In recent years, cancer treatment methods and means are becoming more and more diversified, and single treatment methods often have limited efficacy, while the synergistic effect of immunity combined with chemotherapy can inhibit tumor growth more effectively. Based on this, we constructed a sodium alginate hydrogel composite system loaded with chemotherapeutic agents and tumor vaccines (named SA-DOX-NA) with a view to the combined use of chemotherapeutic agents and tumor vaccines. Firstly, the tumor vaccine (named NA) degradable under acidic conditions was constructed by in situ polymerization using chicken ovalbumin (OVA), acrylamide (AAM) and 2-(dimethylamino) ethyl methacrylate (DMAEMA) monomer. Then a hydrogel composite system SA-DOX-NA co-loaded with chemotherapeutic drug doxorubicin (DOX) and NA was prepared using sodium alginate as a matrix. The results showed that SA-DOX-NA had good in situ gel-forming ability and formed a mesh structure that could realize the co-loading of DOX and NA as well as the slow drug release. The electron microscopy results showed that SA-DOX-NA had good in situ gel-forming ability with good internal connectivity, and the three-dimensional mesh structure could realize the co-loading of DOX and NA as well as the slow drug release. The antitumor and immunomodulatory results showed that SA-DOX-NA both effectively inhibited the growth of tumor cells and efficiently promoted the proliferation and activation of DC2.4 dendritic cells without additional adjuvant. In summary, SA-DOX-NA exerts the dual efficacy of chemotherapy and immunotherapy for tumor treatment, and has a good application prospect in local tumor treatment.

The study investigated the specific mechanism by which oxocrebanine, the anti-hepatic cancer active ingredient in Stephania hainanensis, inhibits the proliferation of hepatic cancer cells. Firstly, methyl thiazolyl tetrazolium(MTT) assay, 5-bromodeoxyuridine(BrdU) labeling, and colony formation assay were employed to investigate whether oxocrebanine inhibited the proliferation of HepG2 and Hep3B2.1-7 cells. Propidium iodide(PI) staining was used to observe the oxocrebanine-induced apoptosis of HepG2 and Hep3B2.1-7 cells. Western blot was employed to verify whether apoptotic effector proteins, such as cleaved cysteinyl aspartate-specific protease 3(c-caspase-3), poly(ADP-ribose) polymerase 1(PARP1), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), Bcl-2 homologous killer(Bak), and myeloid cell leukemia-1(Mcl-1) were involved in apoptosis. Secondly, HepG2 cells were simultaneously treated with oxocrebanine and the autophagy inhibitor 3-methyladenine(3-MA), and the changes in the autophagy marker LC3 and autophagy-related proteins [eukaryotic translation initiation factor 4E-binding protein 1(4EBP1), phosphorylated 4EBP1(p-4EBP1), 70-kDa ribosomal protein S6 kinase(P70S6K), and phosphorylated P70S6K(p-P70S6K)] were determined. The results of MTT assay, BrdU labeling, and colony formation assay showed that oxocrebanine inhibited the proliferation of HepG2 and Hep3B2.1-7 cells in a dose-dependent manner. The results of flow cytometry suggested that the apoptosis rate of HepG2 and Hep3B2.1-7 cells increased after treatment with oxocrebanine. Western blot results showed that the protein levels of c-caspase-3, Bax, and Bak were up-regulated and those of PARP1, Bcl-2, and Mcl-1 were down-regulated in the HepG2 cells treated with oxocrebanine. The results indicated that oxocrebanine induced apoptosis, thereby inhibiting the proliferation of hepatic cancer cells. The inhibition of HepG2 cell proliferation by oxocrebanine may be related to the induction of protective autophagy in hepatocellular carcinoma cells. Oxocrebanine still promoted the conversion of LC3-Ⅰ to LC3-Ⅱ, reduced the phosphorylation levels of 4EBP1 and P70S6K, which can be reversed by the autophagy inhibitor 3-MA. It is prompted that oxocrebanine can inhibit the proliferation of hepatic cancer cells by inducing autophagy. In conclusion, oxocrebanine inhibits the proliferation of hepatic cancer cells by inducing apoptosis and autophagy.
Humans ; Apoptosis/drug effects* ; Autophagy/drug effects* ; Cell Proliferation/drug effects* ; Hep G2 Cells ; Liver Neoplasms/genetics* ; Carcinoma, Hepatocellular/genetics* ; Caspase 3/genetics*

OBJECTIVE: To explore the effect of bear bile powder (BBP) on acute lung injury (ALI) and the underlying mechanism. METHODS: The chemical constituents of BBP were analyzed by ultra-high-pressure liquid chromatography-mass spectrometry (UPLC-MS). After 7 days of adaptive feeding, 50 mice were randomly divided into 5 groups by a random number table (n=10): normal control (NC), lipopolysaccharide (LPS), dexamethasone (Dex), low-, and high-dose BBP groups. The dosing cycle was 9 days. On the 12th and 14th days, 20 µL of Staphylococcus aureus solution (bacterial concentration of 1 × 10^-7 CFU/mL) was given by nasal drip after 1 h of intragastric administration, and the mice in the NC group was given the same dose of phosphated buffered saline (PBS) solution. On the 16th day, after 1 h intragastric administration, 100 µL of LPS solution (1 mg/mL) was given by tracheal intubation, and the same dose of PBS solution was given to the NC group. Lung tissue was obtained to measure the myeloperoxidase (MPO) activity, the lung wet/dry weight ratio and expressions of CD14 and other related proteins. The lower lobe of the right lung was obtained for pathological examination. The concentrations of inflammatory cytokines including interleukin (IL)-6, tumour necrosis factor α (TNF-α ) and IL-1β in the bronchoalveolar lavage fluid (BALF) were detected by enzyme linked immunosorbent assay, and the number of neutrophils was counted. The colonic contents of the mice were analyzed by 16 sRNA technique and the contents of short-chain fatty acids (SCFAs) were measured by gas chromatograph-mass spectrometer (GC-MS). RESULTS: UPLC-MS revealed that the chemical components of BBP samples were mainly tauroursodeoxycholic acid and taurochenodeoxycholic acid sodium salt. BBP reduced the activity of MPO, concentrations of inflammatory cytokines, and inhibited the expression of CD14 protein, thus suppressing the activation of NF-κB pathway (P<0.05). The lung histopathological results indicated that BBP significantly reduced the degree of neutrophil infiltration, cell shedding, necrosis, and alveolar cavity depression. Moreover, BBP effectively regulated the composition of the intestinal microflora and increased the production of SCFAs, which contributed to its treatment effect (P<0.05). CONCLUSIONS BBP alleviates lung injury in ALI mouse through inhibiting activation of NF-κB pathway and decreasing expression of CD14 protein. BBP may promote recovery of ALI by improving the structure of intestinal flora and enhancing metabolic function of intestinal flora.
Animals ; Acute Lung Injury/pathology* ; Lipopolysaccharides ; Ursidae ; Gastrointestinal Microbiome/drug effects* ; Bile/chemistry* ; Lipopolysaccharide Receptors/metabolism* ; Powders ; Male ; Lung/drug effects* ; Mice ; Peroxidase/metabolism* ; Signal Transduction/drug effects* ; Cytokines/metabolism*

The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

To explore screening tools for children with autism spectrum disorder (ASD), which are convenient for primary hospitals, it can provide basic data for formulating ASD prevention policies. This was a cross-sectional study by cluster sampling. Huyi District and Xincheng District were extracted for investigation in Xi′an City. From July 2021 to September 2022, all children aged from 3 months to 36 months who live in the two districts were subjected to primary screening. The child care physician used the routine screening tool "warning signs checklist for screening psychological, behavioral and developmental problems of children" and cartoon pictures of "early high-risk warning signs of autism", the children who were positive in the initial screening were referred to the district level maternal and child health hospital for re-screening, and those who were positive in the re-screening were referred to Xi ′an Children′s Hospital for diagnosis. The results showed that a total of 17 905 children aged from 3 months to 36 months were initially screened in the two districts, including 10 588 children aged from 18 months to 36 months, 50 children who were positive in the initial screening and 50 children who were re-screened. 23 children (18 boys and 5 girls) were diagnosed with ASD. The prevalence rate of ASD in children was 2.17‰ (95% confidence interval:1.29‰-3.06‰). 42 children were positive for "warning signs checklist" at the preliminary screening, and 19 were confirmed as ASD. 27 children were positive for "cartoon pictures" in the preliminary screening, and 23 were confirmed with ASD. The "cartoon pictures" in the preliminary screening and diagnosis of consistent rate was higher than the "warning signs checklist", two kinds of screening methods comparison were statistically significant difference in the odds of consistent (χ 2=11.01, P=0.001). In conclusion, relying on the three-level network of maternal and child health care, it is conducive to the whole process management of screening and diagnosis of children with ASD, and to guide the formulation of prevention policies. The cartoon pictures of "early high-risk warning signs of autism" can assist the identification of children with ASD based on the "warning signs checklist", which is simple, effective and suitable for promotion in the community health care.

Objectives:To present the epidemiological characteristics of stroke incidence and stroke-related mortality among the whole population in national cardiovascular disease surveillance areas from 2015 to 2019. Methods:Data of stroke incidence and stroke-related mortality from 2015 to 2019 were collected from the China Registry of Cardiovascular Events(China RACE),which was established in 2014,covering 100 counties(cities,districts)in 31 provinces in China.The Joinpoint model was used to analyze the annual percentage changes(APC)and trends of stroke incidence rate.The age-standardized incidence rate(ASIR)was calculated using the Seventh National Census data as the standard population.With annual reported stroke events and stroke-related deaths,the mortality to incidence ratio(M/I)were examined. Results:From 2015 to 2019,an increase of 9.41%(APC=2.12%,95%CI:1.43%-2.82%,Ptrend<0.01)resulted in the overall stroke crude incidence rate(CIR)of 468.48/100 000 in 2019 among the whole population,with relatively higher in male and in rural area.The more sharply elevating of CIR appeared in males(11.26%[APC=2.53%,95%CI:1.83%-3.24%,Ptrend<0.01])rather than in females(7.26%[APC=1.63%,95%CI:0.81%-2.46%,Ptrend<0.01]).Meanwhile,the general ASIR decreased 7.47%(APC=-1.72%,95%CI:-3.23%--0.20%,Ptrend<0.05),reaching 523.82/100 000 in 2019.The females generally showed significant descending trend(9.56%[APC=-2.27%,95%CI:-3.99%--0.52%,Ptrend<0.05]),as well as more reduction than that in the males(15.82%vs.11.40%)in urban area.The crude incidence rate of stroke increased with age.From 2015 to 2019,the CIR in 45-49 age group increased 12.48%(APC=3.18%,95%CI:1.67%-4.72%,Ptrend<0.01),compared with an reduction of 15.76%(APC=-4.39%,95%CI:-7.63%--1.04%,Ptrend<0.05)in 80-84 age group.Over the monitoring years,the overall M/I was 0.19,with an age-specific U-shaped distribution.The lowest of M/I(0.10)appeared in those aged 50-54 and 55-59,while the highest(0.45)detected in those aged 85 and over.The M/I of all age in urban areas were consistently lower than that in rural areas. Conclusions:Stroke incidence burden increased from 2015-2019 in the national surveillance areas in China,along with the unfavorable geographic diversity and age-specific divergence.Further efforts are required to improve health care covering all ages and regions in China to reduce the incidence of stroke and stroke-related mortality.

Objectives:The present study aims to investigate the incidence and mortality feature of acute myocardial infarction(AMI)from 2015 to 2019 in China by utilizing national registry data. Methods:Data of AMI incidence and mortality in the surveillance area during 2015 to 2019 were abstracted from China Registry of Acute Cardiovascular Event(China RACE),which was established in 100 counties from 31 provincial regions in China.Incidence rate,age standardized incidence rate(ASIR)and mortality to incidence ratio(M/I)was estimated in AMI cases.A Joinpoint regression was executed and annual percent change(APC)was examined to identify trends in incidence. Results:From 2015 to 2019,a total of 257 686 acute myocardial infarction incidence and 149 169 deaths were registered.The annual incidence rate of AMI in 2019 was 82.76 per 100 000.Over the study period,the incidence rate of AMI increased by 6.05%for men(APC=1.30%,95%CI:0.56%to 2.02%)but decreased by 11.80%for women(APC=-3.10%,95%CI:-4.54%to-1.68%),resulting a steady trend for AMI crude incidence rate for the overall population.The overall ASIR of AMI declined by 16.59%(APC=-4.32%,95%CI:-5.32%to-3.34%)from 113.68 per 100 000 in 2015 to 94.82 per 100 000 in 2019.The ASIR of AMI declined by 11.04%(APC=-2.72%,95%CI:-3.78%to-1.67%)for men,23.96%(APC=-6.56%,95%CI:-8.57%to-4.58%)for women,12.57%(APC=-3.08%,95%CI:-6.01%to-0.08%)for the urban areas,and 19.24%(APC=-5.18%,95%CI:-10.19%to 0.03%)for rural areas respectively.The incidence rate of AMI increases gradually with age in both men and women.The incidence of AMI in urban men of 35-44 and 45-54 year age groups increased by 77.16%(APC=13.52%,95%CI:3.29%to 24.57%)and 26.36%(APC=5.71%,95%CI:-0.95%to 12.68%)over time.However,the incidence of AMI fell in the population above 65 year old,by 26.58%(APC=-6.68%,95%CI:-11.98%to-1.01%),19.85%(APC=-5.64%,95%CI:-11.57%to 0.65%)and 14.53%(APC=-4.44%,95%CI:-7.75%to-1.04%)in the 65-74 year age,75-84 year age and≥85year age groups respectively from 2015 to 2019.The mortality to incidence ratio of AMI was 0.58 over time,higher in women than in men,and higher in rural areas than in urban areas.The M/I ratio of AMI decreased from 0.62 in 2015 to 0.52 in 2019(APC=-4.28%,95%CI:-5.75%to-2.83%).There was a declined trends in M/I of AMI in urban residents of both male and female,and in the rural male residents(all P<0.05),while a steady trend in the rural female residents(P>0.05). Conclusions:The overall incidence of AMI remains steady during 2015 to 2019 in the national surveillance areas in China.Yet,downward trends in elder and female residents and increased trend in middle-aged urban males in AMI incidence are observed.The mortality of AMI in these period are age,sex and urban-rural dependent.Targeted mitigation strategies on AMI prevention and treatment need to be strengthened to reduce its incidence and mortality.

AIM:To investigate the effect of vision therapy system 4D combined with stereoscopic 3D technology training for the treatment of amblyopia.METHODS: Prospective study. A total of 102 children with amblyopia who attended the clinic from January 2018 to January 2022 were selected, and they were randomly assigned into two groups by computer, with 51 cases in each group. Control group received stereoscopic 3D technology training, while observation group participated in vision therapy system 4D on the basis of control group. Then the overall effective rate, binocular visual function, spherical equivalent(SE), axial length(AL), mean corneal curvature(Km), best corrected visual acuity(BCVA)and visual evoked potential were compared between two groups.RESULTS: The overall efficacy rate was 94.1% in observation group, which was obviously higher than control group(74.5%; P<0.05). The improvement in binocular vision parameters simultaneous perception, total fusion, and stereoacuity were all more remarkable in observation group than in control group(P<0.05). The △SE, △AL and △Km yielded no statistical difference between two groups(P>0.05). The latency of two spatial frequencies(1°grid and 15'grid)showed a decline in both groups, and the decline was more notable in observation group than in control group(P<0.05). In both groups, BCVA improved, and the improvement was more significant in observation group compared with control group(P<0.05).CONCLUSION: Application of vision therapy system 4D combined with stereoscopic 3D technology training for amblyopia can effectively ameliorate the visual acuity, promote the reconstruction of simultaneous perception, total fusion, and stereoacuity without additional risk of myopic shift, and improve visual pathway function in children.

OBJECTIVE: To investigate the treatment outcome of laparoscopic partial nephrectomy in the patients with renal tumors of moderate to high complexity (R.E.N.A.L. score 7-10). METHODS: In the study, 186 patients with a renal score of 7-10 renal tumors who underwent laparoscopic partial nephrectomy in Peking University Third Hospital from February 2016 to April 2021 were selected. Laparoscopic partial nephrectomy was performed after examination. The patients were followed-up, and their postoperative hemoglobin, creatinine, complications, and length of hospital stay recorded. The data were represented by mean±standard deviation or median (range). RESULTS: There were 128 males and 58 females in this group, aged (54.6±12.8) years, with body mass index of (25.4 ± 3.4) kg/m²; The tumors were located in 95 cases on the left and 91 cases on the right, with maximum diameter of (3.1±1.2) cm. The patient's preoperative hemoglobin was (142.9±15.8) g/L, and blood creatinine was 78 μmol/L (47-149 μmol/L). According to preoperative CT images, the R.E.N.A.L. score was 7 points for 43 cases, 8 points for 67 cases, 9 points for 53 cases, and 10 points for 23 cases. All the ope-rations were successfully completed, with 12 cases converted to open surgery. The operation time was 150 minutes (69-403 minutes), the warm ischemic time was 25 minutes (3-60 minutes), and the blood loss was 30 mL (5-1 500 mL). There were 9 cases of blood transfusions, with a transfusion volume of 800 mL (200-1 200 mL). Postoperative hemoglobin was (126.2±17.0) g/L. The preoperative crea-tinine was 78 μmol/L (47-149 μmol/L), the postoperative creatinine was 83.5 μmol/L (35-236 μmol/L), the hospital stay was 6 days (3-26 days), and surgical results achieved "the trifecta" in 87 cases (46.8%). In the study, 167 cases were followed up for 12 months (1-62 months), including 1 case with recurrence and metastasis, 4 cases with metastasis, and 2 cases with other tumors (1 case died). CONCLUSION Laparoscopic partial nephrectomy is safe and effective in the treatment of renal tumors with R.E.N.A.L. score of 7-10. Based on the complexity of the tumor, with the increase of difficulty, the warm ischemia time and operation time tend to increase gradually, while "the trifecta" rate gradually decreases. The complications of this operation are less, and the purpose of preserving renal function to the greatest extent is achieved.
Male ; Female ; Humans ; Creatinine ; Retrospective Studies ; Kidney Neoplasms/pathology* ; Nephrectomy/methods* ; Treatment Outcome ; Laparoscopy ; Hemoglobins