ObjectiveTo investigate the effects of Linggui Zhugantang （LGZGT）-containing serum on primary astrocytes （AS） induced by β amyloid 1-42 （Aβ_1-42） in a rat model of Alzheimer's disease （AD） and explore the phagocytic and degradative effects of LGZGT on Aβ. MethodAn AD model was established by inducing AS with Aβ_1-42. The cells were divided into normal group， model group， LGZGT low-， medium-， and high-dose （LGZGT-L， LGZGT-M， and LGZGT-H） groups， and donepezil hydrochloride group. The model group was treated with Aβ_1-42 at a final concentration of 10 μmol∙L^-1. The LGZGT-L， LGZGT-M， and LGZGT-H groups were treated with 10% serum containing LGZGT on the basis of the model group. Cell viability was assessed using a cell counting kit-8 （CCK-8）， lactate dehydrogenase （LDH） activity was measured using an LDH assay kit， and cell morphology was observed using an inverted microscope. The expression of Aβ-related degradation enzymes insulin-degrading enzyme （IDE） and cathepsin D （CTSD） was detected using Western blot， and the fluorescence intensity of cathepsin B （CTSB） was measured using immunofluorescence. The content of Aβ_1-42 in cells was determined using an enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the normal group， the viability of AS in all groups decreased， and Aβ_1-42 at different concentrations had inhibitory effects on AS proliferation. After administration， compared with the normal group， the cell survival rate of the model group decreased significantly （P<0.05）. Compared with the model group， the cell survival rates of the LGZGT-H group and donepezil hydrochloride group increased significantly （P<0.05）. The LDH activity of cells in the model group was significantly increased compared with that in the normal group （P<0.05）， and cell bodies were swollen and enlarged with increased protrusions and elongation， suggesting more obvious cell damage. Compared with the model group， the LDH activity of cells in the donepezil hydrochloride， LGZGT-L， LGZGT-M， and LGZGT-H groups decreased significantly （P<0.05）. After administration， the cell swelling in the LGZGT-M， LGZGT-H， and donepezil hydrochloride groups improved， cell protrusions shortened， and cell clustering decreased. Compared with the normal group， the expression of IDE and CTSD in the model group decreased significantly （P<0.05）. Compared with the model group， the expression of IDE increased significantly in the LGZGT-M and LGZGT-H groups （P<0.05）. Compared with the model group， the expression of CTSD increased significantly in the LGZGT-L， LGZGT-M， LGZGT-H， and donepezil hydrochloride groups （P<0.05）. The average fluorescence intensity of CTSB in the model group was significantly lower than that in the normal group （P<0.05）. Compared with the model group， the average fluorescence intensity of CTSD in the LGZGT-L， LGZGT-M， LGZGT-H， and donepezil hydrochloride groups increased significantly （P<0.05）. The intracellular content of Aβ_1-42 in cells in the model group was significantly higher than that in the normal group （P<0.05）. After administration， compared with the model group， the intracellular content of Aβ_1-42 in cells in the LGZGT-L， LGZGT-M， LGZGT-H， and donepezil hydrochloride groups decreased significantly （P<0.05）， and LGZGT-containing serum reduced Aβ_1-42 in a dose-dependent manner （P<0.05）. ConclusionLGZGT has a protective effect on Aβ_1-42-induced AS and can promote the degradation of Aβ. Its mechanism may be related to reducing Aβ toxicity， enhancing cell viability， promoting the expression of IDE， CTSD， and CTSB， and restoring lysosomal function.

Objective:To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks′ gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021.Methods:This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results:Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions:With the increasing number of extremely preterm infants at 22-25 weeks′ gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.

Objective To evaluate the clinical application value of matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS)in analyzing the homology of Acinetobacter baumannii(AB).Methods After excluding repetitive strains from multiple specimens of the same patient or environment,a total of 46 AB strains isolated from patients'sputum and environmental specimens of neurological intensive care unit(ICU)in a tertiary first-class general hospital from May 2020 to February 2021 were collected.Strains were detected by VITEK-MS mass spectrometer.Cluster analysis was performed by SARAMIS Premium software,and verified by multilocus sequence typing(MLST).Results Cluster analysis and comparison of MALDI-TOF MS and MLST found that among the 46 AB strains,39 were the type MS-a of MALDI-TOF MS,of which 22 strains were the clus-ter MT-A of MLST,including ST208(n=3),ST540(n=3),ST195(n=8),ST369(n=5),ST136(n=1),ST436(n=1)and ST1893(n=1);16 strains were MT-B,including type ST381(n=4),type ST469(n=11),and type ST938(n=1);one strain was cluster MT-C(ST1821);one strain of type MS-b was ST381;two strains of type MS-c were ST369;one strain of type MS-d was ST195;two strains of type MS-e were ST540 and ST369,respectively;one strain of type MS-f was STN1.Conclusion As a homology analysis method,MALDI-TOF MS still has certain limitations such as low consistency with MLST results,low resolution and specificity,thus cannot replace MLST technology.

Objective Little is known about the association between whole-blood nicotinamide adenine dinucleotide(NAD+)levels and nabothian cysts.This study aimed to assess the association between NAD+levels and nabothian cysts in healthy Chinese women. Methods Multivariate logistic regression analysis was performed to analyze the association between NAD+levels and nabothian cysts. Results The mean age was 43.0±11.5 years,and the mean level of NAD+was 31.3±5.3 μmol/L.Nabothian cysts occurred in 184(27.7%)participants,with single and multiple cysts in 100(15.0%)and 84(12.6%)participants,respectively.The total nabothian cyst prevalence gradually decreased from 37.4%to 21.6%from Q1 to Q4 of NAD+and the prevalence of single and multiple nabothian cysts also decreased across the NAD+quartiles.As compared with the highest NAD+quartile(≥34.4 μmol/L),the adjusted odds ratios with 95%confidence interval of the NAD+Q1 was 1.89(1.14-3.14)for total nabothian cysts.The risk of total and single nabothian cysts linearly decreased with increasing NAD+levels,while the risk of multiple nabothian cysts decreased more rapidly at NAD+levels of 28.0 to 35.0 μmol/L. Conclusion:Low NAD+levels were associated with an increased risk of total and multiple nabothian cysts.

Objective This study aimed to explore the diagnostic concordance of fractional flow reserve(FFR)and quantitative flow ratio(QFR)and the characteristics affecting this concordance.Methods Patients with non-acute myocardial infarction admitted to the Department of Cardiology,Peking University Third Hospital between January 2019 and December 2021 were enrolled.The patients were divided into four groups:FFR+/QFR+and FFR-/QFR-,FFR+/QFR-and FFR-/QFR+with FFR or QFR≤0.80 as positive and＞0.80 as negative.Using FFR as the gold standard,the diagnostic value of QFR was analyzed,and differences in clinical features and pathological characteristics among the groups were compared.Results A total of 236 patients were included.The mean age was(64.48±9.63)years,and 67.8％were male.All patients had 30％-70％coronary stenosis.The consistency rate of QFR and FFR was 78.0％(n=184),and the Person correlation coefficient was 0.557(P＜0.001).Among FFR+patients,the minimum lumen diameter was larger[(1.56±0.34)mm vs.(1.39±0.31)mm,P=0.019],lesion length was shorter[(21.37±11.73)mm vs.(36.86±18.09)mm,P＜0.001],and coronary angiography-based index of microcirculartory resistance(AMR)was higher[(277.50±28.87)mmHg·s/m vs.(178.02±49.13)mmHg·s/m,P＜0.001]in the disconcordance group.Multivariate regression analysis suggested that AMR[OR 0.93,95％CI 0.88-0.99,P=0.030]and lesion length[OR 1.27,95％CI 1.01-1.60,P=0.045]were independent predictors of disconcordance.In the FFR-group,the lesion length was longer[(33.08±16.05)mm vs.(21.40±13.36)mm,P=0.020],and AMR[(169.66±24.01)mmHg·s/m vs.(265.95±44.78)mmHg·s/m,P＜0.001]and low-density lipoprotein-C[1.57(1.10,1.97)mmol/L vs.2.15(1.79,2.74)mmol/L,P=0.031]were lower in the disconcordance group.No statistically significant variables were identified by multivariate regression.Conclusions QFR had high diagnostic value compared with FFR.In the FFR+group,AMR and lesion length may have affected the diagnostic consistency of QFR and FFR.The study provided more evidence for the clinical application of QFR.

Objective:To investigate the application effect of the comprehensive innovative teaching model with "3D printed model combined with visual surgical simulation" as the core in the clinical teaching of extremity bone defects.Methods:The physicians who participated in the clinical management of patients with extremity bone defects in Department of Orthopedics, Peking University Third Hospital, from March 2019 to December 2021 were selected as subjects and were divided into standardized training group with 52 physicians and refresher physician group with 58 physicians. Teaching and training was performed for the special disease of extremity bone defects, including basic knowledge teaching, dressing change for infected wounds, multidisciplinary discussion, digital surgical simulation, and practical surgical operation. The assessment indices for teaching quality included the assessment of theoretical knowledge and clinical skills, the objective evaluation of the clinical ability of patient management, and an investigation of the degree of satisfaction. SPSS 22.0 was used for the t-test and the chi-square test. Results:After training, both groups had significant increases in the assessment scores of theoretical knowledge [(32.4±6.7）and (42.2±3.8)] and clinical practice skills [(19.6±2.0), (20.8±2.2), (20.5±2.5), (21.5±2.3)]( P<0.05). After training, the standardized training group had significant increases in the scores of six objective evaluation indicators [(8.3±0.8) vs. (6.9±1.1), (7.4±0.7) vs. (6.3±1.5), (7.2±1.3) vs. (5.0±1.4), (7.9±1.2) vs. (4.0±1.5), (8.4±0.8) vs. (6.4±1.6), (40.3±2.6) vs. (28.6±2.4)]( P<0.01), while the refresher physician group had significant improvements in four aspects, i.e., the understanding of extremity bone defects [(8.1±0.9) vs. (7.2±1.1)], the self-confidence in facing complex extremity bone defects [(8.1±1.2) vs. (6.6±0.9)], spatial thinking ability in repair surgery for bone defects [(8.6±0.8) vs. (7.3±0.9)], and overall clinical performance in actual management of patients with bone defects [(41.4±2.3) vs. (37.3±1.8)] ( P<0.01). The satisfaction score for this comprehensive innovative teaching model was (95.3±3.2) points in the standardized training group and (94.8±2.8) points in the refresher physician group. Conclusions:The comprehensive innovative teaching model with "3D printed model combined with visual surgical simulation" as the core can significantly improve the basic knowledge and clinical skills of physicians in a short period of time and meet the needs for learning surgical techniques and advanced diagnosis and treatment concepts among refresher physicians.

Objective To compare the efficacy of anterior-posterior and posterior-anterior screw fixation for posterior malleolar fractures surgery.Methods A retrospective analysis of 376 cases of posterior malleolar fractures treated with lag screws from January 2011 to October 2022 with more than 12 months of follow-up period was conducted.The patients were divided into two subgroups based on the thickness of the fracture fragment,with 167 cases in the small fracture subgroup having a fracture fragment thickness＜17 mm(screw thread length)and 209 cases in the large fracture subgroup having a fracture fragment thickness ≥ 17 mm.Each subgroup was further divided into anterior-posterior and posterior-anterior groups based on the direction of screw fixation in the posterior malleolar fracture surgery.In the small fracture subgroups,there were 74 cases in the anterior-posterior group and 93 cases in the posterior-anterior group.In the large fracture subgroup,there were 88 cases in the anterior-posterior group and 121 cases in the posterior-anterior group.The American Orthopaedic Foot and Ankle Society(AOFAS)ankle-hindfoot score was measured at the last follow-up.The displacement of the fracture fragment in the direction of the fracture line(Dn)and perpendicular to the fracture line(Dt)were measured on the first day after surgery and at the last follow-up,and the displacement of the fracture fragment was calculated,which was the difference between Dn+Dt at the last follow-up and Dn+Dt on the first day after surgery.Results On the first day after surgery,X-ray showed no significant difference in Dn and Dt between the anterior-posterior and posterior-anterior groups in both of the small and large fracture subgroups(P＞0.05).The entire group was followed up for 12-85 months,with an average of 19.3 months.In the small fracture subgroup,the displacement of the fracture fragment in the posterior-anterior group[(0.11±0.19)mm]was superior to that in the anterior-posterior group[(0.19±0.21)mm;P=0.011],and the AOFAS score was also superior to that in the anterior-posterior group[(80.2±8.4)points vs.(76.2±8.6)points,P=0.003].In the large fracture subgroup,there was no significant difference in fracture displacement between the posterior-anterior group[(0.11±0.18)mm]and the anterior-posterior group[(0.12±0.19)mm;P=0.630],and there was also no significant difference in AOFAS scores[(84.1±7.8)points vs.(82.8±7.6)points,P=0.246].Conclusions There is no significant difference in the reduction effect between anterior-posterior and posterior-anterior lag screw internal fixation for posterior malleolar fractures in trimalleolar fractures.For patients with fracture thickness＜17 mm,posterior-anterior fixation is superior to anterior-posterior fixation;for patients with fracture thickness ≥17 mm,there is no significant difference in the efficacy between anterior-posterior and posterior-anterior fixation.

A 5-year-old girl was admitted due to one episode of melena and one episode of hematemesis.Upon admission,gastroscopy revealed esophageal and gastric varices.Abdominal CT scan,MRI,and color Doppler ultrasound suggested cirrhosis,intrahepatic bile duct dilation,and bilateral kidney enlargement.Genetic testing identified compound heterozygous mutations in the PKHD1 gene:c.2264C>T(p.Pro755Leu)and c.1886T>C(p.Val629Ala).The c.2264C>T(p.Pro755Leu)mutation is a known pathogenic variant with previous reports,while c.1886T>C(p.Val629Ala)is a novel mutation predicted to have pathogenic potential according to Mutation Taster and PolyPhen2.The child was diagnosed with autosomal recessive polycystic kidney disease.In children presenting with gastrointestinal bleeding without obvious causes,particularly those with liver or kidney disease,consideration should be given to the possibility of autosomal recessive polycystic kidney disease,and genetic testing should be conducted for definitive diagnosis when necessary.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Modern Chinese medicine studies have confirmed that the interaction between traditional Chinese medicine(TCM)and intestinal flora is the key to the treatment of diseases with tradi-tional Chinese medicine.This interplay includes such activities as:traditional Chinese medicine can be metabolized by intestinal flora into effective components with different biological activities from its precursors;TCM chemicals improve the composition of gut microbiota,consequently ameliorating its dysfunction as well as associated pathological conditions;and gut microbiota mediate the interactions between the multiple chemicals in TCM.There-fore,it becomes an important way to understand the modern sci-entific connotation of traditional Chinese medicine theory to study the pharmacological mechanism of the efficacy of traditional Chi-nese medicine by targeting Gut microbiota.