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*

Based on a letrozole-induced rat model of polycystic ovary syndrome (PCOS), serum metabolomics was employed to characterize metabolic abnormalities, identify potential biomarkers, and investigate their roles in the pathogenesis and progression of PCOS. Metabolomic analyses revealed significantly decreased levels of cholesterol, pregnenolone, leucine, and citrate in the serum of model rats, accompanied by elevated levels of androsterone glucuronide (ADTG) and linoleic acid, indicating dysregulation of key pathways including steroid biosynthesis, branched-chain amino acid metabolism, tricarboxylic acid (TCA) cycle, and lipid metabolism. To elucidate the tissue origins and molecular mechanisms underlying these metabolic alterations, ovarian proteomics and qRT-PCR analyses were further integrated. The results confirmed the upregulation of key enzymes involved in the related metabolic pathways, such as 17α-hydroxylase (CYP17A1), 11β-hydroxysteroid dehydrogenase (HSD11B1), branched-chain amino acid aminotransferase (BCAT2), fatty acid desaturase 2 (FADS2), and oxoglutarate dehydrogenase (OGDH). These findings suggest that both “cholesterol precursor depletion-androgen accumulation” and “energy/lipid metabolic reprogramming” constitute core features of metabolic disturbances in PCOS. Through multi-omic cross-validation, six serum metabolites with high stability and clinical translational potential were identified as promising combinational biomarkers for the auxiliary diagnosis of PCOS. This study employed a metabolomics-guided strategy, supported by proteomic and transcriptomic validation, which has not only deepened our understanding of PCOS metabolic mechanisms but also provided us with a theoretical foundation for its auxiliary diagnosis.

Objective To analyze the effects of massage therapy on the inflammatory state and lung function of pediatric refractory Mycoplasma pneumonia (RMPP). Methods A total of 320 children with RMPP treated in Hebei Seventh People′s Hospital from September 2022 to August 2023 were selected in the study. According to different treatment methods, they were divided into two groups, with 160 cases in each group. The western medicine group was given conventional anti-inflammatory and other symptomatic treatment, while the massage group was given dialectical massage treatment based on the western medicine group. The clinical efficacy, duration of disappearance of clinical symptoms, pulmonary function indexes, serum inflammatory factors, immune function indexes and total incidence of adverse reactions were compared between the two groups. Results The total effective rate of massage group was higher than that of control group (P < 0.05). The disappearance time of fever, cough, sputum and lung moist rales in observation group was shorter than that in control group (P < 0.05). After treatment, the peak expiratory flow (PEF), maximum mid-expiratory flow (MMEF) and forced vital capacity (FVC) in the massage group were higher than those in the control group (P < 0.05). The levels of serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the massage group were lower than those in the control group after treatment (P < 0.05). After treatment, CD3⁺, CD4⁺, CD4⁺/CD8⁺ in the massage group were higher than those in the control group (P < 0.05), and CD8⁺ was lower than that in the control group (P < 0.05). There was nosignificant difference in the total incidence of adverse reactions between the massage group and the western medicine group (P>0.05). Conclusion Massage based on syndrome differentiation combined with western medicine can effectively relieve fever, cough and other symptoms of RMPP children, reduce inflammatory response, improve lung function and immune function, and has less adverse reactions.

As the continuation of the left ventricle,the left atrium and left ventricle interact and play an important role in the function of the whole heart.At present,there are many techniques to evaluate the atrial structure and function,but the left atrial structure is complex and the myocardium is thin,which brings some challenges to the relevant evaluation.This paper introduces the parameters,precautions and relevant clinical applications in the process of left atrial evaluation from the aspects of myocardial strain and delayed enhancement.

Objective: To evaluate the accuracy and feasibility of coronary artery calcium score ( CACS) on virtual non-contrast scan ( VNC) images obtained from coronary artery CT angiography ( CCTA) scan with dual －layer spectral detector CT (SDCT) ． Methods : The data of 197 patients who underwent CCTA scan in hospital were analyzed retrospectively，and 88 patients with CACS ＞0 were further analyzed． Linear regression analysis of CACS and coronary artery calcium volume ( CACV) of true non-contrast (TNC) images and VNC images ( CACS-TNC， CACS-VNC，CACV-TNC，CACV-VNC) was performed to obtain linear regression equation and correction coefficients λ 1AVG and λ2AVG ．CACS-VNC and CACV-VNC were corrected by the corresponding regression equation and recorded as CCACS-VNC and CCACV-VNC，respectively．Spearman correlation coefficient was used for correlation analysis and Bland-Altman plot was used for consistency test．Mann-Whitney U test was used to compare the difference between the two groups. Results : For the total coronary artery，there was a strong correlation between CACS- TNC and CACS-VNC (rs = 0. 952，P ＜0. 001 ，λ 1AVG = 2. 19 ) ，CACV-TNC and CACV-VNC ( rs = 0. 954，P < 0. 001，λ2AVG = 1. 93) ．The results of Mann-Whitney U test showed that there was no significant difference between CACS-TNC and CCACS-VNC or between CACV-TNC and CCACV-VNC，and the Bland-Altman plot showed good consistency between CACS-TNC and CCACS-VNC ，CACV-TNC and CCACV-VNC． Conclusion VNC images based on SDCT can accurately measure CACS and be used for cardiovascular risk classification，which is expected to replace TNC scan and reduce the radiation dose of patients.

Objective:To analyze the effect of different pretreatments on the in vitrofertilization (IVF) outcome of expected poor ovarian response (POR) patients according to POSEIDON criteria, and explore the appropriate treatment for POR patients. Methods:A retrospective analysis of the clinical data of 364 cycles of expected POR patients who received in vitro fertilization-embryo transfer (IVF-ET) in the Center of Reproductive Medicine, Department of Obstetrics & Gynecology， Peking University Third Hospital from January 2016 to May 2018 was performed. According to the pretreatment prior to gonadotropin (Gn) stimulation, the cycles were divided into oral contraceptive (OCP) group (group A, n=167), estradiol valerate group (group B, n=56) and no pretreatment group (group C, n=141). The clinical data,ovarian stimulation indexes, laboratory status and the clinical pregnancy rate were compared among the three groups. Results:The age of patients in group A [(34.8±4.9) years] was significantly younger than that of group B [(38.0±4.9) years] and group C [(37.9±4.7) years] ( P<0.001). The body mass index (BMI) of group B [(21.9±3.1) kg/m 2] was significantly lower than that of group A [(23.5±3.6) kg/m 2] and group C [(23.2±3.1) kg/m 2] ( P=0.014). There were significant differences in the antral follicle count (AFC) among group A (2.4±2.0), group B (4.1±1.9) and group C (3.5±2.0) ( P<0.001). The proportion of anovulation in group A (32.9%) was significantly higher than that in group B (10.7%) and group C (11.3%) ( P<0.001). The number of IVF cycles in group C (3.0±1.7) was higher than that in group A (2.5±1.5)（ P=0.017）. There was no significant difference in type of infertility, duration of infertility, basal follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH) among the three groups ( P>0.05). The endometrial thickness on the day of human chorionic gonadotropin (hCG) injection in group A [(9.4±1.9) mm] was thinner than that in group B [(10.6±1.5) mm] and group C [(10.1±2.0) mm] ( P<0.001). The fertilization rate of group A (77.1%) and group B (77.6%) was significantly higher than that of group C (71.3%) ( P=0.041). There were no significant differences in Gn used dosage, duration of Gn stimulation, number of eggs obtained, intracytoplasmic sperm injection (ICSI) proportion, cleavage rate, number of embryos available for transfer and number of high-quality embryos among the three groups ( P>0.05). The implantation rate and the clinical pregnancy rate in group A (26.2%, 36.1%) and group B (26.8%, 42.0%) were significantly higher than those in group C (14.5%, 21.2%) ( P=0.014). There were no significant differences in embryo transfer cycle, number of embryos transferred, proportion of blastocyst transfer cycle, abortion rate and cycle cancellation rate among the three groups ( P>0.05). Conclusion:Pretreatment with OCP or estradiol valerate in luteal phase prior to Gn stimulation can improve the clinical outcomes of patients with expected POR. OCP pretreatment is suitable for POR patients with ovulation disorder, while estradiol pretreatment in luteal phase is suitable for POR patients with ovulation.

Objective:To analyze the effect of different pretreatments on the in vitrofertilization (IVF) outcome of expected poor ovarian response (POR) patients according to POSEIDON criteria, and explore the appropriate treatment for POR patients. Methods:A retrospective analysis of the clinical data of 364 cycles of expected POR patients who received in vitro fertilization-embryo transfer (IVF-ET) in the Center of Reproductive Medicine, Department of Obstetrics & Gynecology， Peking University Third Hospital from January 2016 to May 2018 was performed. According to the pretreatment prior to gonadotropin (Gn) stimulation, the cycles were divided into oral contraceptive (OCP) group (group A, n=167), estradiol valerate group (group B, n=56) and no pretreatment group (group C, n=141). The clinical data,ovarian stimulation indexes, laboratory status and the clinical pregnancy rate were compared among the three groups. Results:The age of patients in group A [(34.8±4.9) years] was significantly younger than that of group B [(38.0±4.9) years] and group C [(37.9±4.7) years] ( P<0.001). The body mass index (BMI) of group B [(21.9±3.1) kg/m 2] was significantly lower than that of group A [(23.5±3.6) kg/m 2] and group C [(23.2±3.1) kg/m 2] ( P=0.014). There were significant differences in the antral follicle count (AFC) among group A (2.4±2.0), group B (4.1±1.9) and group C (3.5±2.0) ( P<0.001). The proportion of anovulation in group A (32.9%) was significantly higher than that in group B (10.7%) and group C (11.3%) ( P<0.001). The number of IVF cycles in group C (3.0±1.7) was higher than that in group A (2.5±1.5)（ P=0.017）. There was no significant difference in type of infertility, duration of infertility, basal follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH) among the three groups ( P>0.05). The endometrial thickness on the day of human chorionic gonadotropin (hCG) injection in group A [(9.4±1.9) mm] was thinner than that in group B [(10.6±1.5) mm] and group C [(10.1±2.0) mm] ( P<0.001). The fertilization rate of group A (77.1%) and group B (77.6%) was significantly higher than that of group C (71.3%) ( P=0.041). There were no significant differences in Gn used dosage, duration of Gn stimulation, number of eggs obtained, intracytoplasmic sperm injection (ICSI) proportion, cleavage rate, number of embryos available for transfer and number of high-quality embryos among the three groups ( P>0.05). The implantation rate and the clinical pregnancy rate in group A (26.2%, 36.1%) and group B (26.8%, 42.0%) were significantly higher than those in group C (14.5%, 21.2%) ( P=0.014). There were no significant differences in embryo transfer cycle, number of embryos transferred, proportion of blastocyst transfer cycle, abortion rate and cycle cancellation rate among the three groups ( P>0.05). Conclusion:Pretreatment with OCP or estradiol valerate in luteal phase prior to Gn stimulation can improve the clinical outcomes of patients with expected POR. OCP pretreatment is suitable for POR patients with ovulation disorder, while estradiol pretreatment in luteal phase is suitable for POR patients with ovulation.

Objective: To summarize the clinical and genetic features of β-propeller protein-associated neurodegeneration (BPAN). Methods: The clinical data of 17 patients with BPAN with WDR45 gene variants were retrospectively collected at Children’s Hospital of Fudan University, Peking University First Hospital, Capital Institute of Pediatrics, Shengjing Hospital of China Medical University and Shanghai Children's Hospital from June 2016 to December 2018, and their clinical manifestations, electroencephalogram, neuroimaging and genetics were analyzed. Results: Seventeen cases (13 females, 4 males), aged 1.1-8.8 years, were included. The median age of seizure onset was 14.5 months, from 3 months to 24 months of age, manifested with epileptic spasm in 6 cases and focal seizures in 5 cases. Eight patients had only one seizure type and 8 patients had two or more seizure types. Nine patients had complete remission of seizures. All 16 patients with seizures had developmental delay before the seizure onset, of whom 13 patients had moderate to severe seizures. The brain magnetic resonance imaging (MRI) was abnormal in 13 patients, including cerebral atrophy (10 cases) and thinning of the corpus callosum (9 cases). The brain magnetic susceptibility weighted imaging (SWI) in preschool stage showed prominent T2 hypointense signals in bilateral globus pallidus and brainstem ventral in two cases. Five seizure types (spasm, focal, absence, myodonic and generalized tonic clonic seizures)were found on ictal electroencephalogram(EEG) recordings. Compared to female patients(17(6-24) months of ege), male cases had earlier seizure onset (3, 4, 5, 18 months of age) . All patients had de novo variations in WDR45(6 nonsense, 4 frameshift, 3 missense and 4 splicing variations), with hemizygous variants in 3 males, mosaic variants in a male and heterozygous variants in 13 females, within which 5 variations had not been reported (c.977-1C>T,c.976+1G>C,c.10C>T,c.806del and c.110T>C). Conclusions The patients with BPAN have profound developmental delay and are vulnerable to seizures. The male patients with BPAN tend to have more severer clinical phenotype than females. Early brain SWI could facilitate the timely diagnosis of this disease.

To summarize the clinical and genetic features of β?propeller protein?associated neurodegeneration (BPAN). Methods The clinical data of 17 patients with BPAN with WDR45 gene variants were retrospectively collected at Children's Hospital of Fudan University, Peking University First Hospital, Capital Institute of Pediatrics, Shengjing Hospital of China Medical University and Shanghai Children's Hospital from June 2016 to December 2018, and their clinical manifestations, electroencephalogram, neuroimaging and genetics were analyzed. Results Seventeen cases (13 females, 4 males), aged 1.1-8.8 years, were included. The median age of seizure onset was 14.5 months, from 3 months to 24 months of age, manifested with epileptic spasm in 6 cases and focal seizures in 5 cases. Eight patients had only one seizure type and 8 patients had two or more seizure types. Nine patients had complete remission of seizures. All 16 patients with seizures had developmental delay before the seizure onset, of whom 13 patients had moderate to severe seizures. The brain magnetic resonance imaging (MRI) was abnormal in 13 patients, including cerebral atrophy (10 cases) and thinning of the corpus callosum (9 cases). The brain magnetic susceptibility weighted imaging (SWI) in preschool stage showed prominent T2 hypointense signals in bilateral globus pallidus and brainstem ventral in two cases. Five seizure types (spasm, focal, absence, myodonic and generalized tonic clonic seizures) were found on ictal electroencephalogram(EEG)recordings. Compared to female patients(17(6-24) months of ege), male cases had earlier seizure onset (3, 4, 5, 18 months of age). All patients had de novo variations in WDR45 (6 nonsense, 4 frameshift, 3 missense and 4 splicing variations), with hemizygous variants in 3 males, mosaic variants in a male and heterozygous variants in 13 females, within which 5 variations had not been reported (c.977?1C>T,c.976+1G>C,c.10C>T,c.806del and c.110T>C). Conclusions The patients with BPAN have profound developmental delay and are vulnerable to seizures. The male patients with BPAN tend to have more severer clinical phenotype than females. Early brain SWI could facilitate the timely diagnosis of this disease.

Objective To investigate the association of serum pigment epithelium-derived factor (PEDF) level and polymorphisms in PEDF gene promoter region-358G→A with non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM) of Han Nationality in Fujian Province. Methods A total of 282 T2DM patients with NAFLD (DM1 group) and 170 age- and gender-matched T2DM patients without NAFLD (DM2 group) were examined for PEDF gene SNP-358G→A polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum pigment epithelium-derived factor(PEDF) level, fasting plasma glucose (FPG), fasting insulin (FINS) and glycosylated hemoglobin (HbA1c) were also measured. Results The patients in DM1 group showed a significantly higher mean level of serum PEDF than those in DM2 group (P<0.05). Logistic regression analysis revealed that PEDF level was an independent risk factor for NAFLD in T2DM. The frequencies of PEDF gene-358G→A genotypes (GG, GA, and AA) and alleles (G/A) differed significanly between DM1 and DM2 groups (P<0.05). In terms of PEDF gene SNP-358G→A alleles, the GA genotype carriers had a 2.032 times higher risk of developing NAFLD compared with the GG genotype carriers, and the risk increased to 2.068 times in the carriers of the A allele (GA and AA genotypes;P<0.05). Conclusion Serum PEDF level is an independent risk factor of NAFLD in T2DM. Elevated serum PEDF level is a protective factor against insulin resistance. In T2DM patients, PEDF gene promoter region-358G→A polymorphism is associated with NAFLD, and the A allele contributes to an increased risk of NAFLD.