Plant natural products have a wide range of pharmacological properties, not only can they be used as plant dietary supplements to meet the nutritional needs of the human body in the accelerated pace of life, but also occupy an important position in the research and development of therapeutic drugs for the treatment of tumors, inflammation and other diseases, and have been widely accepted by the public due to their good safety. However, despite the above advantages of plant natural products, limiting factors such as low solubility, poor stability, lack of targeting, high toxicity and side effects, and unacceptable odor have greatly impeded their conversion to clinical applications. Therefore, the development of new avenues for the application of new natural products has become an urgent problem to be solved at present. In recent years, with the continuous development of research, various strategies have been developed to improve the bioavailability of natural products. Among them, nanocarrier delivery system is one of the most attractive strategies at present. In past studies, a large number of nanomaterials (organic, inorganic, etc.) have been developed to encapsulate plant-derived natural products for their efficient delivery to specific organs and cells. Up to now, nanotechnology has not only been limited to pharmaceutical applications, but is also competing in the fields of nanofood processing technology and nanoemulsions. Among the various nanocarriers, liposomes are the largest nanocarriers with the largest market share at present. Liposomes are bilayer nanovesicles synthesized from amphiphilic substances, which have advantages such as high drug loading capacity and stability. Attractively, the flexible surface of liposomes can be modified with various functional elements. Functionalized modification of liposomes with different functional elements such as antibodies, nucleic acids, peptides, and stimuli-responsive moieties can bring out the excellent drug delivery function of liposomes to a greater extent. For example, the modification of functional elements with targeting function such as nucleic acids and antibodies on the surface of liposomes can deliver natural products to the target location and improve the bioavailability of drugs; the modification of stimulus-responsive groups such as photosensitizers, magnetic nanoparticles, pH-responsive groups, and temperature sensitizers on the surface of liposomes can achieve controlled release of drugs, localized targeting, and synergistic thermotherapy. In addition to the above properties, by using functionalized liposomes to encapsulate natural products with irritating properties can also effectively mask the irritating properties of natural products, improve public acceptance, and increase the possibility of application of irritating natural products. There are various strategies for modifying liposomes with functional elements, and the properties of functionalized liposomes constructed by different construction strategies differ. The commonly used construction strategies for functionalized liposomes include covalent modification and non-covalent modification. These two types of construction strategies have their own advantages and disadvantages. Covalent modification has better stability than non-covalent modification, but its operation is cumbersome. With the above background, this review focuses on the three typical problems faced by plant natural products at present, and summarizes the specific applications of functionalized liposomes in them. In addition, this paper summarizes the construction strategies for building different types of functionalized liposomes. Finally, this paper will also review the opportunities and challenges faced by functionalized liposomes to enter clinical therapy, and explore the opportunities to overcome these problems, with a view to better realizing the precise control of plant nanomedicines, and providing ideas and inspirations for researchers in related fields as well as relevant industrial staff.

OBJECTIVE: Omicron, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, is responsible for numerous infections in China. This study investigates the association between the use of Seven-Flavor Herb Tea (SFHT) and the risk of SARS-CoV-2 infection to develop precise and differentiated strategies for control of the coronavirus disease 2019 (COVID-19). METHODS: This case-control study was conducted at shelter hospitals and quarantine hotels in China. A total of 5348 laboratory-confirmed COVID-19 patients were enrolled between April 1 and May 31, 2022, while 2190 uninfected individuals served as healthy controls. Structured questionnaires were used to collect data on demographics, underlying diseases, vaccination status, and use of SFHT. Patients were propensity-score-matched using 1:1 nearest-neighbor matching of the logit of the propensity score. Subsequently, a conditional logistic regression model was used for data analysis. RESULTS: Overall, 7538 eligible subjects were recruited, with an average age of [45.54 ± 16.94] years. The age of COVID-19 patients was significantly higher than that of uninfected individuals ([48.25 ± 17.48] years vs [38.92 ± 13.41] years; t = 22.437, P < 0.001). A total of 2190 COVID-19 cases were matched with uninfected individuals at a 1:1 ratio. The use of SFHT (odds ratio = 0.753, 95% confidence interval: 0.692, 0.820) was associated with a lower risk of SARS-CoV-2 infection compared to untreated individuals. CONCLUSION Our findings suggest that taking SFHT reduces the risk of SARS-CoV-2 infection. This is a useful study in the larger picture of COVID-19 management, but data from large-sample multi-center, randomized clinical trial are warranted to confirm the finding. Please cite this article as: Zhang SX, Chen XX, Zheng Y, Cai BH, Shi W, Ru M, Li H, Zhang DD, Tian Y, Chen YL. Reduced SARS-CoV-2 infection risk is associated with the use of Seven-Flavor Herb Tea: A multi-center observational study in Shanghai, China. J Integr Med. 2023; 21(4):369-376.
Humans ; Adult ; Middle Aged ; Aged ; COVID-19/epidemiology* ; SARS-CoV-2 ; Case-Control Studies ; China/epidemiology* ; Tea

Applying Chinese medicine (CM) is an important strategy for malignant tumor treatment in China. One of the significant characteristics of CM is to treat diseases based on syndrome differentiation. For Western medicine, it is of important clinical significance to formulate guidelines for the diagnosis and treatment of cancer patients based on the characteristics of disease differentiation. In Chinese clinical practice, the combination of disease differentiation and syndrome differentiation is an important feature for cancer treatment in the past. Currently, molecular profiling and genomic analysis-based precision medicine optimizes the anticancer drug design and holds the greatest success in treating cancer patients. Therefore, we want to know which populations of cancer patients can benefit more from CM treatment if the theory of precision medicine is applied to CM clinical practice. So, we developed a novel diagnostic and therapeutic strategy "disease-syndrome differentiation-genomic profiling-prescriptions" for cancer patients by CM syndrome differentiation and precision medicine. As a result, this strategy has greatly enhanced the anti-tumor efficacy of CM and improved clinical outcomes for cancer patients with some gene mutations. Our idea will hopefully establish a novel approach for the inheritance and innovation of CM.
Antineoplastic Agents ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Neoplasms/therapy* ; Precision Medicine ; Syndrome

OBJECTIVE: To study the value of airway pH monitoring in determining the association between chronic cough and laryngopharyngeal reflux (LPR) in children. METHODS: A total of 274 children with chronic cough who were treated from January 2016 to December 2019 were enrolled. The DX-pH detection system was used to conduct 24-hour airway pH monitoring. The association between chronic cough and LPR was analyzed. RESULTS: Among the 274 children, there were 168 boys and 106 girls, with a median age of 62.8 months and a median airway pH value of 7.3. Of all the 274 children, 99 (36.1%) had LPR, and the incidence rate of LPR was 36.9% (62/168) in boys and 34.9% (37/106) in girls ( CONCLUSIONS LPR is highly associated with the development of chronic cough, and airway pH monitoring may be a safe and effective method for the diagnosis of LPR.
Child ; Child, Preschool ; Chronic Disease ; Cough/etiology* ; Esophageal pH Monitoring ; Female ; Humans ; Hydrogen-Ion Concentration ; Laryngopharyngeal Reflux ; Male

OBJECTIVE: To explore the influencing factors of low back pain and the relationship of the influence of bad working posture, weight load and frequency of load and the dose-response relationship among the occupational workers of key industries in China. METHODS: A total of 57 501 employees from 15 key industries in China were selected as research subjects using stratified cluster sampling method. The occurrence of low back pain in the past one year, as well as occupational factors such as job type, labor organization and work posture were investigated by using the Chinese version Musculoskeletal Disorders Questionnaire. RESULTS: The prevalence of low back pain in the occupational population of key industries in China was 16.4%(9 448/57 501). Multivariate Logistic regression analysis showed that the risk of low back pain in females was higher than that in males(P<0.01). Married, obese, occasional and frequent smokers, and a history of lower back disease were associated with increased risk of low back pain(all P<0.05). The risk of low back pain was associated with older age, higher education level, and lower frequency of physical exercise(all P<0.01). The risk of low back pain was higher with longer working time, greater back curvature, and the high frequency of long standing and sitting position work, uncomfortable working posture, repeated operation per minute, and lifting>5 kg weight(all P<0.01). CONCLUSION: The influencing factors of low back pain in the occupational population of key industries in China include bad working posture, high frequency load, weight load and other individual factors. There is a dose-response relationship with low back posture load and frequency of load.

Objective:To explore the effects of Huanglian Wendantang （HLWDT） on pyroptosis of skeletal muscle in rats with impaired glucose tolerance （IGT） and to explain the mechanism based on NOD-like receptor protein 3 （NLRP3）/cysteine aspartate-specific protease-1 （Caspase-1）/gasdermin D （GSDMD）/interleukin-1β （IL-1β）/IL-18 signaling pathway. Method:The SD male rats were fed with 45% high-fat diet for 20 weeks to induce the IGT model. After modeling， the rats were randomly divided into a blank group， a model group， a positive control group （metformin hydrochloride， 0.05 g·kg^-1d^-1）， and an HLWDT （7.8 g·kg^-1d^-1） group based on the body weight of rats. The blank group and the model group were fed with the same volume of distilled water. The dose for each group was set as 10 mL·kg^-1d^-1. After four weeks of continuous gavage， blood was collected and serum was separated. The skeletal muscles of rats were stored in liquid nitrogen. Subsequently， serum IL-1β and IL-18 were detected by the enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of NLRP3， Caspase-1， and GSDMD were detected by real-time quantitative PCR （Real-time PCR） and Western blot， respectively. The expression of GSDMD， IL-1β， and IL-18 proteins in skeletal muscle tissues was detected by immunofluorescence. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of skeletal muscles. Result:Compared with the blank group， the model group showed increased IL-1β and IL-18 in serum， and NLRP3， Caspase-1， and GSDMD gene and protein expression in skeletal muscle tissues （P<0.01）. Immunofluorescence assay showed that GSDMD， IL-18， and IL-1β protein expression in skeletal muscle tissues of the model group was significantly elevated （P<0.01）. HE staining showed obvious pathological changes in skeletal muscles. Compared with the model group， the HLWDT group and the positive control group could decrease IL-1β and IL-18 in serum and NLRP3， Caspase-1， and GSDMD gene and protein expression in skeletal muscle tissues （P<0.01）. In addition， immunofluorescence assay revealed that HLWDT could reduce protein expression levels of GSDMD， IL-1β， and IL-18 in skeletal muscles of IGT rats （P<0.01）. The results of HE staining showed that HLWDT could improve the pathological changes of skeletal muscles in IGT rats. Conclusion:HLWDT can inhibit skeletal muscle pyroptosis of IGT rats， and the mechanism may be closely related to NLRP3/Caspase-1/GSDMD/IL-18/IL-1β signaling pathway.

Objective:To investigate the incidence of hypothyroxinemia in very low birth weight infant (VLBWI) and its effect on early postnatal feeding and weight gain.Methods:This retrospective study analyzed 164 cases of VLBWIs admitted to the Neonatal Intensive Care Unit of Peking University First Hospital from January 2017 to December 2018. According to the gestational age, these VLBWIs were divided into <30 weeks group ( n=85) or ≥30 weeks group ( n=79), and the basic data and thyroid function were compared. According to the levels of serum tetraiodothyronine and free tetraiodothyronine at the first thyroid function test, the subjects were further assigned into normal thyroxine group and hypothyroxinemia group. The risk factors of hypothyroxinemia identified at the first detection were analyzed by single and multiple-facter analysis. The results of the second detection of thyroxine were also analyzed. On the basis of the first detection and receiving treatment or not, the <30 weeks and ≥30 weeks groups were divided into normal thyroxine, hypothyroxinemia treated and hypothyroxinemia untreated subgroups, and differences in the tolerance of early feeding and weight gain were compared between different groups. Two independent samples/paired t-test, rank sum test, Chi-square test and logistic regression were used for statistical analysis. Results:Out of the 164 VLBWIs with the gestational age of (29.7±2.0) weeks and birth weight of (1 210±210) g, 27 cases (16.5%) were extremely low birth weight infants. The age at their first detection was (10.7±3.1) d and the incidence of hypothyroxinemia was 45.1% (74/164), including 71 mild and three severe cases, with a higher incidence in the ≥30 weeks group comparing to the <30 weeks group [55.7%(44/79) vs 35.5%(30/85), χ 2= 6.883, P=0.009]. All the three severe cases were in the ≥30 weeks group. The gestational age ( OR=1.413, 95% CI:1.044-1.912, P=0.025) and male infant ( OR=2.082, 95% CI: 1.047-4.143, P=0.037) were the risk factors of hypothyroxinemia. At the second detection, the incidence of hypothyroxinemia in VLBWIs with normal thyroid function at their first test was 47.6% (39/82), which is higher in the ≥30 weeks group than in the <30 weeks group [64.5%(20/31) vs 37.3%(19/51), χ 2= 5.745, P=0.017]. Among the infants with hypothyroxinemia at the first detection, those untreated had a significantly higher incidence of hypothyroxinemia at the second detection than those treated [81.3%(26/32) vs 38.7%(12/31), χ 2= 11.905, P=0.001]. The incidence of abdominal distension within 21 days, feeding volume on day 7, 14, and 21, and neonatal weight gain within 7, 14, and 21 days were similar between normal thyroxine, hypothyroxinemia treated and hypothyroxinemia untreated subgroups within the ≥30 weeks or the <30 weeks groups (all P>0.05). Conclusions:VLBWI is at high risk of hypothyroxinemia. Two times of postnatal thyroid function tests can help to detect the delayed hypothyroxinemia. Thyroxine level and receiving treatment or not may have no significant effect on the early postnatal feeding and weight gain.

Objective:To analyze the categories and its relations of recreational physical activities and rehabilitation exercise for adult with disabilities based on the theory and method of International Classification of Functioning, Disability and Health (ICF). Methods:An evidence-based scoping review had been implemented. We had developed the framework and coding approaches for recreational physical activities, rehabilitation exercise and functional improvement for the adults with disabilities based on evidence-based literature review. The literature related to recreational physical activities and rehabilitation exercise of adult with disabilities was searched by subject retrieval method. The retrieval database in Chinese included CNKI and Wanfang database, and the retrieval database in English included PubMed and Web of Science. The retrieval time was from establishment to July 31, 2020. The authors, countries, published time, published journals, research objectives, object of the study and their ages, data collection tool, and the key findings were extracted. Results:A total of 2476 literatures were returned, and 18 of them were enrolled, which were published in 14 countries, and most were published in journals on topics related to medicine, public health, exercise and people with disabilities. They were mainly published from 2010 to 2020, and mainly used questionnaire survey, measurement and interviewing method. There were three typical recreational physical activities: physical fitness activities, skills activities and sports activities, mainly including Taiji Quan, wheelchair basketball, leisure outdoor activities, community recreational sports activities and rehabilitation exercises, etc. According to the framework of ICF, recreational physical activities promote functional rehabilitation for adults with disabilities, including physical functions (b1 mental function; b4 cardiovascular, blood, the function of the immune system and respiratory system; b5 digestion, metabolism and function of the endocrine system; and b7 nerve musculoskeletal function related to movement), and activities and participation (d1 study and application of knowledge; d2 the general tasks and requirements; d4 activity; d5 self-care; d7 interpersonal communication and interpersonal relationship; and d9 community, social and civic life). The evidences showed benefits of improvement in the fields of body mass index, body index, athletic ability, balance ability, and cognitive function. There were more gains at individual levels, including support, coping with stress, self-concept development, life satisfaction, happiness, exercise self-efficacy, health perception, etc. The environmental and personal factors had effects on the performance of activity and participation in recreational physical activities, including e1 products and technologies, e4 attitude, e3 support and interpersonal relationships, e5 service system and policy, as well as attitudes and support of family members and colleagues, interpersonal relationships, social support, transportation, equipment and facilities, and policies. Conclusion:Rehabilitation exercise is an important part of health-related services. We scoped the recreational physical activities and its functional effects for adults with disabilities. The categories and structure of recreational physical activities and rehabilitation exercises were constructed based on ICF. Aligning rehabilitation exercises and relevant factors to ICF, the recreational activities and rehabilitation exercises had been reviewed and discussed and several recommendations for further studies had been drawn.

AIM:To observe the changes of autophagy-related indexes during endoplasmic reticulum stress (ERS) induced by dithiothreitol (DTT) and its effect on apoptosis in human normal hepatocytes.METHODS:LO2 cells were treated with DTT at 2.0 mmol/L for 0, 6, 12 and 24 h to induce ERS.The expression of glucose-regulated protein 78 (GRP78) , protein kinase R-like endoplasmic reticulum kinase (PERK) , activating transcription factor 4 (ATF4) , C/EBP homologous protein (CHOP) , autophagy-related gene 12 (Atg12) , autophagy-related gene 5 (Atg5) and microtubule-associated protein 1 light chain 3 (LC3) at mRNA and protein levels was determined by real-time PCR and Western blot.The apoptosis was analyzed by flow cytometry.The formation of autophagosomes was observed under transmission electron microscope.After the LO2 cells were pretreated with rapamycin at 400 nmol/L for 1 h and treated with DTT at 2.0mmol/L for 24 h, the effect of rapamycin pretreatment on the apoptosis was analyzed by flow cytometry.RESULTS:After treatment with DTT at 2.0 mmol/L for 6, 12 and 24 h, the mRNA and protein levels of GRP78, PERK, ATF4, CHOP, Atg12, Atg5 and LC3 in the LO2 cells were significantly higher than those in 0 h group (P<0.05).At the same time, the ratio of LC3Ⅱ/LC3Ⅰwas also increased after DTT treatment (P<0.05).Observation under transmission electron microscope showed that autophagosomes were found in the LO2 cells treated with DTT for 6, 12 and 24 h.After DTT treatment for 6, 12 and 24 h, the apoptosis rate of LO2 cells was significantly higher than that in DTT 0 h group, while the apoptosis induced by DTT was significantly decreased after rapamycin pretreatment (P<0.05).CONCLUSION:ERS induces autophagy and rapamycin pretreatment alleviates the apoptosis of LO2 cells to some extent.

AIM:To investigate the effect of SET7/9 (SET domain containing 7/9) -mediated endoplasmic reticulum stress (ERS) on protein kinase R-like endoplasmic reticulum kinase (PERK) signaling pathway, and to explore the mechanisms of arsenic-induced hepatocyte apoptosis.METHODS:Human liver LO2 cells were divided into control group, arsenic poisoning model group, negative transfection group and SET7/9 siRNA transfection group.The apoptosis of the LO2 cells in each group was analyzed by flow cytometry.The protein levels of SET7/9, glucose-regulated protein 78 (GRP78) , PERK and p-PERK in the LO2 cells of each group were observed by Western blot.RESULTS:Inhibition of SET7/9 expression reduced the apoptotic rate of arsenic-induced LO2 cells.Arsenic exposure increased the expression of SET7/9 in the LO2 cells.Arsenic exposure increased the protein levels of GRP78 and p-PERK in the LO2 cells, but decreased the protein levels of GRP78 and p-PERK after transfection with SET7/9 siRNA (P<0.05).CONCLUSION:Arsenic exposure induces hepatocyte apoptosis by increasing SET7/9 to activate ERS by PERK signaling pathway.