19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

As one of the pathogenic mechanisms contained in The Inner Canon of Yellow Emperor （《黄帝内经》）， “disease with latent pathogen induced by a new pathogen” means that the induced new pathogen resulted to a combination of the latent previous pathogen and the new pathogen， which caused the disease. Based on this， it is believed that the change of “nodule-cancer transformation” of pulmonary nodules is actually based on the deficiency of original qi， and the new pathogen induces the latent pathogens like phlegm coagulation， qi stagnation， blood stasis， toxicity， so healthy qi can not drive the pathogens out， and the long-time detention generated into cancerous turbidity， and deve-loped into cancerous tumour at the end. Therefore， based on the three-stage treatment of unformed cancer， dense cancerous toxin， and developed cancer， the clinical practice applied six methods of clearing， expelling， dissipating， tonifying， harmonizing， and transforming， taking into account both the manifestation and root cause， moving the treatment window of pulmonary nodules forward， attacking the pathogens when the toxin was not yet overbearing， supporting the healthy qi before declining， delaying the process of nodules-cancer transformation， and providing ideas for the prevention and treatment of pulmonary nodules “nodule-cancer transformation” in traditional Chinese medicine.

Objective A simple,sensitive and rapid ultra high performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)method was developed and validated for the determination of ertapenem in human plasma.Methods Using ertapenem-D4 as internal standard,the protein in plasma was precipitated with acetonitrile;chromatographic column:ACQUITY HSS T3(2.1 mm × 50.0 mm,1.8 μm);the mobile phase was 0.1％formic acid aqueous solution(containing 2 mmol·L-1 ammonium formate)-acetonitrile(0.1％formic acid),using a gradient elution;flow rate:0.4 mL·min-1,injection volume:1 μL,column temperature:45 ℃,the analysis time was 4.5 min,the scanning mode is positive ion selective reaction monitoring mode(SRM)with an electric spray ion source(ESI).The specificity,standard curve and lower limit of quantification,precision and recovery,matrix effect,dilution effect and stability were investigated.Results Ertapenem had a good linearity within 0.5-80.0μg·mL-1,and the standard curve was y=4.25 × 10-1x-2.64× 10-2(r2=0.999 0),the lower limit of quantification was 0.5 μg·mL-1,the relative standard deviation within and between batches is 1.39％-4.15％.The extraction recovery rate was 58.36％-64.57％,and the relative standard deviation of dilution effect was 3.30％,and the matrix effect was 99.71％-103.23％.The relative standard deviation of room temperature,repeated freeze-thaw,4 ℃,and long-term stability are all less than 10％.Conclusion The method is sensitive,rapid and specific,which is suitable for clinical monitoring of Ertapenem.

Objective:This paper provides a brief overview of the epidemiology of colorectal cancer in China and around the world, and discusses how to prevent colorectal cancer to reduce its disease burden.Method:Using the official database of GLOBOCAN 2020, the China Cancer Registry Annual Report compiled by the National Cancer Center, and data from CONCORD-3.Data management was performed by Microsoft Excel 2016 and R 4.2.1 Relevant graphs were generated using the ggplot2 package for result visualization.Result:An estimated 1 931 590 people were diagnosed with colorectal cancer worldwide in 2020 with an age-standardized incidence rate of 19.5 per 100 000. There were about 935 173 deaths caused by colorectal cancer internationally, with an age-standardized mortality rate of 9.0 per 100 000. Overall, colorectal cancer was the fourth most commonly diagnosed cancer and the third leading cause of cancer-related death worldwide in 2020. In China, the age-standardized incidence rate and mortality rate of colorectal cancer was 17.3 per 100 000 and 7.8 per 100 000, respectively. Gender differences in trends were observed, with a decreasing trend in incidence and mortality among females and an increasing trend in incidence and mortality among males. The primary risk factors for colorectal cancer include age, genetic factors, gastrointestinal disorders, dietary habits, and lifestyle et al.Conclusions:Colorectal cancer poses a significant burden globally and in China. The occurrence of colorectal cancer is closely related to physiology, genetics, behavioral habits, lifestyle, and disease factors. To better control the colorectal cancer burden with the lowest cost, specific measures should be taken to reduce exposure to established risk factors. By combining the disease prevention and control strategies of tertiary prevention in China with the characteristic factors of colorectal cancer, the incidence and mortality of colorectal cancer may be effectively controlled.

Objective This study aimed to determine the current epidemiological status of PLWHA aged≥50 years in China from 2018 to 2021.It also aimed to recommend targeted interventions for the prevention and treatment of HIV/AIDS in elderly patients. Methods Data on newly reported cases of PLWHA,aged≥50 years in China from 2018 to 2021,were collected using the CRIMS.Trend tests and spatial analyses were also conducted. Results Between 2018 and 2021,237,724 HIV/AIDS cases were reported among patients aged≥50 years in China.The main transmission route was heterosexual transmission(91.24%).Commercial heterosexual transmission(CHC)was the primary mode of transmission among males,while non-marital non-CHC([NMNCHC];60.59%)was the prevalent route in women.The proportion of patients with CHC decreased over time(Z = 67.716,P<0.01),while that of patients with NMNCHC increased(Z = 153.05,P<0.01).The sex ratio varied among the different modes of infection,and it peaked at 17.65 for CHC.The spatial analysis indicated spatial clustering,and the high-high clustering areas were mainly distributed in the southwestern and central-southern provinces. Conclusion In China,PLWHA,aged≥50 years,were predominantly infected through heterosexual transmission.The primary modes of infection were CHC and NMNCHC.There were variations in the sex ratio among different age groups,infected through various sexual behaviors.HIV/AIDS cases exhibited spatial clustering.Based on these results,the expansion of HIV testing,treatment,and integrated behavioral interventions in high-risk populations is recommended to enhance disease detection in key regions.

Lung cancer remains one of the leading cause of global cancer-related mortality, posing a significant burden of disease. Tobacco exposure stands as the foremost risk factor for lung cancer. Since the 1960, global efforts have gradually been implemented to control tobacco exposure, consequently reducing tobacco exposure levels within populations. This shift in exposure levels may have altered the epidemiological characteristics of lung cancer globally. This study aims to describe global lung cancer incidence data across five dimensions: age, gender, region, stage at diagnosis, and survival status, using global cancer registry data and relevant research findings. The objective is to elucidate the current epidemiological features of lung cancer worldwide, providing a scientific basis for lung cancer prevention and control. Furthermore, this study offers corresponding measures and recommendations for lung cancer prevention and control, aligning with the three-tiered cancer prevention strategy. Findings indicate that the incidence and mortality burden of lung cancer is significantly higher among the elderly population (aged 65 years and above) compared to the working-age population (aged 15-64 years). The aged-standardized incidence rate of lung cancer remains higher in males than in females, but the overall aged-standardized incidence rate of lung cancer in males shows a declining trend, while that in females shows an increasing trend. Regions with high and very high human development index (HDI) exhibit a substantially higher incidence and mortality burden of lung cancer compared to regions with low and very low HDI. Japan ranks highest in the diagnosis of stage Ⅰ lung cancer, with a diagnosis rate of 38.6%. Its age-standardized 5-year net survival rate is relatively high at 32.9%. Despite improvements in the survival status of lung cancer in certain countries like China and Japan, the overall prognosis for lung cancer remains pessimistic. Given the current epidemiological characteristics of lung cancer, reinforcing tobacco control measures and reducing female-specific lung cancer risk factors stand as significant goals for primary prevention. Promoting low-dose computed tomography screening for high-risk population, minimizing false-positive rates in lung cancer screening, and promoting medical system reforms and standardized treatment constitute principal measures for secondary and tertiary lung cancer prevention, respectively.

Objective:To analyze the incidence, mortality, and survival status and trends of lung cancer in China.Methods:The data of incidence, mortality, disability-adjusted life year (DALY), and survival status and trends of lung cancer in China were collected from GLOBOCAN 2020, Global Burden of Disease Study in 2019 (GBD2019) databases, and the CONCORD-3 project report. Joinpoint 5.0 software was used to analyze the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of lung cancer in China from 1990 to 2019. Data management was conducted by using Excel 2016, and relevant graphical representations were generated using the ggplot2 package in software R 4.2.1.Results:In 2020, a total of 815 563 lung cancer cases were newly reported in China with the ASIR of 34.8/100 000, in which 539 181 cases were reported in men, with the ASIR of 47.8/100 000, and 276 382 cases were reported in women, with the ASIR of 22.8/100 000. A total of 714 699 lung cancer deaths were reported in 2020, with the ASMR of 30.2/100 000. Among these deaths, there were 471 546 deaths in men with the ASMR of 41.8/100 000, and 243 153 deaths in women with the ASMR of 19.7/100 000. From 1990 to 2019, the ASIR and ASMR of lung cancer in both men and women showed increasing trends ( P<0.05). However, from 2010 to 2019, the ASIR and ASMR of lung cancer in men showed decreasing trends, with annual percent of change (APC) of -0.17% (95% CI: -0.24% - -0.09%) and -0.69% (95% CI: -0.79% - -0.59%), respectively. The ASIR and ASMR of lung cancer in women showed increasing trends from 2016 to 2019, with APC of 3.33% (95% CI: 2.73% - 3.88%) and 2.61% (95% CI: 1.99% - 3.28%), respectively. The five-year net survival rate for lung cancer was 19.8% in China (95% CI:19.4% - 20.2%) from 2010 to 2014. Conclusions:The morbidity and mortality of lung cancer in China remain at high levels, the prognosis of lung cancer was poor, and the disease burden of lung cancer would become more serious in the context of population aging, so three-level prevention of lung cancer should be implemented to address this problem. In addition, attention should be paid to the increasing trends of ASIR and ASMR of lung cancer in women in recent years. Further investigation of risk factors and targeted prevention are needed to curb the rising trend in the incidence of lung cancer in women.

The voltage-gated sodium channel subtype Nav1.7 is highly expressed in nociceptive sensory neurons and is a key pathogenic target in several human hereditary pain syndromes. In recent years, a large number of studies have shown that Nav1.7 plays an important role in inflammatory, neuropathic, and nociceptive pain. Therefore, targeting Nav1.7 is a new strategy and hotspot for the development of novel analgesics. This review introduces the structure and function of Nav1.7, its regulatory role in pain, highlights the development progress of small-molecule Nav1.7 inhibitors in clinical trials, and analyzes the preclinical development of highly specific Nav1.7 inhibitors, with a view to providing reference for the development of Nav1.7 analgesic drugs.

Objective:To evaluate the safety and efficacy of hydroxyapatite-magnesium (HA-Mg) glaucoma drainage plate after implantation in rabbit eyes.Methods:Twelve New Zealand white rabbits were randomly assigned to HA-Mg drainage implant group and trabeculectomy group using the paired comparison method, with 6 rabbits in each group.The right eyes of rabbits were taken as the experimental eyes, and the left eyes of rabbits were taken as a normal control group.HA-Mg drainage implant group underwent implantation of the HA-Mg drainage plate and the trabeculectomy group underwent trabeculectomy.At 1, 3, and 5 months after surgery, the ocular condition was observed by slit-lamp examination with auxiliary lenses and the fixation of the drainage plate in the anterior chamber and subconjunctiva was measured by ultrasound biomicroscopy.At 5 months after surgery, corneal endothelial cell counts were performed with a corneal endothelial cell counter.The intraocular pressure (IOP) was continuously measured weekly for 21 weeks preoperatively and postoperatively.The flow patency of aqueous humor drainage channel was identified by the injection of trypan blue in anterior chamber.The aqueous humor drainage channels and surrounding tissues were evaluated by hematoxylin-eosin (HE) staining after HA-Mg drainage plate was completely degraded.This study was in accordance with China Animal Welfare Law and the ARVO Statement on the use of animals for ophthalmic research, and animal experiments were conducted in accordance with the Regulations on the Administration of Experimental Animals issued by the National Science Council.The study protocol was reviewed and approved by the Ethics Committee of The Third Affiliated Hospital of Chongqing Medical University (No.Kelun Pre-Examination [2021]14).Results:No systemic or ocular side effects were observed in the experimental animals after surgery.All 6 HA-Mg drainage plates were completely degraded about 4 months postoperatively, among which 4 plates were well-fixed and 2 plates had a minimal rotation, and no plate moved into the anterior chamber.At 5 months after surgery, the number of corneal endothelial cells in the HA-Mg drainage implant group and normal control group was 2 535.2±274.4 and 2 521.0±175.8, respectively, and there was no statistical significance between them ( t=0.073, P=0.857).There were statistically significant differences in IOP among the three groups at different time points before and after surgery ( Fgroup=26.409, P<0.001; Ftime=7.843, P<0.001), in which the IOP in trabeculectomy group and normal control group at different time points after surgery was higher than that in HA-Mg drainage implant group, and the IOP in HA-Mg drainage implant group at different time points after surgery was lower than that before surgery (all at P<0.05).The patency test revealed that the trypan blue could still drain from the anterior chamber to the subconjunctiva 5 months after HA-Mg drainage plate implantation.The scleral linear aqueous humor drainage channel and anterior synechia were observed after drainage plate completely degraded 6 months postoperatively, and no obvious inflammatory cell infiltration was seen. Conclusions:After implantation of HA-Mg drainage plate in rabbit eyes, the intraocular pressure can be effectively lowered and the safety is good.

Objective To investigate the trends of major thyroid function indices in Chinese adolescent females at different ages and the differences from adult reference intervals.Methods A total of 791 female students from 4 junior high schools were enrolled in the study by selecting one junior high school in each of the following locations:Minhang District of Shanghai,Haimen City of Jiangsu Province,Yuhuan City of Zhejiang Province,and Deqing County of Zhejiang Province from Oct to Nov 2017 and from Jan to Mar 2019.The subjects were subjected to physical examination as well as thyroid hormone levels;and the Pubertal Developmental Events Self-Assessment Scale(PDS)was used to evaluate the staging of pubertal development.Follow-ups were conducted after 2 years,with the same survey content.Thyroid function levels were assessed in 5 age groups between 11 to 15 years old,95%CI were calculated,and mixed linear models were used to analyze the effects of age and pubertal developmental stage on hormone levels.Results The reference intervals for thyroid stimulating hormone(TSH),free triiodothyronine(FT3)and free thyroxine(FT4)in adolescent females differed significantly from those of adults,with misclassification rates ranging from 2.98%to 5.17%.Statistically significant differences were found for age,pubertal development staging,and the interaction of age and pubertal staging after correcting for BMI,waist circumference(all P<0.05).TSH levels were more affected by age before the completion of pubertal development,the level of the 12-year-old group was higher than that of the 11-year-old group(P=0.001 2)and the 13-year-old group(P<0.000 1);FT3 levels showed greater variability with age during late pubertal stage,with levels significantly higher at 13 years of age than at 11 and 12 years of age(P<0.0001),and gradually decreasing after 13 years of age(P<0.000 1).In contrast,FT4 levels were generally less affected by age between 11 and 15 years of age,with levels slightly higher at 13-15 years of age than at 11-12 years of age(P<0.000 1).Conclusion The levels of TSH,FT3,and FT4,as indicators of thyroid function in adolescent females,differ significantly from those of adults,and are differently affected by age and the stages of pubertal development;further refinement of the reference intervals for age-and pubertal-development-specific thyroid indicators is necessary.