Objective:To explore the intimal injury of two kinds of hemostatic clips under different clamping forces, and to optimize and verify the calculation formula of minimum occlusion force (MOF), so as to provide theoretical basis for selecting appropriate hemostatic clips to reduce vascular injury.Methods:A total of 96 male SD rats with body weight ranging from 280 to 300 g (Animal Experimental Center of Shanxi Medical University) were randomly assigned to metal hemostatic clip group ( n=48) and disposable hemostatic clip group ( n=48) by random number table method. Each group was further divided into four subgroups with clamping forces of 0.3, 0.6, 0.9 and 1.2 N for abdominal aortic injury experiments. The damage to the vascular intima was observed under a scanning electron microscope. A vascular closure model was established for mathematical analysis to derive the theoretical calculation formula of the arterial blood management factor (MOF). According to blood pressure (BP), blood vessel diameter (D) and hemostatic clamp width (W), the average values of theoretical and actual MOF data were analyzed by paired t test to verify the accuracy of the formula. From January 2021 to December 2022, six patients (with 12 branch arteries) who presented with oral and maxillofacial malignancies at the Department of Oral and Maxillofacial Surgery, Shanxi Medical University School and Hospital of Stomatology, were included to validate the accuracy of the MOF formula. Results:Under electron microscopy, when the clamping force was 0.3 N, the one-time hemostatic clip caused very little damage to the vascular intima (grade 1 injury), with only a few folds being flattened. When the clamping force was 0.6 N, both types of hemostatic clips caused partial peeling of the intima surface (grade 2-3 injury). However, when the clamping force was adjusted to 0.9 and 1.2 N, the damage caused by both types of hemostatic clips was more severe (grade 3-4 injury), with large areas of intima peeling or even disappearance. In some specimens of the metal hemostatic clip group, the damage even reached the muscular layer. Vascular closure model analysis showed that MOF=2×(1/2×π×D×W×BP), the mean diameter of abdominal aorta of 24 SD rats was (1.41±0.07) mm, the blood pressure was (83.29±11.56) mmHg (1 mmHg=0.133 kPa). The theoretical MOF value was (0.096±0.015) N, the actual clamping force (ACF) was (0.095±0.012) N, there was no statistical significance between the two groups ( t=-0.35, P=0.725). In clinical application, the MOF calculation formula was used to select the appropriate hemostatic clip for 12 arteries, successfully blocking the blood flow, verifying the accuracy of the formula. Conclusions:Hemostatic clips can cause damage to the inner membrane of blood vessels, and the greater the clamping force, the more severe the damage. Disposable hemostatic clips have certain advantages in avoiding excessive damage to the inner membrane of blood vessels. The theoretical MOF calculation formula has a certain degree of reliability and can be used as a reference to select the appropriate hemostatic clip with low damage.

Objective To observe the clinical efficacy Yizhi Qingxin Prescription combined with warming-needle muxibustion in the treatment of vascular cognitive impairment(VCI)after cerebral infarction,and to explore its effect on cognitive function.Methods A total of 110 cases of patients with definitive diagnosis of VCI after cerebral infarction admitted to Beijing Bo'ai Hospital from February 2020 to February 2023 were selected for the study.The patients were randomly divided into a control group and an observation group according to random number table method,with 55 cases in each group.The control group was treated with Donepezil Hydrochloride,and the observation group was treated with Yizhi Qingxin Prescription combined with warming-needle muxibustion on the basis of the treatment of the control group,the course of treatment covered four consecutive weeks.After one month of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the scores of the Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment(MoCA),as well as the measurements of cerebral blood perfusion were observed before and after the treatment of the patients in the two groups.The changes of C-reactive protein(CRP),interleukin 6(IL-6),and tumor necrosis factor α(TNF-α)before and after treatment were compared between the two groups.The safety and incidence of adverse reactions in the two groups were also evaluated.Results(1)The total effective rate was 96.36％(53/55)in the observation group and 74.55％(41/55)in the control group.The efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P＜0.05).(2)After treatment,the MMSE scores and MoCA scores of the patients in the two groups were improved significantly(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05).(3)After treatment,the CBV,MTT,and CBF of the basal ganglia region of the two groups were significantly improved(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05).(4)After treatment,the serum CRP,IL-6,and TNF-α levels of patients in the two groups were significantly improved(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05).(5)The incidence of adverse reactions in the observation group was 7.27％(4/55),and that in the control group was 5.45％(3/55),the comparison between the two groups showed that the difference being not statistically significant(P＞0.05).Conclusion Yizhi Qingxin Prescription combined with warming-needle muxibustion in the treatment of VCI after cerebral infarction can effectively alleviate the cognitive function of patients,improve their cerebral blood perfusion,and inhibit the release of inflammatory factors,so as to enhance their quality of life.

Cholera toxin B subunit(CTB)can enhance antigen presentation and promote T cell pro-liferation,B cell differentiation and B cell isotype conversion.Moreover,woodchuck hepatitis virus post transcriptional regulatory element(WPRE)can enhance gene expression efficiency by optimi-zing RNA polyadenylation,denuclearization and/or translation.In order to construct porcine epi-demic diarrhea virus like particles(VLPs)chimerized with CTB and WPRE and evaluate their im-munogenicity,the G Ⅱ type PEDV S gene,combined with the elements promoting the protein ex-pression and enhancing immune effects,was synthesized by the company and cloned into pET32a(+).Af-ter double enzyme digestion and gel recovery,the gene named as TSCW was cloned into pFastBacl to construct the recombinant plasmid pFastBac-TSCW.pFastBac-TSCW was further transformed into DH10Bac competent cells to obtain recombinant bacmid Bacmid-TSCW.Subsequently,the Bacmid-TSCW was transfected into sf9 cells to obtain recombinant baculovirus BV-TSCW.After co-infection of BV-TSCW and BV-M into sf9 cells,viral like particles VLP-TSCW was obtained and used to immunize mice to evaluate its immunogenicity.The results showed that the recombi-nant plasmid pFastBac-TSCW and bacmid Bacmid-TSCW were successfully constructed.After transfection of sf9 cells with recombinant baculovirus,significant cytopathic effects were observed.PCR and Western blot results showed that the recombinant baculoviruses existed stably in sf9 cells and the target proteins was also expressed stably.In addition,the electron microscopy results showed that BV-TSCW and BV-M successfully assembled into viral like particles VLP-TSCW.Furthermore,ELISA results indicated that VLP-TSCW induced high level specific antibodies.The above results laid the foundation for further optimization,design and development of PEDV VLPs subunit vaccines.

As a highly prevalent disease in a specific geographical area, endemic diseases pose a serious challenge to public health. This article systematically reviews the epidemiology, etiology, and preventive and control measures of major endemic diseases in Japan, such as schistosomiasis, Shinshu cardiomyopathy, iodine deficiency disorders, and endemic fluorosis, and compares and analyzes the similarities and differences in endemic diseases between China and Japan. Research has found that Japan has successfully controlled the prevalence of schistosomiasis, Shinshu cardiomyopathy, iodine deficiency disorders, and endemic fluorosis through comprehensive intervention measures such as snail control projects, selenium supplementation, iodized salt promotion, and water improvement to reduce fluoride levels. China has also accomplished remarkable feats in the continuous elimination of endemic diseases. The two countries have both similarities and differences in the distribution of endemic disease, epidemic factors, and prevention and control experience. Japan's experience in refined public health management is worth learning from, and China's large-scale prevention and control network construction also provides reference for Japan.

Objective:To explore the intimal injury of two kinds of hemostatic clips under different clamping forces, and to optimize and verify the calculation formula of minimum occlusion force (MOF), so as to provide theoretical basis for selecting appropriate hemostatic clips to reduce vascular injury.Methods:A total of 96 male SD rats with body weight ranging from 280 to 300 g (Animal Experimental Center of Shanxi Medical University) were randomly assigned to metal hemostatic clip group ( n=48) and disposable hemostatic clip group ( n=48) by random number table method. Each group was further divided into four subgroups with clamping forces of 0.3, 0.6, 0.9 and 1.2 N for abdominal aortic injury experiments. The damage to the vascular intima was observed under a scanning electron microscope. A vascular closure model was established for mathematical analysis to derive the theoretical calculation formula of the arterial blood management factor (MOF). According to blood pressure (BP), blood vessel diameter (D) and hemostatic clamp width (W), the average values of theoretical and actual MOF data were analyzed by paired t test to verify the accuracy of the formula. From January 2021 to December 2022, six patients (with 12 branch arteries) who presented with oral and maxillofacial malignancies at the Department of Oral and Maxillofacial Surgery, Shanxi Medical University School and Hospital of Stomatology, were included to validate the accuracy of the MOF formula. Results:Under electron microscopy, when the clamping force was 0.3 N, the one-time hemostatic clip caused very little damage to the vascular intima (grade 1 injury), with only a few folds being flattened. When the clamping force was 0.6 N, both types of hemostatic clips caused partial peeling of the intima surface (grade 2-3 injury). However, when the clamping force was adjusted to 0.9 and 1.2 N, the damage caused by both types of hemostatic clips was more severe (grade 3-4 injury), with large areas of intima peeling or even disappearance. In some specimens of the metal hemostatic clip group, the damage even reached the muscular layer. Vascular closure model analysis showed that MOF=2×(1/2×π×D×W×BP), the mean diameter of abdominal aorta of 24 SD rats was (1.41±0.07) mm, the blood pressure was (83.29±11.56) mmHg (1 mmHg=0.133 kPa). The theoretical MOF value was (0.096±0.015) N, the actual clamping force (ACF) was (0.095±0.012) N, there was no statistical significance between the two groups ( t=-0.35, P=0.725). In clinical application, the MOF calculation formula was used to select the appropriate hemostatic clip for 12 arteries, successfully blocking the blood flow, verifying the accuracy of the formula. Conclusions:Hemostatic clips can cause damage to the inner membrane of blood vessels, and the greater the clamping force, the more severe the damage. Disposable hemostatic clips have certain advantages in avoiding excessive damage to the inner membrane of blood vessels. The theoretical MOF calculation formula has a certain degree of reliability and can be used as a reference to select the appropriate hemostatic clip with low damage.

Cholera toxin B subunit(CTB)can enhance antigen presentation and promote T cell pro-liferation,B cell differentiation and B cell isotype conversion.Moreover,woodchuck hepatitis virus post transcriptional regulatory element(WPRE)can enhance gene expression efficiency by optimi-zing RNA polyadenylation,denuclearization and/or translation.In order to construct porcine epi-demic diarrhea virus like particles(VLPs)chimerized with CTB and WPRE and evaluate their im-munogenicity,the G Ⅱ type PEDV S gene,combined with the elements promoting the protein ex-pression and enhancing immune effects,was synthesized by the company and cloned into pET32a(+).Af-ter double enzyme digestion and gel recovery,the gene named as TSCW was cloned into pFastBacl to construct the recombinant plasmid pFastBac-TSCW.pFastBac-TSCW was further transformed into DH10Bac competent cells to obtain recombinant bacmid Bacmid-TSCW.Subsequently,the Bacmid-TSCW was transfected into sf9 cells to obtain recombinant baculovirus BV-TSCW.After co-infection of BV-TSCW and BV-M into sf9 cells,viral like particles VLP-TSCW was obtained and used to immunize mice to evaluate its immunogenicity.The results showed that the recombi-nant plasmid pFastBac-TSCW and bacmid Bacmid-TSCW were successfully constructed.After transfection of sf9 cells with recombinant baculovirus,significant cytopathic effects were observed.PCR and Western blot results showed that the recombinant baculoviruses existed stably in sf9 cells and the target proteins was also expressed stably.In addition,the electron microscopy results showed that BV-TSCW and BV-M successfully assembled into viral like particles VLP-TSCW.Furthermore,ELISA results indicated that VLP-TSCW induced high level specific antibodies.The above results laid the foundation for further optimization,design and development of PEDV VLPs subunit vaccines.

As a highly prevalent disease in a specific geographical area, endemic diseases pose a serious challenge to public health. This article systematically reviews the epidemiology, etiology, and preventive and control measures of major endemic diseases in Japan, such as schistosomiasis, Shinshu cardiomyopathy, iodine deficiency disorders, and endemic fluorosis, and compares and analyzes the similarities and differences in endemic diseases between China and Japan. Research has found that Japan has successfully controlled the prevalence of schistosomiasis, Shinshu cardiomyopathy, iodine deficiency disorders, and endemic fluorosis through comprehensive intervention measures such as snail control projects, selenium supplementation, iodized salt promotion, and water improvement to reduce fluoride levels. China has also accomplished remarkable feats in the continuous elimination of endemic diseases. The two countries have both similarities and differences in the distribution of endemic disease, epidemic factors, and prevention and control experience. Japan's experience in refined public health management is worth learning from, and China's large-scale prevention and control network construction also provides reference for Japan.

BACKGROUND:There are many treatment methods for knee osteoarthritis,among which electroacupuncture,as an important non-drug treatment,is effective in the treatment of knee osteoarthritis,but its exact mechanism is not clear. OBJECTIVE:Effect of electroacupuncture on the expression of p53 and P21 in articular cartilage and subchondral bone of aged rats with knee osteoarthritis. METHODS:Eight 6-month-old male Sprague-Dawley rats were included in the young group and sixteen 24-month-old male Sprague-Dawley rats were randomly divided into old group(n=8)and electroacupuncture group(n=8).The rats in the electroacupuncture group received electroacupuncture stimulation once a day,5 days a week,for 8 continuous weeks,and the other two groups did not do any treatment.Eight weeks later,the level of type Ⅱ collagen C-terminal peptide in peripheral blood was detected by ELISA,the morphology of left knee cartilage and subchondral bone was observed by safranin O-fast green staining,the degree of knee cartilage degeneration was evaluated by modified Mankin's score,the microstructure of left knee cartilage and subchondral bone was detected by micro-CT,and the expression levels of matrix metalloproteinase 13,P53,P21 Mrna and protein were detected by RT-PCR and western blot respectively. RESULTS AND CONCLUSION:Compared with the young group,the level of C-terminal peptide of type Ⅱ collagen in the peripheral blood was increased in the old group(P<0.05).The micro-CT results showed that the bone volume fraction,bone mineral density and the number of bone trabeculae were decreased in the old group compared with the young group(P<0.05),while the trabecular separation increased(P<0.05).Safranin O-fast green staining showed that in the old group,the surface layer of cartilage was uneven with fissures,the morphology of chondrocytes was irregular and stained unevenly,the boundary between the cartilage and subchondral bone was blurred,and the matrix loss was serious.The Mankin's score was higher in the old group than the young group(P<0.05).The expression of matrix metalloproteinase 13,P53,P21 at Mrna and protein levels increased in the old group compared with the young group(P<0.05).Compared with the old group,electroacupuncture decreased the level of C-terminal peptide of type Ⅱ collagen(P<0.05),increased the bone volume fraction,bone mineral density and the number of bone trabeculae(P<0.05),and decreased the trabecular separation(P<0.05).Safranin O-fast green staining showed that in the electroacupuncture group,the surface of cartilage was smooth and red staining was uniform,and the cell morphology and structure were between the young group and the old group.Following electroacupuncture treatment,the Mankin's score(P<0.05),matrix metalloproteinase 13 and P21 Mrna expression(P<0.05),and matrix metalloproteinase 13 and P53 protein expression decreased(P<0.05),while there was a decreasing trend of P53 Mrna and P21 protein expression,but with no statistical significance(P>0.05).To conclude,electroacupuncture may delay articular cartilage degeneration and subchondral osteoporosis in aged rats by inhibiting the expression of P53 and P21,so as to protect joints and delay joint aging.

Objective:To compare the therapeutic efficacy, safety and drug cost between generic enteric-coated mycophenolate sodium (EC-MPS) and branded EC-MPS in immunosuppressive treatment for adult recipients of renal transplantation (RT) .Methods:From January, 2022 to October, 2023, 60 adult RT patients were continuously enrolled and randomized into two groups. Patients receiving generic EC-MPS were selected as cohort 1 (n=30) while those taking branded EC-MPS designated as cohort 2 (n=30). Hepatic/renal function, blood routine parameters, drug concentrations, adverse events (AEs) and drug costs were recorded and compared between two cohorts at baseline (<3 days before/after day of RT, W0), week 1 (W1), week 4 (W4), week 8 (W8), week 12 (W12) and week 24 (W24) post-RT.Results:Only urine protein was elevated at W24[0.4 (0-0.6) vs 0 (0-0.2) g/24 h, P=0.049]in cohort 1 as compared with cohort 2. Aspartate aminotransferase at W12 (15.6±3.3 vs 20.3±9.7 U/L, P=0.010), leucocyte count at W1 (8.4±2.3 vs 10.1±3.8 ×10 9/L, P=0.045) and platelet count at W1 (158.5±51.5 vs 185.8±46.8 ×10 9/L, P=0.036) all declined in cohort 1 as compared with cohort 2. However, these parameters at other timepoints did not vary between two cohorts (all P>0.050). In addition, blood concentration of MPS after dosing, area under the concentration-time curve and trough concentration of tacrolimus at different timepoints were not different between two cohorts (all P>0.050). Similarly, helper T cells (Th), suppressor T cells (Ts), Th/Ts and B cells at W4/12 did not vary between two cohorts (all P>0.050). Concerning drug cost, no difference existed in the number of tablets or length of stay between two cohorts (both P>0.050). However, cost of EC-MPS (￥1 333.5±419.6 vs ￥2 368.6±596.0, P<0.001) and total cost during hospitalization (￥96 403.3±29 159.8 vs ￥117 062.8±28 782.1, P=0.001) were lower in cohort 1 than cohort 2. The most common AEs in cohort 1 included acid regurgitation (n=19, 63.3%), hypoalbuminemia (n=16, 53.3%), anemia (n=12, 40.0%) and hypokalemia (n=11, 36.7%). And the most common AEs in cohort 2 included acid regurgitation (n=20, 66.7%), anemia (n=14, 46.7%) and hypoalbuminemia (n=9, 30.0%). Notably, the incidence of all AEs was not different between two cohorts (all P>0.050) . Conclusion:Generic EC-MPS has comparable therapeutic efficacy and safety profile with lower drug cost in adult RT patients. It provides more options for maintenance treatment in RT patients.

Objective:To compare the therapeutic efficacy, safety and drug cost between generic enteric-coated mycophenolate sodium (EC-MPS) and branded EC-MPS in immunosuppressive treatment for adult recipients of renal transplantation (RT) .Methods:From January, 2022 to October, 2023, 60 adult RT patients were continuously enrolled and randomized into two groups. Patients receiving generic EC-MPS were selected as cohort 1 (n=30) while those taking branded EC-MPS designated as cohort 2 (n=30). Hepatic/renal function, blood routine parameters, drug concentrations, adverse events (AEs) and drug costs were recorded and compared between two cohorts at baseline (<3 days before/after day of RT, W0), week 1 (W1), week 4 (W4), week 8 (W8), week 12 (W12) and week 24 (W24) post-RT.Results:Only urine protein was elevated at W24[0.4 (0-0.6) vs 0 (0-0.2) g/24 h, P=0.049]in cohort 1 as compared with cohort 2. Aspartate aminotransferase at W12 (15.6±3.3 vs 20.3±9.7 U/L, P=0.010), leucocyte count at W1 (8.4±2.3 vs 10.1±3.8 ×10 9/L, P=0.045) and platelet count at W1 (158.5±51.5 vs 185.8±46.8 ×10 9/L, P=0.036) all declined in cohort 1 as compared with cohort 2. However, these parameters at other timepoints did not vary between two cohorts (all P>0.050). In addition, blood concentration of MPS after dosing, area under the concentration-time curve and trough concentration of tacrolimus at different timepoints were not different between two cohorts (all P>0.050). Similarly, helper T cells (Th), suppressor T cells (Ts), Th/Ts and B cells at W4/12 did not vary between two cohorts (all P>0.050). Concerning drug cost, no difference existed in the number of tablets or length of stay between two cohorts (both P>0.050). However, cost of EC-MPS (￥1 333.5±419.6 vs ￥2 368.6±596.0, P<0.001) and total cost during hospitalization (￥96 403.3±29 159.8 vs ￥117 062.8±28 782.1, P=0.001) were lower in cohort 1 than cohort 2. The most common AEs in cohort 1 included acid regurgitation (n=19, 63.3%), hypoalbuminemia (n=16, 53.3%), anemia (n=12, 40.0%) and hypokalemia (n=11, 36.7%). And the most common AEs in cohort 2 included acid regurgitation (n=20, 66.7%), anemia (n=14, 46.7%) and hypoalbuminemia (n=9, 30.0%). Notably, the incidence of all AEs was not different between two cohorts (all P>0.050) . Conclusion:Generic EC-MPS has comparable therapeutic efficacy and safety profile with lower drug cost in adult RT patients. It provides more options for maintenance treatment in RT patients.