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.

Objective:To explore the effect of early quantitative pulmonary rehabilitation assessment in adult Intensive Care Unit (ICU) patients with mechanical ventilation in high altitude area.Methods:From March 2019 to October 2021, convenience sampling was used to select 287 adult ICU patients with mechanical ventilation of Qinghai Red Cross Hospital as the research object. According to the time of admission, the patients were divided into the control group (142 cases) and the experimental group (145 cases) . The control group was given the routine pulmonary rehabilitation, and the experimental group received the early pulmonary rehabilitation based on quantitative assessment. The Acute Physiology and Chronic Health EvaluationⅡ (APACHEⅡ) score and the Intensive Care Units Mobility Scale (IMS) score were compared between the two groups before enrollment, on the eighth and sixteenth days of pulmonary rehabilitation. The oxygenation index of the two groups of patients before enrollment and on the first, fourth, sixth, eighth and sixteenth days of pulmonary rehabilitation, the time of ICU stay, the time of mechanical ventilation, the success rate of ventilator removal and the complications of the two groups of patients with mechanical ventilation were also compared.Results:On the eighth and sixteenth days of pulmonary rehabilitation, the APACHE Ⅱ score of the experimental group was lower than that of the control group, and the IMS score was higher than that of the control group, with statistical differences ( P<0.05) . On the sixth, eighth and sixteenth days of pulmonary rehabilitation, the oxygenation index of the experimental group was higher than that of the control group, and the difference was statistically significant ( P<0.05) . The ICU stay time and mechanical ventilation time in the experimental group were lower than those in the control group, and the success rate of ventilator removal in the experimental group was higher than that in the control group, with statistical differences ( P<0.05) . Conclusions:Implementing early pulmonary rehabilitation for adult ICU patients with mechanical ventilation in high altitude area is conducive to promoting pulmonary rehabilitation of patients, improving the success rate of ventilator removal, and reducing patients' ICU stay time, mechanical ventilation time and the occurrence of complications.

Objective:To explore the effect of early quantitative pulmonary rehabilitation assessment in adult Intensive Care Unit (ICU) patients with mechanical ventilation in high altitude area.Methods:From March 2019 to October 2021, convenience sampling was used to select 287 adult ICU patients with mechanical ventilation of Qinghai Red Cross Hospital as the research object. According to the time of admission, the patients were divided into the control group (142 cases) and the experimental group (145 cases) . The control group was given the routine pulmonary rehabilitation, and the experimental group received the early pulmonary rehabilitation based on quantitative assessment. The Acute Physiology and Chronic Health EvaluationⅡ (APACHEⅡ) score and the Intensive Care Units Mobility Scale (IMS) score were compared between the two groups before enrollment, on the eighth and sixteenth days of pulmonary rehabilitation. The oxygenation index of the two groups of patients before enrollment and on the first, fourth, sixth, eighth and sixteenth days of pulmonary rehabilitation, the time of ICU stay, the time of mechanical ventilation, the success rate of ventilator removal and the complications of the two groups of patients with mechanical ventilation were also compared.Results:On the eighth and sixteenth days of pulmonary rehabilitation, the APACHE Ⅱ score of the experimental group was lower than that of the control group, and the IMS score was higher than that of the control group, with statistical differences ( P<0.05) . On the sixth, eighth and sixteenth days of pulmonary rehabilitation, the oxygenation index of the experimental group was higher than that of the control group, and the difference was statistically significant ( P<0.05) . The ICU stay time and mechanical ventilation time in the experimental group were lower than those in the control group, and the success rate of ventilator removal in the experimental group was higher than that in the control group, with statistical differences ( P<0.05) . Conclusions:Implementing early pulmonary rehabilitation for adult ICU patients with mechanical ventilation in high altitude area is conducive to promoting pulmonary rehabilitation of patients, improving the success rate of ventilator removal, and reducing patients' ICU stay time, mechanical ventilation time and the occurrence of complications.

Proteins and peptides have become a significant therapeutic modality for various diseases because of their high potency and specificity. However, the inherent properties of these drugs, such as large molecular weight, poor stability, and conformational flexibility, make them difficult to be formulated and delivered. Injection is the primary route for clinical administration of protein and peptide drugs, which usually leads to poor patient's compliance. As a portable, minimally invasive device, microneedles (MNs) can overcome the skin barrier and generate reversible microchannels for effective macromolecule permeation. In this review, we highlighted the recent advances in MNs-mediated transdermal delivery of protein and peptide drugs. Emphasis was given to the latest development in representative MNs design and fabrication. We also summarize the current application status of MNs-mediated transdermal protein and peptide delivery, especially in the field of infectious disease, diabetes, cancer, and other disease therapy. Finally, the current status of clinical translation and a perspective on future development are also provided.

Membrane-disruptive peptides/peptidomimetics (MDPs) are antimicrobials or anticarcinogens that present a general killing mechanism through the physical disruption of cell membranes, in contrast to conventional chemotherapeutic drugs, which act on precise targets such as DNA or specific enzymes. Owing to their rapid action, broad-spectrum activity, and mechanisms of action that potentially hinder the development of resistance, MDPs have been increasingly considered as future therapeutics in the drug-resistant era. Recently, growing experimental evidence has demonstrated that MDPs can also be utilized as adjuvants to enhance the therapeutic effects of other agents. In this review, we evaluate the literature around the broad-spectrum antimicrobial properties and anticancer activity of MDPs, and summarize the current development and mechanisms of MDPs alone or in combination with other agents. Notably, this review highlights recent advances in the design of various MDP-based drug delivery systems that can improve the therapeutic effect of MDPs, minimize side effects, and promote the co-delivery of multiple chemotherapeutics, for more efficient antimicrobial and anticancer therapy.

Malignant tumor has become an urgent threat to global public healthcare. Because of the heterogeneity of tumor, single therapy presents great limitations while synergistic therapy is arousing much attention, which shows desperate need of intelligent carrier for co-delivery. A core‒shell dual metal-organic frameworks (MOFs) system was delicately designed in this study, which not only possessed the unique properties of both materials, but also provided two individual specific functional zones for co-drug delivery. Photosensitizer indocyanine green (ICG) and chemotherapeutic agent doxorubicin (DOX) were stepwisely encapsulated into the nanopores of MIL-88 core and ZIF-8 shell to construct a synergistic photothermal/photodynamic/chemotherapy nanoplatform. Except for efficient drug delivery, the MIL-88 could be functioned as a nanomotor to convert the excessive hydrogen peroxide at tumor microenvironment into adequate oxygen for photodynamic therapy. The DOX release from MIL-88-ICG@ZIF-8-DOX nanoparticles was triggered at tumor acidic microenvironment and further accelerated by near-infrared (NIR) light irradiation. The

Pulmonary drug delivery has attracted increasing attention in biomedicine, and porous particles can effectively enhance the aerosolization performance and bioavailability of drugs. However, the existing methods for preparing porous particles using porogens have several drawbacks, such as the inhomogeneous and uncontrollable pores, drug leakage, and high risk of fragmentation. In this study, a series of cyclodextrin-based metal-organic framework (CD-MOF) particles containing homogenous nanopores were delicately engineered without porogens. Compared with commercial inhalation carrier, CD-MOF showed excellent aerosolization performance because of the homogenous nanoporous structure. The great biocompatibility of CD-MOF in pulmonary delivery was also confirmed by a series of experiments, including cytotoxicity assay, hemolysis ratio test, lung function evaluation,

Objective: To analyze the teaching environment of primary, middle and high schools in Suzhou, and to explore the relevance of students’ myopia with teaching environment, as well as the key problems in teaching environment. Methods: 1 253 classrooms in 204 schools rom 10 districts and counties in Suzhou were selected by proportionate stratified sampling. The qualified rate of each indices was described and the teaching environment by county, learning stage were compared by using chi-squared test. The Spearman test is used to explore correlations between myopia with monitoring indicators. Results: The qualified rate of the distance from lamp to table was the highest (98.56%), while matching rate of student desk and chair was the lowest(0.96%). Minimum lamp table spacing, blackboard average illumination, reflectance from blackboard wall, classroom per capita area, classroom microclimate differed significantly in urban and rural (P<0.05); daylighting coefficient, reflectance from walls, average illumination of desktop and blackboard, classroom per capita area, and microclimate indicator were statistically different by learning stages(r=0.42,P<0.05). Prevalence of myopia correlated with the index of lighting. Conclusion Qualified desks and matched chairs, as well as the daylighting design in classroom should receive more attention in Suzhou. The findings lend support to identification of key health priorities and formulation of the localized health practice for health administrations.

Objective: To understand the antigenicity and genetic characterization of influenza B virus HA gene in B/Victoria-lineage virus (BV) in Beijing during 2017-2018. Methods: Thirty BV virus strains isolated from MDCK cell culture by 17 laboratories in Beijing were collected. The antigenicity was analyzed by comparing with the vaccine strain recommended by WHO. The total viral nucleic acid was extracted and HA gene was amplified by RT-PCR and sequenced. The phylogenetic tree was constructed by HA and mutant sites were analyzed. Results: Among 30 strains of BV, 23 strains (76.7%) were low-reactive strains, other 7 strains (23.3%) were related to the vaccine. The phylogenetic analysis showed that the HA gene of all 30 strains located in Clade 1A branch. In addition, amino acid mutations occurred in 8 sites, and 6 of them located in the antigen determining region. Conclusions There was a correlation between the high proportion of low-reactive antigenicity and 6 aa variation in antigenic determinants involved in HA region of BV influenza virus between 2017-2018, which provides an important laboratory basis for the recommendation of BV influenza vaccine.

Dissolving microneedles carried drug molecules can effectively penetrate the stratum corneum of skin to improve the transdermal drug delivery. The traditional Chinese medicine acupuncture is based on the needle stimulation at a specific location (acupoint) to generate and transmit biochemical and physiological signals which alter the pathophysiological state of patients. However, the pain associated with conventional acupuncture needles and the requirement of highly trained professionals limit the development of acupuncture in non-Asian countries. The purpose of this study is to investigate whether the dissolving microneedles can be utilized as a self-administered painless replacement for acupuncture and locally released drug molecules can achieve expected therapeutic outcomes. Immunosuppressive rats were treated with acupuncture at Zusanli (ST36) acupoint using microneedles containing thymopentin. The immune functions and psychological mood of the immunosuppressed animals were examined. The proliferation of splenocytes was examined by CCK-8 assay. CD4 and CD8 expression patterns in spleen cells were detected by flow cytometry. The current study showed that use of either microneedles containing thymopentin or conventional acupuncture both resulted in immune cell proliferation, which was confirmed by flow cytometry. Furthermore, either conventional acupuncture or microneedles were able to effectively mitigate the anxiety caused by immune-suppression when applied on the ST36.