NARCDs between lung adenocarcinoma tissues and normal tissues with R software. NARCDs signature was constructed with univariate Cox regression analysis and the least absolute shrinkage and selection operator Cox regression. The prognostic predictive capacity of NARCDs signature was assessed by Kaplan-Meier survival curve, receiver operating characteristic curve, and univariate and multivariate Cox regression analyses. Functional enrichment of NARCDs signature was analyzed with gene set variation analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes. In addition, differences in tumor mutational burden, tumor microenvironment, tumor immune dysfunction and exclusion score, and chemotherapeutic drug sensitivity were analyzed between the high and low NARCDs score groups. Finally, a protein-protein interaction network of NARCDs and immune-related genes was constructed by STRING and Cytoscape software. Results We identified 34 differentially expressed NARCDs associated with the prognosis, of which 16 genes (ATIC, AURKA, CA9, ITGB4, DDIT4, CDK5R1, CAV1, RRM2, GAPDH, SRXN1, NLRC4, GLS2, ADRB2, CX3CL1, GDF15, and ADRA1A) were selected to construct a NARCDs signature. NARCDs signature was identified as an independent prognostic factor (P < 0.001). Functional analysis showed that there were significant differences in mismatch repair, p53 signaling pathway, and cell cycle between the high NARCDs score group and low NARCDs score group (all P < 0.05). The NARCDs low score group had lower tumor mutational burden, higher immune score, higher tumor immune dysfunction and exclusion score, and lower drug sensitivity (all P < 0.05). In addition, the 10 hub genes (CXCL5, TLR4, JUN, IL6, CCL2, CXCL2, ILA, IFNG, IL33, and GAPDH) in protein-protein interaction network of NARCDs and immune-related genes were all immune-related genes. Conclusion The NARCDs prognostic signature based on the above 16 genes is an independent prognostic factor, which can effectively predict the clinical prognosis of patients of lung adenocarcinoma and provide help for clinical treatment.

EPCs-exos combined with tanshinone Ⅱ_A protect vascular endothelium cells from oxidative damage via PI3K/Akt pathway / 中国中药杂志

This study aims to investigate the molecular mechanism of tanshinone Ⅱ_(A )(TaⅡ_A) combined with endothelial progenitor cells-derived exosomes(EPCs-exos) in protecting the aortic vascular endothelial cells(AVECs) from oxidative damage via the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt) pathway. The AVECs induced by 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphocholine(POVPC) were randomly divided into model, TaⅡ_A, EPCs-exos, and TaⅡ_A+EPCs-exos groups, and the normal cells were taken as the control group. The cell counting kit-8(CCK-8) was used to examine the cell proliferation. The lactate dehydrogenase(LDH) cytotoxicity assay kit, Matrigel assay, DCFH-DA fluorescent probe, and laser confocal microscopy were employed to examine the LDH release, tube-forming ability, cellular reactive oxygen species(ROS) level, and endothelial cell skeleton morphology, respectively. The enzyme-linked immunosorbent assay was employed to measure the expression of interleukin(IL)-1β, IL-6, and tumor necrosis factor(TNF)-α. Real-time fluorescence quantitative PCR(qRT-PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of PI3K and Akt. Compared with the control group, the model group showed decreased cell proliferation and tube-forming ability, increased LDH release, elevated ROS level, obvious cytoskeletal disruption, increased expression of IL-1β, IL-6, and TNF-α, and down-regulated mRNA and protein levels of PI3K and Akt. Compared with the model group, TaⅡ_A or EPCs-exos alone increased the cell proliferation and tube-forming ability, reduced LDH release, lowered the ROS level, repaired the damaged skeleton, decreased the expression of IL-1β, IL-6, and TNF-α, and up-regulated the mRNA and protein levels of PI3K and Akt. TaⅡ_A+EPCs-exos outperformed TaⅡ_A or EPCs-exos alone in regulating the above indexes. The results demonstrated that TaⅡ_A and EPCs-exos exerted a protective effect on POVPC-induced AVECs by activating the PI3K/Akt pathway, and the combination of the two had stronger therapeutic effect.

Advances in Molecular Targeted Drugs for Hepatocellular Carcinoma / 中山大学学报(医学科学版)

Being the most common solid malignant tumor in the digestive system and the third leading cause of cancer-related death worldwide， hepatocellular carcinoma （HCC） is characterized by insidious onset， early recurrence/metastasis and poor prognosis. With the advantages of targeted precision， high specificity， minimal drug resistance， remarkable therapeutic efficacy and fewer side effects， molecular targeted drugs have become the hotspot and focus of tumor therapy research in recent years. As more is learned about the mechanism and clinical efficacy， some molecular targeted drugs have been recommended by HCC treatment guidelines. This paper reviewed the mechanism of HCC targeted therapy， molecular targeted drugs， relevant therapeutic protocols and outcomes so as to provide reference and evidence for subsequent research.

Psychological and behavioral characteristics of children with autism spectrum disorder using Psycho-educational Profile (Third Edition) / 中国康复理论与实践

ObjectiveTo explore psychological and behavioral characteristics of children with autism spectrum disorder (ASD) using Psycho-educational Profile (Third Edition) (PEP3). MethodsFrom October, 2021 to October, 2022, 192 children with ASD without intervention in the Binzhou Medical University Hospital were selected as observation group, and 96 healthy children who visited at the same time were selected as control group. They were assessed with PEP3. ResultsThe development of receptive language significantly delayed behind expressive language (t = 5.383, P < 0.001) in the observation group. The cognitive, expressive language, receptive language, fine motor, gross motor, imitation and personal self-care correlated with age (r = 0.540 to 0.795, P < 0.001). The Cronbach's α of PEP3 for the observation group was 0.810 to 0.947. The original score of each subtest of PEP3 was less in the observation group than in the control group (|t| > 4.267, P < 0.001). ConclusionThe development of receptive language retards behind the expressive language in children with ASD. Cognitive and motor functions develop with age, while the correlation between maladaptive behavior and age is weak. PEP3 is reliable in internal consistency, and valid in discrimination.

Therapeutic Effect of Ziziphi Spinosae Semen-Albiziae Flos on Depression in Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Ziziphi Spinosae Semen-Albiziae Flos on the nucleotide-binding oligomerization domain，NOD-like receptor thermal protein domain associated protein 1 （NLRP1）/chemokine ligand 1 （CXCL1）/chemokine receptor 2 （CXCR2） pathway in the hippocampus of the rat model of chronic unpredictable mild stress （CUMS）-induced depression. MethodA total of 120 male SD rats were randomized into blank，CUMS，CUMS + low-，medium-，and high-dose （4，8，16 g·kg-1） Ziziphi Spinosae Semen-Albiziae Flos，and CUMS + venlafaxine hydrochloride （0.008 g·kg-1） groups，with 20 rats in each group.The rat model of depression was established by solitary feeding combined with CUMS.The behaviors and spatial learning and memory abilities of rats were examined by sugar water consumption test，tail suspension test，forced swimming test，and Morris water maze test.Quantitative real-time PCR （Real-time PCR） and Western blot were employed to determine the expression of factors associated with the NLRP1/CXCL1/CXCR2 pathway in the hippocampus.Enzyme-linked immunosorbent assay was employed to determine the levels of tumor necrosis factor-α （TNF-α），interleukin （IL）-18，IL-1β，and IL-6 in the hippocampus.The immunofluorescence assay was used to measure the levels of reactive oxygen species （ROS） in the hippocampus. ResultCompared with the blank group，the CUMS group showed decreased preference to sugar water and times of crossing the platform （P<0.01），and increased immobility time of tail suspension，forced swimming floating time，and escape latency （P<0.01）.Compared with the CUMS group，the administration of Ziziphi Spinosae Semen-Albiziae Flos and venlafaxine hydrochloride alleviated the effects of CUMS on the above-mentioned behaviors and spatial learning and memory abilities of the rats （P<0.05，P<0.01）.Compared with the blank group，the CUMS group showed up-regulated protein levels of NLRP1，CXCL1，and CXCR2 （P<0.01） and elevated levels of IL-18，IL-1β，TNF-α，and IL-6 （P<0.01） in the hippocampus.The treatment with Ziziphi Spinosae Semen-Albiziae Flos and venlafaxine hydrochloride attenuated the activation of NLRP1/CXCL1/CXCR2 signaling pathway and lowered the levels of inflammatory cytokines in the hippocampus of CUMS rats （P<0.05，P<0.01）.In addition，Ziziphi Spinosae Semen-Albiziae Flos lowered the level of ROS in the hippocampus （P<0.05，P<0.01）. ConclusionZiziphi Spinosae Semen-Albiziae Flos can mitigate the depressive behaviors of the rat model of CUMS-induced depression by inhibiting the activation of NLRP1/CXCL1/CXCR2 signaling pathway.

Comparison of the myopia control effects of orthokeratology lens and peripheral defocus spectacles / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of peripheral defocus spectacles and orthokeratology lenses on the control of axial length in children and adolescents with myopia.METHODS: Prospective study. A total of 71 cases(134 eyes)of children and adolescents with myopia who visited the Second Hospital of Longyan from June 2019 to June 2021 were selected. They were fitted with peripheral defocus spectacles for 12mo and then switched to orthokeratology lenses. The growth of axial length was observed at 3, 6, and 12mo after wearing peripheral defocus spectacles and orthokeratology lenses.RESULTS: The median axial length growth after wearing peripheral defocus spectacles and orthokeratology lenses for 12mo was 0.35 and 0.14mm, respectively. The axial growth at 3, 6, and 12mo after wearing orthokeratology lenses was lower than those after wearing peripheral defocus spectacles(P&#x0026;#x003C;0.001), and the growth rate of axial length was significantly reduced. The patients were divided into a rapid progression group(axial growth ≥0.4 mm, 29 cases, 54 eyes)and a non-rapid progression group(axial growth &#x0026;#x003C;0.4mm, 42 cases, 80 eyes)according to the axial growth of peripheral defocus spectacles for 12mo. The median axial growth after wearing peripheral defocus spectacles for 12mo in the two groups was 0.70 and 0.24mm, respectively, while the median axial growth after wearing orthokeratology lenses was 0.31 and 0.09mm, respectively. The growth rate was reduced by 56% and 63% respectively in the two groups after wearing orthokeratology lens. The axial growth of cases wearing orthokeratology lenses for 12mo in the non-rapid progression group was lower than that in the rapid progression group, and it did not change with age or diopter. There was no significant difference among different ages and different diopters in the rapid progression group(P&#x0026;#x003E;0.05). In the non-rapid progression group, axial growth of cases aged 7-12 years was higher than those aged 13-16 years(P&#x0026;#x003C;0.05), but there was no significant difference among different diopters(P&#x0026;#x003E;0.05).CONCLUSION: Orthokeratology lens is more effective than peripheral defocus spectacles in controlling axial growth in children and adolescents with myopia, and the control effect of orthokeratology lens on rapid-progressing myopia is remarkable.

Exploration of human resource management practice for organ donation coordinators in public hospitals / 中华医院管理杂志

The human resource management of organ donation coordinators in China is still in its infancy stage, plagued by such problems as unclear career orientation, poor management and unclear career planning. In March 2010, a tertiary public hospital was approved as a medical institution in a national pilot province for organ donation. In recent years, the hospital had kept exploring human resource management of coordinators and established a relatively complete management mode for organ donation coordinators. This mode featured the establishment of full-time recruitment positions, development of human resource management plans, refinement of job descriptions, establishment of performance evaluation plans, optimization of assessment and incentive mechanisms, and innovation of talent cultivation modes. The management practice had achieved certain results, ensuring the sustainable development of hospital organ donation operation, and providing a reference for the scientific and standardized development of organ donation and transplantation in China.