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.

Breast cancer remains a leading cause of mortality in women worldwide.Triple-negative breast cancer(TNBC)is a particularly aggressive subtype characterized by rapid progression,poor prognosis,and lack of clear therapeutic targets.In the clinic,delineation of tumor heterogeneity and development of effective drugs continue to pose considerable challenges.Within the scope of our study,high hetero-geneity inherent to breast cancer was uncovered based on the landscape constructed from both tumor and healthy breast tissue samples.Notably,TNBC exhibited significant specificity regarding cell prolif-eration,differentiation,and disease progression.Significant associations between tumor grade,prog-nosis,and TNBC oncogenes were established via pseudotime trajectory analysis.Consequently,we further performed comprehensive characterization of the TNBC microenvironment.A crucial epithelial subcluster,E8,was identified as highly malignant and strongly associated with tumor cell proliferation in TNBC.Additionally,epithelial-mesenchymal transition(EMT)-associated fibroblast and M2 macrophage subclusters exerted an influence on E8 through cellular interactions,contributing to tumor growth.Characteristic genes in these three cluster cells could therefore serve as potential therapeutic targets for TNBC.The collective findings provided valuable insights that assisted in the screening of a series of therapeutic drugs,such as pelitinib.We further confirmed the anti-cancer effect of pelitinib in an orthotopic 4T1 tumor-bearing mouse model.Overall,our study sheds light on the unique characteristics of TNBC at single-cell resolution and the crucial cell types associated with tumor cell proliferation that may serve as potent tools in the development of effective anti-cancer drugs.

BACKGROUND:Scaffold materials serve as platforms that provide space and structure,playing a crucial role in the regeneration of cartilage tissue.Scholars from around the world are exploring different approaches to fabricate more ideal scaffold materials. OBJECTIVE:To review the design principles and preparation methods of cartilage scaffolds,and to further explore the advantages and limitations of various preparation methods. METHODS:Literature searches were conducted on the databases of CNKI,WanFang Data,PubMed,and FMRS from 1998 to 2023.The search terms were"cartilage repair,cartilage tissue engineering,cartilage scaffold materials,preparation"in Chinese and English.A total of 57 articles were ultimately reviewed. RESULTS AND CONCLUSION:(1)The articular cartilage has a unique structure and limited self-repair capacity after injury.Even if self-repair occurs,the newly formed cartilage is typically fibrocartilage,which is far inferior to normal articular cartilage in terms of structure and mechanical properties.It is difficult to maintain normal function and often leads to degenerative changes.Currently,the design and fabrication of scaffold materials for cartilage repair need to consider the following aspects:biocompatibility and biodegradability,suitable pore structure and porosity,appropriate mechanical properties,and bioactivity.(2)Research on the preparation of cartilage scaffolds has made significant progress,continuously introducing new preparation methods and optimization strategies.These methods have their advantages and disadvantages,providing more possibilities for customized preparation and functional design of cartilage scaffolds according to specific requirements.

ObjectiveTo analyze the epidemiological characteristics and trends of influenza‑like illness (ILI) in Jiading District from 2013 to 2023, to explore the prevalence patterns, so as to provide a scientific basis for a better prevention and control of influenza. MethodsData of ILI cases, pathogenetic surveillance results and pathogen detection data from influenza surveillance network laboratories in Jiading District from 2013 to 2023 were collected for statistical analysis. ResultsFrom 2013 to 2023, the overall proportion of medical visits for ILI cases in Jiading District was 2.70%. ILI cases were mainly distributed in the age group of ≥25 years, with a seasonal prevalence characteristic, mainly concentrated in the winter and spring, with an occasional small peak in the summer. A total of 12 423 specimens were tested for pathogenetic surveillance and monitoring, 3 651 of which were tested positive for nucleic acid detection, with a positive rate of 29.39%. The dominant strain was influenza A (H3N2) virus, accounting for 55.05%. There were statistical significant differences in the positive detection rates by different streets and townships(χ²=24.73，P<0.05）. The influenza network laboratory isolated and cultured influenza viruses from 3 154 nucleic acid‑positive samples sent by national influenza sentinel surveillance hospitals using 2 methodsMadin‑Darby canine kidney (MDCK) cells and specific pathogen free (SPF) chicken embryos, respectively, with a total isolation rate of 39.51%, and the isolation rate of MDCK cells (35.45%) was higher than that of SPF chicken embryos (5.36%). From 2013 to 2023, a total of 14 ILI outbreaks were reported in Jiading District, mainly in primary schools, kindergartens and secondary schools. ConclusionInfluenza in Jiading District, Shanghai, is mainly prevalent in the winter and spring, with different subtypes of influenza viruses alternating or co⁃circulating in different monitoring year. It is recommended to promote influenza vaccination, further improve influenza prevention and control measures, enhance health promotion to the age group of ≥25 years in winter and spring, and strengthen surveillance and monitoring on ILI outbreaks in collective units such as primary schools and childcare institutions, so as to reduce the disease burden.

convalescents, and to screen for broad-spectrum neutralizing antibodies against the SARS-CoV-2 RBD. Methods Using biotinylated RBD as a molecular probe, flow cytometry was employed to perform single-cell sorting of B cells from peripheral blood mononuclear cells (PBMCs) of convalescents. The obtained B cells were lysed and subjected to reverse transcription, followed by nested PCR amplification of the heavy and light chains of antibodies was conducted using random primers. The amplified products were cloned into corresponding expression vectors, and the respective matched heavy-light chain plasmids were co-transfected into 293F cells for expression. Monoclonal antibodies were then purified using Protein A column chromatography. Neutralization experiments were conducted with the wild-type (WT) pseudovirus, and antibodies with IC50<0.1 μg/mL were selected for further testing of neutralizing breadth and potency against the wild-type (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and currently prevalent pseudovirus strains (XBB, BA.5, BF.7). Results A total of 21 RBD-specific monoclonal B cells were obtained from two recovered patients, resulting in the isolation of 13 pairs of antibody light/heavy chains. Nine antibodies were successfully expressed, with P1-A1, P1-B6, and P1-B9 exhibiting IC50 values below 0.1 μg/mL against the pseudovirus of the wild-type strain (WT). Specifically, P1-B6 effectively neutralized the wild-type strain (WT), Beta variant (B.1.351), and Delta variant (B.1.617.2), with IC50 values reaching 0.01 μg/mL. P1-B9 demonstrated effective neutralization against the wild-type strain (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and Gamma variant (P.1) pseudoviruses, with IC50 values of 0.42 μg/mL, 0.63 μg/mL, 0.28 μg/mL, and 2.50 μg/mL, respectively. Additionally, P1-B6 exhibited good neutralization against BA.5 and BF.7 pseudoviruses, with IC50 values of 0.06 μg/mL and 0.09 μg/mL, respectively. Conclusions Infection with the SARS-CoV-2 WT strain can induce the generation of neutralizing antibodies with broad-spectrum activity. Generating these broadly neutralizing antibodies does not require an excessively high somatic hypermutation. The obtained antibodies can be used as candidates for SARS-CoV-2 diagnosis and prevention.

Objective:To investigate the impact of switching to low iodine drinking water in areas with high water iodine levels on the iodine nutritional status and thyroid function of pregnant women.Methods:A cross-sectional survey was conducted in Gaoqing County, Zibo City, Shandong Province. Pregnant women who underwent prenatal examinations at the Obstetrics Clinic of Gaoqing County People's Hospital from 2019 to 2021 were selected as the survey subjects. With reference to the Criteria for the Classification of Water Source High Iodine Areas and High Iodine Disease Areas (GB/T 19380-2016), pregnant women with drinking water iodine > 100 μg/L were considered as the high water iodine group and ≤100 μg/L was the non-high water iodine group. Basic information, one random urine sample, fasting blood sample, 24-hour urine sample and drinking water sample of pregnant women were collected, and thyroid ultrasound examination was performed on pregnant women. Urinary iodine (UI) concentration (UIC) and drinking water iodine concentration (WIC) were measured by inductively coupled plasma mass spectrometry, and 24-hour urinary iodine excretion (UIE) and daily iodine intake (TII) of pregnant women were calculated. Serum thyroid hormone (TSH), free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid peroxidase antibody (TPOAb) and anti-thyroid autoantibodies (TgAb) were determined by automatic chemiluminescence immunoassay. Creatinine (CR) was determined using deproteinized endpoint microplate method and UI/CR was calculate. Results:A total of 797 pregnant women were included, and the UIC was 150.2 (88.1, 281.3) μg/L, the iodine nutrition was generally at an appropriate level. Among them, 584 pregnant women in the non-high water iodine group had a UIC of 120.9 (74.9, 191.5) μg/L, which was at the iodine deficiency level; 213 pregnant women in the high water iodine group had a UIC of 321.1 (201.9, 569.1) μg/L, which was at the iodine super-appropriate level; the differences in WIC, UIC, UIE, TII, and UI/CR between the two groups were statistically significant ( Z = 21.63, 13.34, 15.14, 15.14, 11.81, P < 0.001). After stratification by different gestational periods, the differences were statistically significant when comparing WIC and TSH in pregnant women in the non-high water iodine group and UI/CR in pregnant women in the high water iodine group by gestational period ( H = 59.13, 7.30, 13.60, P < 0.05). A total of 744 pregnant women were tested for thyroid function, and 128 cases of TSH > 2.5 mU/L, 15 cases of hypothyroxemia, and 19 cases of subclinical hypothyroidism were detected, with detection rates of 17.2%, 2.0%, and 2.6%, respectively. The differences were statistically significant when comparing TSH and TPOAb levels and the proportion of pregnant women with TSH > 2.5 mU/L in the high water iodine and non-high water iodine groups ( Z = 3.04, - 2.17, χ 2 = 6.94, P = 0.002, 0.030, 0.008). The thyroid glands of pregnant women were examined in 720 cases, and 30 cases of goiter and 150 cases of thyroid nodules were detected, with detection rates of 4.2% and 20.8%, respectively. The median thyroid volume was 8.92 ml in the high water iodine group and 8.60 ml in the non-high water iodine group, which were both within the normal range, with no statistically significant difference between the groups ( Z = - 0.75, P = 0.455). Conclusions:After changing to low iodine water, the overall iodine nutrition of pregnant women in Gaoqing County is now at an appropriate level, and the reduction of water iodine effectively reduces the risk of TSH abnormalities in local pregnant women. However, pregnant women in the non-high water iodine group are iodine deficiency, and pregnant women in the high water iodine group are at iodine super-appropriate, and the iodine nutrition level of pregnant women in this area is highly variable, which causes the "illusion" that the overall iodine level of local pregnant women is suitable.

Mitophagy is a process whereby cells selectively remove mitochondria through the mechanism of autophagy, which plays an important role in maintaining cellular homeostasis. In order to explore the effect of mitophagy genes on the antioxidant activities of Saccharomyces cerevisiae, mutants with deletion or overexpression of mitophagy genes ATG8, ATG11 and ATG32 were constructed respectively. The results indicated that overexpression of ATG8 and ATG11 genes significantly reduced the intracellular reactive oxygen species (ROS) content upon H₂O₂ stress for 6 h, which were 61.23% and 46.35% of the initial state, respectively. Notable, overexpression of ATG8 and ATG11 genes significantly increased the mitochondrial membrane potential (MMP) and ATP content, which were helpful to improve the antioxidant activities of the strains. On the other hand, deletion of ATG8, ATG11 and ATG32 caused mitochondrial damage and significantly decreased cell vitality, and caused the imbalance of intracellular ROS. The intracellular ROS content significantly increased to 174.27%, 128.68%, 200.92% of the initial state, respectively, upon H₂O₂ stress for 6 h. The results showed that ATG8, ATG11 and ATG32 might be potential targets for regulating the antioxidant properties of yeast, providing a new clue for further research.
Mitophagy/genetics* ; Saccharomyces cerevisiae/genetics* ; Antioxidants ; Hydrogen Peroxide/pharmacology* ; Reactive Oxygen Species

Objective To explore the effect of mucle force on contact force, peak pressure and contact area of foot joint in in vitro biomechanical experiment of foot and ankle, so as to provide references for choosing appropriate loading modes. Methods In neutral position of the ankle joint, fresh calf and foot specimens were simulated with or without mucle force loading. The contact force, peak pressure and contact area of the 1st metatarsophalangeal joint, the 2nd metatarsophalangeal joint, the 1st tarsometatarsal joint, the 2nd tarsometatarsal joint, the medial cuneonavicular joint, the intermediate cuneonavicular joint, the talonavicular joint, the calcicocuboid joint, the subtalar joint ( posterior articular surface) and the tibiotalar joint of normal foot under loading were measured, the results are compared and analyzed. Results Under muscle force loading, the contact force of the 1st metatarsophalangeal joint, the 2nd metatarsophalangeal joint, the 1st tarsometatarsal joint,the 2nd tarsometatarsal joint, the medial cuneonavicular joint, the intermediate cuneonavicular joint, the talonavicular joint and the tibiotalar joint were significantly greater than those without muscle force loading (P<0. 05), and the change percentages were 719. 28% , 311. 37% , 128. 67% , 50. 82% , 54. 89% , 57. 63% ,79. 98% and 50. 34% , respectively. The peak pressures of the 1st metatarsophalangeal joint , the 1st tarsometatarsal joint and the talonavicular joint under muscle force loading were significantly higher than those without muscle force loading ( P < 0. 05), and the change percentages were 176. 14% , 62. 91% and 40. 07% ,respectively. The contact area of the 1st metatarsophalangeal joint, the 1st tarsometatarsal joint, the intermediate cuneonavicular joint and the subtalar joint ( posterior articular surface) under muscle force loading increased significantly (P<0. 05), and the change percentages were 132. 20% , 55. 41% , 30. 97% and 26. 87% , respectively. Conclusions In biomechanical experiment of foot and ankle specimens, muscle force loading has a significant effect on contact force, peak pressure and contact area of each foot joint, especially the forefoot.Therefore, it is necessary to consider the effect of muscle force loading on stress of foot and ankle in the study ofrelated in vitro specimens

Objective:Healthy life expectancy (HLE), which combines life expectancy with health, is an essential comprehensive measure of life length and quality. This article aimed to systematically review the methods for defining and measuring HLE and describe application studies published, providing a reference for decision makers to select and develop methods suitable for China's conditions to measure HLE.Methods:Seven Chinese and English literature databases were searched up to May 7, 2022, and several related reviews and bibliography were manually retrieved. Systematic reviews and empirical research were included concerning HLE indicators and measurement of HLE. Information including the study area, type of the study, study population, HLE index, measurement method, data sources, and results from application studies published in the last five years were extracted. The evolution of the definition of HLE, the scope of different indicators, the measurement scale of health, and measurement methods, were all collected. Results of the empirical research related to measurement methods of indicators were summarized. The study followed the scoping review framework and was written according to the PRISMA-ScR statement.Results:A total of 84 articles were included, including 13 reviews, 17 original studies related to HLE index definition, ten original studies related to index measurement, and 44 empirical studies conducted in the past five years. There were as many as 20 indicators related to HLE, and each scale had its emphasis. A total of ten methods measuring HLE were identified, which vary in the definition of health, whether using weight, and the data type. The most commonly used indicators in the past five years were disability-free life expectancy and HLE. For the method of HLE calculation, Sullivan's method was mainly used for cross-sectional data, and the multistate life table was mainly used for longitudinal data.Conclusions:There are various definitions and measurement methods of HLE, but none are suitable for all scenarios. To summarize the HLE concept, health evaluation techniques, measurement methods, and application studies published worldwide can provide a reference for the localization of HLE measurement in China.

【Objective】 To conduct a retrospective study of the population characteristics, efficacy and influencing factors of rheumatoid arthritis (RA) patients who received iguratimod (IGU) treatment for at least 6 months from July 2015 to October 2020 and had more than 3 follow-up records. 【Methods】 In this study, 105 patients with RA were enrolled, and all the patients received IGU treatment for at least 6 months and were followed up three times. We observed their clinical manifestations before and after treatment, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease activity index (DAS28), rheumatoid factor (RF), anticyclic citrullinated peptide (ACPA), immunoglobulins (IgG, IgA, and IgM), lymphocyte subsets, and observed and recorded adverse reactions. 【Results】 The course of disease and the positive rate of ACPA were significantly lower in IGU group than in the group of IGU combined with (MTX) treatment (P<0.05). The DAS28-ESR of the patients in IGU group was significantly lower than that in the IGU+MTX treatment group and IGU+leflunomide (LEF) treatment group (P<0.05). After 6 months of continuous treatment, visual analogue scale/score (VAS), CRP and DAS28 (ESR/CRP) in IGU group were significantly reduced. As the treatment time was extended to one year, the above indicators further improved, and the number of joint swelling (SW) and the number of joint tenderness (TEN) also significantly improved. After one year’s continuous treatment, the incidence of adverse reactions in IGU group was 32.3%(10/31). 【Conclusion】 For RA patients with early onset, short-course, and antibody-negative, IGU is an effective therapeutic drug and a treatment option for RA patients with interstitial lung disease. IGU is well tolerated and is also an effective and a safe combination therapy option.