Microorganisms, abundant in nature, are prolific producers of a diverse array of natural products (NPs) that are fundamental in the development of innovative therapeutics. Despite their significant potential, the field faces considerable challenges, including the continuous emergence of potential health threats, as well as novel pathogen strains and viruses. The advent and implementation of advanced technologies, such as culture strategies, genomics mining, and artificial intelligence (AI), are facilitating a paradigm shift in pharmaceutical research, introducing innovative methodologies and perspectives. The development and maturation of these technologies have enhanced the exploration of microbial-derived NPs, thereby advancing pharmaceutical research and development. This review synthesizes recent developments in this context, emphasizing their applications in pharmaceutical discovery and development. Through systematic analysis and synthesis, it provides objective insights into the promising prospects and future direction of this essential field.
Biological Products/chemistry* ; Drug Discovery ; Humans ; Artificial Intelligence ; Bacteria/metabolism*

OBJECTIVE To analyze the ethanol extracts,total phenols,total flavonoids contents and HPLC fingerprints of typi-cal propolis samples from 6 foreign countries and 5 domestic regions,optimize the extraction process and evaluate the antioxidant activi-ty,so as to provide data support for improving the quality control system of propolis.METHODS The optimization of the propolis ex-traction process utilized flavonoid content as an indicator.Three flavonoid detection methods-namely,the aluminum trichloride meth-od,aluminum nitrate method,and polyamide method-were compared.The content of ethanol extract,total phenol content,and the scavenging ability of DPPH free radicals for each sample were determined.Further analysis was conducted using HPLC fingerprint pro-filing.RESULTS The propolis extract with the highest flavonoid content was obtained using 80%ethanol as the extraction solvent,operating at 50℃,with a stirring time of 3 h,ultrasonic power of 180 W,and ultrasonic time of 15 min.The aluminum trichloride method was proved to be the most effective for determining total flavonoids in propolis.While the ethanol extract,total flavonoids,and total phenols of propolis from Xinjiang,China were relatively low,their antioxidant activity exhibited superiority.HPLC analysis re-vealed,Brazilian red propolis lacked of chrysin,galangin,caffeic acid phenethyl ester and Brazilian green propolis lacked ferulic acid,apigenin,p-coumaric acid,chrysin,and pinocembrin.In contrast,the content of these four compounds in other samples varied,with the antioxidant capacity of the extracts not precisely corresponding to the compound content.CONCLUSION Propolis exhibits a complex chemical composition with significant variations among varieties.Key quality control indexes must be comprehensively consid-ered,encompassing physicochemical characteristics and biological activity.Establishing a multi-angle assessment system with a mate-rial basis-functional linkage is essential.This approach facilitates the realization of high quality and cost-effectiveness,thereby promo-ting the healthy development of the industry.

OBJECTIVE To analyze the ethanol extracts,total phenols,total flavonoids contents and HPLC fingerprints of typi-cal propolis samples from 6 foreign countries and 5 domestic regions,optimize the extraction process and evaluate the antioxidant activi-ty,so as to provide data support for improving the quality control system of propolis.METHODS The optimization of the propolis ex-traction process utilized flavonoid content as an indicator.Three flavonoid detection methods-namely,the aluminum trichloride meth-od,aluminum nitrate method,and polyamide method-were compared.The content of ethanol extract,total phenol content,and the scavenging ability of DPPH free radicals for each sample were determined.Further analysis was conducted using HPLC fingerprint pro-filing.RESULTS The propolis extract with the highest flavonoid content was obtained using 80%ethanol as the extraction solvent,operating at 50℃,with a stirring time of 3 h,ultrasonic power of 180 W,and ultrasonic time of 15 min.The aluminum trichloride method was proved to be the most effective for determining total flavonoids in propolis.While the ethanol extract,total flavonoids,and total phenols of propolis from Xinjiang,China were relatively low,their antioxidant activity exhibited superiority.HPLC analysis re-vealed,Brazilian red propolis lacked of chrysin,galangin,caffeic acid phenethyl ester and Brazilian green propolis lacked ferulic acid,apigenin,p-coumaric acid,chrysin,and pinocembrin.In contrast,the content of these four compounds in other samples varied,with the antioxidant capacity of the extracts not precisely corresponding to the compound content.CONCLUSION Propolis exhibits a complex chemical composition with significant variations among varieties.Key quality control indexes must be comprehensively consid-ered,encompassing physicochemical characteristics and biological activity.Establishing a multi-angle assessment system with a mate-rial basis-functional linkage is essential.This approach facilitates the realization of high quality and cost-effectiveness,thereby promo-ting the healthy development of the industry.

Objective:To investigate the relationship between the levels of serum cytokines and chemokines and the prognosis of patients with acute B-ALL after receiving chimeric antigen receptor (CAR)-T cell immunotherapy and acute graft-versus-host disease (aGVHD) in patients after bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:According to the case-control principle, Forty-two patients with B-ALL who received CD19-CAR-T cell immunotherapy bridged to allo-HSCT at Heibei Yanda Ludaopei Hospital from September 18, 2019 to May 9, 2022 were enrolled. Mann-Whitney U test was used to compare the changes of aGVHD-related cytokines and chemokine levels between CAR-T cell immunotherapy and bridging transplantation in different patients at the same time. Their plasma levels of cytokines and chemokines related to aGVHD were monitored at the day before CAR-T therapy and after CAR-T treatment at day 4, 7,14,21,28. The receiver operating characteristic curve was drawn to evaluate the predictive value of cytokines and chemokines in predicting the occurrence and the death of aGVHD patients. Kaplan-Meier method and Log-rank tests were used for Overall survival (OS) analysis. Results:Twenty-four of total 42 patients had aGVHD, of which 11 patients died and 31 patients survived. There was no significant difference in cytokines and chemokines between the aGVHD group and the non-aGVHD group on the day before CAR-T cell treatment. According to statistical analysis, the serum Elafin levels of aGVHD group was higher than that of non-aGVHD group at the 21st day [4 482 (2 811, 6 061) ng/L vs 2 466 (1 948, 3 375) ng/L, Z=3.145, P=0.001] and the 28st day [4 391 (2 808, 5594) ng/L vs 2 463 (1 658, 2 830) ng/L, Z=2.038, P=0.048] separately. At the 14th day, serum cytokines and chemokines levels between the two group were as follows,MIP-1 α [21.02 (12.36, 30.35) ng/L vs 5.56 (3.64, 10.79) ng/L], sCD25 [422.47 (257.99, 1 233.78) IU/ml vs 216.11 (133.75,457.39) IU/ml], Elafin [4 101 (2 393, 5 006) ng/L vs 2 155 (1 781, 3 033) ng/L], IL-6 [119.08 (23.97, 183.43) ng/L vs 8.39 (2.91, 17.42) ng/L] and IL-8 [13.56 (12.50, 24.52) ng/L vs 2.83 (1.73,6.87) ng/L] were at higher levels ( Z=2.653, P=0.007; Z=2.176, P=0. 030; Z=2.058, P=0.041; Z=3.329, P<0.001; Z=3.162, P=0.001). The KM survival curve showed that the cumulative survival rates of patients with higher serum levels of MIP-1α, sCD25, Elafin, IL-6 and IL-8 were lower than those with low levels at day 14, and the difference was statistically significant (χ 2=12.353, 4.890, 6.551, 10.563, 20.755, P<0.05). Conclusion:The outcomes of patients treated with CAR-T cell therapy bridged to allo-HSCT was correlated with serum MIP-1α, sCD25, Elafin, IL-6 and IL-8 levels after receiving CAR-T therapy. High concentrations of MIP-1α, sCD25, Elafin, IL-6 and IL-8 suggest poor prognosis and can be used as biomarkers to suggest appropriate clinical selection of therapy.

Since the outbreak of corona virus disease 2019(COVID 19), the epidemic has spread rapidly, which brings great challenge to the surgical diagnosis, treatment and management of lung neoplasm Sichuan International Medical Exchange &Promotion Association organized thoracic surgery experts to sum up experiences from experts in major hospital, and formulated the Guidance suggestion on surgical diagnosis, treatment and management of lung neoplasm during the outbreak of COVID-19 to provide references for thoracic surgeons.

Objective To investigate the effects of mild thalassemia on hypoxia tolerance of civil aviation student pilots ,and provide the basis for aviation medical identification of thalassemia in civil aviation pilots. Methods The parameters of red blood cells and hemoglobin were analyzed in 1 711 subjects including the student candidates who were checked in the physical examination for recruitment and the student pilots of flight college.The thalassemia gene tests were performed for the subjects with small cell and low pigmented anemia to diagnose if they were with thalassemia.Twenty-five mild thalassemia cases and 19 healthy cases were chosen for the comparison according to the principles of proximity and phone call reachable.The hypoxia test was conducted at 7.5 km simulated altitude by Model 2007 anti-G/anti-hypoxia Detector.SaO2, heart rate and blood pressure were respectively recorded at 20 s ,60s and 120 s of the test.In case of the test did not reach to 120 s but the SaO2had been lower than 60% the test was terminated and the SaO2,heart rate and blood pressure were marked at the moment.The subjects were tested by writing digits with down sequence before and after hypoxia test.In 7.5 km simulated altitude test if the SaO 2level had decreased to 60% within 120 s the test would be terminated and the actual test duration was recorded. Results ①Ninety-seven cases of thalassemia were found in 1 711 students (5.67%) and all cases were mild thalassemia.The highest detection rate was found in the students of Hainan Province ,accounting for 20%.②The difference of test duration was statistically significant between mild thalassemia group and health group under simulated 7.5 km altitude hypoxia environment (Z＝3.630 ,P＜0.01).The difference of SaO2at 60 s was not statistically significant between two groups (P＞0.05) ,but the difference at the end of test was statistically significant (t＝5.248 ,P＜0.01).The differences of heart rate at 60 s and at the end of test were not statistically significant between two groups (P＞ 0.05).The difference of systolic pressure at 60 s and the difference of diastolic pressure at the end of test were statistically significant between two groups [(t＝ 2.215 , P＝ 0.029) and (t＝ 2.518 , P＝ 0.018)].The difference on the number of correctly writing digits with down sequence was insignificant between two groups before the hypoxia test (P＞0.05) ,but was significant after the test (t＝3.489 , P＜0.01). Conclusions The hypoxia tolerance of the patients with mild thalassemia is lower than that of the healthy population.It is suggested that more attention should be paid to the candidates with mild thalassemia in the physical examination for recruiting student pilots.The pilots with mild thalassemia should minimize the flying on plateau.

Objective To investigate the effects of mild thalassemia on hypoxia tolerance of civil aviation student pilots ,and provide the basis for aviation medical identification of thalassemia in civil aviation pilots. Methods The parameters of red blood cells and hemoglobin were analyzed in 1 711 subjects including the student candidates who were checked in the physical examination for recruitment and the student pilots of flight college.The thalassemia gene tests were performed for the subjects with small cell and low pigmented anemia to diagnose if they were with thalassemia.Twenty-five mild thalassemia cases and 19 healthy cases were chosen for the comparison according to the principles of proximity and phone call reachable.The hypoxia test was conducted at 7.5 km simulated altitude by Model 2007 anti-G/anti-hypoxia Detector.SaO2, heart rate and blood pressure were respectively recorded at 20 s ,60s and 120 s of the test.In case of the test did not reach to 120 s but the SaO2had been lower than 60% the test was terminated and the SaO2,heart rate and blood pressure were marked at the moment.The subjects were tested by writing digits with down sequence before and after hypoxia test.In 7.5 km simulated altitude test if the SaO 2level had decreased to 60% within 120 s the test would be terminated and the actual test duration was recorded. Results ①Ninety-seven cases of thalassemia were found in 1 711 students (5.67%) and all cases were mild thalassemia.The highest detection rate was found in the students of Hainan Province ,accounting for 20%.②The difference of test duration was statistically significant between mild thalassemia group and health group under simulated 7.5 km altitude hypoxia environment (Z＝3.630 ,P＜0.01).The difference of SaO2at 60 s was not statistically significant between two groups (P＞0.05) ,but the difference at the end of test was statistically significant (t＝5.248 ,P＜0.01).The differences of heart rate at 60 s and at the end of test were not statistically significant between two groups (P＞ 0.05).The difference of systolic pressure at 60 s and the difference of diastolic pressure at the end of test were statistically significant between two groups [(t＝ 2.215 , P＝ 0.029) and (t＝ 2.518 , P＝ 0.018)].The difference on the number of correctly writing digits with down sequence was insignificant between two groups before the hypoxia test (P＞0.05) ,but was significant after the test (t＝3.489 , P＜0.01). Conclusions The hypoxia tolerance of the patients with mild thalassemia is lower than that of the healthy population.It is suggested that more attention should be paid to the candidates with mild thalassemia in the physical examination for recruiting student pilots.The pilots with mild thalassemia should minimize the flying on plateau.

Objective: To investigate the fatigue status of military personnel stationed in plateau and high cold region, and to analyze the mediator effect of trait coping style on job stress and fatigue. Methods: In October 2010, with the method of cluster random sampling survey, 531 military personnel stationed in plateau and high cold region were chosen as subject. The fatigue status were evaluated by the Chinese version multidimensional fatigue inventory (MFI-20) , job stress were evaluated by the Job Stress Survey (JSS) , and trait coping style were evaluated by the Trait Coping Style Questionnaire (TCSQ) . Results: According to the information of different population characteristics, mean rank of physical fatigue about the urban (town) group were higher than that of rural group (Z=-2.200, P<0.05) ; mean rank of reduced motivation about the urban (town) group were higher than that of rural group (Z=-2.781, P<0.05) ; mean rank of general fatigue scores about the urban (town) group were higher than that of rural group (Z=-3.026, P<0.05) ; mean rank of physical fatigue about the up or equal 20-years old age group were higher than that of below 20-years old age group (Z=-4.045, P<0.05) ; mean rank of reduced motivation about the up or equal 20-years old age group were higher than that of below 20-years old age group (Z=-2.182, P<0.05) ; mean rank of mental fatigue about the up or equal 20-years old age group were higher than that of below 20-years old age group (Z=-2.879, P<0.05) ; mean rank of general fatigue scores about the up or equal 20-years old age group were higher than that of below 20-years old age group (Z=-3.647, P<0.05) ; mean rank of reduced motivation were significant statistical difference among the military officers, sergeancy and soldier group (F=18.965, P<0.05) ; mean rank of general fatigue scores were significant statistical difference among the military officers, sergeancy and soldier group (F=14.711, P<0.05) . The score of negative coping style were positively correlated with the score of physical fatigue (r_s=0.129) , reduced activity (r_s=0.123) , reduced motivation (r_s=0.149) and general fatigue (r_s=0.174) respectively, the score of organizational support lack strength were positively correlated with the score of physical fatigue (r_s=0.090) , reduced activity (r_s=0.098) , reduced motivation (r_s=0.099) and general fatigue (r_s=0.130) respectively. The mediator effect of negative coping style on the job stress and fatigue was 0.013 (P<0.01) . Conclusion The fatigue statuses of the urban (town) group and the up or equal 20-years old age group are poor, and the negative coping style plays mediator effect on the job stress and fatigue.

Objective To investigate the assoCI ation between DRD2 gene polymorphism and postoperative delirium in the patients undergoing coronary artery bypass grafting (CABG) and to analyze the risks of postoperative delirium.Methods A total 150 patients afteRcoronary artery bypass grafting were enrolled.And delirium rating scale-revised-98 was used as diagnosis tool foRthe analysis of morbidity and risks of postoperative delirium.DRD2 genotypes were determined by sequenCI ng analysis.The assoCI ation of rs6275 and rs6277 with delirium was studied.Results Delirium occurred in 12 patients and morbidity of postoperative delirium was 8.0%.Univariate logistic regression analysis results showed that delirium was assoCI ated with previous cerebral infarction (OR=0.784,95% CI 0.631 to 0.975,P=0.024),extracorporeal CI rculation time(OR=1.057,95% CI 0.703 to 1.590,P=0.029),surgery time (OR=2.251,95% CI 0.941 to 5.380,P=0.048) and intensive care unit time (OR=1.890,95% CI 1.201 to 2.973,P=0.005).There were no significant differences in frequencies of genotype and alleles of rs6275 polymorphism between patients with delirium and controls(OR=1.265,95% CI 0.697 to 2.303,P=0.651).There were significant differences on frequencies of genotype and alleles of rs6277 polymorphism between patients with delirium and controls(OR=2.276,95% CI 1.142 to 4.523,P=0.049).The multiple logisticstepwise regression analysis indicated that the perioperative risk factors of delirium included cerebral infarction (OR=1.861,95% CI 1.082 to 3.163,P=0.024),ICU duration time (OR=6.757,95% CI 2.376 to 19.267,P=0.001)and CC genotype of rs6277 (OR=4.019,95% CI 1.395 to 12.341,P=0.012).Conclusion DRD2 gene testing in patients with high risks may be helpful foRthe prevention of postoperative delirium.

Objective To investigate the assoCI ation between DRD2 gene polymorphism and postoperative delirium in the patients undergoing coronary artery bypass grafting (CABG) and to analyze the risks of postoperative delirium.Methods A total 150 patients afteRcoronary artery bypass grafting were enrolled.And delirium rating scale-revised-98 was used as diagnosis tool foRthe analysis of morbidity and risks of postoperative delirium.DRD2 genotypes were determined by sequenCI ng analysis.The assoCI ation of rs6275 and rs6277 with delirium was studied.Results Delirium occurred in 12 patients and morbidity of postoperative delirium was 8.0%.Univariate logistic regression analysis results showed that delirium was assoCI ated with previous cerebral infarction (OR=0.784,95% CI 0.631 to 0.975,P=0.024),extracorporeal CI rculation time(OR=1.057,95% CI 0.703 to 1.590,P=0.029),surgery time (OR=2.251,95% CI 0.941 to 5.380,P=0.048) and intensive care unit time (OR=1.890,95% CI 1.201 to 2.973,P=0.005).There were no significant differences in frequencies of genotype and alleles of rs6275 polymorphism between patients with delirium and controls(OR=1.265,95% CI 0.697 to 2.303,P=0.651).There were significant differences on frequencies of genotype and alleles of rs6277 polymorphism between patients with delirium and controls(OR=2.276,95% CI 1.142 to 4.523,P=0.049).The multiple logisticstepwise regression analysis indicated that the perioperative risk factors of delirium included cerebral infarction (OR=1.861,95% CI 1.082 to 3.163,P=0.024),ICU duration time (OR=6.757,95% CI 2.376 to 19.267,P=0.001)and CC genotype of rs6277 (OR=4.019,95% CI 1.395 to 12.341,P=0.012).Conclusion DRD2 gene testing in patients with high risks may be helpful foRthe prevention of postoperative delirium.