ObjectiveTo establish an adjusted Serfling regression model to estimate the excess cases and the excess epidemic period of hand-foot-mouth disease (HFMD) in Beijing from 2011 to 2019, so as to provide data support and decision-making basis for HFMD prevention and control. MethodsThe weekly number of HFMD cases in Beijing from 2011 to 2019 was utilized for adjusted the Serfling regression model. Then the adjusted model was used to fit the baseline and epidemic threshold of HFMD in Beijing from 2011 to 2019, calculating the excess cases and determining the excess epidemic period. ResultsA total of 279 306 cases of HFMD were reported in Beijing from 2011 to 2019, with the climax of the disease occurring in summer and autumn. After adjusting the fitting R² of the Serfling regression model to 0.773, a total of 10 excess epidemic periods totaling 92 weeks were estimated, mainly occurring in summer. The highest number of excess cases during an excess epidemic period was found in 2014 (1 272 cases, 95%CI: 990‒1 554), accounting for 65.04% of the actual cases (95%CI: 50.62%‒79.46%). ConclusionThe adjusted Serfling regression model fits well and can be utilized for early warning of HFMD and estimating the disease burden caused by HFMD.

BACKGROUND:Tissue engineering has brought new hope to the clinical challenge of liver failure,and the preparation of plant-derived decellularized fiber scaffolds holds significant importance in liver tissue engineering. OBJECTIVE:To prepare apple tissue decellularized scaffold material by using fresh apple slices and a solution of sodium dodecyl sulfate,and assess its biocompatibility. METHODS:Fresh apples were subjected to decellularization using phosphate buffer saline and sodium dodecyl sulfate solution,separately.Afterwards,the decellularized apple tissues and apple decellularized scaffold materials were decontaminated with phosphate buffer saline.Subsequently,scanning electron microscopy was used to assess the effectiveness of decellularization of the apple materials.Adipose-derived mesenchymal stem cells were extracted from the inguinal fat BALB/C of mice,and their expression of stem cell-related markers(CD45,CD34,CD73,CD90,and CD105)was identified through flow cytometry.The cells were then divided into a scaffold-free control group and a scaffold group.Equal amounts of adipose-derived mesenchymal stem cells were seeded onto both groups.The biocompatibility of the decellularized scaffold with adipose-derived mesenchymal stem cells was evaluated using CCK-8 assay,hematoxylin-eosin staining,and phalloidine staining.Cell adhesion and growth on the scaffold were observed under light microscopy and scanning electron microscopy.Furthermore,the scaffold was subdivided into the non-induced group and the hepatogenic-induced group.Adipose-derived mesenchymal stem cells were cultured on the decellularized apple scaffold,and they were cultured for 14 days in regular culture medium or hepatogenic induction medium for comparison.Immunofluorescent staining using liver cell markers,including albumin,cytokeratin 18,and CYP1A1,was performed.Enzyme-linked immunosorbent assay was used to detect the secretion of alpha fetoprotein and albumin.Additionally,scanning electron microscopy was employed to observe the morphology of the induced cells on the scaffold,verifying the expression of liver cell-related genes on the decellularized scaffold material.Finally,the cobalt-60 irradiated and sterilized decellularized apple scaffolds were transplanted onto the surface of mouse liver and the degradation of the scaffold was observed by gross observation and hematoxylin-eosin staining after 28 days. RESULTS AND CONCLUSION:(1)The scanning electron microscopy results revealed that the decellularized apple scaffold material retained a porous structure of approximately 100 μm in size,with no residual cells observed.(2)Through flow cytometry analysis,the cultured cells were identified as adipose-derived mesenchymal stem cells.(3)CCK-8 assay results demonstrated that the prepared decellularized apple tissue scaffold material exhibited no cytotoxicity.Hematoxylin-eosin staining and phalloidine staining showed that adipose-derived mesenchymal stem cells were capable of adhering and proliferating on the decellularized apple tissue scaffold.(4)The results obtained from immunofluorescence staining and enzyme-linked immunosorbent assay revealed that adipose-derived mesenchymal stem cells cultured on the decellularized apple scaffolds exhibited elevated expression of liver-specific proteins,including albumin,alpha-fetoprotein,cytokeratin 18,and CYP1A1.These results suggested that they were induced differentiation into hepatocyte-like cells possessing functional characteristics of liver cells.(5)The decellularized apple scaffold implanted at 7 days has integrated with the liver,with partial degradation of the scaffold observed.By 28 days,the decellularized apple scaffold has completely degraded and has been replaced by newly-formed tissue.(6)The results indicate that the decellularized scaffold material derived from apple tissue demonstrates favorable biocompatibility,promoting the proliferation,adhesion,and hepatic differentiation of adipose-derived mesenchymal stem cells.

Objective:To investigate the phylogenetic and antigenic characteristics of hemagglutinin (HA) gene of influenza B/Victoria lineage (BV) viruses in Beijing during the 2021-2022 influenza surveillance season, and to analyze whether the circulating BV viruses match the vaccine strain.Methods:Pharyngeal swab specimens from influenza like-illness (ILI) cases in the 2021-2022 influenza surveillance season were collected from surveillance network labs in Beijing and cultured in MDCK cells and chicken embryo to isolate BV viruses. Nucleic acids of the viruses were extracted, and the HA gene was amplified and sequenced. The nucleotide and amino acid sequence identity of the HA gene was analyzed using MEGA5.0 software. A phylogenetic tree of HA gene was constructed using the maximum likelihood method. The N-glycosylation sites in HA were predicted online. Three-dimensional structure of HA was constructed using SWISS-MODEL homologous modeling. Hemagglutination inhibition (HI) test was performed to analyze the antigenicity of BV viruses.Results:A total of 402 BV viruses were collected and 58 strains with full-length HA gene sequences were chosen for further analysis. Compared with the HA gene of this year′s vaccine strain (B/Washington/02/2019), there were 27 amino acid mutations, 11 of which were located in four different antigenic determinants. The phylogenetic analysis revealed that three subgroups of 1A.3, 1A.3a1, and 1A.3a2 co-circulated in Beijing with 54 strains (54/58, 93.10%) clustered to the Clade 1A.3a2, two strains (2/58, 3.45%) clustered to the Clade 1A.3a1, and two strains (2/58, 3.45%) in the same subgroup (Clade 1A.3) as the vaccine component BV strain in 2021-2022. Compared with the vaccine strain (B/Washington/02/2019), two BV strains had an additional N-glycosylation site at residue 197, while the other 56 strains showed no change in N-glycosylation sites. Antigenic analysis showed that 35 BV strains (35/58, 60.34%) were antigenically similar to the vaccine strain and 23 strains (23/58, 39.66%) were low-response strains.Conclusions:Three subgroups of BV viruses co-circulated in Beijing during the 2021-2022 influenza surveillance season. The predominant subgroup was Clade 1A.3a2 (93.10%), showing a certain genetic distance with the vaccine strain (B/Washington/02/2019). Nearly 40% (39.66%) of the viruses were low-response strains. This study indicated that continuous monitoring of the variations of influenza epidemic strains and timely providing laboratory basis for screening vaccine component strains were the basic technical guarantee for coping with influenza pandemic.

Articular cartilage (AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis (OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intra-articular drug delivery systems (DDSs) in the future.

Objective Due to the increasing number but unknown quality of the existing systematic reviews meta-analyses(SRs/MAs)of acupuncture and moxibustion in the treatment of cancer-related fatigue(CRF),this overview aimed to systematically evaluate and synthesize these SRs/MAs.Methods SRs/MAs were searched via 8 databases from inception to February 22,2022.AMSTAR 2,PRISMA and GRADE evaluation tools were used to evaluate the quality of reports,methodologies and evidence included in MAs/SRs.All analyses were performed with radar plots.Results 16 SRs/MAs were included.The main outcome index was the degree of fatigue.The results of 12 articles showed that acupuncture could effectively alleviate CRF.According to AMSTAR-2,4 SRs/MAs were considered being of high quality,10 medium quality and 2 low quality.There are 12 articles with PRISMA score of 16-24 and 4 articles with PRISMA score of 15-20.5,which mainly have defects in protocol registration and inter study bias.Amstar 2 evaluation includes 4 high-quality studies,studies.Grade rating shows that the evidence quality of acupuncture treatment of CRF is mostly medium,and the main factor of degradation is inaccuracy.Conclusions At present,the SRS/MAS report of acupuncture and moxibustion in the treatment of CRF is complete,and the quality of methodology and evidence is medium.It is suggested that SRS/MAS improve the program registration and funding source description in the future to enhance the assessment of the risk of inter study bias.

Objective To investigate the protective effect of adult human liver-derived stem cell exosomes (HLSC-exo) intravenously injected at different time points against acute liver injury induced by concanavalin A (ConA) in mice. Methods HLSC-exo was extracted by differential centrifugation. Western blot was used to measure the expression of the marker proteins CD9 and CD63, and nanoparticle tracking analysis was used to investigate particle size distribution. A total of 56 male C57BL/6 mice were randomly divided into blank control group, ConA model group, and HLSC-exo treatment group. The ConA model group and the HLSC-exo treatment group were further divided into 3-, 6-, and 12-hour subgroups according to the interval between phosphate buffer or HLSC-exo injection and ConA injection. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) were measured, and the gross morphology and histopathology of the liver were compared between groups. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results HLSC-exo was a membranous vesicle with a diameter of 90-110 nm, with a clear saucer-like structure under an electron microscope and marked expression of its specific marker proteins CD9 and CD63. In the blank control group, the levels of ALT and AST were 31.81±6.74 U/L and 69.75±8.30 U/L, respectively. Compared with the blank control group, the 3-, 6-, and 12-hour ConA model groups had significant increases in the levels of ALT and AST (all P < 0.001); compared with the 3-and 6-hour ConA model groups, the 3-and 6-hour HLSC-exo treatment groups had significant reductions in the levels of ALT and AST (225.58±115.59 U/L vs 1989.32±347.67 U/L, 1174.71±203.30 U/L vs 2208.33±349.96 U/L, 303.53±126.68 U/L vs 2534.27±644.72 U/L, 1340.70±262.56 U/L vs 2437.13±288.13 U/L, all P < 0.001); compared with the 6-hour HLSC-exo treatment group, the 3-hour HLSC-exo treatment group had significantly greater reductions ( P < 0.001). In the blank group, the levels of IL-10 and TNF-α were 313.51±10.97 pg/ml and 476.05±7.31 pg/ml, respectively. Compared with the blank control group, the 3-, 6-, and 12-hour ConA model groups had a significant reduction in the level of IL-10 (all P < 0.001); compared with the 3-and 6-hour ConA model groups, the 3-and 6-hour HLSC-exo treatment groups had a significant increase in the level of IL-10(331.61±10.46 pg/ml vs 266.20±8.15 pg/ml, 288.13±10.74 pg/ml vs 264.41±9.12 pg/ml, both P < 0.001); compared with the 6-hour HLSC-exo treatment group, the 3-hour HLSC-exo treatment group had a significantly greater increase ( P < 0.001). Compared with the blank control group, the 3-, 6-, and 12-hour ConA model groups had a significant increase in the level of TNF-α (all P < 0.001); compared with the 3-and 6-hour ConA model groups, the 3-and 6-hour HLSC-exo treatment groups had a significant reduction in the level of TNF-α (478.26±12.99 pg/ml vs 551.31±17.70 pg/ml, 515.58±7.18 pg/ml vs 556.21±11.15 pg/ml, both P < 0.001); compared with the 6-hour HLSC-exo treatment group, the 3-hour HLSC-exo treatment group had a significantly greater reduction ( P < 0.001). Compared with the 3-and 6-hour ConA model groups in terms of the gross morphology and histopathology of the liver, the 3-and 6-hour HLSC-exo treatment groups had a significant reduction in the degree of hepatocyte necrosis, and the 3-hour HLSC-exo treatment group had a basically complete lobular structure, with sporadic spotty necrosis; the 12-hour HLSC-exo treatment group had no significant improvement in hepatocyte necrosis compared with the 12-hour ConA model group. Conclusion Intravenous injection of adult HLSC-exo can alleviate acute liver injury induced by ConA in mice, and injection at 3 hours in advance has the most significant protective effect. Regulation of cytokines is one of the important mechanisms for HLSC-exo to alleviate liver injury.

Objective:To clarify the M protein ( emm gene) types and drug susceptibility characteristic variations of Group A Streptococcus (GAS) in children in Beijing. Methods:The GAS strains isolated from throat swab samples of children diagnosed with scarlet fever and pharyngeal infection in scarlet fever etiology surveillance sentinel hospitals in 16 districts of Beijing in 2018, 2019 and 2021 were analyzed retrospectively.PCR amplification and sequencing were used for emm genotyping, and the minimum inhibitory concentrations (MIC) of 10 antibiotics were determined by the broth microdilution method.The data were analyzed using χ2 test and Fisher′ s exact method between groups. Results:A total of 557 GAS strains were collected, and 11 emm genotypes ( emm1, emm3, emm4, emm6, emm11, emm12, emm22, emm75, emm89, emm128, and emm212) were detected.Of 557 strains, 238 trains were of emm1 type (42.73%), 271 strains were of emm12 type (48.65%) and 48 strains were of other emm types (8.62%). The detection rates of emm1, emm12 and other emm type genes in 2018, 2019, and 2021 were [37.50% (105/280 strains), 57.14% (160/280 strains), 5.36% (15/280 strains)], [49.05% (129/263 strains), 39.54% (104/263 strains), 11.41% (30/263 strains)], and [28.57% (4/14 strains), 50.00% (7/14 strains), 21.43% (3/14 strains)], respectively.In children infected with emm12 in 2018 and 2019, there were more children under 6 years old than children over 6 years old (62.50% vs.46.88%, 46.36% vs.30.36%) (χ 2=7.182, 6.973; all P<0.05). Drug susceptibility testing results suggested that 225 randomly selected GAS strains were all 100.00% sensitive to 7 antibiotics including Penicillin, Levofloxacin, Meropenem, Linezolid, Cefotaxime, Cefepime and Vancomycin.The rates of resistance to Erythromycin, Tetracycline and Clindamycin were [88.57% (93/105 strains), 87.62% (92/105 strains), 86.67% (91/105 strains)], and [94.34% (100/106 strains), 94.34% (100/106 strains), 87.74% (93/106 strains)] in 2018 and 2019, respectively.The test strains were 100.00% (14/14 strains) resistant to the above 3 antibiotics in 2021.MIC 50 and MIC 90 values of Penicillin in 2018, 2019, and 2021 were (0.03 mg/L, 0.03 mg/L), (0.03 mg/L, 0.06 mg/L), and (0.06 mg/L, 0.06 mg/L), respectively.Among 225 GAS strains, 207 strains had drug resistance and were resistant to more than one drug.Specifically, 94.69% (196/207 strains) were resistant to Erythromycin, Tetracycline and Clindamycin.About 4.35% (9/207 strains) were resistant to both Erythromycin and Clindamycin.A total of 0.97% (2/207 strains) were resistant to Erythromycin and Tetracycline. Conclusions:The emm genotypes of GAS in children in Beijing are diverse in 2018, 2019 and 2021.The dominant genotypes are emm12 and emm1, and emm12 is the main epidemiological type.GAS strains maintain highly resistant to Erythromycin, Clindamycin and Tetracycline, and sensitive to Penicillin and other antibiotics.However, MIC 50 and MIC 90 of Penicillin shows an ascending trend.

Objective:To observe the etiological distribution, clinical presentations and imaging features of pulmonary mycosis that is diagnosed by pathology.Methods:The etiological distribution, clinical presentations and imaging features of patients with pulmonary mycosis, who were collected in the Affiliated Hospital of Jining Medical University from January 2018 to July 2020, were retrospectively analyzed. The diagnosis of all the patients were confirmed by pathological examination, of lung or bronchi tissue that were obtained through operation, bronchoscope or percutaneous lung puncture biopsy.Results:There were 26 patients' (60.47%, 26/43) pathological specimens were obtained by operation, 14 cases (32.56%, 14/43) were obtained by bronchoscope, and 3 cases (6.98%, 3/43) were obtained by percutaneous lung puncture biopsy. Of the 43 patients who were diagnosed pulmonary mycosis by pathology, 27 patients (62.79%, 27/43) suffered from pulmonary aspergillosis, 11 patients (25.58%, 11/43) suffered from pulmonary cryptococcosis, 3 patients (6.98%, 3/43) suffered from pulmonary mucormycosis, and 2 patients (4.65%, 2/43) suffered from pulmonary candidiasis. There were 27 patients (62.79%, 27/43) with pulmonary fungal disease complicating risk factors of fungal infection, including diabetes mellitus (23.26%,10/43), malignant tumor (16.28%, 7/43), bronchiectasis (9.30%, 4/43), hepatitis B virus (HBV) carrier (6.98%, 3/43), taking glucocorticoids (4.65%, 2/43), pulmonary tuberculosis (4.65%, 2/43), and chemotherapy following colon carcinoma operation (2.33%, 1/43). The common clinical presentations included cough (55.81%, 24/43), expectoration (48.84%, 21/43), hemoptysis (37.21%, 16/43), fever (20.93%, 9/43), gasping (18.60%, 8/43), chest pain (16.28%, 7/43), and hoarseness (3.13%, 1/43). Imaging features of chest included lung nodes in 20 cases (46.51%, 20/43), vascular welt sign in 12 cases (27.91%, 12/43), exudative process in 10 cases (23.26%, 10/43), lung mass or consolidation in 8 cases (18.60%, 8/43), cavitary lesions in 7 cases (16.28%, 7/43), thicken bronchus wall and narrow lumina in 6 cases (13.95%, 6/43), air crescent in 5 cases (11.63%, 5/43).Conclusions:The pulmonary aspergillosis and cryptococcosis are mainly in pulmonary mycosis diagnosed by pathology. The common complications are diabetes mellitus and malignant tumor. The common clinical presentations are cough, expectoration, and hemoptysis. The main imaging features of chest are lung nodes and vascular welt sign can be found in most of pulmonary cryptococcosis.

Due to good mechanical properties and biocompatibility, tissue engineering scaffolds have become the vital method for repairing and regenerating articular cartilage defects. With the continuous development of tissue engineering technology, many scaffolds preparation and formation methods have been developed and tested in the past decade, however, the preparation of ideal regenerative scaffolds remain controversial. As load-bearing tissue inside the body joints, the matrix structure and cell composition of articular cartilage are hierarchical, and there are several smooth natural gradients from the cartilage surface to the subchondral bone layer, including cell phenotype and number, specific growth factors, matrix composition, fiber arrangement, mechanical properties, nutrient and oxygen consumption. Therefore, in the design of regenerative scaffolds, it is necessary to achieve these gradients to regenerate articular cartilage in situ. In recent studies, many new biomimetic gradient scaffolds have been used to simulate the natural gradient of articular cartilage. These scaffolds show different mechanical, physicochemical or biological gradients in the structure, and have achieved good repair effects. The related articles on tissue engineering for the treatment of articular cartilage defects were retrieved by searching databases with key wordsarticular cartilage injury, cartilage repair and gradient scaffolds. In this work,the structural, biochemical, biomechanical and nutrient metabolism gradients of natural articular cartilage were studied and summarized firstly. Then, the latest design and construction of articular cartilage gradient scaffolds were classified. Besides that, the material composition (such as hydrogels, nanomaterials, etc.) and the preparation process (such as electrospinning, 3D printing, etc.) of grandient scaffolds were further enhanced. Finally, the prospect and challenge of biomimetic gradient scaffolds in cartilage engineering are discussed, which provides a theoretical basis for the successful application of gradient scaffolds in clinical transformation.

The treatment of articular cartilage (AC) injury caused by various reasons is still a major clinical problem. The emergence of cartilage tissue engineering brings new hope for the treatment of AC injury. In general, AC tissue engineering can be divided into two categories, including cell-based tissue engineering and cell-free tissue engineering. Although cell-based tissue engineering can repair cartilage damage to a certain extent, existing therapeutic strategies still suffer from limited cell sources, high costs, risk of disease transmission, and complex procedures. However, the cell-free tissue engineering avoids these shortcomings and brings hope for in-situ AC regeneration. Non-cellular tissue engineering is mainly used to recruit endogenous stem cells/progenitor cells (SCPCs) to reach the site of cartilage injury, and provide a suitable regenerative microenvironment to promote cell proliferation and chondrogenic differentiation, then the maturation of new cartilage tissue was promoted. Therefore, it is also called as cell-homing in situ tissue engineering. Successful recruitment of endogenous SCPCs is the first step in in-situ cartilage tissue engineering. This review aims to introduce chemokine response of cartilage injury, systematically summarize traditional chemoattractant (chemokines and growth factors etc.) and emerging chemoattractant (functional peptides, exosomes and nucleic acid adapters etc.), evaluate the combination mode between chemoattractant and delivery devices, discuss the prospects and challenges of chemoattractant-mediated in situ tissue engineering and provide theoretical basis for the design of endogenous SCPCs homing-based in situ tissue engineering.