BACKGROUND: Epidermal growth factor receptor (EGFR) and cellular-mesenchymal to epithelial transition factor (c-Met) are widely expressed on cancer cells. There is a synergistic effect of EGFR and HGF/c-Met pathways on proliferation, downstream activation of signal transduction and an additive effect. Studies show that combination of both signaling pathways could potentially be targeted in a synergistic fashion. Amivantamab, a bispecific monoclonal antibody targeting EGFR and c-Met, yielded robust and durable responses in a variety of clinicals trials. However, few researches have reported its efficacy in Chinese non-small cell lung cancer (NSCLC) patients. This study was conducted to evaluate the effectiveness and tolerance of Amivantamab in NSCLC patients with EGFR/MET gene abnormalities at Peking University Cancer Hospital. METHODS: The study enrolled NSCLC patients who received Amivantamab in our hospital between August 2020 and December 2021, and analyzed the response, survival, and treatment-related adverse events. RESULTS: Fifteen patients were enrolled in this research, and six of them received Amivantamab treatment and the other nine patients received Amivantamab plus Lazertinib treatment. The rates of partial response (PR), stable disease (SD), and progressive disease (PD) were 46.7% (7/15), 46.7% (7/15) and 6.7% (1/15), respectively. The overall response rate (ORR) and disease control rate (DCR) were 28.6% (2/7) and 100.0% (7/7) in seven patients with EGFR exon 20 insertion, respectively. The ORR and DCR were 40.0% (2/5) and 100.0% (5/5) in five post-osimertinib EGFR-mutant patients, respectively. After a median follow-up of 8.7 months, the median progression-free survival and overall survival were not reached. The most common treatment-related adverse events were rash (86.7%), paronychia (80.0%), and infusion-related reactions (60.0%), and most of them were graded as 1 to 2. Grade 3 to 4 adverse events included rash (33.3%), alanine aminotransferase elevation (13.3%), gamma-glutamyl transpeptidase elevation (13.3%), peripheral edema (6.7%), thromboembolism (6.7%), interstitial lung disease (6.7%), and thrombocytopenia (6.7%). CONCLUSIONS Amivantamab was effective in Chinese NSCLC patients with EGFR exon 20 insertion and post-Osimertinib EGFR-mutant patients, similar to the results of clinical trials conducted in western countries. Amivantamab was well tolerated and emphases should be put on adverse events such as rash, paronychia, and infusion-related reactions.
Antibodies, Bispecific ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Exanthema/drug therapy* ; Humans ; Lung Neoplasms/genetics* ; Mutation ; Paronychia/drug therapy* ; Protein Kinase Inhibitors/therapeutic use*

AIM: To observe the growth status and morphological changes of primary cultured bulbar conjunctival fibroblasts in different stages of conjunctivochalasis(CCH), and to determine the best passage time, so as to obtain stable and consistent CCH bulbar conjunctival fibroblasts.METHODS: CCH primary bulbar conjunctival fibroblasts were obtained by tissue block adhesion method. The fibroblasts were purified by trypsin differential digestion method. The growth status and morphological changes of fibroblasts in different periods were observed and recorded under inverted microscope. The fibroblasts were identified by immunofluorescence cytochemical staining.RESULTS: After 24h of CCH conjunctival tissue adherent to the wall, a small number of cells would be seen crawling out around the tissue blocks. The logarithmic phase of cell growth was from the 2-7d. The cells grew fast, with vigorously proliferation, clear outline, uniform distribution, increas in numbers and clear nuclei. From the 9-15d, the cell growth entered the plateau stage, the tissue blocks gradually aged and lost activity. The cells grew slowly, arranged loosely, the volume became larger, the shape became flat, and a large number of granular substances and vesicles were produced in the cytoplasm. Some cells fell off from the bottom of the culture bottle, and large gaps appeared between the cells. After subculture and purification, the size and morphology of fibroblasts were basically the same. Through cell identification, fibroblasts were long spindle, flat star or multi-process spindle, wide in the middle, oval nucleus, relatively small at both ends, with 2-3 slender processes of different lengths extending outward.CONCLUSION: Primary CCH bulbar conjunctival fibroblasts can be successfully obtained by tissue block adhesion method. When the cells grow to the 8d, they can be digested and passaged to obtain stable and consistent CCH conjunctival fibroblasts.

BACKGROUND: Chronic noise exposure is one environmental hazard that is associated with genetic susceptibility factors that increase Alzheimer's disease (AD) pathogenesis. However, the comprehensive understanding of the link between chronic noise stress and AD is limited. Herein, we investigated the effects of chronic noise exposure on AD-like changes in senescence-accelerated mouse prone 8 (SAMP8). METHODS: A total of 30 male SAMP8 mice were randomly divided into the noise-exposed group, the control group, and aging group (positive controls), and mice in the exposure group were exposed to 98 dB SPL white noise for 30 consecutive days. Transcriptome analysis and AD-like neuropathology of hippocampus were examined by RNA sequencing and immunoblotting. Enzyme-linked immunosorbent assay and real-time PCR were used to further determine the differential gene expression and explore the underlying mechanisms of chronic noise exposure in relation to AD at the genome level. RESULTS: Chronic noise exposure led to amyloid beta accumulation and increased the hyperphosphorylation of tau at the Ser202 and Ser404 sites in young SAMP8 mice; similar observations were noted in aging SAMP8 mice. We identified 21 protein-coding transcripts that were differentially expressed: 6 were downregulated and 15 were upregulated after chronic noise exposure; 8 genes were related to AD. qPCR results indicated that the expression of Arc, Egr1, Egr2, Fos, Nauk1, and Per2 were significantly high in the noise exposure group. These outcomes mirrored the results of the RNA sequencing data. CONCLUSIONS These findings further revealed that chronic noise exposure exacerbated aging-like impairment in the hippocampus of the SAMP8 mice and that the protein-coding transcripts discovered in the study may be key candidate regulators involved in environment-gene interactions.

Objective To investigate the radiosensitization effect of stattic on the xenograft of esophageal squamous cell carcinoma ( ESCC ) ECA109 cells in nude mouse and explore the underlying mechanisms. Methods Male nude mice inoculated subcutaneously with ECA109 cells were used to examine the radiosensitization effect of stattic in vivo. When average volume of tumors was about 150 mm3 , mice were randomly divided into 4 groups:control group, 25 mg/kg stattic alone group, ionizing radiation (IR) (6 Gy) alone group, and 25 mg/kg stattic plus IR group. During the term of treatment, the volume of tumors was measured every 2 days. On 25 days after treatment, the mice were killed and the expressions of pSTAT3, STAT3, HIF-1α and VEGF in ECA109 xenografts were assessed by Western blot and immunohistochemistry analysis. Results The volume of tumor in nude mice was (705. 1 ± 75. 5) mm3 in stattic plus IR group, which was significantly smaller than that in IR group (113. 5 ± 101. 4) mm3 and stattic alone group(1696.5 ±100.6)mm3(t=4.35, 14.14,P<0.0). The inhibition rate was (66.1 ± 3. 2)％ in stattic plus IR group. The expression levels of pSTAT3, HIF-1α and VEGF were obviously decreased in the stattic plus IR group compared with other groups (t=17. 07, 5. 05, 3. 54, P<0. 05). Conclusions Stattic play a radiosensitization role in the xenograft of esophageal carcinoma in nude mice probably by inhibiting the signaling pathways of pSTAT3, HIF-1α and VEGF.

Objective To study the effect of gastrodin on arterial blood gas and brain injury of rats under simulated high altitude hypoxia environment. Methods A total of 60 adult healthy male Wistar rats were randomly divided into normal (N) group, hypoxia model (M) group, rhodiola crenulata (RC) group, low dose of gastrodin (GAS-L) group, medium dose of gastrodin (GAS-M) group and high dose of gastrodin (GAS-H) group (10 for each group). The intragastric administration on rats was continued for 7 days timely in each day. Under simulated 8000m altitude using low pressure oxygen cabin, the arterial blood gas of each group were tested, pathological changes of brain tissues were observed and related indexes of brain were detected after 12h hypoxia. Results Comparing with group N, the blood oxygen partial pressure (PO2), value of blood oxygen saturation (SO2), oxygenation index (PO2/FIO2), Na+ concentration (Na+), actual bicarbonate radical (HCO3–) significantly decreased (P<0.01), lactic acid (Lac), hemoglobin concentration (Hb) significantly increased (P<0.01) and pathological damage was inflicted in group M; and contents of malondialdehyde (MDA), hydrogen peroxide (H2O2) in brain tissue significantly increased (P<0.01), content of glutathione(GSH) and activity of glutathione peroxidase (GSH-Px) in brain tissue significantly decreased (P<0.01) in group M. Compared with group M, PO2, SO2 and PO2/FIO2 significantly increased (P<0.01, P<0.05) in group GAS-L; Na+ and HCO3– significantly increased (P<0.01, P<0.05) in three dose groups of GAS; Lac significantly decreased (P<0.01, P<0.05) in group GAS-L and GAS-H. Hb significantly increased (P<0.01) in group GAS-H, a rising trend appeared in group GAS-L but with no statistical significance. Damages of brain tissue were alleviated in group RC and three dose groups of GAS comparing with group M. Compared with group M, MDA significantly decreased (P<0.01) in three dose groups of GAS; there was a decreasing trend of H2O2 but with no statistical significance in three dose groups of GAS; GSH and GSH-Px significantly increased (P<0.01, P<0.05) in three dose groups of GAS. However, three groups of GAS has no dose dependent. Conclusion There was an protective effect of gastrodin on arterial blood gas and brain injury of rats under simulated high altitude hypoxia environment.

BACKGROUNDThree-dimensional (3D) printing technology holds great promise for treating diseases or injuries that affect human bones with enhanced performance over traditional techniques. Different patterns of design can lead to various mechanical properties and biocompatibility to various degrees. However, there is still a long way to go before we can fully take advantage of 3D printing technologies.

METHODSThis study tailored 3D printed scaffolds with gelatin and platelets to maximize bone regeneration. The scaffolds were designed with special internal porous structures that can allow bone tissue and large molecules to infiltrate better into the scaffolds. They were then treated with gelatin and platelets via thermo-crosslinking and freeze-drying, respectively. Vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β1 were measured at different time points after the scaffolds had been made. Cell proliferation and cytotoxicity were determined via cell counting kit-8 (CCK-8) assay.

RESULTSThere was a massive boost in the level of VEGF and TGF-β1 released by the scaffolds with gelatin and platelets compared to that of scaffolds with only gelatin. After 21 days of culture, the CCK-8 cell counts of the control group and treated group were significantly higher than that of the blank group (P < 0.05). The cytotoxicity test also indicated the safety of the scaffolds.

CONCLUSIONSOur experiments confirmed that the 3D printed scaffolds we had designed could provide a sustained-release effect for growth factors and improve the proliferation of preosteoblasts with little cytotoxicity in vitro. They may hold promise as bone graft substitute materials in the future.

3T3 Cells ; Animals ; Biocompatible Materials ; chemistry ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Gelatin ; chemistry ; Mice ; Printing, Three-Dimensional ; Tissue Engineering ; methods ; Tissue Scaffolds ; chemistry ; Transforming Growth Factor beta1 ; chemistry ; pharmacology ; Vascular Endothelial Growth Factor A ; chemistry ; pharmacology

The chemotaxis response of Erwinia carotovora to different sugars and amino acids in four kinds of chemotactic parameters (concentration, time, temperature and pH ) was determined by capillary method. The results showed that when pH was 8, concentration was 0.025 mg•L ⁻¹, culture temperature was 25 ℃ and the duration was 60 minutes, the optimal chemotaxis rate of lysine was 2.509,when pH was 6, concentration was 0.25 mg•L ⁻¹, culture temperature was 25 ℃ and the duration was 60 minutes, the optimal chemotaxis rate of arginine was 2.218 8,when pH was 7, concentration was 0.25 mg•L ⁻¹, culture temperature was 30 ℃ and the duration was 60 minutes, the optimal chemotaxis rate of L-rhamnose was 3.091 2, when pH was 6, concentration was 0.25 mg•L ⁻¹, culture temperature was 30 ℃ and the duration was 45 minutes, the optimal chemotaxis rate of D-arabinose was 3.026 3. Sugars and amino acids had obvious chemotaxis with E. carotovora,the high concentration of carbohydrate and amino acid exited an inhibitory effect on chemotaxis response of E. carotovora, and the chemotaxis response decreased with the increase of concentration of carbohydrates and amino acids.

Objective To investigate the effects of preoperative use of parecoxib Na during anesthesia recovery period on the fast track anesthe-sia with remifentanil.Methods A total of 105 cases who received lapa-roscopic cholecystectomy were randomly divided into three groups with 35 cases in each group.Patients in group A received parecoxib Na 40 mg dissolved in normal saline 10 mL through injection 20 min before induc-tion of anesthesia.Patients in group B received parecoxib Na 40 mg dis-solved in normal saline10 mL through injection 20 min before the end of surgery.Patients in group C received normal saline 10 mL through injec-tion 20 min before induction of anesthesia.The data of mean arterial pressure(MAP), heart rate (HR) and oxygen saturation (SPO2), ver-bal rating scale ( VRS) , sedation-agitation scale ( SAS) , ramsay sada-tion scale ( RSS ) and comfort score ( BCS ) were compared among three groups.Results The data of MAP, SAS and HR in group A and group B were significantly lower than those in group C, and the data of MAP, SAS and HR in group A were significantly lower than those in group B ( P<0.05).The data of RSS in group A was significantly lower than that in group B and RSS in group A and group B significantly higher than those in group C from T2 to T4 (P<0.05).The data of VRS in group A and group B were significantly lower than those in group C, and that in group A was signifi-cantly lower than group B each time point( P<0.05).Postoperative BCS in group A and group B were significantly higher than those in group C, and that in group A was significantly higher than group B( P<0.05).Conclusion Pre-operative use of parecoxib Na can significantly reduce the acute pain of the fast track anesthesia with remifentanil, effectively inhibiting hyperalgesia and reducing the patient's agitation.

Mesenchymal stem cells (MSCs) could be obtained from many sources, and there are differences between them. This study was purposed to compare and analyze the basic biological characteristics of umbilical cord, adipose tissue-and bone marrow-derived MSC (UC-MSCs, AD-MSCs and BM-MSCs). The MSCs were isolated from umbilical cord, adipose tissue and bone marrow were cultured; the morphology of UC-MSCs, AD-MSCs and BM-MSCs was observed by using microscopy; the immunophenotype, differentiation potential and expression of peroxisome proliferation-activated receptor-γ (PPAR-γ) mRNA were detected by using flow cytometry, differentiation test (von kossais and 0:1 red O staining) and quantitative fluorescent PCR, respectively. The results showed that the UC-MSCs, AD-MSCs and BM-MSCs displayed similar morphology under confocal microscope after being stained with rhodamine phalloidin and DAPL. The immunophenotypes of these three originated cells conform to coincide with identification criterion for MSCs, and showed similar expression level. During adipogenic induction the adipogenic potential of these MSCs was different, AD-MSCs exhibited the highest adipogenic potential, UC-MSCs displayed the lowest, while potential of BM-MSCs get between; however, the osteogenic differentiation potential of UC-MSCs, AD-MSCs and BM-MSCs was similar. The PCR detection showed that the expression level of PPAR-γ mRNA was the highest in AD-MSCs and the lowest in UC-MSCs, while expression level in BM-MSCs get between, these results were identical with the adipogenic potential, suggest that the difference of adipogenic potential in 3 kinds of MSCs was associated with basic expression level of PPAR-γ mRNA. It is concluded that UC-MSCs, AD-MSCs and BM-MSCs exhibit similar morphology, the immunophenotypes of these MSCs coincide with identification criterion for MSCs, the osteogenic potential of these MSCs is similar, while the adipogenic potential and the expression level of PPAR-γ mRNA are different. The difference-associated mechanisms need to further study.
Adipogenesis ; Adipose Tissue ; cytology ; Bone Marrow Cells ; cytology ; Cell Separation ; Cells, Cultured ; Humans ; Mesenchymal Stromal Cells ; cytology ; Umbilical Cord ; cytology

OBJECTIVETo investigate the relationship between renal clear cell carcinoma and type 2 diabetes mellitus (DM).

METHODSTwo hundreds and sixty-four patients with renal clear cell carcinoma and four hundred controls who suffered from non-urinary system, non-neoplastic or non-hormone-related disorders, were enrolled from January 2008 to December 2012. The incidence of diabetes between the 2 groups and the relationship between renal clear cell carcinoma and duration of diabetes were compared, moreover, renal clear cell carcinoma patients with DM were compared with patients without DM for their clinical features, laboratory examinations and histological characteristics.

RESULTSThe comparison of renal clear cell carcinoma group and control group: the incidence of DM in the two groups were 19.7% and 12.8% respectively, and the difference was significant (&chi;(2) = 5.86, P < 0.05, OR = 1.68). In the renal clear cell carcinoma group, the proportion of patients with DM diagnosed within 2-4 years was 4.92%, which were significant higher than those in the control group 1.70% (&chi;(2) = 5.49, P < 0.05, OR = 2.91). And men with diabetes had high occurrence risk 86% of renal clear cell carcinoma (OR = 1.86, 95%CI: 1.09-3.15). The comparison of diabetes patients subgroup and non-diabetic patients subgroup in renal clear cell carcinoma group: in respect of clinical features, greatest tumor diameter in the two subgroups were (4.9 ± 2.3) cm and (4.2 ± 2.1) cm respectively, and the difference was significant (t = 1.96, P < 0.05). However, there was no significant difference in terms of age, gender and cancer location between the two subgroups (P > 0.05). In respect of laboratory examinations, serum creatinine in the two subgroups were (72 ± 20) µmol/L and (65 ± 17) µmol/L, and the difference was significant (t = 2.34, P < 0.05); serum urea nitrogen in the 2 subgroups were (7.1 ± 2.1) mmol/L and (6.0 ± 1.5) mmol/L respectively, and the difference was significant too (t = 1.47, P < 0.05). In respect of histological characteristics, the proportion of well differentiated clear cell carcinoma were 80.8% and 81.1% respectively, and the difference was significant (&chi;(2) = 4.23, P < 0.05). The proportion of stage II were 25.0% and 27.8% respectively and the difference was significant (&chi;(2) = 4.08, P < 0.05).

CONCLUSIONSDM is closely related with renal clear cell carcinoma and DM may be a possible risk factor for the tumor. And for elderly patients with diabetes who appear waist discomfort or hematuria, a careful examination of kidney is important to make early diagnosis, give timely treatment and improve survival prognosis.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Renal Cell ; complications ; Case-Control Studies ; Diabetes Mellitus, Type 2 ; complications ; Female ; Humans ; Incidence ; Kidney Neoplasms ; complications ; Male ; Middle Aged ; Prognosis