1.Relationship between TFA-irAE after anti-PD-1 therapy and survival in advanced cancer patients
Wei GUO ; Donghui WANG ; Zhenhua WANG ; Zhaojun XUE
Journal of International Oncology 2024;51(8):481-486
		                        		
		                        			
		                        			Objective:To investigate the relationship between thyroid function abnormality-immune related adverse event (TFA-irAE) and treatment efficacy and survival in advanced cancer patients treated with programmed death-1 (PD-1) inhibitors.Methods:The clinical data of 90 patients with advanced cancer who received 6 cycles of PD-1 inhibitor treatment from January 2021 to June 2022 in Department of Oncology of Yuncheng Central Hospital Affiliated to Shanxi Medical University were collected. Serum levels of thyroid stimulating hormone (TSH), free thyroxine (FT 4), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) were measured by chemiluminescence immunoassay in patients after PD-1 inhibitor treatment, and the incidence of TFA-irAE was observed in the patients after 6 cycles of therapy. According to the occurrence of TFA-irAE, the patients were divided into TFA-irAE occurrence group ( n=40) and TFA-irAE non-occurrence group ( n=50), the therapeutic efficacy and survival of the two groups were calculated and compared. The thyroid function indexes of patients with different efficacy (33 cases in effective group and 57 cases in ineffective group) and patients with different prognosis (30 cases in survival group, 60 cases in death group) were compared, and the influencing factors of efficacy and survival were analyzed by multivariate logistic regression and Cox analysis. Kaplan-Meier survival curve was drawn, and the survival of TFA-irAE occurrence group and TFA-irAE non-occurrence group were compared by log-rank test. Results:One year after treatment, the treatment effective rate of TFA-irAE occurrence group and TFA-irAE non-occurrence group were 42.5% (17/40), 32.0% (16/50), respectively, with no statistically significant difference ( χ2=1.06, P=0.304). After 6 cycles of PD-1 inhibitor treatment, serum levels of TSH [ (2.56±0.41) mU/ml vs. (3.11±0.53) mU/ml], TPOAb [ (56.78±5.72) U/ml vs. (62.67±6.31) U/ml] and TGAb [ (81.57±8.23) U/ml vs. (92.34±9.31) U/ml] in the effective group were significantly lower than those in the ineffective group, with statistically significant differences ( t=4.45, P<0.001; t=3.89, P<0.001; t=5.29, P<0.001). The serum levels of TSH [ (2.69±0.46) mU/ml vs. (3.06±0.65) mU/ml], FT 4 [ (10.45±1.13) pmol/L vs. (11.50±1.36) pmol/L], TPOAb [ (56.27±5.61) U/ml vs. (62.47±6.34) U/ml] and TGAb [ (81.62±8.31) U/ml vs. (91.73±9.35) U/ml] in the survival group were significantly lower than those in the death group, with statistically significant differences ( t=2.27, P=0.025; t=3.02, P=0.003; t=3.79, P<0.001; t=4.19, P<0.001). Multivariate logistic regression analysis showed that TSH ( OR=1.52, 95% CI: 1.13-2.05, P=0.006), TPOAb ( OR=1.42, 95% CI: 1.13-1.78, P=0.002) and TGAb ( OR=1.35, 95% CI: 1.05-1.73, P=0.018) were all independent factors affecting the efficacy of patients with advanced cancer treated with PD-1 inhibitors. Multivariate Cox regression analysis showed that TSH ( HR=1.42, 95% CI: 1.06-1.92, P=0.030), TPOAb ( HR=1.31, 95% CI: 1.05-1.64, P=0.018), TGAb ( HR=1.41, 95% CI: 1.09-1.83, P=0.008) and FT 4 ( HR=1.36, 95% CI: 1.02-1.81, P=0.038) were all independent factors affecting the survival of patients with advanced cancer treated with PD-1 inhibitors. Survival analysis showed that the median overall survival in the TFA-irAE occurrence group and the TFA-irAE non-occurrence group were 10.8 and 8.0 months, respectively, with a statistically significant difference ( χ2=9.53, P=0.002) . Conclusion:Although the occurrence of TFA-irAE may have less effect on the efficacy of advanced tumor patients treated with PD-1 inhibitors, it may affect the survival of patients. TSH, TPOAb and TGAb are all independent influencing factors for the efficacy of patients with advanced tumors treated with PD-1 inhibitors, while TSH, TPOAb, TGAb and FT 4 are independent influencing factors for the survival of patients with advanced tumors treated with PD-1 inhibitors.
		                        		
		                        		
		                        		
		                        	
2.Targeted trace ingredients coupled with chemometric analysis for consistency evaluation of Panax notoginseng saponins injectable formulations.
Jingxian ZHANG ; Zijia ZHANG ; Zhaojun WANG ; Tengqian ZHANG ; Yang ZHOU ; Ming CHEN ; Zhanwen HUANG ; Qingqing HE ; Huali LONG ; Jinjun HOU ; Wanying WU ; Dean GUO
Chinese Journal of Natural Medicines (English Ed.) 2023;21(8):631-640
		                        		
		                        			
		                        			Evaluating the consistency of herb injectable formulations could improve their product quality and clinical safety, particularly concerning the composition and content levels of trace ingredients. Panax notoginseng Saponins Injection (PNSI), widely used in China for treating acute cardiovascular diseases, contains low-abundance (10%-25%) and trace saponins in addition to its five main constituents (notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, and ginsenoside Rd). This study aimed to establish a robust analytical method and assess the variability in trace saponin levels within PNSI from different vendors and formulation types. To achieve this, a liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) method employing multiple ions monitoring (MIM) was developed. A "post-column valve switching" strategy was implemented to eliminate highly abundant peaks (NR1, Rg1, and Re) at 26 min. A total of 51 saponins in PNSI were quantified or relatively quantified using 18 saponin standards, with digoxin as the internal standard. This study evaluated 119 batches of PNSI from seven vendors, revealing significant variability in trace saponin levels among different vendors and formulation types. These findings highlight the importance of consistent content in low-abundance and trace saponins to ensure product control and clinical safety. Standardization of these ingredients is crucial for maintaining the quality and effectiveness of PNSI in treating acute cardiovascular diseases.
		                        		
		                        		
		                        		
		                        			Ginsenosides
		                        			;
		                        		
		                        			Saponins
		                        			;
		                        		
		                        			Chemometrics
		                        			;
		                        		
		                        			Panax notoginseng
		                        			;
		                        		
		                        			Cardiovascular Diseases
		                        			;
		                        		
		                        			Chromatography, Liquid
		                        			;
		                        		
		                        			Tandem Mass Spectrometry
		                        			
		                        		
		                        	
3.Application of maxillary osteotomy and positioning guide plates in orthognathic surgery
Tingyi GAO ; Kai ZHANG ; Dong WANG ; Rui HAN ; Zhenfei GUO ; Zhaojun ZHAN
Chinese Journal of Plastic Surgery 2021;37(7):777-783
		                        		
		                        			
		                        			Objective:The aim of this study was to explore the application of maxillary osteotomy plate and positioning guide plate in maxillary Le Fort Ⅰ osteotomy to eliminate the postoperative error caused by condylar displacement.Methods:Patients suffered from skeletal malocclusion and needed Le Fort Ⅰ osteotomy between January 2018 and November 2020 were selected from the Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Bengbu Medical College. All patients were scanned with 64 slice spiral CT. The DICOM format data were analyzed using the Simplant software to reconstruct the virtual three-dimensional model of the jaw before operation. Then, the measurement of indexes and the maxillary Le Fort Ⅰ osteotomy were carried out on the virtual three-dimensional model, respectively. 3D-printed osteotomy guide plate and positioning guide plate were used to determine the osteotomy line and the position of maxillary advancement. 3D-printed tooth supported occlusal plate was used to support the mandibular sagittal split and retraction. The differences of 10 indexes between the two groups (virtual operation and surgery) were analyzed by paired t test using SPSS 22.0. Results:A total of 8 patients (5 males and 3 females) needed maxillary Le Fort Ⅰ osteotomy aged from 18 to 39 years old were recorded. The deviation of age in these patients was 24.8. The 3D-printed guide plate and tooth supporting occlusal plate were positioned accurately in surgery. All the operations were successful with primary healing of the incision and stable occlusion, and without joint clicking. There was no significant difference on the 10 indexes between the groups of virtual operation and surgery ( P>0.05). Conclusions:The application of maxillary osteotomy plate and positioning guide plate can effectively and accurately control the three-dimensional movement of the maxilla and improve the precision of maxillary Le fort Ⅰ osteotomy in orthognathic surgery, making the surgical effect highly consistent with the preoperative design.
		                        		
		                        		
		                        		
		                        	
4.Application of maxillary osteotomy and positioning guide plates in orthognathic surgery
Tingyi GAO ; Kai ZHANG ; Dong WANG ; Rui HAN ; Zhenfei GUO ; Zhaojun ZHAN
Chinese Journal of Plastic Surgery 2021;37(7):777-783
		                        		
		                        			
		                        			Objective:The aim of this study was to explore the application of maxillary osteotomy plate and positioning guide plate in maxillary Le Fort Ⅰ osteotomy to eliminate the postoperative error caused by condylar displacement.Methods:Patients suffered from skeletal malocclusion and needed Le Fort Ⅰ osteotomy between January 2018 and November 2020 were selected from the Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Bengbu Medical College. All patients were scanned with 64 slice spiral CT. The DICOM format data were analyzed using the Simplant software to reconstruct the virtual three-dimensional model of the jaw before operation. Then, the measurement of indexes and the maxillary Le Fort Ⅰ osteotomy were carried out on the virtual three-dimensional model, respectively. 3D-printed osteotomy guide plate and positioning guide plate were used to determine the osteotomy line and the position of maxillary advancement. 3D-printed tooth supported occlusal plate was used to support the mandibular sagittal split and retraction. The differences of 10 indexes between the two groups (virtual operation and surgery) were analyzed by paired t test using SPSS 22.0. Results:A total of 8 patients (5 males and 3 females) needed maxillary Le Fort Ⅰ osteotomy aged from 18 to 39 years old were recorded. The deviation of age in these patients was 24.8. The 3D-printed guide plate and tooth supporting occlusal plate were positioned accurately in surgery. All the operations were successful with primary healing of the incision and stable occlusion, and without joint clicking. There was no significant difference on the 10 indexes between the groups of virtual operation and surgery ( P>0.05). Conclusions:The application of maxillary osteotomy plate and positioning guide plate can effectively and accurately control the three-dimensional movement of the maxilla and improve the precision of maxillary Le fort Ⅰ osteotomy in orthognathic surgery, making the surgical effect highly consistent with the preoperative design.
		                        		
		                        		
		                        		
		                        	
5. A family of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy
Weixin LI ; Yu LIU ; Xiaoyue GUO ; Zhaojun XU ; Hong LU ; Xiangdong KONG ; Yiwen ZHAI
Chinese Journal of Neurology 2019;52(10):823-830
		                        		
		                        			 Objective:
		                        			To investigate the clinical features, imaging features, pathological features and gene diagnosis of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL).
		                        		
		                        			Methods:
		                        			Clinical manifestations, signs and imaging characteristics of a female patient hospitalized in the First Affiliated Hospital of Zhengzhou University for more than 10 days due to headache were analyzed, and skin biopsy and HTRA1 and Notch3 gene detection were performed. The pedigree of the proband was investigated in detail, and HTRA1 gene test and related imaging examination were conducted in parallel. Due to the deceased parents of the patient, relevant genetic testing could not be conducted. A control group of 100 healthy people were analyzed.
		                        		
		                        			Results:
		                        			The clinical manifestations of proband were headache after insomnia, hearing loss in the right ear, easy to wake up and sweat at night. Brain MRI showed diffuse patchy long T1 and long T2 signals in bilateral fronto-parietal temporal occipital insula, internal and external capsule areas, bilateral basal ganglia areas, and bilateral thalamus. Fluid attenuated inversion recovery sequence showed high signals. Magnetic sensitive weighted imaging showed scattered patchy low signals in bilateral cerebral and cerebellar hemispheres, bilateral basal ganglia area, left thalamus and brain stem. The proband had consanguineous parents. A homozygous mutation C to T transition at position 589 (c.589C>T) was found in exon 3 of HTRA1 gene with the proband and both siblings. The heterozygous c.589C>T mutation appeared in another sister of the proband. Under the light microscope of skin biopsy, pigmentation in the basal layer of the skin could be seen, collagen fiber hyperplasia in the dermis was accompanied by a small amount of inflammatory cell infiltration, and no definite amyloidosis was found. No mutations were found in Notch3 gene. Because the patient′s parents were deceased, genetic testing was not possible. One hundred healthy controls had no such mutation.
		                        		
		                        			Conclusions
		                        			The CARASIL family with HTRA1 gene c.589C>T homozygous mutation was reported, and the pathogenicity of the mutation was confirmed. HTRA1 genetic testing is recommended for diagnosis and differential diagnosis of CARASIL with family history or clinical suspicion. 
		                        		
		                        		
		                        		
		                        	
6.A family of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy
Weixin LI ; Yu LIU ; Xiaoyue GUO ; Zhaojun XU ; Hong LU ; Xiangdong KONG ; Yiwen ZHAI
Chinese Journal of Neurology 2019;52(10):823-830
		                        		
		                        			
		                        			Objective To investigate the clinical features, imaging features, pathological features and gene diagnosis of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Methods Clinical manifestations, signs and imaging characteristics of a female patient hospitalized in the First Affiliated Hospital of Zhengzhou University for more than 10 days due to headache were analyzed, and skin biopsy and HTRA1 and Notch3 gene detection were performed. The pedigree of the proband was investigated in detail, and HTRA1 gene test and related imaging examination were conducted in parallel. Due to the deceased parents of the patient, relevant genetic testing could not be conducted. A control group of 100 healthy people were analyzed. Results The clinical manifestations of proband were headache after insomnia, hearing loss in the right ear, easy to wake up and sweat at night. Brain MRI showed diffuse patchy long T1 and long T2 signals in bilateral fronto?parietal temporal occipital insula, internal and external capsule areas, bilateral basal ganglia areas, and bilateral thalamus. Fluid attenuated inversion recovery sequence showed high signals. Magnetic sensitive weighted imaging showed scattered patchy low signals in bilateral cerebral and cerebellar hemispheres, bilateral basal ganglia area, left thalamus and brain stem. The proband had consanguineous parents. A homozygous mutation C to T transition at position 589 (c.589C>T) was found in exon 3 of HTRA1 gene with the proband and both siblings. The heterozygous c.589C>T mutation appeared in another sister of the proband. Under the light microscope of skin biopsy, pigmentation in the basal layer of the skin could be seen, collagen fiber hyperplasia in the dermis was accompanied by a small amount of inflammatory cell infiltration, and no definite amyloidosis was found. No mutations were found in Notch3 gene. Because the patient′s parents were deceased, genetic testing was not possible. One hundred healthy controls had no such mutation. Conclusions The CARASIL family with HTRA1 gene c.589C>T homozygous mutation was reported, and the pathogenicity of the mutation was confirmed. HTRA1 genetic testing is recommended for diagnosis and differential diagnosis of CARASIL with family history or clinical suspicion.
		                        		
		                        		
		                        		
		                        	
7.Testing System for Biomechanical Properties of Bone.
Zhanshe GUO ; Zhaojun GUO ; Xiangdang LIANG
Chinese Journal of Medical Instrumentation 2018;42(2):84-87
		                        		
		                        			
		                        			A novel testing system is designed to simulate the mechanical performance and evaluate the biomechanical properties of the bone and the corresponding bone fixator. It is mainly composed of movement platform and servo motor system, sensors and hardware circuit system and software system. In order to prove the feasibility of the design, on the basis of the calibration for the force sensor, the fatigue experiment is carried out using the tibia of the sheep. It is concluded from the result that under the condition of 1 Hz in frequency, 50 kg in loading force and 18 000 cycles, the bone fixator can be still in good condition, which proves the feasibility of the design.
		                        		
		                        		
		                        		
		                        			Animals
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		                        			Biomechanical Phenomena
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		                        			Bone Screws
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		                        			Mechanical Phenomena
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		                        			Sheep
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		                        			Stress, Mechanical
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		                        			Tibia
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		                        			physiology
		                        			
		                        		
		                        	
8.Clinical characteristics of rheumatoid arthritis caused by pauciarticular arthritis
Bin WANG ; Zhu CHEN ; Xiangpei LI ; Zhaojun GUO
Chinese Journal of Disease Control & Prevention 2017;21(9):935-938
		                        		
		                        			
		                        			Objective To improve the comprehensive understanding and treatment level of the disease by analyzing the clinical characteristics of rheumatoid arthritis (RA) caused by pauciarticular arthritis.Methods The method was retrospective analysis and summary of clinical and laboratory data of 198 cases of patients with RA,in which 98 cases of pauciarticular arthritis belonged to the observation group and 100 cases of polyarticular arthritis belonged to the control group.Results Male patients in observation group were obviously more than those in the control group (t =2.456,P =0.015).Courses of disease was obviously shorter than those in the control group (t =-2.450,P =0.018).The number of involved joints was obviously less than those in the control group (t =-6.316,P <0.001).The incidence of morning.stiffness was significantly less than those in the control group (t =-3.884,P < 0.001).Rating scores of disease activity score 28 were significantly lower than those in the control group (t =-8.694,P < 0.001).And positive rate of anti-cyslic citrullinated peptide antibody is significantly higher than those in the control group (t =-2.299,P =0.022).Thyrotrophin levels were significantly higher than those in the control group (t =3.809,P < 0.001).There was no significant differences in age,erythrocyte sedimentation rate and C reactive protein,immunoglobulin and complement level,free triiodothyronine,free thyroxine,blood lipids,blood system and kidney involvement between the two groups (all P > 0.05).Conclusions The conclusion turns out to be that there are no typical clinical manifestations showing that rheumatoid arthrifts is caused by pauciarticular arthritis.Maybe it is the early performance of disease.It is worth attention that concurrent subclinical hypothyroidism turns out to be more.
		                        		
		                        		
		                        		
		                        	
9.P14 Rotavirus VP8* protein specifically binds to a type histo-blood group antigen
Xiaoman SUN ; Nijun GUO ; Ziqian XU ; Dandi LI ; Zhaojun DUAN
Chinese Journal of Experimental and Clinical Virology 2016;30(3):315-318
		                        		
		                        			
		                        			Objective To explore the binding specificity of the P[14] RV detected directly from the stool samples.Methods The P[14] VP8* protein was expressed and purified and then the binding pattern to synthetic oligosaccharides and saliva samples was carried out.Results The P[14] VP8 * protein showed significant binding to A type HBGA while almost no binding was detected to other HBGAs.Conclusions A-HBGA may be the attachment factor for the P[14] rotavirus.Therefore,the research of the interaction between P [14] RV and HBGAs provides the basis for further characterization of binding patterns of other RV genotypes and the RV surveillance.
		                        		
		                        		
		                        		
		                        	
10.Inactivation of EV71 by Exposure to Heat and Ultraviolet Light.
Jing XIE ; Dandi LI ; Guangcheng XIE ; Yaqian HU ; Qing ZHANG ; Xiangyu KONG ; Nijun GUO ; Yuning LI ; Zhaojun DUAN
Chinese Journal of Virology 2015;31(5):500-506
		                        		
		                        			
		                        			Enterovirus 71 (EV71) is a major agent of hand, foot and mouth disease that can cause a severe burden of disease to children. To identify an effective method for the control and prevention of EV71, we studied the effect of exposure to heat and ultraviolet (UV) light upon EV71 inactivation. We found that exposure to 50 degrees C could not inactivate the infectivity of EV71. However, exposure to 60 degrees C and 70 degrees C could inactivate EV71 effectively. EV71 could be inactivated after exposure to UV light at a distance between the sample and a lamp of 30 cm for 30 min or 60 min because viral genomic RNA was destroyed. However, fetal bovine serum (FBS) could attenuate the inactivation proffered by heat and UV light. Attenuation effects of FBS were correlated positively with FBS concentration. Hence, EV71 can be inactivated by exposure to heat and UV light, and our results could provide guidance on prevention of the spread of EV71.
		                        		
		                        		
		                        		
		                        			Disinfection
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		                        			instrumentation
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		                        			methods
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		                        			Enterovirus A, Human
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		                        			genetics
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		                        			physiology
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		                        			radiation effects
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		                        			Enterovirus Infections
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		                        			virology
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		                        			Hot Temperature
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		                        			Humans
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		                        			Ultraviolet Rays
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		                        			Virus Inactivation
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		                        			radiation effects
		                        			
		                        		
		                        	
            
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