Pharmacological theory based on natural phenomena(abbreviated as natural-phenomena-based pharmacology)belongs to the traditional theory of Chinese herbal medicine,and is originated from Huang Di Nei Jing(The Yellow Emperor's Inner Classic).By analyzing the correlation of four properties and five flavors of medicines with the seasonal changes of nature,Zhang Yuansu,a famous physician of Yuan Dynasty,put forward the view that medicines'properties accord with the features of climatic factors of nature,showing that wind has the properties of ascending and generating,heat has the properties of going up and growing,dampness has the properties of transforming and developing,dryness has the properties of descending and reaping,and cold has the properties of sinking and storing,and then established the theory of natural-phenomena-based pharmacology.As a promotion of the theory,Li Dongyuan advocated that the medication should adapt to the seasonal changes and to the ascending,descending,floating and sinking of qi movement of human body.By reviewing the viewpoints of Zhang Yuansu and Li Dongyuan on natural-phenomena-based pharmacology,this paper discussed the application of natural-phenomena-based pharmacological theory,such as wind-medicine having the properties of ascending and generating,heat-medicine having the properties of going up and growing,damp-medicine having the properties of transforming and developing,dry-medicine having the properties of descending and reaping,and cold-medicine having the properties of sinking and storing,in the identification and treatment of gynecological diseases.The unique way of classification of Chinese herbal medicines according to the theory of natural-phenomena-based pharmacology reflects the view of correspondence between human being and nature.And medication following the theory of natural-phenomena-based pharmacology accords with the thinking of traditional Chinese medicine(TCM),and is in line with the seasonal changes,which reflects the biological rhythm of the human body.Identification of gynecological diseases from the disorders of qi movement,and medication following the theory of medicinal-feature-based pharmacology for gynecological diseases in TCM will provide a novel approach to homotherapy for heteropathy of gynecological diseases in TCM.

Objective:To evaluate the effectiveness of a rotation training program for primary care general practitioners (GPs) in Taizhou, China, designed around three core competencies.Methods:A longitudinal study was conducted. A total of 111 primary care GPs participating in the 1st to 5th sessions of the Taizhou GP rotation training program at Taizhou Hospital (the designated training center) in Zhejiang Province from July 2022 to December 2024 were included. Based on the World Organization of Family Doctors (WONCA) competency model, combined with literature review and expert consultation, 15 potential training components were identified. A needs assessment survey among primary care GPs was then conducted, leading to the finalization of three core competencies for the training: ①Evidence-based management of common diseases, frequently-occurring diseases, and common symptoms; ②Early identification, management, and referral of critically ill patients; ③Chronic disease management and health promotion capabilities. A 4-month full-time immersion training program was structured around these competencies, comprising three phases: theoretical training (1 week), clinical comprehensive skills training (14 weeks), and primary care practice training (1 week). Assessments included a pre-and post-training theoretical knowledge test and a final clinical assessment. The final assessment utilized a three-station Objective Structured Clinical Examination (OSCE) evaluating patient consultation, clinical reasoning & decision-making, and clinical procedural skills. A self-administered satisfaction survey was also distributed post-training.Results:The 111 participants were predominantly aged 30-49 years (72.1% (80/111)), held bachelor′s degrees (87.4% (97/111)), were licensed physicians (78.4% (87/111)), and had junior or intermediate professional titles (87.4% (97/111)). Post-training theoretical scores were significantly higher than pre-training scores (76.26±7.00 vs. 69.94±6.40, t=-10.45, P<0.001). All participants 100%(111/111) passed the final OSCE assessment. The mean scores for the OSCE stations were: patient consultation 85.99±7.30, clinical reasoning & decision-making 82.72±7.61, and clinical procedural skills 89.60±5.65. Satisfaction rates were 100.0% (111/111) for the overall program, the three-phase design, the core competency training content, theoretical training, clinical skills training, and clinical rotation departments. Satisfaction was 98.2% (109/111) for the 4-month full-time duration, 99.1% (110/111) for the "2+X" clinical rotation model (2 weeks each in General Practice and Emergency Medicine+elective rotations in 4 other departments), and 97.3% (108/111) for the primary care practice base. Conclusions:The competency-based rotation training program for primary care GPs in Taizhou effectively enhanced participants′ theoretical knowledge and clinical practical skills, and achieved high levels of participant satisfaction. This model offers valuable insights for optimizing primary care GP training in similar settings.

Objective:To evaluate the effectiveness of a rotation training program for primary care general practitioners (GPs) in Taizhou, China, designed around three core competencies.Methods:A longitudinal study was conducted. A total of 111 primary care GPs participating in the 1st to 5th sessions of the Taizhou GP rotation training program at Taizhou Hospital (the designated training center) in Zhejiang Province from July 2022 to December 2024 were included. Based on the World Organization of Family Doctors (WONCA) competency model, combined with literature review and expert consultation, 15 potential training components were identified. A needs assessment survey among primary care GPs was then conducted, leading to the finalization of three core competencies for the training: ①Evidence-based management of common diseases, frequently-occurring diseases, and common symptoms; ②Early identification, management, and referral of critically ill patients; ③Chronic disease management and health promotion capabilities. A 4-month full-time immersion training program was structured around these competencies, comprising three phases: theoretical training (1 week), clinical comprehensive skills training (14 weeks), and primary care practice training (1 week). Assessments included a pre-and post-training theoretical knowledge test and a final clinical assessment. The final assessment utilized a three-station Objective Structured Clinical Examination (OSCE) evaluating patient consultation, clinical reasoning & decision-making, and clinical procedural skills. A self-administered satisfaction survey was also distributed post-training.Results:The 111 participants were predominantly aged 30-49 years (72.1% (80/111)), held bachelor′s degrees (87.4% (97/111)), were licensed physicians (78.4% (87/111)), and had junior or intermediate professional titles (87.4% (97/111)). Post-training theoretical scores were significantly higher than pre-training scores (76.26±7.00 vs. 69.94±6.40, t=-10.45, P<0.001). All participants 100%(111/111) passed the final OSCE assessment. The mean scores for the OSCE stations were: patient consultation 85.99±7.30, clinical reasoning & decision-making 82.72±7.61, and clinical procedural skills 89.60±5.65. Satisfaction rates were 100.0% (111/111) for the overall program, the three-phase design, the core competency training content, theoretical training, clinical skills training, and clinical rotation departments. Satisfaction was 98.2% (109/111) for the 4-month full-time duration, 99.1% (110/111) for the "2+X" clinical rotation model (2 weeks each in General Practice and Emergency Medicine+elective rotations in 4 other departments), and 97.3% (108/111) for the primary care practice base. Conclusions:The competency-based rotation training program for primary care GPs in Taizhou effectively enhanced participants′ theoretical knowledge and clinical practical skills, and achieved high levels of participant satisfaction. This model offers valuable insights for optimizing primary care GP training in similar settings.

Objective:To construct the rpoN gene knockout strain (Δ rpoN) and the complemented strain (CΔ rpoN) of Vibrio vulnificus ( V. vulnificus), and investigate the role of the rpoN gene in regulating bacterial motility and biofilm formation. Methods:The Δ rpoN strain of V. vulnificus was constructed using homologous recombination. Bacterial motility was assessed via swimming assays, and flagellar morphology was observed by transmission electron microscopy. Biofilm formation capacity was evaluated using crystal violet and Congo red staining assays, as well as colony morphology analysis. Real-time quantitative RT-PCR (qRT-PCR) was used to detect mRNA levels of target genes associated with flagellar synthesis and biofilm formation in Δ rpoN and the wild-type strains. Results:The V. vulnificus genome harbored a single rpoN gene, encoding a protein with high amino acid sequence similarity to RpoN homologs in other bacterial species. The Δ rpoN strain was successfully constructed. Compared with the wild-type strain, the Δ rpoN strain exhibited complete loss of motility on soft agar plates, absence of flagellar, and downregulated mRNA levels of flagellar synthesis-related genes. Conclusions:In V. vulnificus, RpoN regulates flagellar assembly by modulating the expression of flagellar synthesis genes, thereby controlling bacterial motility and biofilm formation.

Objective:To construct the rpoN gene knockout strain (Δ rpoN) and the complemented strain (CΔ rpoN) of Vibrio vulnificus ( V. vulnificus), and investigate the role of the rpoN gene in regulating bacterial motility and biofilm formation. Methods:The Δ rpoN strain of V. vulnificus was constructed using homologous recombination. Bacterial motility was assessed via swimming assays, and flagellar morphology was observed by transmission electron microscopy. Biofilm formation capacity was evaluated using crystal violet and Congo red staining assays, as well as colony morphology analysis. Real-time quantitative RT-PCR (qRT-PCR) was used to detect mRNA levels of target genes associated with flagellar synthesis and biofilm formation in Δ rpoN and the wild-type strains. Results:The V. vulnificus genome harbored a single rpoN gene, encoding a protein with high amino acid sequence similarity to RpoN homologs in other bacterial species. The Δ rpoN strain was successfully constructed. Compared with the wild-type strain, the Δ rpoN strain exhibited complete loss of motility on soft agar plates, absence of flagellar, and downregulated mRNA levels of flagellar synthesis-related genes. Conclusions:In V. vulnificus, RpoN regulates flagellar assembly by modulating the expression of flagellar synthesis genes, thereby controlling bacterial motility and biofilm formation.

Bronchial asthma （asthma for short） is a common clinical respiratory disease mainly characterized by chronic airway inflammation， with complicated pathogenesis and a long treatment cycle. It is lingering and difficult to be cured， and lack specific drugs. Oxidative stress is a new focus in the research on the pathogenesis of asthma and a potential key target for the treatment. Under physiological conditions， the oxidative and antioxidative systems in the body are in a dynamic balance， and the two antagonize each other to maintain normal life activities. In the case of asthma attack， oxidation products such as reactive oxygen species （ROS）， malondialdehyde （MDA）， and nitric oxide （NO） are produced excessively， while the content of antioxidants such as superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH） is reduced. As a result， the oxidation exceeds the removal of oxidation products， which aggravates oxidative stress. In addition， the overproduction of ROS activates oxidative stress-related signaling pathways to produce pro-inflammatory factors， exacerbating inflammation， which leads to lung and airway tissue damage. In recent years， traditional Chinese medicine has garnering increasing attention because of the unique advantages in the treatment of asthma， especially in regulating redox balance， alleviating oxidative stress in asthma patients， and reducing inflammation. On the one hand， by inhibiting the mitogen-activated protein kinase （MAPK） and transcription factor （NF）-κB signaling pathways， traditional Chinese medicine can reduce the content of oxidation products and pro-inflammatory factors from the source. On the other hand， by activating the nuclear factor-erythroid 2-related factor 2 （NrF2） signaling pathway， traditional Chinese medicine can elevate the levels of antioxidant enzymes and enhance the antioxidant system to neutralize the excessive accumulation of oxidation products. Therefore， the adjustment of redox balance state by traditional Chinese medicine may be a new means and a new direction for the prevention and treatment of asthma in the future. This paper summarizes the oxidative stress-related pathways in the pathogenesis of asthma and reviews the latest research progress in the regulation of oxidative stress-related pathways by Chinese medicine extracts and prescriptions in the treatment of asthma， with a view to providing a fuller， more solid， and more scientific theoretical basis for the clinical and basic research on the prevention and treatment of asthma by traditional Chinese medicine.

Endometriosis(EMs)is a chronic inflammatory disease.It has been proved that inflammatory microenvironment is the key role in EMs occurance and development.Chinese medicine posits that the theory of"same disease of blood and water",which generally refers to"intermingling dampness and blood stasis",serves as a crucial pathogenesis in EMs.The inflammatory microenvironment is the main manifestation of dampness and blood stasis in EMs,while the insufficiency of vital qi results in endogenous dampness.The stagnation of blood stasis serves as the foundation for the formation of intermingling dampness and blood stasis.Based on contemporary theories in molecular biology,the macrophage-mediated inflammatory microenvironment serves as the foundation for the formation of dampness,while the participation of macrophages in angiogenesis is crucial for the formation of blood stasis.Investigating the intrinsic connection between the inflammatory microenvironment in EMs and the theory of"same disease of blood and water"can contribute to a better understanding of the pathogenesis of EMs from a novel perspective.Remodeling of the inflammatory microenvironment in endometriosis by targeting macrophages may provide a new strategy for EMs treatment.

The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to inves-tigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar.We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation.Spatial transcriptomics(ST)analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods.During the early stage,sustained microglial depletion induced disorganized astrocytic scar,enhanced neutrophil infiltration,and impaired tissue repair.ST analysis indicated that microglia-derived insulin like growth factor 1(IGF1)modulated astrocytic scar formation via mechanistic target of rapamycin(mTOR)signaling activation.Moreover,repopulating microglia(RM)more strongly activated mTOR signaling,facilitating a more protective scar formation.The combination of IGF1 and osteopontin(OPN)was necessary and sufficient for RM function,rather than IGF1 or OPN alone.At the chronic stage of ICH,the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this.The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH.Inversely,early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy.This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes,and develop elaborate treatment strategies at precise time points after ICH.

Objective:To investigate the clinical value of early gastroscopy for patients with hypopharyngeal cancer.Methods:A total of 231 cases of hypopharyngeal cancer diagnosed and treated in the First Affiliated Hospital of Xiamen University from January 2010 to December 2014 were included in the retrospective analysis. The 5-year survival rate of hypopharyngeal cancer and patients accompanied with synchronous esophageal cancer (including early and advanced esophageal cancer), as well as the detection rate of synchronous esophageal cancer by gastroscopy and systemic PET-CT examination were statistically analyzed.Results:The 5-year survival rate of hypopharyngeal cancer was 38.96% (90/231). The 5-year survival rates of 62 patients accompanied with synchronous esophageal cancer and 169 patients without were 27.42% (17/62) and 43.20% (73/169), respectively, with statistic difference ( χ2=4.747, P=0.029). The 5-year survival rate of 49 patients accompanied with synchronous early esophageal cancer was 30.69% (17/49). Among the 13 patients with synchronous progressive esophageal cancer, none had a survival period of 5 years, which was significantly different compared with the patients with synchronous early esophageal cancer ( P=0.013). The detection rates of synchronous esophageal carcinoma by gastroscopy and by systemic PET-CT were 26.84% (62/231) and 14.29% (33/231), respectively, with statistic difference ( χ2=11.14, P<0.01). The detection rates of synchronous early esophageal carcinoma by gastroscopy and by systemic PET-CT were 21.21% (49/231) and 8.66% (20/231), respectively, and the difference was also statistically significant ( χ2=14.328, P<0.01). Conclusion:Hypopharyngeal cancer accompanied with synchronous esophageal cancer is of high risk, which affects the survival rate of patients. Early gastroscopy in hypopharyngeal cancer patients can significantly improve the detection rate of synchronous esophageal cancer, which helps to design individualized regimen to improve the survival rate of patients.

Objective:To study the efficacy of dental floss traction-assisted endoscopic submucosal dissection (ESD) for gastric angle mucosal lesions.Methods:Data of 127 patients with gastric angle mucosal lesions admitted to the endoscopic center of the First Affiliated Hospital of Xiamen University from January 2015 to December 2018 were retrospectively analyzed. According to the surgical methods, patients were divided into the dental floss traction-assisted ESD group (the traction group, n=51) and the traditional ESD group (the traditional group, n=76). The 41 fibrosis cases were further divided into the traction group (n=23) and the traditional group (n=18). The operation time, en block resection rate, curative resection rate and the incidence of adverse events such as bleeding, muscle layer injury and perforation were compared between the two groups.Results:There was no significant difference in age, sex, lesion size or morphology between the traction group and the traditional group ( P > 0.05). The operation time of the traction group was significantly shorter than that of the traditional group (65.4±36.5 min VS 103.5±43.2 min, P=0.012). The en block resection rate was higher in the traction group [100.00% (51/51) VS 90.79% (69/76), P=0.026], and the curative resection rate was higher too [94.12% (48/51) VS 81.58% (62/76), P=0.042]. The incidences of muscular layer damage [5.88% (3/51) VS 25.00% (19/76), P=0.010] and intraoperative bleeding [47.06% (24/51)VS 82.89% (63/76), P=0.010] were lower in the traction group. Perforation occurred in two patients (2.63%) of fibrosis in the traditional group; no perforation occurred in the traction group. There was no significant difference in the perforation incidence ( P=0.243). In the cases of fibrosis, the operation time of the traction group was significantly shorter compared with that of the traditional group (81.4±29.3 min VS 119.3±37.6 min, P=0.010). The en block resection rate and curative resection rate were also higher in the traction group [100.00% (23/23) VS 72.22% (13/18), P=0.007; 95.65% (22/23) VS 72.22% (13/18), P=0.035]. The incidences of muscular layer damage [8.70% (2/23) VS 72.22% (13/18), P=0.001] and intraoperative bleeding [78.26% (18/23) VS 100.00% (18/18), P=0.035] were lower in the traction group. Conclusion:The dental floss traction-assisted ESD is safe and effective for gastric angle mucosal lesions and fibrotic lesions, with shorter operation time, higher curative resection rate and lower incidence of adverse events.