Research progress of SARS-CoV-2 main protease inhibitors / 药学学报

As a common protease with high similarity among coronavirus species, the main protease (Mpro) of SARS-CoV-2 is responsible for the catalytic hydrolysis of viral precursor proteins into functional proteins, which is essential for coronavirus replication and is one of the ideal targets for the development of broad-spectrum antiviral drugs. This paper reviews the main protease inhibitors of SARS-CoV-2, including their molecular structures, potencies and drug-like profiles, binding modes and structure-activity relationships, etc.

Efficacy of vitrectomy for highly myopic macular hole with or without foveoschisis / 中华眼底病杂志

Objective:To observe the clinical effects of pars plana vitrectomy (PPV) combined with internal limiting membrane (ILM) peeling and C 3F 8 tamponade for patients with highly myopic macular hole (HM-MH) with and without foveoschisis. Methods:A retrospective case controlled study. From January 2017 to February 2022, 23 eyes of 23 patients with highly myopic macular hole with and without foveoschisis diagnosed in the Shandong Eye Hospital were included in the study. Among them, 5 males had 5 eyes, and 18 females had 18 eyes, the age was (54.43±12.96) years old. The patients with or without foveoschisis were 12 eyes in 12 cases and 11 eyes in 11 cases. Studies were divided into two groups, depending on the presence of a concomitant myopic foveoschisis or not. The groups are high myopia macular hole with foveoschisis (group A) and high myopia macular hole without foveoschisis (group B). Best-corrected visual acuity (BCVA), B-scan ultrasonography, optical coherence tomography and axial length (AL) measurement were performed in all eyes. Snellen chart was used for BCVA examination, and the visual acuity was converted into logarithm of minimum angle of resolution (logMAR) during statistics. The age of the two groups, sex, macular hole (MH) diameter, logMAR BCVA, AL, posterior scleral staphyloma, there was no significant difference ( P>0.05). PPV combined with ILM peeling and C 3F 8 filling were performed in all eyes. Follow-up was at least 3 months after the last operation. BCVA changes and MH closure were compared between the two groups after surgery. Wilcoxon test was used to compare BCVA before and after operation. Mann-whiteny U test was used to compare preoperative and postoperative BCVA between groups. Results:After initial surgery, MH was closed in 17 of 23 eyes (74%, 17/23). MH was closed in 8 eyes in group A (66.7%, 8/12). Four eyes were not closed (33.3%, 4/12); MH closed in 9 eyes in group B (81.8%, 9/11). There was no significant difference between the two groups after initial operation ( P>0.05). At 1 and 3 months after surgery, the logMAR BCVA of patients in group A and group B were 1.00±0.46, 1.03±0.83 and 0.53±0.63, 0.55±0.41, respectively. Compared with before operation, there was no significant difference at 1 month ( P=0.783, 0.358), but the difference was statistically significant at 3 months ( P=0.012, 0.007). There was no significant difference in logMAR BCVA between group A and group B at 1 and 3 months after operation ( P=0.687, 0.950). Conclusion:PPV combined with ILM peeling and C 3F 8 tamponade can promote MH closure and improve visual acuity in most affected eyes with HM-MH with and without foveoschisis.

Screening methods of SARS-CoV-2 main protease inhibitors and current applications / 药学学报

COVID-19 epidemic continues to spread around the world till these days, and it is urgent to develop more safe and effective new drugs. Due to the limited P3 biosafety laboratories for directly screening inhibitors of virulent viruses with high infectivity, it is necessary to develop rapid and efficient screening methods for viral proteases and other related targets. The main protease (Mpro), which plays a key role in the replication cycle of SARS-CoV-2, is highly conserved and has no homologous proteases in humans, making it an ideal target for drug development. From two different levels, namely, molecular level and cellular level, this paper summarizes the reported screening methods of SARS-CoV-2 Mpro inhibitors through a variety of representative examples, expecting to provide references for further development of SARS-CoV-2 Mpro inhibitors.

Comparison of corneal higher order aberration after femtosecond laser-assisted laser in situ keratomileusis and small incision lenticule extraction / 中华实验眼科杂志

Objective:To analyze and compare the corneal higher order aberration (HOA) after femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) and small incision lenticule extraction (SMILE).Methods:A non-randomized controlled study was conducted.Sixty myopic patients (60 eyes) who underwent FS-LASIK or SMILE correction at Shandong Eye Hospital from April 2018 to January 2020 were enrolled and the data from the right eye were collected for analysis.Thirty cases (30 eyes) who received FS-LASIK in FS-LASIK group and 30 cases (30 eyes) who received SMILE in SMILE group had a preoperative equivalent spherical diopter of (-5.36±1.11)D and (-4.93±1.03)D, respectively.The HOA of the 6-mm anterior surface, posterior surface, and whole cornea were measured before surgery and at 1, 3, 6, and 12 months after surgery using Pentacam.The root mean square values (μm) of total corneal HOA, spherical aberration, coma and trefoil were obtained.Differences in the above root mean square values at different time points were compared between the two groups.The study protocol adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Shandong Eye Hospital (No.SDSYKYY20180306). Written informed consent was obtained from each subject.Results:The preoperative and 1-, 3-, 6-, 12-month postoperative total HOA of the anterior corneal surface were (0.428±0.126), (0.775±0.169), (0.811±0.194), (0.759±0.214), (0.704±0.199)μm in the FS-LASIK group and (0.409±0.094), (0.656±0.148), (0.681±0.161), (0.668±0.175), (0.648±0.160)μm in the SMILE group, with a significant overall difference ( Fgroup=5.652, P=0.024; Ftime=107.169, P<0.01). Compared with SMILE group, the postoperative total HOA of anterior corneal surface and spherical aberration at different time points were increased in FS-LASIK group, showing statistically significant differences (all at P<0.05). Compared with before surgery, the postoperative total HOA of the anterior corneal surface and spherical aberration at different time points were increased in both groups, showing statistically significant differences (all at P<0.05). In the two groups, the 6- and 12-month postoperative total HOA of the anterior corneal surface were reduced in comparison with the 3-month postoperative ones of the anterior corneal surface, and the 12-month postoperative spherical aberrations of the anterior corneal surface were significantly reduced in comparison with the 1- and 3-month postoperative ones of the anterior corneal surface, showing statistically significant differences (all at P<0.05). There were significant differences in the coma and trefoil of the anterior corneal surface between before and after the operation (coma: Ftime=47.848, P<0.01; trefoil: Ftime=2.497, P=0.046). Compared with before surgery, the postoperative coma was significantly increased in the two groups (all at P<0.05). There were significant differences in total corneal HOA and spherical aberration at different postoperative time points between the two groups (total HOA: Fgroup=8.093, P=0.008; Ftime=125.019, P<0.01.spherical aberration: Fgroup=4.771, P=0.037; Ftime=34.033, P<0.01). Compared with SMILE group, the total corneal HOA and spherical aberration were significantly increased in FS-LASIK group at different postoperative time points (all at P<0.05). Compared with before surgery, postoperative total HOA of the anterior corneal surface and spherical aberration at different postoperative time points were significantly increased in both groups (all at P<0.05). In both groups, the 12-month postoperative corneal spherical aberration was significantly reduced in comparison with the 1- and 3-month postoperative ones (all at P<0.05). There was a significant difference in coma between before and after surgery ( Ftime=30.829, P<0.01). Compared with before surgery, the postoperative coma was significantly increased at different time points in both groups (all at P<0.05). Conclusions:Both FS-LASIK and SMILE increase the HOA of the anterior corneal surface and the whole cornea.Compared with FS-LASIK, SMILE introduces less HOA of the anterior corneal surface and the whole cornea as well as spherical aberrations.

Diagnosis and treatment strategy of periodontitis with diabetes / 中华口腔医学杂志

The number of diabetic patients visiting stomatology for periodontal disease is increasing, and the symptoms are relatively severe, and often complications increase the complexity of periodontal treatment. This article briefly describes the research progress and clinical manifestations of the epidemiology and related pathological mechanisms of periodontitis with diabetes, focusing on the treatment and providing reference for stomatologists in the clinical diagnosis and treatment of patients with diabetic periodontitis.

The impact of extended waiting time on tumor regression after neoadjuvant chemoradiotherapy for locally advanced rectal cancer / 中华外科杂志

Objective: To investigate the influence of extending the waiting time on tumor regression after neoadjuvant chemoradiology (nCRT) in patients with locally advanced rectal cancer (LARC). Methods: Clinicopathological data from 728 LARC patients who completed nCRT treatment at the First Affiliated Hospital, Naval Medical University from January 2012 to December 2021 were collected for retrospective analysis. The primary research endpoint was the sustained complete response (SCR). There were 498 males and 230 females, with an age (M(IQR)) of 58 (15) years (range: 22 to 89 years). Logistic regression models were used to explore whether waiting time was an independent factor affecting SCR. Curve fitting was used to represent the relationship between the cumulative occurrence rate of SCR and the waiting time. The patients were divided into a conventional waiting time group (4 to <12 weeks, n=581) and an extended waiting time group (12 to<20 weeks, n=147). Comparisons regarding tumor regression, organ preservation, and surgical conditions between the two groups were made using the t test, Wilcoxon rank sum test, or χ2 test as appropriate. The Log-rank test was used to elucidate the survival discrepancies between the two groups. Results: The SCR rate of all patients was 21.6% (157/728). The waiting time was an independent influencing factor for SCR, with each additional day corresponding to an OR value of 1.010 (95%CI: 1.001 to 1.020, P=0.031). The cumulative rate of SCR occurrence gradually increased with the extension of waiting time, with the fastest increase between the 9th to <10th week. The SCR rate in the extended waiting time group was higher (27.9%(41/147) vs. 20.0%(116/581), χ2=3.901, P=0.048), and the organ preservation rate during the follow-up period was higher (21.1%(31/147) vs. 10.7%(62/581), χ2=10.510, P=0.001). The 3-year local recurrence/regrowth-free survival rates were 94.0% and 91.1%, the 3-year disease-free survival rates were 76.6% and 75.4%, and the 3-year overall survival rates were 95.6% and 92.2% for the conventional and extended waiting time groups, respectively, with no statistical differences in local recurrence/regrowth-free survival, disease-free survival and overall survival between the two groups (χ2=1.878, P=0.171; χ2=0.078, P=0.780; χ2=1.265, P=0.261). Conclusions: An extended waiting time is conducive to tumor regression, and extending the waiting time to 12 to <20 weeks after nCRT can improve the SCR rate and organ preservation rate, without increasing the difficulty of surgery or altering the oncological outcomes of patients.

Methodological study on the establishment of limit values in the Standards of Drinking Water Quality / 中华预防医学杂志

The establishment of limit values for standards of drinking water quality is an important and complex process. This study systematically introduced the methodology of the establishment of standard limit values for drinking water quality and elaborated on the workflow of setting limit values of water quality indicators, principles and methods of selecting water quality indicators, derivation of safety reference values, and establishment of limit values. It also aimed to provide reference and support for the future revision of relevant standards.

Research on the standard limits for vinyl chloride and trichloroethylene in the "Standards for Drinking Water Quality（GB5749-2022）" in China / 中华预防医学杂志

The usage of vinyl chloride and trichloroethylene in China has been increasing year by year, and they have been detected in both drinking water and environmental water, making them important environmental pollutants. Based on the latest research results on the health effects of vinyl chloride and trichloroethylene, the newly issued, "Standards for Drinking Water Quality (GB5749-2022)" in China has adjusted the standard limit of vinyl chloride from 0.005 mg/L to 0.001 mg/L and the standard limit of trichloroethylene from 0.07 mg/L to 0.02 mg/L. This article analyzed and discussed the relevant technical contents for determining the above standard limits, including the levels and exposure conditions of vinyl chloride and trichloroethylene in the water environment, health effects, derivation of safety reference values, and determination of hygiene standard limits. Suggestions were also made for the implementation of this standard.

Research on the determination of the limit value of perchlorate in the "Standards for Drinking Water Quality（GB5749-2022）" in China / 中华预防医学杂志

Perchlorate is an environmental pollutant that has been a focus of attention in recent years. It has been detected in many environmental water bodies and drinking water in China, with a high level of presence in some areas of the Yangtze River Basin. The human body may ingest perchlorate through exposure pathways such as drinking water and food, and its main health effect is to affect the thyroid's absorption of iodine. The "Standards for Drinking Water Quality" (GB5749-2022) includes perchlorate as an expanded indicator of water quality, with a limit value of 0.07 mg/L. This article analyzes the technical content related to the determination of hygiene standard limits for perchlorate in drinking water, including the environmental presence level and exposure status of perchlorate, main health effects, derivation of safety reference values, and determination of hygiene standard limits.

Inhibitory Effect of Kaempferol on Proliferation of KG1a Cells and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of kaempferol on proliferation of acute myeloid leukemia (AML) KG1a cells and its mechanism.@*METHODS@#Human AML KG1a cells in logarithmic growth stage were taken and set at 25, 50, 75 and 100 μg/ml kaempferol group, another normal control group (complete medium without drug) and solvent control group (add dimethyl sulfoxide) were also set. After 24 and 48 hours of intervention, the cell proliferation rate was detected by CCK-8 assay. In addition, interleukin-6 (IL-6) combined with kaempferol group (Plus 20 μg/l IL-6 and 75 μg/ml kaempferol) was set up, 48 hours after culture, the cell cycle and apoptosis of KG1a cells were detected by flow cytometry, the mitochondrial membrane potential (MMP) of KG1a cells was detected by MMP detection kit (JC-1 method), and the expression of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway related proteins in KG1a cells were detected by Western blot.@*RESULTS@#The cell proliferation rate of 25, 50, 75 and 100 μg/ml kaempferol group decreased significantly (P<0.05), and with the increase of kaempferol dose (r24 h=-0.990, r48 h= -0.999), the cell proliferation rate decreased gradually (P<0.05). The inhibitory effect of 75 μg/ml kaempferol on cell proliferation reached half of effective dose after 48 hours of intervention. Compared with normal control group, the G0/G1 phase cell proportion and apoptosis rate of cells in 25, 50 and 75 μg/ml kaempferol group increased, while the S phase cell proportion, MMP, phosphorylated JAK2 (p-JAK2)/JAK2 and phosphorylated STAT3 (p-STAT3)/STAT3 protein expression decreased in a dose-dependent manner (r=0.998, 0.994, -0.996, -0.981, -0.997, -0.930). Compared with 75 μg/ml kaempferol group, the G0/G1 phase cell proportion and apoptosis rate of cells in IL-6 combined with kaempferol group decreased, while the S phase cell proportion, MMP, p-JAK2/JAK2 and p-STAT3/STAT3 protein expression increased significantly (P<0.05).@*CONCLUSION@#Kaempferol can inhibit KG1a cell proliferation and induce KG1a cell apoptosis, its mechanism may be related to the inhibition of JAK2/STAT3 signal pathway.

Mechanism of cleft palate in C57BL/6N mice induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin / 中华口腔医学杂志

Objective: To explore the molecular mechanism of cleft palate in mice induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). Methods: The pregnant mice were randomly divided into TCDD-treated group (n=42) and control group (n=42). TCDD-treated group was given by gavage a single dose of TCDD (64 μg/kg) at 8: 00 AM on gestation day 10 (GD10) and the control group was given by gavage the isopyknic corn oil. At GD13-GD15, the fetal mice palate development was observed by HE staining. The mouse embryonic palatal mesenchymal cell proliferation was detected by 5-bromo-2-deoxyuridine (BrdU) immunofluorescence. The localization and expression of maternally expressed gene3 (MEG3) in mouse embryonic palatal mesenchymal cells was detected by situ hybridization and real-time PCR (RT-PCR). The key protein expressions of transforming growth factor-β (TGF-β)/Smad signaling pathway in mouse embryonic palatal mesenchyme were analyzed by Western blotting. The interaction of MEG3 and TGF-β receptor Ⅰ (TGF-βRⅠ) was examined by RNA binding protein immunoprecipitation (RIP). Results: At GD13 and GD14, compared with the control group, the ratio of BrdU-positive cells in the palatal mesenchyme of TCDD-treated fetuses decreased significantly (GD13, t=6.66, P=0.003; GD14, t=6.56, P=0.003). However, at GD15, the ratio of BrdU-positive cells was significantly increased (t=-5.98, P=0.004). MEG3 was mainly expressed in the nuclei of fetal mouse palatal mesenchymal cells, and the expression of MEG3 in TCDD group was significantly increased at GD13, GD14 and GD15(GD13, t=39.28, P=0.012; GD14, t=18.75, P=0.042; GD15, t=28.36, P=0.045). At GD14, TCDD decreased the levels of p-Smad2 and Smad4 in embryonic palate mesenchymal cells (p-Smad2, t=9.48, P=0.001;Smad4, t=63.10, P=0.001), whereas the expression of Smad7 was significantly increased at GD14 (t=30.77, P<0.001). The results of the RIP experiment showed that the amount of TGF-βRⅠ-bound MEG3 in mouse embryonic palatal mesenchymal cells in the TCDD group (23.940±1.301) was higher than that in the control group (8.537±1.523)(t=24.55, P<0.001). Conclusions: MEG3 is involved in the suppression of mouse embryonic palatal mesenchymal cell proliferation, functioning at least in part via interacting with the TGF-βRⅠ protein and thereby suppressing Smad signaling in the context of TCDD induced cleft palate.

Correlation between Serum Homocysteine Level, MTHFR Gene Polymorphism and Patients with Hematological Diseases Complicated with Coronary Heart Disease / 中国实验血液学杂志

OBJECTIVE@#To observe the expression level of serum homocysteine (Hcy) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism in patients with hematological diseases complicated with coronary heart disease, and analyze the relationship between serum Hcy level, MTHFR gene polymorphism and coronary heart disease.@*METHODS@#The medical records of 80 patients with coronary heart disease who completed treatment of hematological diseases during the period from March 2018 to March 2020 were selected as observation group. In addition, the medical records of 92 patients with hematological diseases who completed treatment in our hospital during the same period were selected as control group. Venous blood samples of the two groups were collected to detect serum Hcy level and MTHFR gene polymorphism. The serum Hcy levels of the two groups with different MTHFR genotypes were compared, and the effects of the above indicators on hematological diseases complicated with coronary heart disease were analyzed.@*RESULTS@#The detection rates of MTHFR gene TT and TC in the observation group were higher than those in the control group, while the distribution frequency of MTHFR genotype CC was lower (P<0.05). The serum Hcy levels of the patients with MTHFR genotype TT and TC in the observation group was higher than the control group (P<0.05). Binary logistic regression analysis showed that MTHFR gene TC/CC genotype serum Hcy overexpression may be influencing factor which induced coronary heart disease in patients with hematological diseases (OR=2.107/OR=1.634, P<0.05). ROC curves showed that the AUC of serum Hcy level of MTHFR gene TC/CC genotype and hematological disease complicated with coronary heart disease were both > 0.8. When MTHFR gene TC reaching the optimal threshold of 22.165 μmol/L, the sensitivity was 0.950 and the specificity was 0.837, While MTHFR gene CC reached the optimal threshold of 19.630 μmol/L, the sensitivity was 0.938 and the specificity was 0.826, the best predictive value could be obtained.@*CONCLUSION@#The changes of serum Hcy and MTHFR gene polymorphisms may be involved in the pathological process in patients with hematological diseases complicated with coronary heart disease. In the future, early detection of serum Hcy levels and MTHFR gene polymorphisms in patients with hematological diseases can be used to predict the risk of coronary heart disease.

Clinical observation of chiropractic manipulation in the treatment of degenerative scoliosis / 中国骨伤

OBJECTIVE@#To observe clinical efficacy of chiropractic manipulation in the treatment of degenerative scoliosis (DS).@*METHODS@#From June 2017 to September 2019, 120 patients with degenerative scoliosis were randomly divided into treatment group (60 cases) and control group(60 cases). The patients in treatment group were treated with chiropractic manipulation once every other day for 4 weeks. The patients in control group were treated with eperisone hydrochloride tablets combined with thoracolumbar orthopedic(TSLO)brace, oral eperisone hydrochloride tablets 50 mg three times a day, wearing TSLO brace for not less than 8 hours a day. The course of treatment was 4 weeks. After the patients were selected into the group, visual analogue scale (VAS) and Oswestry Disability Index (ODI) were recorded before treatment, 1, 2, 3, 4 weeks after treatment and 1 month after treatment. The full length X-ray of the spine was taken before and 4 weeks after treatment, and the scoliosis Cobb angle, sagittal vertical axis (SVA) and lumbar lordosis (LL) were measured and compared. The adverse reactions during the treatment were recorded.@*RESULTS@#There were significant differences in VAS and ODI between two groups at each time point after treatment (P<0.001), VAS and ODI at 2 weeks after treatment (PVAS=0.025, PODI=0.032) and 3 weeks after treatment(PVAS=0.040, PODI=0.044) in treatment group were significantly different from those in control group, but there was no significant difference in VAS and ODI at other time points between treatment group and control group (P>0.05). There was significant difference in Cobb angle between treatment group(P=0.010) and control group(P=0.017) after treatment, but there was no significant difference in LL and SVA between treatment group and control group. There was no significant difference in Cobb angle, LL and SVA between two groups before and after treatment. During the treatment, there were 4 mild adverse reactions in the control group and no adverse reactions in the treatment group.@*CONCLUSION@#Chiropractic manipulation can effectively relieve pain and improve lumbar function in patients with degenerative scoliosis. The onset of action is faster than that oral eperisone hydrochloride tablets combined with TSLO brace, and it has better safety and can improve Cobb angle of patients with degenerative scoliosis.

Effects of exogenous AGR2 on the proliferation and invasion abilities of colon cancer cells / 国际肿瘤学杂志

Objective:To detect the expressions of anterior gradient protein 2 (AGR2) in the cultures of three colon cancer cell lines SW480, SW620 and COLO205, and to investigate the effects of different concentrations of exogenous AGR2 on the proliferation, migration and invasion abilities of SW620 cells.Methods:Western blotting was used to detect the expression levels of AGR2 protein in SW480, SW620 and COLO205 colon cancer cell cultures. SW620 cells were divided into blank control group, anterior gradient protein 2 homologous human recombinant protein (rAGR2) low concentration group (100 μg/ml) and rAGR2 high concentration group (200 μg/ml), and CCK-8 assay, cell scratch assay and Transwell migration and invasion assay were used to detect the effects of different concentrations of rAGR2 on the biological behaviors of SW620 cells.Results:Western blotting results showed that the expression levels of AGR2 protein in SW480, SW620 and COLO205 cells were 0.545±0.097, 0.662±0.040 and 0.882±0.156 respectively, with a statistically significant difference ( F=7.46, P=0.024). The level of AGR2 protein in COLO205 cell line was significantly higher than that in SW480 and SW620 cell lines ( P=0.009; P=0.047). The results of CCK-8 experiment showed that the proliferative activities of SW620 cells in the blank control group, rAGR2 low concentration group and rAGR2 high concentration group were 0.422±0.031, 0.542±0.040 and 0.574±0.033 respectively, with a statistically significant difference ( F=26.35, P<0.001), and the rAGR2 low concentration group and rAGR2 high concentration group were significantly higher than the blank control group (both P<0.001). The results of cell scratching assay showed that the percentage of 36 h cell scratching area was (28.029±2.107)%, (20.642±0.983)% and (16.951±1.608)% for the three groups of cells respectively, with a statistically significant difference ( F=35.85, P<0.001), the rAGR2 low concentration group was higher than the blank control group ( P=0.001), and the rAGR2 high concentration group was higher than the rAGR2 low concentration group ( P=0.032). The results of cell migration assay showed that the number of cells migrated in the three groups was 447.1±32.3, 513.1±55.8 and 632.4±50.3 respectively, with a statistically significant difference ( F=35.62, P<0.001), the rAGR2 low concentration group was more than the blank control group ( P=0.007), and the rAGR2 high concentration group was more than the rAGR2 low concentration group ( P<0.001). The results of the invasion assay showed that the number of cells invaded in the three groups was 369.1±56.1, 505.1±34.4 and 579.0±71.5 respectively, with a statistically significant difference ( F=32.40, P<0.001), the rAGR2 low concentration group was more than the blank control group ( P<0.001), and the rAGR2 high concentration group was more than the rAGR2 low concentration group ( P=0.010). Conclusion:The expression of AGR2 protein varies in the extracellular fluid of different invasive colon cancer cells and increases with the invasive ability. AGR2 protein can increase the proliferation, migration and invasive abilities of colon cancer cells SW620.

Investigation on prevalence of Schistosoma japonicum infections in wild mice in Shitai County, Anhui Province, 2018 / 中国血吸虫病防治杂志

Objective To investigate the prevalence of Schistosoma japonicum infection in wild mice in Shitai County, Anhui Province, so as to provide insights into precise control of the source of S. japonicum infections. Methods Wild mice were captured using the trapping method for three successive nights at snail-infested settings from Jitan Village of Jitan Township, and Shiquan Village and Xibai Village of Dingxiang Township, Shitai County, Anhui Province in June and October, 2018. All trapped wild mice were sacrificed and liver and mesenteric vein specimens were collected for detection of S. japonicum eggs using microscopy, while the fecal samples in mouse intestines were collected for identification of S. japonicum infections using Kato-Katz technique. In addition, the population density of trapped wild mice was estimated and the prevalence of S. japonicum infection was calculated in trapped wild mice. Results A total of 376 wild mice were trapped from three villages in Shitai County. The population density of trapped wild mice was 9.1% (376/4 124), and the prevalence of S. japonicum infection was 24.2% (91/376) in trapped wild mice. The highest prevalence of S. japonicum infection was detected in Shiquan Village of Dingxiang Township (30.1%), and the lowest prevalence was seen in Xibai Village of Dingxiang Township; however, there was no significant difference in the prevalence of S. japonicum infection in trapped wild mice among three villages (χ2= 4.111, P > 0.05). In addition, there was no significant difference in the prevalence of S. japonicum infection in wild mice captured between on June (26.8%, 34/127) and October (22.9%, 57/249) (χ2 = 0.690, P = 0.406). The trapped wild mice included 6 species, including Rattus norvegicus, Niviventer niviventer, R. losea, Apodemus agrarius, Mus musculus and N. coning, and the two highest prevalence of S. japonicum infection was detected in R. losea (34.9%, 22/63) and R. norvegicus (31.2%, 44/141). Conclusions The prevalence of S. japonicum infections is high in wild mice in Shitai County, and there is a natural focus of schistosomiasis transmission in Shitai County.

Spatio-temporal distribution characteristics of Oncomelania hupensis in Anhui Province from 2011 to 2020 / 中国血吸虫病防治杂志

OBJECTIVE@#To analyze the spatial-temporal distribution characteristics of Oncomelania hupensis snails in Anhui Province from 2011 to 2020, to provide insights into precision control of O. hupensis snails in Anhui Province.@*METHODS@#O. hupensis snail distribution data were collected in Anhui Province from 2011 to 2020 and descriptively analyzed, including actual area of snail habitats, area of emerging snail habitats and area of Schistosoma japonicum-infected snails. The actual area of snail habitats and area of emerging snail habitats were subjected to spatial autocorrelation analysis, hotspot analysis, standard deviation ellipse analysis and space-time scanning analysis, and the clusters of snail distribution and settings at high risk of snail spread were identified in Anhui Province from 2011 to 2020.@*RESULTS@#The actual area of snail habitats gradually decreased in Anhui Province from 2011 to 2020. The actual area of snail habitats were 26 238.85 hm2 in Anhui Province in 2020, which were mainly distributed in marshland and lake regions. There was a large fluctuation in the area of emerging snail habitats in Anhui Province during the period from 2011 to 2020, with the largest area seen in 2016 (1 287.65 hm2), and 1.96 hm2 emerging infected snail habitats were detected in Guichi District, Chizhou City in 2020. Spatial autocorrelation and hotspot analyses showed spatial clusters in the distribution of actual areas of snail habitats in Anhui Province from 2011 to 2020 (Z = 3.00 to 3.43, all P values < 0.01), and the hotspots were mainly concentrated in the marshland and lake regions and distributed along the south side of the Yangtze River, while the cold spots were mainly concentrated in the mountainous regions of southern Anhui Province. There were no overall spatial clusters in the distribution of areas of emerging snail habitats (Z = -2.20 to 1.71, all P values > 0.05), and a scattered distribution was found in local regions. Standard deviation ellipse analysis showed relatively stable distributions of the actual areas of snail habitats in Anhui Province from 2011 to 2020, which was consistent with the flow direction of the Yangtze River, and the focus of the distribution of areas of emerging snail habitats shifted from the lower reaches to upper reaches of Anhui section of the Yangtze River. Space-time scanning analysis identified two high-value clusters in the distribution of actual areas of snail habitats in lower and middle reaches of Anhui section of the Yangtze River from 2011 to 2020, and two high-value clusters in the distribution of areas of emerging snail habitats were identified in mountainous and hilly regions.@*CONCLUSIONS@#There were spatial clusters in the distribution of O. hupensis snails in Anhui Province from 2011 to 2020, which appeared a tendency of aggregation towards the south side and upper reaches of the Yangtze River; however, the spread of O. hupensis snails could not be neglected in mountainous and hilly regions. Monitoring of emerging snail habitats should be reinforced in mountainous and hilly regions and along the Yangtze River basin.

mRNA cancer vaccines: Advances, trends and challenges

Patients exhibit good tolerance to messenger ribonucleic acid (mRNA) vaccines, and the choice of encoded molecules is flexible and diverse. These vaccines can be engineered to express full-length antigens containing multiple epitopes without major histocompatibility complex (MHC) restriction, are relatively easy to control and can be rapidly mass produced. In 2021, the U.S. Food and Drug Administration (FDA) approved the first mRNA-based coronavirus disease 2019 (COVID-19) vaccine produced by Pfizer and BioNTech, which has generated enthusiasm for mRNA vaccine research and development. Based on the above characteristics and the development of mRNA vaccines, mRNA cancer vaccines have become a research hotspot and have undergone rapid development, especially in the last five years. This review analyzes the advances in mRNA cancer vaccines from various perspectives, including the selection and expression of antigens/targets, the application of vectors and adjuvants, different administration routes, and preclinical evaluation, to reflect the trends and challenges associated with these vaccines.

Concentration of growth factors in platelet rich plasma under different activators / 中国输血杂志

【Objective】 To study the effects of different activators and doses on the concentration of growth factor in platelet rich plasma(PRP). 【Methods】 15 healthy volunteers, recruited to prepare PRP by COM.TEC blood cell separator, were divided into 5 groups: PRP group with no activator, Calcium gluconate PRP group, Thrombin 100U/ mL-PRP group, Thrombin 50U/ mL-PRP group, and Thrombin 100U/ml-calcium gluconate -PRP group. The white blood cell count and platelet count in PRP and whole blood were detected. The concentrations of PDGF-AA, TGF-βand VEGF in PRP inactive group and 4 different activators 1 hour after activation were determined by ELISA. 【Results】 The mean concentration of platelets in PRP was 1 462.86×109/L, which was 5.77 times that in the whole blood. The mean concentrations (pg/mL) of PDGF-AA(174 348.00±132 872.39 vs 217 909.67±182 517.96 vs 221 020.38±153 321.51 vs 208 550.35±177 100.47), TGF-β(12 573.14±3 173.20 vs 14 678.45±5 880.96 vs 14 694.39±5 083.90 vs 12 675.65±4 981.83) and VEGF (653.45±489.82 vs 671.61±506.68 vs 690.05±416.13 vs 678.93±501.07) in 4 different activator groups were significantly higher than those in inactivated group (P<0.05). There was no significant difference in the concentrations of PDGF-AA, TGF-βand VEGF among different activators. Platelet concentration(1 462.86±628.41×109/L) in PRP had a strong positive correlation with PDGF concentration (221 020.38±153 321.51 pg/mL)in thrombin 50 U/ mL-PRP group (P<0.05) and TGF-βconcentration(pg/mL) (12 573.14±3 173.20 vs 14 678.45±5 880.96 vs 14 694.39±5 083.90 vs 12 675.65±4 981.83, respectively) in four different activator groups (P<0.05), but had no correlation with VEGF in each group. 【Conclusion】 PRP was prepared by blood cell separator with high purity. There was no difference in the concentrations of PDGF-AA, TGF-βand VEGF among different activators and different thrombin doses. The correlation between platelet concentration and growth factor concentration in PRP was related to the type of activator and growth factor.

Epidemiological characteristics of imported malaria in Zhengzhou City from 2016 to 2020 / 中国血吸虫病防治杂志

Objective To analyze the epidemiological characteristics of reported imported malaria cases in Zhengzhou City from 2016 to 2020, so as to provide insights into the management of imported malaria in the city. Methods All data pertaining to cases with definitive diagnosis of malaria in Zhengzhou City from 2016 to 2020 were captured from the National Notifiable Disease Report System and the Information Management System for Parasitic Disease Control in China, including individual demographic data, and malaria onset, initial diagnosis and definitive diagnosis data. All data were descriptively analyzed. The duration from malaria onset to initial diagnosis, from initial diagnosis to definitive diagnosis and from onset to definitive diagnosis was compared among cases. In addition, the diagnoses of imported malaria cases in which definitive diagnosis was made were compared with the reexaminations by Zhengzhou Municipal Malaria Diagnosis Reference Laboratory. Results A total of 302 cases with definitive diagnosis of malaria were reported in Zhengzhou City from 2016 to 2020, and all were imported cases, with Plasmodium falciparum malaria as the predominant type (230 cases, 76.2%). There were 293 malaria cases imported from Africa (293 cases, 97.0%), which mainly included Nigeria (48 cases, 15.9%), Angola (40 cases, 13.2%), and the Democratic Republic of the Congo (29 cases, 9.6%). There was no obvious seasonality found in the date of malaria onset and time of reporting malaria. The ratio of male to female malaria cases was 49.3:1, and there were 103 cases (34.1%) with the current residency address in Zhengzhou City, 193 cases (63.9%) with the current residency address in other cities of Henan Province and 6 cases (2.0%) in other provinces of China. There were 271 cases (89.7%) seeking initial diagnosis in medical institutions, and the diagnostic accuracy of malaria was 56.6% (171/302) at initial diagnosis institutions. A total of 122 cases (40.4%) sought medical care on the day of malaria onset, and 252 cases (86.4%) within 3 days; however, only 22 cases (7.3%) were definitively diagnosed on the day of onset, and 162 cases (53.6%) diagnosed within 3 days. There were no significant differences between malaria cases seeking initial diagnosis at medical institutions and disease control and prevention institutions in terms of the duration from malaria onset to initial diagnosis (Z = −1.663, P > 0.05), from initial diagnosis to definitive diagnosis (Z = −0.413, P > 0.05) or from malaria onset to definitive diagnosis (Z = −0.838, P > 0.05). The median duration (interquartile range) from initial diagnosis to definitive diagnosis of malaria was 3.00 (2.00), 3.00 (6.00), 2.00 (4.00) d and 1.00 (1.00) d among cases seeking medical care at township-level and lower, county-, city- and province-level medical institutions, and the median duration from initial diagnosis to definitive diagnosis of malaria was significantly longer among cases seeking medical care at township-level and lower medical institutions than at city (Z = −3.286, P < 0.008 33) and province-level medical institutions (Z = −9.119, P < 0.008 33), while the median duration from initial diagnosis to definitive diagnosis [1.00 (3.00) d vs. 2.00 (4.00) d; Z = −4.099, P < 0.016] and from malaria onset to definitive diagnosis [3.00 (4.00) d vs. 4.00 (5.00) d; Z = −2.868, P < 0.016] among malaria cases with the current residency address in Zhengzhou City was both shorter than in other cities of Henan Province. The diagnostic accuracy was 89.1% (269/302) among malaria cases in which definitive diagnosis was made, and the accuracy of malaria reexaminations was 94.0% (284/302) in Zhengzhou Municipal Malaria Diagnosis Reference Laboratory. Conclusions P. falciparum malaria was predominant among reported imported malaria cases in Zhengzhou City from 2016 to 2020, and these imported malaria cases were predominantly diagnosed at medical institutions; however, the diagnostic capability of malaria is poor in township-level and lower medical institutions. Strengthening the collaboration between medical institutions and disease control and prevention institutions and improving the diagnostic capability building at medical institutions are recommended to consolidate malaria elimination achivements.

Pharmacoeconomic Systematic Review of Osimertinib for Advanced Non-small Cell Lung Cancer / 中国药房

OBJECTIVE：To s ystematically review the economics of osimertinib for advanced non-small cell lung cancer （NSCLC），and to provide the reference for clinical application and healthcare decision makers. METHODS ：Retrieved from PubMed，Embase，the Cochrane L ibrary，Health Technology Assessment ，CNKI，Wanfang database ，VIP，CBM，etc.， pharmacoeconomic studies on osimertinib in the treatment of advanced NSCLC were collected from the inception to Apr. 2020. After screening and extracting relevant data ，the quality of the included studies was evaluated by using the Quality of Health Economics Studies （QHES），and the economic research results of the included literatures were systematically evaluated by using descriptive analysis method. RESULTS & CONCLUSIONS ：A total of 10 studies from 7 different countries were included ；QHES scores of the included literatures were 73-93，with an average of 86.8，and the quality of the researches was generally high. All the 10 studies were cost-effectiveness analysis ，including 6 first-line treatment ，4 second-line treatment. Six studies reported the cost discount rate ；only one study used the cost of osimertinib after price reduction for evaluation and analysis. Compared with other epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKI），six studies from different countries showed that osimertinib as the first-line treatment drug had no cost-effectiveness advantage ；cost-effectiveness of second-line treatment of osimertinib was controversial ，compared to chemotherapy. For advanced NSCLC patients ，the second-line treatment of osimertinib after the national centralized negotiation of price reduction has a more cost-effectiveness advantage in China ’s medical service system，while the first-line treatment of osimertinib before price reduction does not have this advantage compared with other EGFR-TKI drugs.