Abstract Hyperuricemia (HUA) is a metabolic disorder syndrome caused by purine metabolism dysregulation, and its prevalence increases year by year. The development and progression of HUA are accompanied by significant alterations in the composition of intestinal microbiota, making probiotics a potential and safe method to reduce serum uric acid. Probiotics ameliorate HUA through three pathways: competing with intestinal epithelial cells for purine absorption to decrease uric acid synthesis, inhibiting xanthine oxidase activity through modulation of inflammatory cytokines to reduce the conversion of purine to uric acid, as well as restoring and maintaining an orderly state of the gut microbiota to facilitate normal uric acid excretion. This article reviews the role of probiotics in ameliorating HUA, so as to provide the reference for the application of probiotics in the prevention and intervention of HUA.

Objective: To investigate the prevalence and associated factors of depressive symptoms among middle and high school students in Zhejiang Province, so as to provide scientific basis for the implementation of depressive intervention. Methods: Based on the health status and associated factors of middle and high school students in the project "Monitoring of Common Diseases and Health Influencing Factors of Students" during 2018 to 2021, a total of 73 309 students including middle school, ordinary high school and vocational high school surveyed in 11 cities of Zhejiang Province were selected by multi stage stratified cluster random sampling method. From 2018 to 2021, there were 6 008, 21 917, 23 712 and 21 672 students, respectively. The Chi square test and Logistic regression model were used to analyze the influencing factors of depressive symptoms in middle and high school students. Results: From 2018 to 2021, depressive symptoms detection rate of middle school students was 14.8%, with higher rate in girls (17.1%) than in boys (12.7%), higher rate in high school (17.1% in ordinary high school, 17.6% in vocational high school) than middle school (12.5%)( χ 2=278.77, 327.22, P <0.05). Univariate analysis showed that there were statistically significant differences in depressive symptoms detection rate among middle school students with different years (2018: 16.7%，2019: 17.9% , 2020: 13.1%, 2021: 13.0%), residence (yes: 16.3%, no:13.5%), body mass index classification (not overweight or obesity: 14.8%, overweight: 14.2%, Obesity: 15.7%), weekly exercise days (0-2 d: 17.1%, 3-5 d: 12.5%, 6-7 d: 13.1%) and bullying (yes: 35.5%, no: 10.7%) ( χ 2=293.40, 118.35, 7.83, 287.24, 4 978.84, P <0.05). Multivariate Logistic regression analysis showed that female students, ordinary high schools, vocational high schools, obesity, school bullying were positively correlated with depression ( OR =1.65, 1.70, 1.60, 1.12, 5.21), exercise 3 to 5 days per week, exercise 6 to 7 days per week were negatively correlated with depression ( OR=0.77, 0.81, P <0.01). Conclusions Depressive symptoms among middle and high school students in Zhejiang Province are prominent. Strengthening mental health education for students and providing attention and support from families, schools, and society are essential steps to reduce the occurrence of depressive symptoms among these students.

AIM:To investigate the effect of Bushen formulae(BHF)on bone metabolism and its possible mechanism in ovariectomized rats with high salt intake.METHODS:According to the random number table method,80 SPF-grade Sprague-Dawley rats were divided into sham group,ovariectomy(OVX)group,medium-high-salt diet(MSD)group,high-salt diet(HSD)group,BHF group,BHF with normal saline(BHF+NS)group,BHF+MSD group,and BHF+ HSD group,with 10 rats in each group.After modeling,different diets and BHF formula interventions were administered,and the concentrations of sodium chloride added to MSD group and HSD group were 2%(w/w)and 8%(w/w),respective-ly.The dose of BHF was 7.8 g·kg-1·d-1,once a day,and the treatment lasted for 12 weeks.Bone density,bone microar-chitecture,bone parameters,bone metabolism biomarkers,bone histopathological changes,the expression of epithelial sodium channel α(ENaCα),Na-Cl cotransporter(NCC),and voltage-gated chloride channel 3(ClC-3)proteins in bone tissue were detected in each group.RESULTS:Compared with sham group,the rats in OVX group had reduced bone density and destroyed bone microstructure.Compared with OVX group,the bone microstructure in MSD and HSD groups was more significantly damaged,while the levels of bone formation markers,bone glycoprotein(BGP)and type Ⅰ procolla-gen N-terminal peptide(PINP),were significantly increased in HSD group(P<0.05).Moreover,the levels of bone re-sorption markers,such as amino-terminal cross-linked telopeptides of type Ⅰ collagen(NTX),carboxy-terminal cross-linked telopeptides of type Ⅰ collagen(CTX)and tartrate-resistant acid phosphatase(TRACP),were significantly in-creased(P<0.05),indicating that bone metabolism was in high-conversion state.High-salt diet accelerated the structural destruction of bone trabeculae,and Western blot results showed that high-salt diet caused decreases in the protein expres-sion levels of ENaCα and ClC-3 and an increase in the protein expression level of NCC in femoral tissues(P<0.05).After BHF intervention,the expression of relevant ion channels caused by high salt could be regulated to different degrees.CONCLUSION:Bushen formulae could differentially regulate the expression of relevant ion channels ENaCα,ClC-3,and NCC induced by high salt to different degrees,which has certain ameliorative and therapeutic effects on the imbalance of bone metabolism.

ObjectiveThe human angiotensin converting enzyme2 （hACE2） transgenic mouse model was used to clarify the antiviral efficacy of BD-77 against a novel coronavirus SARS-CoV-2 and explore the action mechanism of BD-77 against SARS-CoV-2. MethodSARS-CoV-2 Omicron and Delta variant strains-infected VeroE6 cell models were established and administered with BD-77 to observe the antiviral effect of BD-77 in vitro. A kit was used to detect the effect of BD-77 in vitro on the binding of spike S protein of SARS-CoV-2 virus （Delta/Omicron） to angiotensin converting enzyme2 （ACE2）. Chromatography was adopted to detect the binding of BD-77 to the S protein and N protein of the novel coronavirus. hACE2 transgenic C57BL/6 mice were divided into a blank control group， SARS-CoV-2 infection group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1， with eight mice in each group. The pneumonia model of SARS-CoV-2-infected hACE2 transgenic mice was built to observe the survival of the mice， detect the virus titer of the lung tissue of the mice， and observe the lesions in the lung tissue. ResultBD-77 had a certain inhibitory effect on Omicron and Delta variant strains in vitro， with median inhibitory concentration （IC₅₀） of 526.3 mg·L^-1 and 653.0 mg·L^-1， respectively. BD-77 had no significant inhibitory effect on the binding of the S protein of WT， Omicron， and Delta variant strains of SARS-CoV-2 to ACE2 and had no binding effect with the S protein and N protein of the novel coronavirus. No mice in the blank group died， while the mortality rate of SARS-CoV-2-infected mice was 75%. There was a large amount of virus replication in the lung tissue of the mice and large areas of inflammatory infiltration in the lung tissue and interstitium. Compared with the model group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1 could reduce the mortality of mice， significantly lower the virus titer in the lung tissue of mice （P<0.05）， and improve lung lesions. ConclusionBD-77 demonstrated significant inhibitory effects against SARS-CoV-2 virus in vitro and in vivo. However， its mechanism of action did not involve direct inhibition of the virus itself or intervention in the virus-host binding process. This finding suggests that the mechanism of action of BD-77 needs to be thoroughly investigated and elucidated by further experiments.

Objective: To understand current status and related factors of breakfast among primary and secondary school students in Zhejiang Province, so as to provide a scientific basis for improving breakfast habits of primary and secondary school students. Methods: During May to November of 2023, 33 326 students from grade four to six of primary schools and grade one to two of secondary schools were selected from 90 counties and cities in Zhejiang Province by using the stratified cluster random sampling method. General information and breakfast consumption were collected by questionnaire. Multivariate Logistic regression was used to analyze the related factors of breakfast. Results: About 81.29% of the primary and secondary school students reported regular breakfast consumption. The rate of regular breakfast consumption was higher on the school days (92.23%) than on the weekends (85.17%), and higher in primary school students (85.83%) compared to secondary school students (74.71%), with statistically significant differences ( χ 2=827.42, 655.03, P <0.01). About 49.19% of primary and secondary school students had their breakfast within 10 minutes or less, and 83.30% of primary and secondary school students had 3-5 food groups for breakfast. The proportions of students who consumed cereals and potatoes, milk, and eggs were respectively 18.76%, 28.85%, 14.63%. About 22.84%, 28.00 %, 32.60% and 32.23% of the students had no meat, soybeans, vegetables and fruits in their breakfast. The results of multivariate Logistic regression analysis showed that girls, rural area, secondary school, place of living (dormitory, others), migrant parent (one or both outside the hometown), late bedtime (22:00-22:59, 23:00 and later) and late wake up time (9:00 and later) on the weekends were positively correlated with no having breakfast every day ( OR=1.22, 1.40, 1.46, 1.20, 1.20, 1.34, 1.36, 1.41 , 3.51, 2.32, P <0.05). The time of physical activity per day (30-<60, 60-<90, 90-120, >120 min), bedtime (21:00-21:59, 22:00-22:59) and wake up time (6:00-6:59, 7:00-7:59) on school days were negatively correlated with no having breakfast every day ( OR=0.75, 0.64, 0.67, 0.64, 0.77, 0.82, 0.75, 0.67, P <0.05). Conclusions There is a considerable number of primary and secondary school students with irregular breakfast consumption, which are related to multiple factors. Therefore, it is necessary to strengthen nutrition education and improve the behavior of breakfast for primary and secondary school students.

AIM:To investigate the effect of protopanaxatriol(PPT)on the drug resistance of paclitaxel(PTX)-resistant human breast cancer MDA-MB-231 cells(MB231-PR cells).METHODS:The MB231-PR cells were constructed as cell models.They were treated with PPT,and incubated for a certain period of time according to the experi-mental settings.CellTiter-Glo was used to determine the viability of MB231-PR cells and MDA-MB-231 parental cells(MB231-PT cells).The change of sub-G1 phase was detected by flow cytometry.Western blot was used to evaluate the apoptosis-related proteins,such as cleaved caspase-3,cleaved poly(ADP-ribose)polymerase(PARP),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax)and survivin.The activity of nuclear factor-κB(NF-κB)was detected by lu-ciferase reporter assay and immunofluorescence assay.The mRNA expression levels of interleukin-6(IL-6),IL-8,chemo-kine CXC motif ligand 1(CXCL1),chemokine CC motif ligand 2(CCL2),CD44,NANOG,octamer-binding transcrip-tion factor 4(OCT4),sex-determining region Y-box 2(SOX2)and aldehyde dehydrogenase 1(ALDH1)were detected by qPCR.The protein levels of IL-6 and IL-8 were measured by ELISA.Tumor sphere formation assay was used to evaluate the characteristics of stem cells.RESULTS:(1)The viability of MB231-PR cells was suppressed by PPT treatment in a dose-dependent manner compared with MB231-PT cells(P<0.01).Besides,the viability of MB231-PR cells was de-creased after combined treatment with PPT and PTX(P<0.01),the accumulation of sub-G1 phase was induced(P<0.01),the ratio of Bax/Bcl-2 was elevated(P<0.01),and the protein levels of survivin,cleaved PARP and cleaved cas-pase-3 were increased(P<0.05).(2)After PPT treatment combined with PTX,the mRNA expression of inflammatory cy-tokines(IL-6,IL-8,CXCL1 and CCL2)and cancer stem cell-related markers(OCT4,SOX2,NANOG,ALDH1 and CD44)was reduced(P<0.05),and the protein levels of IL-6 and IL-8 were decreased(P<0.01).The activity of NF-κB in MB231-PR cells was suppressed(P<0.05),and the growth of tumor spheres from MB231-PR cells was damaged(P<0.05).(3)Immunofluorescence assay showed that PTX induced nuclear p-p65 expression,but this effect was attenuated by PPT.CONCLUSION:Combined treatment with PPT and PTX could attenuate PTX resistance of MB231-PR cells by inhibiting inflammatory cytokines and cancer stem cells.

Objective:To investigate the effects and mechanism of baicalin on the wound healing of full-thickness skin defects in diabetic mice.Methods:This study was an experimental research. Mononuclear cells were isolated from five male C57BL/6J mice aged 8-12 weeks and induced to differentiate into macrophages for conducting the subsequent experiments. According to the random number table (the same grouping method below), macrophages in a high-glucose environment were divided into 0 μmol/L baicalin group (no baicalin was added), 5 μmol/L baicalin group, 15 μmol/L baicalin group, 25 μmol/L baicalin group, 50 μmol/L baicalin group, and 75 μmol/L baicalin group treated with the corresponding final molarity of baicalin and 1 μg/mL endotoxin/lipopolysaccharide (LPS). After treatment for 48 hours, the cell proliferation activity was detected using a microplate reader. Macrophages in a high-glucose environment were divided into LPS group treated with 1 μg/mL LPS and LPS+baicalin group treated with 50 μmol/L baicalin+1 μg/mL LPS. After treatment for 48 hours, the percentage of double-positive cells for inducible nitric oxide synthase (iNOS) and CD80, as well as that for arginase 1 (Arg1) and CD206 among the cells, were detected using immunofluorescence method, the secretion levels of interleukin 1β (IL-1β), IL-6, IL-23, IL-10, insulin-like growth factor (IGF), and transforming growth factor β 1 (TGF-β 1) by the cells were detected using enzyme-linked immunosorbent assay, the expression of reactive oxygen species in the cells was detected using a fluorescent probe method, the protein expression of nuclear factor κB in the cells were detected using Western blotting, and the expression of nuclear factor 2 in the cells was observed using immunofluorescence method. The number of cell experimental samples was 3. Twenty-four 8-week-old male db/db mice were selected. After preparing full-thickness skin defect wounds on their backs, they were divided into baicalin group and normal saline group (with 12 mice in each group). On the third day after injury, 50 μmol/L baicalin and normal saline were injected into the wounds of mice, respectively. The wound healing situation was observed and the percentage of the residual wound area was calculated on the 4 th, 8 th, and 12 th day after injury. The wound tissue was sampled on the 8 th day after injury, hematoxylin-eosin staining was performed to observe the epithelial regeneration and inflammatory cell infiltration, the protein expression of CD31 was detected by Western blotting, and the expression of reactive oxygen species was detected by a microplate reader. The number of animal experimental samples was 6. Results:After treatment for 48 hours, only the proliferation activity of macrophages in 50 μmol/L baicalin group was significantly higher than that in 0 μmol/L baicalin group ( P<0.05). After treatment for 48 hours, the percentage of double-positive cells for iNOS and CD80 among the macrophages in LPS+baicalin group was (21.0±2.4)%, which was significantly lower than (66.6±4.5)% in LPS group ( t=15.63, P<0.05); the percentage of double-positive cells for Arg1 and CD206 among the macrophages in LPS+baicalin group was (59.1±2.1)%, which was significantly higher than (18.6±1.7)% in LPS group ( t=25.38, P<0.05); compared with those in LPS group, the secretion levels of IL-1β, IL-6, and IL-23 by the macrophages in LPS+baicalin group were significantly decreased (with t values of 14.26, 15.95, and 12.23, respectively, P<0.05), while the secretion levels of IL-10, IGF, and TGF-β 1 were significantly increased (with t values of 8.49, 11.98, and 13.84, respectively, P<0.05); the expression of reactive oxygen species in the macrophages in LPS+baicalin group was significantly lower than that in LPS group ( t=5.54, P<0.05); compared with those in LPS group, the protein expression of nuclear factor κB in the nucleus of the macrophages in LPS+baicalin group was significantly decreased ( t=36.22, P<0.05), while that in the cytoplasm was significantly increased ( t=14.47, P<0.05), and the expression of nuclear factor 2 in the nucleus was increased. On the 4 th and 8 th day after injury, the wound area of mice in baicalin group was significantly smaller than that in normal saline group, and the wounds of mice in baicalin group completely healed on the 12 th day after injury. On the 4 th, 8 th, and 12 th day after injury, the residual wound area percentage of mice in baicalin group was significantly lower than that in normal saline group (with t values of 13.29, 10.08, and 11.72, respectively, P<0.05). On the 8 th day after injury, compared with those in normal saline group, the wound tissue of mice in baicalin group showed significant re-epithelization, the infiltration of inflammatory cells was reduced, the expression of CD31 protein was significantly increased ( t=17.23, P<0.05), and the expression of reactive oxygen species was significantly reduced ( t=5.78, P<0.05). Conclusions:Baicalin alleviates the inflammatory response of macrophages by lowering the level of reactive oxygen species in cells and promoting the polarization of macrophages to the M2 type, thereby facilitating the healing of full-thickness skin defect wounds in diabetic mice.

AIM: To evaluate the bioequivalence of cinacalcet hydrochloride tablets in healthy Chinese volunteers. METHODS: A randomized, open, double-period and crossover trial was conducted, 48 healthy volunteers were administered a single dose of cinacalcet test tablets or reference tablets orally under each fasting and fed condition. The concentration of cinacalcet was determined by validated LC-MS/MS method. Pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 to study its bioequivalence. RESULTS: The main pharmacokinetic parameters of test tablets and reference tablets under fasting condition were as follows: C

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

Objective To study dynamic compression performance of adipose tissues, so as to further reveal the damage mechanism, and provide references for medical treatment.Methods Based on the improved split Hopkinson pressure bar (SHPB) experimental device, the adipose tissue dynamic compression experiment was conducted. The stress-strain curves of adipose tissues at different strain rates were obtained. Then the numerical model of SHPB was established, and the experimental process was simulated and analyzed. The numerical simulation for penetration process of 32 mm diameter rubber non-lethal projectile into the simulated target in human abdomen was carried out.Results Adipose tissues had a noticeable strain rate effect. The stress-strain curves at two high strain rates were approximately straight lines. The slope was similar, and the elastic modulus was 3.25 MPa, which was about 6 times of that under a quasi-static state. The simulation curves of fat SHPB were consistent with the experimental curves, which verified correctness of the constitutive model. In the process of non-lethal projectile penetrating human abdomen, an annular convex area similar to water wave appeared on skin surface, and the fat layer absorbed about 67% of the impact kinetic energy.Conclusions The experimental data of adipose tissues are very accurate. Numerical simulation can reproduce the penetration process well, and provide references for studying the damaging effect of non-lethal weapons on human body.