Synthesis and anti-SARS-CoV-2 activity and mechanism research of lycorine derivatives / 药学学报

We designed and synthesized eighteen lycorine derivatives with five different structural types, and evaluated their antiviral activities on a HCoV-OC43-infected H460 cell model. Structure-activity relationships suggested that the introduction of appropriate substituents on the 6N atom of lycorine was beneficial to activity. Compound 6a gave a good activity with the half effective concentration (EC50) and selectivity index (SI) values of 2.36 μmol·L-1 and 16.52, respectively. Surface plasmon resonance (SPR) result indicated that 6a might target the non-structural protein 12 (NSP12) subunit in RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 with the dissociation constant (KD) value of 1.36 μmol·L-1. Molecular docking indicated that 6a might act on nidovirus RdRp-associated nucleotidyltransferase (NiRAN) catalytic center of NSP12, distinct from the mechanism of nucleoside-like drugs such as remdesivir. This study provides scientific data for the development of lycorine derivatives into a new class of anti-SARS-CoV-2 small molecule inhibitors.

Human Gingival Stem Cells Prevent Diabetes in NOD Mice by Reducing Follicular B Cells / 中山大学学报(医学科学版)

BackgroundType 1 diabetes is caused by a chronic immune response that destroys islet beta cells， resulting in elevated blood glucose. Mesenchymal stem cells can prevent and treat the development of diabetes and its complications. However， little is known about the effects and potential mechanisms of Gingival mesenchymal stem cells （GMSCs） in preventing diabetes. The aim of this study is to investigate the mechanism of GMSCs in preventing type 1 diabetes in mice and to find targets for clinical treatment of diabetes. MethodsWe injected human GMSCs into NOD mice to observe the trend of blood glucose， observed the survival of pancreatic β-cells by immunohistochemistry， and detected the change of immune cells in the spleen of mice by flow analysis. Finally， the immune cells in NOD mice were transfused into NOD-SCID mice to observe the onset of diabetes in NOD-SCID mice. ResultsGMSCs significantly reduced the incidence of diabetes in NOD mice， with 64% of control mice developing diabetes at 27 weeks of age compared with 35% in the GMSC group， P=0.013. The percentage of Follicular B cells（FO B cell） in the spleen of GMSCs-treated mice decreased from （52.2±4.1）% to （43.2±5.3）%， P=0.008， while other types of immune cells did not change significantly. The immunohistochemical results showed that GMSCs could effectively improve the survival of pancreatic β-cells， which could continuously produce insulin to control blood glucose. Finally， we found the spleen cells transfusion could prevent the development of diabetes in NOD-SCID mice. ConclusionGMSCs can reduce diabetes in mice by reducing FO B cells in the spleen.

Correlation of anti-phosphatidylserine/prothrombin antibodies with unexplained recurrent miscarriages / 北京大学学报(医学版)

OBJECTIVE@#To investigate whether anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes were correlated with unexplained recurrent miscarriages.@*METHODS@#In our a single-center retrospective study, 283 patients with at least one unexplained miscarriage who visited the Third Hospital of Peking University between January 2021 and August 2023, aged between 18-40 years, and tested for anti-phosphatidylserine/prothrombin antibodies IgG or IgM subtypes, were included. The patients with either positive IgG or IgM anti-phosphatidylserine/prothrombin antibody were regarded as positive for anti-phosphatidylserine/prothrombin antibody. SPSS 26.0 software was used for statistical analysis. Chi-square test and Logistic regression analysis were used to study the correlation of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes with unexplained recurrent miscarriages. And the diagnostic sensitivity, specificity, the positive predictive value, the negative predictive value of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes in unexplained miscarriages was calculated with four-fold table.@*RESULTS@#Chi-square analysis showed that anti-phosphatidylserine/prothrombin antibodies and its IgM subtypes were correlated with recurrent miscarriages (both P < 0.05), while the IgG subtype was not correlated with recurrent miscarriages (P>0.05). After adjusting with anticardiolipin antibodies, anti-β2 glycoprotein antibodies, lupus anticoagulants, antinuclear antibodies, and age by Logistic regression analysis, anti-phosphatidylserine/prothrombin antibodies were correlated with unexplained recurrent miscarriages (OR=2.084, 95%CI 1.045-4.155, P < 0.05), and anti-phosphatidylserine/prothrombin antibody IgM subtypes were correlated with unexplained recurrent miscarriages (OR=2.368, 95%CI 1.187-4.722, P < 0.05).The sensitivity of anti-phosphatidylserine/prothrombin antibody in recurrent miscarriage was 65.43%, the specificity was 48.51%, the positive predictive value was 33.76%, and the negative predictive value was 77.78%. In the patients with recurrent miscarriages with negative classical antiphospholipid antibodies, the sensitivity of anti-phosphatidylserine/prothrombin antibody was 59.09%, the specificity was 63.23%, the positive predictive value was 40.63%, and the negative predictive value was 78.40%. The sensitivity of the anti-phosphatidylserine/prothrombin antibody IgM subtype for the diagnosis of recurrent miscarriage was 65.43%, the specificity was 50.99%, the positive predictive value was 34.87%, and the negative predictive value was 78.63%.@*CONCLUSION@#Anti-phosphatidylserine/prothrombin antibody and IgM subtype antibody are correlated with unexplained recurrent miscarriages in patients with at least one unexplained miscarriage. Whether positive anti-phosphatidylserine/prothrombin antibody or IgM subtype could predict future unexplained recurrent miscarriages warrants a prospective study.

Medical visit status and clinical features in patients with IgG4 related disease / 北京大学学报(医学版)

OBJECTIVE@#To understand the medical treatment and clinical characteristics of patients with IgG4-related disease (IgG4-RD) with complex clinical manifestations and easy to be misdiagnosed and missed, and to improve the recognition of this disease among doctors from relevant medical departments.@*METHODS@#A retrospective analysis was conducted on the medical records of patients diagnosed with IgG4-RD who were hospitalized and discharged from Peking University Third Hospital from January 1, 2012 to December 31, 2022. The patient' s medical visit status, clinical manifestations, laboratory examinations, diagnosis, and treatment information were summarized.@*RESULTS@#A total of 116 patients diagnosed with IgG4-RD were included in this study, with a male to female ratio of 2. 52∶ 1 and an average age of (61.83±10.80) years. The departments for initial visits were gastroenterology, general surgery, and ophthalmology. While the departments responsible for definitive diagnosis were gastroenterology, rheumatology and immunology, and respiratory medicine. Twenty-one patients (18. 10%) required consultation and treatment from three or more departments before receiving a definitive diagnosis. The median time from symptom onset to the initial clinic visit was 2 (1, 7) months, and the median time from symptom onset to diagnosis was 1 (1, 12) month. Twenty-four patients (20.69%) underwent surgical resection of the affected sites before diagnosis. According to the classification criteria of IgG4-RD, sixty-eight (58.62%) cases were diagnosed definitively, eight (6.9%) cases were likely to be diagnosed, and 40 (34.48%) cases were suspected to be diagnosed. In the 68 definitively diagnosed patients, the most commonly affected organs were submandibular gland, the pancreas, biliary tract, parotid in sequence. The median serum IgG4 (IgG4, immunoglobulin G4) level was 6.16 (3. 61, 12. 30) g/L. Fifty-seven patients (83.82%) were treated with glucocorticoids, and 14 patients (20.59%) were treated with immunosuppressants. The use of immunosuppressants was mainly in the rheumatology and immunology department (78. 57%).@*CONCLUSION@#IgG4-RD is more common in elderly males, with submandibular gland, the pancreas, biliary tract, and parotid being most commonly affected. The distribution of initial visit departments in patients is wide. The proportion of definitive diagnosis based on pathology is relatively low. In terms of treatment, the main approach is steroid treatment, while the use of immunosuppres-sants is not widespread.

Hospitalization costs of pediatric community-acquired pneumonia in Shanghai / 中华儿科杂志

Objective: To investigate the epidemiology and hospitalization costs of pediatric community-acquired pneumonia (CAP) in Shanghai. Methods: A retrospective case summary was conducted on 63 614 hospitalized children with CAP in 59 public hospitals in Shanghai from January 2018 to December 2020. These children's medical records, including their basic information, diagnosis, procedures, and costs, were extracted. According to the medical institutions they were admitted, the patients were divided into the children's hospital group, the tertiary general hospital group and the secondary hospital group; according to the age, they were divided into <1 year old group, 1-<3 years old group, 3-<6 years old group, 6-<12 years old group and 12-18 years old group; according to the CAP severity, they were divided into severe pneumonia group and non-severe pneumonia group; according to whether an operation was conducted, the patients were divided into the operation group and the non-operation group. The epidemiological characteristics and hospitalization costs were compared among the groups. The χ2 test or Wilcoxon rank sum test was used for the comparisons between two groups as appropriate, and the Kruskal-Wallis H test was conducted for comparisons among multiple groups. Results: A total of 63 614 hospitalized children with CAP were enrolled, including 34 243 males and 29 371 females. Their visiting age was 4 (2, 6) years. The length of stay was 6 (5, 8) days. There were 17 974 cases(28.3%) in the secondary hospital group, 35 331 cases (55.5%) in the tertiary general hospital group and 10 309 cases (16.2%) in the children's hospital group. Compared with the hospitalizations cases in 2018 (27 943), the cases in 2019 (29 009) increased by 3.8% (1 066/27 943), while sharply declined by 76.2% (21 281/27 943) in 2020 (6 662). There were significant differences in the proportion of patients from other provinces and severe pneumonia cases, and the hospitalization costs among the children's hospital, secondary hospital and tertiary general hospital (7 146 cases(69.3%) vs. 2 202 cases (12.3%) vs. 9 598 cases (27.2%), 6 929 cases (67.2%) vs. 2 270 cases (12.6%) vs. 9 397 cases (26.6%), 8 304 (6 261, 11 219) vs. 1 882 (1 304, 2 796) vs. 3 195 (2 364, 4 352) CNY, χ2=10 462.50, 9 702.26, 28 037.23, all P<0.001). The annual total hospitalization costs of pediatric CAP from 2018 to 2020 were 110 million CNY, 130 million CNY and 40 million CNY, respectively. And the cost for each hospitalization increased year by year, which was 2 940 (1 939, 4 438), 3 215 (2 126, 5 011) and 3 673 (2 274, 6 975) CNY, respectively. There were also significant differences in the hospitalization expenses in the different age groups of <1 year old, 1-<3 years old, 3-<6 years old, 6-<12 years old and 12-18 years old (5 941 (2 787, 9 247) vs. 2 793 (1 803, 4 336) vs. 3 013 (2 070, 4 329) vs. 3 473 (2 400, 5 097) vs. 4 290 (2 837, 7 314) CNY, χ2=3 462.39, P<0.001). The hospitalization cost of severe pneumonia was significantly higher than that of non-severe cases (5 076 (3 250, 8 364) vs. 2 685 (1 780, 3 843) CNY, Z=109.77, P<0.001). The cost of patients who received operation was significantly higher than that of whom did not (10 040 (4 583, 14 308) vs. 3 083 (2 025, 4 747) CNY, Z=44.46, P<0.001). Conclusions: The number of children hospitalized with CAP in Shanghai decreased significantly in 2020 was significantly lower than that in 2018 and 2019.The proportion of patients from other provinces and with severe pneumonia are mainly admitted in children's hospitals. Hospitalization costs are higher in children's hospitals, and also for children younger than 1 year old, severe cases and patients undergoing operations.

Responses of blood parameters and hemoglobin subtypes in plateau zokors and plateau pikas to different altitude habitats / 生理学报

The plateau zokor (Myospalax baileyi) and plateau pika (Ochotona curzoniae) are native species unique to the Qinghai-Tibetan Plateau with successful adaptation to the hypoxic environment. In this study, the number of red blood cells, hemoglobin concentration, mean hematocrit and mean volume of red blood cells were measured in plateau zokors and plateau pikas at different altitudes. Hemoglobin subtypes of two plateau animals were identified by mass spectrometry sequencing. The forward selection sites in two animals' hemoglobin subunits were analyzed by PAML4.8 program. Homologous modeling was used to analyze the effect of forward selection sites on the affinity of hemoglobin to oxygen. The adapting strategies of plateau zokors and plateau pikas to hypoxia at different altitudes were analyzed through comparing blood parameters between the two species. The results indicated that, with increasing altitudes, plateau zokors responded to hypoxia by increasing red blood cell count and decreasing red blood cell volume, while plateau pikas took the opposite strategies to plateau zokors. In erythrocytes of plateau pikas, both adult α2β2 and fetal α2ε2 hemoglobins were identified, while erythrocytes of plateau zokors only had adult α2β2 hemoglobin, however the affinities and the allosteric effects of the hemoglobin of plateau zokors were significantly higher than those of plateau pikas. Mechanistically, in the α and β subunits of hemoglobin of plateau zokors and pikas, the numbers and the sites of the positively selected amino acids as well as the side chain groups polarities and orientations of the amino acids differed significantly, which may result in the difference of the affinities to oxygen of hemoglobin between plateau zokors and pikas. In conclusion, the adaptive mechanisms to respond to hypoxia in blood properties of plateau zokors and plateau pikas are species-specific.

Interaction of polycyclic aromatic hydrocarbon DNA adducts and telomere length on missed abortion / 中华预防医学杂志

Objective: To analyze the contribution and interaction of polycyclic aromatic hydrocarbons (PAH)-DNA adducts and changes of telomere length (TL) on missed abortion. Methods: From March to December 2019, patients with missed abortion in the First Hospital of Shanxi Medical University and pregnant women with normal pregnancy but voluntary abortion in the same department during the same period were selected and divided into a case group and a control group. Questionnaire was used to investigate the general situation and the pregnancy situation of the subjects. The abortion villi were collected and the content of PAH-DNA adducts and TL was detected. Logistic regression model was used to analyze the associated factors of missed abortion. R epiR package and Mediation package were used to analyze the effect and relationship between PAH-DNA adducts and TL on missed abortion. Results: The age of the subjects was(29.92±5.69)years old. The M(Q1,Q3)of PAH-DNA adducts was 453.75(404.61, 504.72) pg/ml. The M(Q1,Q3)of TL was 1.21(0.77, 1.72). The content of PAH-DNA adducts in the case group was higher than that in the control group (Z=-2.10, P=0.036), while the TL was lower than that in the control group (Z=-4.05, P<0.001). Multivariate logistic regression showed that low, medium and high levels of PAH-DNA adducts (OR=3.17,95%CI:1.41-7.14;OR=2.85,95%CI:1.25-6.52;OR=2.46,95%CI:1.07-5.64), and long, medium and short levels of TL (OR=2.50,95%CI:1.11-5.63;OR=3.32,95%CI:1.45-7.56;OR=3.22,95%CI:1.42-7.26) were all risk factors for missed abortion. The medium level of PAH-DNA adducts had a 2.76-fold higher risk of shortened TL than those with the lowest level, and no mediating role of TL was found. The stratified analysis showed that when the TL level was longer (>1.21), the low and high levels of PAH-DNA adducts were associated with missed abortion (all P<0.05); when the TL level was shorter (<1.21), the medium level of PAH-DNA adducts was associated with abortion (P=0.025). At lower levels of PAH-DNA adducts, no effect of TL on missed abortion was observed, while, at higher levels, TL was strongly associated with missed abortion (OR=7.50,95%CI:1.95-28.82;OR=6.04,95%CI:1.54-23.65;OR=9.05,95%CI:2.34-35.04). The interaction analysis found that the AP was 0.72 (95%CI: 0.46-0.99), and the SI was 5.21 (95%CI: 2.30-11.77). Conclusion: The high level of PAH-DNA adducts and shortened TL may increase the risk of missed abortion, and there may be a positive additive interaction between the two factors on missed abortion.

Cloning and functional analysis of IPI gene from Fritillaria unibracteata Hsiao et K. C. Hsia / 药学学报

An open reading frame (ORF) of isopentenyl-diphosphate delta isomerase gene (FuIPI) was cloned from Fritillaria unibracteata Hsiao et K. C. Hsia. (F. unibracteata). Furthermore, the bioinformatics and functional analyses of FuIPI were performed in this study. The result showed that, the ORF of FuIPI gene was 825 bp, encoding a polypeptide of 274 amino acids in length, with a relative molecular mass of about 31 kD and a theoretical isoelectric point of 5.61. Sequence analysis showed that FuIPI contained conserved structural domains and key residues involved in the catalyzing process. The phylogenetic analysis exhibited that FuIPI was closely related to IPIs of Dendrobium officinale and Musa acuminate. Real-time PCR analysis showed that FuIPI was distributed in different tissues of F. unibracteata, but had the highest transcriptional level in leaves, followed by stems, bulbs, and flowers. Furthermore, the FuIPI protein was successfully expressed in Escherichia coli BL21(DE3). The purified FuIPI protein successfully catalyzed the conversion from isopentenyl diphosphate (IPP) to dimethylallyl pyrophosphate (DMAPP). The above results provided a theoretical basis for further investigation of the molecular role of FuIPI in the biosynthesis of alkaloids.

Effect of 25G+pars plana vitrectomy combined with preoperative intravitreal injection of Conbercept on proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical effect of 25G+pars plana vitrectomy(PPV)combined with preoperative intravitreal injection of conbercept in the treatment of patients with proliferative diabetic retinopathy(PDR), and analyze the influence on visual acuity, central foveal thickness(CMT)and serum vascular endothelial growth factor(VEGF)level.METHODS: A retrospective study was conducted from October 2019 to January 2022. A total of 80 patients(87 eyes)with PDR were divided into the two groups according to the treatment method, with 40 patients(45 eyes)treated with 25G+PPV in the control group, and 40 patients(42 eyes)treated with 25G+PPV combined with preoperative intravitreal injection of conbercept in the observation group. The two groups were compared in terms of the best corrected visual acuity(BCVA), intraocular pressure, CMT and serum VEGF level before treatment and at 2wk, 1 and 3mo after treatment. The patients were followed up for 3mo, with postoperative complications and recurrence recorded.RESULTS: The incidence of intraoperative bleeding in the observation group was significantly lower than that in the control group(P&#x0026;#x003C;0.05). After treatment, the BCVA of the two groups was improved(P&#x0026;#x003C;0.05), CMT and serum VEGF level were decreased(P&#x0026;#x003C;0.05), but there was no significant change in intraocular pressure(P&#x0026;#x003E;0.05). The BCVA and CMT of observation group were lower than those of control group at 1 and 3mo after treatment(P&#x0026;#x003C;0.05). Serum VEGF level in the observation group was lower than that in the control group at 3mo after treatment(P&#x0026;#x003C;0.05). The incidence of complications in observation group(5%)within 3mo after treatment was significantly lower than that in control group(18%; P&#x0026;#x003C;0.05). There was no statistically significant difference in recurrence rate of PDR between the two groups(P&#x0026;#x003E;0.05).CONCLUSION: With few complications, 25G+PPV combined with preoperative intravitreal injection of conbercept is effective in the treatment of patients with PDR, which can better promote postoperative vision recovery, improve macular edema, and reduce serum VEGF level.

Diquafosol sodium combined with intense pulsed light in the treatment of meibomian gland dysfunction dry eye after corneal refractive surgery / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the therapeutic effect of the diquafosol sodium combined with intense pulsed light(IPL)on meibomian gland dysfunction(MGD)dry eye after refractive surgery.METHODS:A total of 64 patients(128 eyes)with MGD dry eye diagnosed within 6mo after laser corneal refractive surgery in our hospital from March 2021 to December 2021 were selected. They were randomly divided into control group and experimental group. A total of 33 patients(66 eyes)in the control group were treated with sodium hyaluronate combined with IPL, and 31 patients(62 eyes)in the experimental group were treated with diquafosol sodium combined with IPL. Ocular symptom scores were performed before each IPL treatment in both groups to examine non-invasive tear breakup time(NIBUT), tear meniscus height, lipid layer grade of tear film, meibomian gland deletion rate and uncorrected visual acuity.RESULTS:After IPL treatment, ocular symptom scores and meibomian gland deletion rate score of two groups were decreased continuously. NIBUT, tear meniscus height and lipid layer grade of tear film were increased continuously, and there was no significant change in uncorrected visual acuity. NIBUT of patients in the experimental group was better than that in the control group before the third IPL treatment(6.24±0.27s vs. 5.51±0.24s, P=0.046).CONCLUSIONS:Both diquafosol sodium and sodium hyaluronate combined with IPL showed good therapeutic effect on MGD dry eye, but there was no significant difference in the short-term efficacy between the two groups.

Multicenter epidemiological characteristics of Mycoplasma pneumoniae infection in children in Hainan Province, 2012-2020 / 中国热带医学

@#Abstract: Objective　To analyze the epidemiological characteristics (season, age, gender, mixed infection and clinical manifestations, etc.) of Mycoplasma pneumoniae (MP) infection in children in Hainan Province, so as to provide epidemiological evidence-based medical basis for the prevention and control of MP infection in children in Hainan Province. Methods　The serum IgM antibodies of MP, Legionella pneumophila, Chlamydia pneumoniae, adenovirus, respiratory syncytial virus (RSV), Q fever Rickettsia, parainfluenza virus, influenza A virus and influenza B virus in children with respiratory tract infections (RTIs) who were hospitalized in pediatrics of many hospitals in Hainan Province from March 2012 to February 2020 were detected by indirect immunofluorescence method. The positive serum MP-IgM antibody was defined as MP infection. The epidemiological and clinical data of MP infected cases were analyzed retrospectively. Results　From March, 2012 to February, 2020, a total of 35 731 qualified pediatric inpatients with RTIs in many hospitals in Hainan Province were tested for serum MP-IgM with the total positive rate of 39.12% (13 978/35 731). The yearly positive rates of MP-IgM from 2012 to 2020 were 48.39%, 56.23%, 56.62%, 47.04%, 29.71%, 24.14%, 47.55%, 36.84% and 24.46% respectively. The positive rates of MP-IgM in 2013 and 2014 were significantly higher than those in other years (P<0.05). The positive rate of MP-IgM in summer in Hainan Province was the highest (41.34%) and the lowest in winter (35.77%) (P<0.05). MP infection occurred in all age groups, the positive rate of MP-IgM in children of preschool (51.80%) was significantly higher than that in other age groups (P<0.01), and the positive rate of MP IgM in children of infancy (15.36%) was lower than that in other age groups (P<0.01). The positive rate of MP-IgM in female was 44.77%, which was significantly higher than that in male (35.83%) (P<0.05). MP infection combined with positive IgM of another pathogen accounted for 32.63% (4 561 cases), positive IgM of another two pathogens accounted for 1.26% (176 cases). MP infection was mostly found in pneumonia (68.73%), and the main clinical symptoms were cough (84.72%), fever (51.01%) and wheezing (3.16%). Conclusions　MP is an important pathogen of respiratory tract infection in children in Hainan Province, and infection is more common in children in early school age and early childhood. Mp-specific tests should be performed to identify the pathogen in children suspected of MP infection. In the high incidence season, health education should be strengthened in kindergartens, schools and other places to prevent respiratory tract infection.

Correlation between monocyte to high-density lipoprotein cholesterol ratio and insulin resistance in male patients with type 2 diabetes mellitus combined with metabolic-related fatty liver disease / 中国热带医学

@#Abstract: Objective　To explore the correlation between monocyte to high-density lipoprotein cholesterol ratio (MHR) and insulin resistance (IR) in male patients with type 2 diabetes mellitus (T2DM) combined with metabolic-related fatty liver disease (MAFLD). Methods A total of 454 male patients with T2DM combined with MAFLD in National Metabolic Management Center (MMC) of the Affiliated Hospital of Jiangsu University from May 2018 to July 2020 were enrolled. The general clinical data of subjects were collected, blood routine and biochemical indexes were tested, homeostasis model insulin resistance index (HOMA-IR) was calculated, visceral fat area (VFA) and subcutaneous fat area (SFA) were measured. Accordingtothe MHR quartile, patients were divided into group Q1 (MHR≤0.38), group Q2 (0.38<MHR≤0.48), group Q3 (0.48<MHR≤0.64) and group Q4 (MHR>0.64) to compare the differences in measured indicators above. In addition, patients were divided into two groups according to HOMA-IR, HOMA-IR<2.5 and HOMA-IR≥2.5, and the differences in MHR were compared. Results The patients were divided into four groups according to MHR:group Q1 (n=115), group Q2 (n=110), group Q3 (n=120) and group Q4 (n=109). Fasting insulin (FINS) were respectively 6.17(4.20,9.76), 7.73(4.94,10.66), 8.92(5.32,11.33) and 9.13(5.25,12.27) mU/L, 2-hour postprandial insulin were 22.75(12.87,39.59), 27.55(16.44,39.77), 30.98(17.46,43.11) and 31.28(18.54,45.92) U/L. HOMA-IR were 3.12(1.63,4.25), 3.72(2.26,4.66), 3.87(2.48,5.44) and 3.95(2.42,5.31). Neutrophil (Neu) were 3.10(2.60,3.70), 3.20(2.50,3.93), 3.60(2.80,4.28), 4.20(3.30,5.00)×109/L. Subcutaneous fat area (SFA) were (181.27±53.60), (192.64±62.41), (199.53±61.40) and (203.69±71.51) cm2. They all increased gradually. However, the levels of high-density lipoprotein cholesterol (HDL-c) [1.18(1.06,1.35), 1.02(0.86,1.17), 0.96(0.80,1.03) and 0.80(0.69,0.92) mmol/L] and low-density lipoprotein cholesterol (LDL-c) [(3.00±0.79), (2.76±0.83), (2.67±0.85) and (2.59±0.92) mmol/L] decreased gradually. Pearson's or Spearman's correlation analysis showed that MHR was positively correlated with FINS, 2-hour postprandial insulin (2hINS), HOMA-IR, VFA and SFA (r=0.190, 0.153, 0.184, 0.114, 0.127, P<0.05). The coronary heart disease history, systolic blood pressure,diastolic blood pressure,fasting plasmaglucose (FPG), FINS, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood uric acid (Ur), body mass index (BMI), VFA, SFA and MHR of patients in group HOMA-IR≥2.5 were higher than group HOMA-IR<2.5 (P<0.05). Conclusion　MHR is positively correlated with IR in male patients with T2DM combined with MAFLD, and as MHR increases, the degree of IR is higher.

The risk surveillance of schistosomiasis in Yunnan, 2021 / 中国热带医学

@#Abstract: Objective　To evaluate the potential transmission risk of schistosomiasis in Yunnan Province, and to provide strategic basis for the prevention and control. Methods　Based on the prevalence of schistosomiasis, the social and environmental factors that may lead to the epidemic, 1-3 villages from 3 provincial-level and 15 county-level counties (cities and districts) were selected as the evaluated villages in 2021. The risk of schistosomiasis spread was analyzed comprehensively by consulting, reviewing and collecting routine surveillance data of schistosomiasis in the villages, combined with snail and wild feces survey. The risk level was evaluated for the positive snails, positive wild feces, resident infection, average density of live snails and snail frame occurrence rate. Results　Totally 7 snail counties schistosomiasis transmission was blocked of 18 epidemic counties and the rest were eliminated counties. A total of 152 447 snail frames were investigated and 3 043 frames with snails, 15 895 snails were captured and included 15 727 live snails in the 32 evaluated villages. The total area of snail was 58.87 hm2 and the area of reoccurrence was 34.19 hm2 with snail frame occurrence rate of 2.00% and average density of live snails 0.103 2/0.11 m2, and no positive snails were found by loop-mediated isothermal amplification (LAMP) assay. A total of 1 374 wild feces were collected in 27 evaluated villages of 14 epidemic counties, mainly from cattle, dogs, sheep, equine animals, pigs and so on, all of which were negative. According to the risk assessment of epidemic spread, Yongle Village and Yongsheng Village in Eryuan County, Zhiming Village in Chuxiong City were Ⅱ risk, and the rest were Ⅲ risk. Conclusions　Although the risk of transmission is low in Yunnan Province, the risk of transmission and spread still exists. It is necessary to strengthen the risk monitoring, control of snail and effective management of livestock to prevent the rebound of the epidemic.

Research advances in natural killer cell-based immunotherapy in liver cancer / 临床肝胆病杂志

Natural killer (NK) cells are important immune cells in the human body and are also the main lymphocytes in the liver. They are considered the first defense mechanism against tumor and have a significant impact on the development and progression of liver cancer. The characteristics of NK cells help them become a new choice for immunotherapy, and NK cell-based immunotherapy may succeed in the treatment of liver cancer. This article reviews the biological characteristics of NK cells, their role in the development and progression of liver cancer, and the research advances in related treatment.

Differences in related indicators after Toric intraocular lens implantation in cataract patients with different axial lengths / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the differences in visual recovery, corneal astigmatism, and rotation stability of Toric intraocular lens(TIOL)implantation in cataract patients with different axial lengths.METHODS: Retrospective analysis. A total of 132 patients(132 eyes)with age-related cataract and corneal astigmatism who underwent phacoemulsification cataract extraction combined with TIOL implantation in our hospital's ophthalmology department from February 2021 to September 2022 were selected. They were divided into two groups based on the axial length: the group with axial length ≤24mm(79 cases, 79 eyes)and the group with axial length &#x003E;24mm(53 cases, 53 eyes). Compare the best corrected distance visual acuity(BCDVA), corneal astigmatism, and TIOL rotation between the two groups of patients at 3mo after surgery.RESULT: After 3mo of surgery, both groups of patients had improved BCDVA and significantly decreased corneal astigmatism compared to those before surgery(P&#x003C;0.001). However, there was no difference in BCDVA and corneal astigmatism between the two groups(P&#x003E;0.05), and there was no significant difference in TIOL rotation between the two groups [(5.24±3.72)° vs.(6.36±4.21)°, P=0.110].CONCLUSION: There is no significant difference in visual recovery, corneal astigmatism, and TIOL rotational stability after TIOL implantation in cataract patients with different axial lengths.

Overall planning and optimization: characteristics analysis of the medical doctoral supervisor and consideration of the current situation of enrollment / 中华医学教育探索杂志

This study has combed and analyzed the characteristics of medical doctoral supervisors and the enrollment status from 2015 to 2018 in Tongji University School of Medicine. The results show that the distribution of doctoral supervisors' age, gender and professional title is relatively balanced. The enrollment situation shows the clustering trend. There are obvious differences in enrollment among clinical medical disciplines, and the scales of doctoral supervisors and doctoral students are not matched and unevenly distributed. It is essential to give an overall consideration in discipline resources and optimize enrollment allocation, for improving the construction of doctoral supervisors and the quality of doctoral training.

Analysis of influencing factors for breakthrough cancer pain in patients with advanced pancreatic cancer / 中华胰腺病杂志

Objective:To investigate the influencing factors of breakthrough cancer pain (BTcP) in patients with advanced pancreatic cancer.Methods:According to the inclusion and exclusion criteria, patients with advanced pancreatic cancer who were diagnosed and followed up by outpatient service in the 909th Hospital of the Joint Logistic Support Force from January 2019 to December 2020 were prospectively selected as the study subjects. According to whether breakthrough cancer pain occurred, all patients were divided into observation group (breakthrough cancer pain) and control group (no breakthrough cancer pain). The relevant clinical data of the included patients including age, gender, presence or absence of vomit, constipation, sleep disruption, frequency of basic pain every week, with or without regular medication, heavy physical labor, with or without vascular invasion, bone metastasis, abdominal metastasis and lung metastasis, as well as whether surgery, radiotherapy or chemotherapy were collected and the data of evaluation indicators during follow-up were recorded. Digital pain score (NRS) and visual analog score (VAS) were used as pain evaluation score. Univariate and logistic regression were used to analyze the related influencing factors of breakthrough cancer pain. Receiver operating characteristic curve (ROC) was drawn, and area under curve (AUC), sensitivity and specificity were calculated to analyze the predictive value for breakthrough cancer pain.Results:A total of 173 patients were included in the study, with 49 cases in the observation group and 124 cases in the control group. Univariate analysis showed that aged ≥50 years old, constipation, sleep disruption, frequency of basic pain ≥3 times, irregular medication, heavy physical labor, bone metastasis, lung metastasis, radiochemotherapy, high NRS score and high VAS score were the influencing factors for breakthrough cancer pain (all P value <0.05). Multivariate analysis showed that irregular medication ( OR=1.879, 95% CI 2.473-4.757, P=0.002), basal pain ≥3 times ( OR=2.067, 95% CI 1.364-6.825, P=0.004), bone metastasis ( OR=2.756, 95% CI 1.153-5.846, P<0.001), NRS score ( OR=3.787, 95% CI 2.647-5.958, P<0.001), VAS score ( OR=2.684, 95% CI 1.545-7.878, P<0.001), were the risk factors for breakthrough cancer pain. The AUC of NRS score for predicting the occurrence of breakthrough cancer pain was 0.665 (95% CI0.573-0.757, P=0.001), and the cut-off value was 2.5 score with a sensitivity of 61.2% and a specificity of 77.1%. The AUC for predicting breakthrough cancer pain by VAS score was 0.608 (95% CI0.515-0.701, P=0.028), and the cut-off value was 2.5 score with a sensitivity of 67.9% and a specificity of 63.7%. The AUC of NRS+ VAS score for predicting breakthrough cancer pain was 0.692 (95% CI0.604-0.780), and the cut-off value was 4.5 score with a sensitivity of 81.6% and a specificity of 79.8%. Conclusions:Patients with advanced pancreatic cancer have a high incidence of breakthrough cancer pain, which was related to a variety of factors. NRS combined with VAS score can effectively predict the occurrence of breakthrough cancer pain.

Comparison of corneal epithelial remodeling and corneal aberration changes after FS-LASIK and FS-LASIK Xtra / 中华实验眼科杂志

Objective:To investigate the status of corneal epithelial remodeling and changes in corneal aberration after femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) and FS-LASIK combined with corneal collagen cross-linking (FS-LASIK Xtra), and to analyze the relationship between corneal epithelial thickness (CET) and corneal aberration.Methods:A cohort study was conducted.A total of 172 patients (172 eyes) who underwent FS-LASIK at Yinhai Eye Hospital of Chengdu University of Traditional Chinese Medicine were enrolled from June 2021 to February 2022.The 172 eyes were divided into FS-LASIK group (94 eyes) and FS-LASIK Xtra group (78 eyes) according to the surgical procedure, with a total follow-up of 6 months.The cornea was divided into a central 2-mm ring and a ring of 2-5 mm centered on the central cornea.CET at 9 regions in the central 0-5 mm area was measured by OCT before and at 1, 3 and 6 months after surgery, and the corneal higher-order aberration (HOA) was measured by the iTrace visual function analyzer.The main outcomes were the increase in CET (ΔCET), and corneal HOA at 6 months after surgery.The relationship between central corneal ΔCET and corneal aberration was analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Yinhai Eye Hospital of Chengdu University of Traditional Chinese Medicine (No.2021yh-009). Written informed consent was obtained from each subject.Results:At 1, 3 and 6 months after surgery, the central, superior, superior nasal, nasal, inferior nasal, inferior, inferior temporal, temporal and superior temporal ΔCET were significantly smaller in FS-LASIK Xtra group than in FS-LASIK group (all at P<0.05). In FS-LASIK Xtra group, 6-month postoperative central, superior, superior nasal, inferior and inferior temporal ΔCET were significantly larger than those at 1 month after surgery, and 3- and 6-month postoperative temporal ΔCET were significantly larger than that at 1 month after surgery, and 6-month postoperative superior temporal ΔCET was significantly larger than those at 1 and 3 months after surgery (all at P<0.05). In FS-LASIK group, 3- and 6-month postoperative central, superior, inferior and inferior temporal ΔCET were significantly larger than those at 1 month after surgery, and 6-month postoperative superior nasal ΔCET was significantly larger than that at 3 months after surgery, and 6-month postoperative nasal, inferior nasal, temporal, superior temporal ΔCET were significantly larger than those at 1 and 3 months after surgery (all at P<0.05). There was no significant difference in vertical trefoil, vertical and horizontal coma changes at different time points after surgery between both groups (vertical trefoil: χ2group=4.27, P=0.118; χ2time=0.01, P>0.05.vertical coma: χ2group=5.74, P=0.057; χ2time=0.08, P=0.957.horizontal coma: χ2group=3.97, P=0.137; χ2time=0.51, P=0.773). The tilted trefoil changes at 1, 3 and 6 months after surgery of FS-LASIK Xtra group were significantly larger than those of FS-LASIK group (all at P<0.05). The 6-month spherical aberration change in FS-LASIK Xtra group was significantly higher than that at 1 month after surgery, and the 6-month spherical aberration change in FS-LASIK group was significantly higher than that at 1 and 3 months after surgery (all at P<0.05). The 6-month total HOA change in FS-LASIK group was significantly lower than that at 1 and 3 months after surgery (all at P<0.05). In FS-LASIK group, central corneal ΔCET was weakly positively correlated with spherical aberration at 1 and 6 months after surgery ( rs=0.257, P=0.008; rs=0.244, P=0.012), and was weakly positively correlated with total HOA ( rs=0.253, P=0.009; rs=0.279, P=0.004). Conclusions:The postoperative ΔCET after FS-LASIK Xtra is smaller than that after FS-LASIK, but the homogeneity of ΔCET in each region is similar between the two groups.The changes in corneal HOA after surgery are similar in both groups, and there is a certain association between the overall epithelial distribution and corneal aberration.

Effect of peripheral plus ring diameter and its relationship with pupil diameter on axial elongation in myopic patients after wearing orthokeratology lenses / 中华实验眼科杂志

Objective:To investigate the effect of peripheral plus ring size and its potential associations with pupil diameter (PD) on axial length (AL) elongation in myopic patients after wearing orthokeratology lenses.Methods:A case-control study was conducted.One hundred eyes from 100 myopic patients who underwent orthokeratolokgy lenses fitting were enrolled at Beijing Ming Vision and Ophthalmology from January to June 2020.AL and central corneal thickness (CCT) measurements were obtained using Lenstar LS900 ocular biometry, and steep keratometry (Ks), flat keratometry (Kf) were assessed using the TMS-4 corneal topographer.The patients were divided into larger peripheral plus ring diameter (LPPRD) group consisting of 55 eyes with PD<PPRD-0.9 mm and smaller PPRD (SPPRD) group consisting of 45 eyes with PPRD-0.9 mm <PD<PPRD+ 0.9 mm based on PPRD and PD sizes in the tangential difference map.Differences in the above parameters before and after wearing orthokeratology lenses were compared between the two groups.The study followed the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Ineye Hospital of Chengdu University of Traditional Chinese Medicine (No.2021yh-008). All the subjects and their guardians understood the purpose and method of the study and signed the informed consent voluntarily.Results:The PPRD of LPPRD group was (5.15±0.37)mm 12 months after wearing orthokeratology lenses, which was significantly higher than (4.75±0.32)mm of SPPRD group ( t=0.214, P<0.01). The elongation of AL at 3, 6, 9 and 12 months after wearing orthokeratology lenses were (0.13±0.07), (0.23±0.11), (0.31±0.13) and (0.36±0.41)mm in LPPRD group, and (0.06±0.05), (0.11±0.06), (0.14±0.07) and (0.17±0.08)mm in SPPRD group, respectively.There were significant differences in AL elongation at different time points after wearing orthokeratology lenses between the two groups ( Fgroup=30.527, P<0.01; Ftime=16.528, P<0.01), and the AL elongation at different time points was smaller in SPPRD group than in LPPRD group, showing statistically significant differences (all at P<0.01). Compared to before wearing orthokeratology lenses, Ks and Kf were significantly smaller and CCT was thinner 3, 6, 9, and 12 months after wearing orthokeratology lenses in both groups (all at P<0.01). There was no significant difference in Ks, Kf, and CCT between the two groups (all at P>0.05). There was no significant difference in PD at different time points before and after wearing orthokeratology lenses between the two groups ( Fgroup=1.133, P=0.293; Ftime=231.427, P=0.112). Conclusions:The size of peripheral plus ring and its relationship with PD are key factors influencing the AL elongation rate in myopic patients after wearing orthokeratology lenses.With smaller PPRD, patients have slower AL elongation and better myopia control.

The Effect of Intense Pulsed Light Treatment for Chronic Hordeolum / 生物医学与环境科学（英文）

OBJECTIVE@#To evaluate the effect of intense pulsed light (IPL) in the treatment of chronic hordeolum.@*METHODS@#Patients with chronic hordeolum who underwent IPL treatment were enrolled in this study. According to the severity of hordeolum, the patients were treated with IPL 3 to 5 times. Patients' satisfaction and visual analog scale scores for ocular discomfort symptoms before and after treatment were collected. The number, congestion, long diameter, short diameter and area of nodules were also recorded and measured. Finally, eyelid margin signs, meibum quality, meibomian gland expressibility, meibomian gland dropout, tear meniscus height, and corneal fluorescein staining were scored.@*RESULTS@#20 patients were enrolled in this study. The eyelid margins were congestive and swollen, with blunt rounding or irregularity. The meibum was cloudy or toothpaste-like. The meibomian gland expressibility, meibomian gland dropout and tear meniscus height were reduced. The cornea showed scattered fluorescein staining. After treatment, score of visual analog scale, congestion and size of nodules were significantly reduced. Eyelid margin signs, meibum quality, meibomian gland expressibility, tear meniscus height and corneal fluorescein staining scores were improved. Meibomian gland dropout had no significant change. No side effects occurred during treatment.@*CONCLUSIONS@#IPL is beneficial for the treatment of chronic hordeolum.