OBJECTIVE To evaluate the clinical value of anlotinib in third-line treatment for patients with advanced non-small cell lung cancer （NSCLC） through real-world data. METHODS Clinical data of patients with advanced NSCLC who received treatment at the First Affiliated Hospital of Anhui University of Chinese Medicine from February 2021 to December 2024 were retrospectively collected. They were divided into anlotinib group （27 cases， receiving anlotinib therapy） and immunotherapy group （22 cases， receiving immunotherapy agents alone or in combination with chemotherapy drugs） according to treatment regimens. The progression-free survival （PFS） and overall survival （OS） of patients were compared between the two groups， and the occurrence of adverse drug reactions during the treatment period was recorded. Using a partitioned survival model， an economic evaluation of the two treatment regimens was conducted with a cost-utility analysis approach from the perspective of the healthcare system. RESULTS The median PFS and OS of patients in the anlotinib group were 5.93 months and 11.27 months， respectively； the median PFS and OS of patients in the immunotherapy group were 5.33 months and 9.77 months， respectively； the difference was not statistically significant （P＞0.05）. There was no statistical difference in the total incidence of adverse drug reactions and grade 3-4 serious adverse drug reactions between the two groups （P＞0.05）. Compared with the immunotherapy group， the incremental cost-effectiveness ratio of the anlotinib group was 1 806 724.60 yuan/quality-adjusted life year （QALY）， which was significantly higher than three times China’s per capita gross domestic product in 2024 （287 247 yuan/QALY）. CONCLUSIONS For third-line treatment of advanced NSCLC patients， the efficacy of anlotinib is no worse than that of immunotherapy alone or in combination with chemotherapy drugs， and the safety of the two groups is comparable. However， anlotinib is not cost-effective.

In recent years, the number of lung surgeries has increased year by year, and the number of patients with postoperative cough has also increased gradually. Chronic cough after lung surgery seriously affects patients' quality of life and surgical outcome, and has become one of the clinical problems that clinicians need to solve. However, there is currently no guideline or consensus for the treatment of chronic cough after lung surgery in China, and there is no standardized treatment method. Therefore, we searched databases such as PubMed, Web of Science, CNKI, and Wanfang databases ect. from 2000 to 2023 to collected relevant literatures and research data, and produced the first expert consensus on chronic cough after lung surgery in China by Delphi method. We gave 11 recommendations from five perspectives including timing of chronic cough treatment, risk factors (surgical method, lymph node dissection method, anesthesia method), prevention methods (preoperative, intraoperative, postoperative), and treatment methods (etiological treatment, cough suppressive drug treatment, traditional Chinese medicine treatment, and postoperative physical therapy). We hope that this consensus can improve the standardization and effectiveness of chronic cough treatment after lung surgery, provide reference for clinical doctors, and ultimately improve the quality of life of patients with chronic cough after lung surgery.

On August 2-4,2023,the"Third Summit Forum on'Building a Community of Shared Future for Doctors and Patients'"was jointly organized by institutions such as the Chinese Medical Ethics,the Hospital Humanities Management and Talent Training Special Committee of the China Population and Culture Promotion Association,Center for Ethical Studies of Renmin University of China,the Newspaper for China's Physicians,the China Health Law Society,the China Anti-Cancer Association,and the China Association For Ethical Studies in Harbin.The conference arranged a sub-forum for the"Seminar on the Construction of Chinese Medical Humanities",with domestic medical humanities scholars attending the conference.After heated discussions at the seminar,the Scholars'Consensus on the Construction and Development of Chinese Medical Humanities was formed.It was proposed that in the new era,it is urgent to build the medical humanities discipline,as well as lead the academic integration and development of medical humanities under the core socialist values.At the same time,for the construction of the medical humanities discipline,it is necessary to optimize the organizational mechanism,prosper and develop the overall framework of the medical humanities discipline,accelerate the construction of a professional teaching team for the medical humanities discipline,promote the establishment of a new carrier medical humanities education and teaching in cultivating morality and nurturing talents,as well as focus on solving problems related to the cultivation of medical humanities graduate students.

Objective:To evaluate the effect of different reconstruction points of intrauterine applicator on the source dwell positions and plan dosimetry in intracavitary brachytherapy for cervical cancer.Methods:Clinical data of 43 patients with cervical cancer who had completed radical radiotherapy in Liuzhou Workers' Hospital from May 2020 to October 2022 were retrospectively analyzed. Among 43 patients, aged 32-79 years, 40 cases were diagnosed with squamous carcinoma and 3 cases of adenocarcinoma. All patients received external irradiation for 50.4 Gy / 28 fractions and CT-guided intracavitary brachytherapy (45° intrauterine applicator) was 36 Gy / 6 fractions. Brachytherapy was performed by using Fletcher applicator, the curvature of intrauterine applicator were 15°, 30°and45°. Two sets of brachytherapy plans were simulated for each patient. One set of plans extracted the simulated CT positioning images and the original plan of the patient's brachytherapy. The reconstruction point of the curved part of the 45° intrauterine applicator was adjusted to slice-by-slice reconstruction. The plan was optimized to meet clinical requirements according to the prescription, which was called the slice-by-slice group. In the other set of plans, slice-by-slice group was used as a template. The reconstruction points of the curved section of the 45° intrauterine applicator were adjusted to 1, 3, 5, and 7, without modifying the applicator weights and other parameters, which was called the average group 1, 3, 5 and 7. The deviation analysis of 15°, 30° and 45° intrauterine applicator with different number of reconstruction points was carried out, the reconstruction deviation of 45°, 30° and 15° intrauterine applicator at different reconstruction points was compared. Paired-sample t-test or Wilcoxon signed rank test were used to compare the differences in high-risk clinical target volume (HR-CTV) D 50%, D 90%, D 100%, V 100%, V 150%, V 200% and conformity index (CI) as well as D 2 cm3, D 1 cm3 and D 0.1 cm3 in bladder, rectum, and small intestine between two groups of 45° intrauterine applicator. Results:The reconstruction deviation in the average group was mainly from the vertical direction of the 45° intrauterine applicator. The mean reconstruction deviations of 45° (1, 3, 5, 7 reconstruction points), 30° (1, 3, 5 reconstruction points) and 15° (1, 2 reconstruction points) were 1.30 mm, 0.32 mm, 0.14 mm and 0.08 mm; 0.57 mm, 0.14 mm and 0.06 mm; 0.14 mm and 0.06 mm, respectively. There was no significant difference in the parameters of high-risk clinical target volume (HR-CTV) in the slice-by-slice group compared with the average group 5 and 7 (all P>0.005), and no significant difference was found between the average group 5 and 7 (all P>0.005). There were no statistically significant differences in bladder and rectum doses between the slice-by-slice group and the average groups or within the average groups (all P>0.005). The parameters of small intestine in the slice-by-slice group were higher than those of the average group 1, the difference was statistically significant ( P=0.002,<0.001,<0.001). The dose of small intestine in the slice-by-slice group was not statistically significant compared with those in the average group 5 and 7 (both P>0.005). The dose of small intestine in the average group 5 was not statistically significant compared with that in the average group 7 ( P>0.005). The small intestine dose deviations of D 0.1 cm3, D 1 cm3 and D 2 cm3 in the average groups at 1 reconstruction point were 2.41%±1.70%, 1.95%±1.27% and 1.71%±1.10%, respectively. Conclusion:The number of reconstruction points is recommended to be no less than 1, 3 and 5 of the curved part of the 15°, 30°and 45° Fletcher intrauterine applicator, respectively, during intracavitary brachytherapy for cervical cancer.

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the main pathogen that causes COVID-19,which is fast-mutating and highly transmissible.The infection has led to a global epidemic.As the main preventive and control measure,vaccination plays a critical role in fighting a-gainst COVID-19.Although a large number of epitope-based and mucosal vaccines have been stud-ied,few peptide epitope vaccines targeting the mucosa and their functional evaluation have been re-ported.In this study,we used SARS-CoV-2 structural protein M peptide epitope predicted by the IEDB database as an antigenic target to design the MS-3S gene containing 3 050 and 1 229 signal peptides and DCpep optimized for insertion into MS2 phage coat proteins.The expression plasmid pSIP:MS-3S was constructed by cloning the PCR fragments seamlessly and was transformed into Lactiplantibacillus plantarum 18 to obtain the recombinant bacterium LP18:MS-3S.Expression conditions such as induction time,inducer concentration,rotational speed and initial pH were opti-mized.The intranasal immunization experiments were performed to examine the vaccine efficacy.The results showed that the 916 bp-long target gene MS-3S modified and optimized was amplified and used to successfully construct the recombinant bacterial strain LP18:MS-3S.The optimal con-ditions for recombinant protein expression were obtained and verified by Western blot,flow cy-tometry,immunofluorescence and other detection methods.The optimal expression conditions were determined as follows:induction time was 4 h with 100 pg/L of SppIP as the optimal induction concentration.Antibody-specific for the epitope was verified by ELISA experiments in serum,alve-olar lavage fluid and fecal dilutions of mice.In summary,a recombinant bacterial strain expressing the epitope antigen of the SARS-CoV-2 M protein peptide was constructed.The obtained protein can induce the body to produce humoral and mucosal immunity,which lays the foundation for the development of a vaccine candidate for the mucosal immunity of COVID-19.

Objective:To predicate whether China can achieve the United Nations Sustainable Development Goals (SDGs) 3.4.1 to reduce the age-standardized mortality rate of four major non-communicable diseases (NCDs) in residents aged 30-70 years by 2030 based on the trend of the mortality from 1990 to 2019.Methods:We collected the mortality data on cardiovascular diseases, cancers, chronic respiratory diseases, and diabetes by age, gender and year in China from the Global Disease Burden Study 2019 (GBD2019). The age-period-cohort (APC) Bayesian model was applied for modeling the age-standardized mortality rate of four major NCDs in China during 2020-2030 according to the trend of the mortality during 1990-2019, and comparing the predicted value in 2030 with the observed value in 2015 to evaluate the possibility of achieving SDGs 3.4.1.Results:The age-standardized mortality rate of the four major NCDs in China showed a downward trend during 1990-2019. It is predicted that the number of death of the four NCDs in Chinese residents aged 30-70 years would increase from 2.96 million in 2020 to 3.19 million in 2030, while the age-standardized mortality rate would decrease from 308.49/100 000 in 2020 to 277.80/100 000 in 2030. The age-standardized mortality rate in 2030 would only decrease by 15.94% (18.73% for males and 14.31% for females) compared with 330.46/100 000 in 2015, with a 25.09% decrease for cardiovascular diseases, 4.76% for cancers, 37.21% for chronic respiratory diseases, and unchanged for diabetes.Conclusion:Although the age-standardized mortality rate of four major NCDs declined from 1990 to 2019 in China, it is difficult to achieve the SDGs of a 1/3 mortality rate reduction by 2030 according to the current declining trend, suggesting more active and effective efforts for NCD prevention and control are needed.

The development and implement of microbial chassis cells can provide excellent cell factories for diverse industrial applications, which help achieve the goal of environmental protection and sustainable bioeconomy. The synthetic biology strategy of Design-Build-Test-Learn (DBTL) plays a crucial role on rational and/or semi-rational construction or modification of chassis cells to achieve the goals of "Building to Understand" and "Building for Applications". In this review, we briefly comment on the technical development of the DBTL cycle and the research progress of a few model microorganisms. We mainly focuse on non-model bacterial cell factories with potential industrial applications, which possess unique physiological and biochemical characteristics, capabilities of utilizing one-carbon compounds or of producing platform compounds efficiently. We also propose strategies for the efficient and effective construction and application of synthetic microbial cell factories securely in the synthetic biology era, which are to discover and integrate the advantages of model and non-model industrial microorganisms, to develop and deploy intelligent automated equipment for cost-effective high-throughput screening and characterization of chassis cells as well as big-data platforms for storing, retrieving, analyzing, simulating, integrating, and visualizing omics datasets at both molecular and phenotypic levels, so that we can build both high-quality digital cell models and optimized chassis cells to guide the rational design and construction of microbial cell factories for diverse industrial applications.
Bacteria/genetics* ; Metabolic Engineering ; Synthetic Biology

Objective:To explore the regulation of macrophage polarization and its effects on liver cancer invasion, metastasis and apoptosis by CCAAT/enhancer binding protein δ (CEBPD).Methods:THP-1 stable transfected cells with knockdown CEBPD (shCEBPD) and negative control shNC were constructed by lentviral transfection technique. THP-1 transfected cells were induced into macrophages, lipopolysaccharide (LPS) and interferon γ(IFNγ) by phorbol 12-tetradecanoate 13-acetate (PMA), and then the polarized macrophages were further induced to M1 type. The quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect M1 type macrophage related interleukin 1β (IL-1β) genes, IL-6, tumor necrosis factor α (TNFα), and inducible nitric oxide synthase (iNOS) mRNA expression level. Flow cytometry was used to detect M1 macrophage-specific surface marker CD80 expression levels. M1-induced macrophages were co-cultured with liver cancer MHCC97H cells using Transwell non-contact small sized co-culture dishes. MHCC97H cells invasion and metastasis were detected by Transwell and scratch assay under co-culture conditions, and the MHCC97H cells apoptosis was detected by flow cytometry.Results:The mRNA expression levels of M1 macrophage marker genes iNOS, TNFα, IL-6 and IL-1β in THP-1 derived macrophages were decreased after CEBPD knockdown. M1 macrophage-specific surface marker CD80 expression levels were decreased (23.7% ± 2.1% and 62.5% ± 2.0%, t = 9.58, P < 0.05). THP-1 were co-cultured with MHCC97H in shCEBPD and shNC group, respectively. Compared with shNC group, the invasion [(158.0 ± 3.5) and (75.0 ± 4.5), t = 39.87, P < 0.01] and metastatic ability (54.6% ± 1.5% and 24.3% ± 1.0%, P < 0.01) of MHCC97H cells co-cultured in shCEBPD group were stronger and the apoptosis rate was reduced [(9.4% ± 1.0%) vs. (23.7% ± 1.2%), t = 12.68, P < 0.01]. Conclusion:CEBPD can inhibit the invasion and metastasis and increase the apoptosis by amplifying M1 type macrophages polarization in liver cancer cells.

Objective To investigate the effects of Kruppel-like factor 6 (KLF6) on the apoptotic and migration ability of HepG2 cell, and the developmental role of KLF6 on zebrafish liver.Methods Constructed plasmid with shRNA-KLF6 was transfected in HepG2 and L-02.The impacts of loss of KLF6 on HepG2 was investigated by Western bolt, apoptosis analyses, cell cycle detection and scratch experiment;KLF6 morpholino oligonucleotides was microinjected into the Tg(lfabp:eGFP) transgenic zebrafish embryos.The morphant phenotype of the liver was imaged and the protein expression of KLF6 after knockdown of KLF6 was analyzed by Immunofluorescence staining.Results The expression of KLF6 in L-02 was significantly higher than in HepG2.After knockout of KLF6, KLF6 protein expression and apoptosis were significantly reduced.In addition, the cell cycle mainly stated in S phase and the migration ability of HepG2 was enhanced.After klf6 knockdown in transgenic zebrafish larvae, the development of zebrafish liver was delayed and KLF6 expression was obviously decreased in the liver.Conclusions The reduction of KLF6 expression increased the proliferation and migration ability, and reduced the apoptosis of HepG2.Loss of KLF6 affects the development of zebrafish liver, which may open a possibility to use zebrafish as a liver cancer model and for anti-liver cancer drug screening.

Objective To develop a new-type animal dental stent for the experiment of canine pulp regeneration.Methods The stent was composed of an upper support frame,an oral limit bracket and a lower support frame,which were aligned from top to bottom.A sleeve joint was made for the connection structure of the bracket,and the height and the width both could be adjusted to adapt to different animals' mouths.The rubber dam could be spread into tension and concave form by rotating the upper and lower support frames' ends.Results By resizing the animal dental stent based on the structure of animal facies maxillaris,medical staffs could proceed the examination and treatment to animals effectively,including the throat examination,oral examination,oral care,dental treatment (such as root canal therapy and dental filling) and other medical behaviors.Conclusion The experimental result shows the feasibility of utilizing the stent in the process of animal experiment or diagnosis and treatment.Moreover,the stent proves the capacity in protecting the soft tissue,widening the vision of operation field,getting rid of the saliva contamination,which is worthy popularizing in animal experiments and animal medical care.