Objective: To investigate the trends in mortality and life loss of gastric cancer in Wenzhou City, Zhejiang Province from 2014 to 2023, so as to provide the evidence for formulating the prevention and control strategy for gastric cancer. Methods: The surveillance on causes of death data of permanent residents in Wenzhou City were collected through the Wenzhou Chronic Disease Monitoring and Management Information System from 2014 to 2023. The crude mortality of gastric cancer was calculated, and standardized by the data from the Sixth Chinese National Population Census in 2010. The life loss were measured using potential years of life lost (PYLL) and rate of potential years of life lost (PYLLR). The characteristics of mortality and life loss of gastric cancer in different genders and age groups were described. The trends in mortality and PYLLR of gastric cancer were analyzed using the average annual percent change (AAPC). Results: Totally 17 080 deaths were reported due to gastric cancer in Wenzhou City from 2014 to 2023, accounting for 12.58% and ranking third in the order of malignant tumor deaths. The crude mortality of gastric cancer was 20.73/105, and the standardized mortality was 15.22/105, showing decreasing trends (AAPC=-3.311%, -6.470%, both P<0.05). The crude mortality of gastric cancer was 29.22/105 in men and 11.61/105 in women, with standardized mortality rates of 20.81/105 and 8.74/105 (both P<0.05). The crude mortality of gastric cancer appeared a tendency towards a rise with increasing age (P<0.05), reaching the highest rate of 225.88/105 in the group aged 80 to <85 years. The PYLL and PYLLR of gastric cancer were 107 607.50 person-years and 1.37‰. The PYLLR appeared a tendency towards a decline from 2014 to 2023, with AAPC of -6.667% (P<0.05). Conclusions The mortality and PYLLR of gastric cancer in Wenzhou City appeared a tendency towards a decline from 2014 to 2023. Men and the elderly populations were the key groups for the prevention and treatment of gastric cancer.

BACKGROUND:Impaired postural control is an important risk factor for falls and secondary damage in patients with idiopathic normal pressure hydrocephalus.Most of the existing studies have analyzed the gait parameters of patients during straight-line walking,but few have analyzed the postural stability characteristics of patients during static and dynamic activities. OBJECTIVE:To analyze the characteristics of postural stability in elderly patients with idiopathic normal pressure hydrocephalus. METHODS:Twenty-two patients clinically diagnosed with idiopathic normal pressure hydrocephalus at the Department of Neurosurgery,Huadong Hospital Affiliated to Fudan University,Shanghai,China,from September 2022 to February 2023 were selected as the patient group,and 18 healthy accompanying family members were selected as the healthy control group.The postural stability characteristics of the subjects were assessed using the Timed Up-and-Go Test,Multi-Directional Reach Test,Berg Balance Scale,and Static Balance Function Test(reaction time,speed of movement,directional control,maximum offset distance,and endpoint travel). RESULTS AND CONCLUSION:The time required to complete the Timed Up-and-Go Test was significantly longer in the patient group than in the healthy control group(P＜0.05).The results of the stretching test in the four directions of anterior,posterior,leftand right were significantly lower in the patient group than in the healthy control group(P＜0.05).The Berg Balance Scale scores in the patient group were lower than those in the healthy control group(P＜0.05).In the Static Balance Function Test,the results of reaction,movement speed,directional control,maximum offset distance and endpoint travel index were smaller in the patient group than the healthy control group(P＜0.05).To conclude,patients with idiopathic normal pressure hydrocephalus exhibit overall postural control deficits,and impaired reaction and execution abilities make these patients unable to make timely and accurate motor responses in the face of disturbances from internal or external sources,resulting in postural instability and increasing the risk of falls.

Objective: To investigate the environmental contamination of norovirus in nurseries and primary/secondary schools, so as to provide a scientific basis for effective prevention and control measures. Methods: A total of 483 external environmental samples were collected from 34 cluster outbreaks of norovirus gastroenteritis in kindergartens and primary/secondary schools in Linhai City from 2021 to 2024. Pathogen detection was conducted using a rapid nucleic acid extraction kit and realtime fluorescence RT-PCR, and the results were analyzed using the χ2 test or Fishers exact test. Results: Among the collected external environmental samples, the total positive rate of surface contamination was 13.66%. The positive rates in kindergartens and primary/secondary schools were 12.20% and 15.82%, respectively. In kindergartens, the five surfaces with the highest detection rates were desks/chairs (23.33%), toilet stool troughs (20.69%), urinal troughs (12.00%), washbasins/sinks (11.11%), and toilet mops (9.38%). In primary/secondary schools, the top five were toilet stool troughs (38.30%), urinal troughs (23.53%), toilet door handles (13.04%), toilet mops (12.50%), and drinking cups (11.11%). The difference in positive detection rates among different external environments in primary/secondary schools was statistically significant (Fishers exact probability test, P<0.01). The positive detection rate in sanitary toilets was higher than that in classroom environments (χ2=17.38), while the positive detection rate in classroom environments of kindergartens was higher than that in primary/secondary schools (χ2=5.42)(P<0.05). Conclusions Norovirus exhibits a high contamination rate in nurseries and schools, particularly in restroom areas. Strengthening sanitation and disinfection in highrisk environments, and improving hygiene awareness among children and staff, are essential for the effective prevent and control of norovirus.

The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

Objective: To design and establish a new method for flow cytometry-based detection of commonly observed highly expressed antigens on red blood cells, and to further evaluate the differences and distribution characteristics of antigen expression levels between ABO blood type homozygotes and heterozygotes in healthy individuals. Methods: Residual blood samples after donor blood type identification by Shanghai Blood Center in April 2024 were collected. Among them, samples of 19 homozygous and 19 heterozygous individuals of type A and type B were selected. Then the expression level of ABO antigen on red blood cells were detected using the new method established in this study and the traditional aldehyde fixed red blood cell method. Both methods were tested independently three times and the results were compared. Results: The mean values of the three detection results of the new method was (×10 /RBC): AA homozygous 3.3±0.5, AO heterozygous 2.8±0.3, BB homozygous 3.6±0.3, BO heterozygous 3.1±2.8. The mean values of the three detection results of the aldehyde fixation method were AA homozygous 5.9±0.9, AO heterozygous 5.0±1.4, BB homozygous 3.8±0.6, and BO heterozygous 3.3±0.4. The average antigen distribution of each genotype followed a normal distribution. Comparing the average antigen expression levels of homozygotes and heterozygotes, both methods showed that A/B homozygotes had higher antigen levels than heterozygotes, with AA being 1.17 to 1.18 times that of AO and BB being 1.15 to 1.16 times that of BO. Comparing the inter batch differences in the three test results of two methods, the new method showed no significant difference in the three test results for four genotypes (P>0.05). The aldehyde fixation method showed significant differences in the test results for all three genotypes (P<0.01) except for BB homozygotes (P>0.05). The reliability and reproducibility of the new method were better than those of the traditional aldehyde fixation method. Conclusion: The antigen expression level of ABO homozygotes is higher than that of heterozygotes, and the difference in antigen level between type A homozygotes and heterozygotes is slightly higher than that of type B. The new method is superior to traditional aldolization fixation methods.

Objective To modify YC-1,an inhibitor of hypoxia-inducible factor-1α(HIF-1α)into nanoparticles and explore its effect on reversing chemoresistance of colorectal cancer cells.Methods Nano-inhibitor mPEG350-YC-1(MYC-1)was prepared by the carboxyl condensation reaction of the active functional group hydroxyl(-OH)in the YC-1 molecule with methoxy polyethylene glycol carboxylic acid,and was verified by 1H nuclear magnetic resonance(1H-NMR).Its morphology was analyzed by transmission electron microscope(TEM),and its particle size distribution was analyzed by dynamic light scattering(DLS).By interacting FITC-labeled MYC-1(FYC-1)with HCT15 cells,the uptake ability of FYC-1 by the cells was observed using laser confocal microscopy.The cytotoxicity of MYC-1 was measured with CCK-8 assay.The sensitization effect of MYC-1 on the chemotherapy drug 5-Fu was detected through toxicity tests of resistant HCT15 cells(resistant HCT15,R-HCT15)and live/dead cell staining.The mechanism of MYC-1 reversing drug resistance was determined with immunofluorescence staining of HIF-1α and western blotting.Finally,a subcutaneous transplanted tumor model of R-HCT15 cells was constructed.The tumor bearing mice were randomly divided into PBS,5-Fu,MYC-1,and MYF groups,with 3 mice in each group.The tumor volume and weight were observed after treatment in each group to evaluate the ability of MYC-1 to reverse 5-Fu resistance in colorectal cancer.Results The nano-inhibitor MYC-1 was successfully prepared.TEM and DLS showed that MYC-1 could self-assemble into nanoparticles with a diameter of approximately 19.96±2.97 nm in aqueous solution.FYC-1 was also successfully prepared.When FYC-1 was interacted with HCT15 cells,FYC-1 could be better taken up by the cells,indicating that the amphiphilic MYC-1 could be better endocytosed into the cells to exert its function.When MYC-1 and 5-Fu acted in combination in colon cancer R-HCT15 cells,the resistance index(RI)was decreased from 7.99 to 1.55,and the relative reversal rate(RRR)of RI was 80.6%.Live(green)/dead(red)cell staining revealed that MYC-1 increased the toxicity of 5-Fu to R-HCT15 cells.Immunofluorescence staining(P<0.01)and Western blotting indicated that MYC-1 effectively inhibited the intracellular expression of HIF-1α.The combined action of MYC-1 and 5-Fu on mice with R-HCT15 subcutaneous transplanted tumors had the best therapeutic effect when compared with PBS(P<0.001),5-Fu(P<0.01),and MYC-1(P<0.01).Immunofluorescence staining of HIF-1α in tumor tissues displayed that the expression of HIF-1α was decreased in the MYC-1 and MYF groups.HE staining showed that there was no obvious damage to the important organs in each treatment group.Conclusion Nano-inhibitor MYC-1 can reverse the drug resistance of colorectal cancer to 5-Fu chemotherapy by reducing the expression of HIF-1α protein in colorectal cancer cells,thereby effectively improving the therapeutic effect of 5-Fu.

Objective:To retrospectively analyze and compare the clinical effects of rigid neuroendoscopic hematoma removal and drilling irrigation drainage in the treatment of chronic subdural hematomas with mixed density on head CT, and explore the appropriate surgical methods for chronic subdural hematomas with mixed density.Methods:A retrospective case-control study was conducted to analyze the clinical data of 80 patients with CSDH with mixed density CT findings admitted to the Department of Neurosurgery of Guizhou Medical University Affiliated Hospital from January 2021 to November 2023. There were 57 males and 23 females. According to the surgical method, patients were divided into endoscopic group ( n=36) and drilling group ( n=44). Patients in the endoscopic group underwent hard neuroendoscopic hematoma removal surgery, while patients in the drilling group underwent drilling flushing and drainage surgery. Compared the surgical time, drainage time, hematoma clearance rate, length of hospital stay, markwalder neurological function grading, and activities of daily living (ADL) score between two groups 30 days after surgery. Followed up for 3 months to record the recurrence situation.Measurement data with a normal distribution were expressed as mean±standard deviation ( ± s), and t-test was used for inter-group comparison. Measurement data with a non-normal distribution were expressed as M( Q1, Q3), and rank sum test was used for inter-group comparison. Chi-square test or Fisher′s exact test was used for inter-group comparison of count data. Rank sum test was used for inter-group comparison of ordinal data. Results:The operation time, postoperative drainage time, 24-hour hematoma clearance rate, midline deviation distance and hospital stay in the endoscopic group respectively were (77.50±8.15) min, 1.00(1.00, 2, 00) d, (95.00±2.66)%, 1.00(0.00, 2.00) mm, (9.47±2.52) d. The drilling group were (44.77±6.56) min, 3.00(2.25, 3.00) d, (87.86±3.43)%, 3.00(2.00, 3.00) mm, (11.84±3.28) d, the difference was statistically significant between the two groups ( P<0.05). Comparison of long-term efficacy in the endoscopic group, the hematoma clearance rate at 30 days after operation, the ADL score at 30 days after operation, and the number of recurrence cases at 3 months after operation respectively were 99.00(97.25, 100.00)%, (88.06±7.86) points, and 1 case. The drilling group were 93.50(91.25, 95.75)%, (83.29±9.58) points and 10 cases, with statistical difference between the two groups( P<0.05). 30 day postoperative Markwalder neurological functional grading, there were 27 cases grades 0, 9 cases of grade I, and 0 cases of grade II in endoscopic surgery. In the drilling group, there were 24 cases, 15 cases, and 5 cases, respectively. The difference between the two groups was statistically significant ( P<0.05). Conclusions:Compared with drilling and drainage irrigation surgery, neuroendoscopic treatment of mixed density chronic subdural hematoma takes a relatively long time, but the hematoma clearance rate is higher, the hospitalization time is shorter, the postoperative recovery is faster and the recurrence rate is lower. Neuroendoscopic therapy has unique advantages and may be more suitable for the treatment of mixed density CSDH.

Acupuncture treatment of chronic pain combined with depression (CPDC) is the result of a multi-target, multi-pathway approach. Acupuncture can treat CPDC by inhibiting the activation of glial cells, regulating the release of inflammatory mediators, regulating the expressions of neurotransmitters, changing the plasticity of neural synapses, regulating related epigenetic effects, regulating the microbiota-brain-gut axis, inhibiting nerve cell apoptosis, and antagonizing oxidative stress. The mechanism of its effect mainly involves anti-inflammatory related signaling pathways, regulation of neural synapse-related signaling pathways, and exerts its therapeutic effect through hippocampus, cerebral cortex, and amygdala.

Based on the α7 nicotinic acetylcholine receptor(α7nAChR), this study examined how tetrahydropalmatine(THP) affected BV2 microglia exposed to lipopolysaccharide(LPS), aiming to clarify the possible mechanism underlying the anti-depression effect of THP from the perspectives of preventing inflammation and regulating polarization. First, after molecular docking and determination of the content of Corydalis saxicola Bunting total alkaloids, THP was initially identified as a possible anti-depression component. The BV2 microglia model of inflammation was established with LPS. BV2 microglia were allocated into a normal group, a model group, low-and high-dose(20 and 40 μmol·L~(-1), respectively) THP groups, and a THP(20 μmol·L~(-1))+α7nAChR-specific antagonist MLA(1 μmol·L~(-1)) group. The CCK-8 assay was used to screen the safe concentration of THP. A light microscope was used to examine the morphology of the cells. Western blot and immunofluorescence were used to determine the expression of α7nAChR. qRT-PCR was performed to determine the mRNA levels of inducible nitric oxide synthase(iNOS), cluster of differentiation 86(CD86), suppressor of cytokine signaling 3(SOCS3), arginase-1(Arg-1), cluster of differentiation 206(CD206), tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1β. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. The experimental results showed that THP at concentrations of 40 μmol·L~(-1) and below had no effect on BV2 microglia. THP improved the morphology of BV2 microglia, significantly up-regulated the protein level of α7nAChR, significantly down-regulated the mRNA levels of iNOS, CD86, SOCS3, TNF-α, IL-6, and IL-1β, significantly up-regulated the mRNA levels of Arg-1 and CD206, and dramatically lowered the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. However, the antagonist MLA abolished the above-mentioned ameliorative effects of THP on LPS-treated BV2 microglia. As demonstrated by the aforementioned findings, THP protected LPS-treated BV2 microglia by regulating the M1/M2 polarization and preventing inflammation, which might be connected to the regulation of α7nAChR on BV2 microglia.
Berberine Alkaloids/chemistry* ; alpha7 Nicotinic Acetylcholine Receptor/chemistry* ; Microglia/metabolism* ; Mice ; Animals ; Cell Line ; Corydalis/chemistry* ; Humans ; Molecular Docking Simulation ; Inflammation/drug therapy* ; Nitric Oxide Synthase Type II/immunology* ; Tumor Necrosis Factor-alpha/immunology*

This study aims to investigate the polarized microscopic mineral phase characteristics, inorganic element content, and potential health risks associated with the intake of raw and calcined fossil mineral Chinese medicinal material Draconis Os. Microscopy was employed to observe the mineralogical characteristics of Draconis Os and compare the microscopic features and phase composition of raw and calcined Draconis Os under monochromatic and orthogonal polarized light. Inductively coupled plasma mass spectrometry(ICP-MS) was employed to determine the content of 30 inorganic elements. Health risk assessment was conducted by calculating the single pollution index(P_i), average daily intake of elements for adults(ADI), target hazard quotient(THQ), non-carcinogenic assessment method-hazard quotient(HQ), and the carcinogenic risk of elements(CR). The results indicated that under monochromatic polarized light, the Draconis Os powder sections exhibited light gray-brown to gray-brown irregular fragments, some with undulating textures that were slightly curved. Under crossed polarized light, they appeared dark gray, grayish-white, and yellowish-white. Clear apatite was visible in the ground sections of Draconis Os under crossed polarized light. P_i results indicated that Draconis Os samples were free from contamination and were of good quality. According to the maximum allowable limits of heavy metals stipulated in ISO Traditional Chinese Medicine: Determination of heavy metals in herbal medicines used in Traditional Chinese Medicine, ADI, THQ, HQ, and CR were taken as assessment indicators. Only the THQ value for As(arsenic) in raw Draconis Os was greater than 1, while the THQ values for other heavy metal elements in the Draconis Os samples were all less than 1. The study demonstrates that the primary mineral phase of raw and calcined Draconis Os is apatite, with some samples co-existing with calcite, which can serve as one of the means for quality control of Draconis Os. The elemental analysis results from ICP-MS provide scientific evidence for the safety assessment of Draconis Os, indicating that Draconis Os is safe in clinical application.
Drugs, Chinese Herbal/analysis* ; Risk Assessment ; Minerals/chemistry* ; Fossils ; Humans ; Drug Contamination ; Mass Spectrometry