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 evaluate the clinical safety and effectiveness of intravascular stent combined with 125I seed strip implantation in the treatment of superior vena cava syndrome(SVCS)caused by malignant tumors.Methods The clinical data of 43 patients with SVCS,who were admitted to the Affiliated Hospital of Xuzhou Medical University of China from May 2017 to October 2022,were retrospective analyzed.Of the 43 patients,27 received intravascular stent combined with l25I seed strip implantation(observation group),and 16 received simple intravascular stent implantation(control group).The stent patency rate,clinical symptom relief rate,and survival time were compared between the two groups.Results Successful operation was accomplished in all the 43 patients.In the observation group,the postoperative 3-month stent patency rate and average survival time were 88.7％and 39.1 weeks respectively,which were significantly higher than 62.5％and 21.8 weeks respectively in the control group,the differences between the two groups were statistically significant(P=0.033 and P=0.035 respectively).After treatment,all the clinical symptoms were relieved.Conclusion For the treatment of SVCS,intravascular stent combined with 125I seed strip implantation is clinically safe and effective,it can be used as the preferred treatment option.(J Intervent Radiol,2024,33:632-635)

The precise localization of pulmonary nodules has become an important technical key point in the treatment of pulmonary nodules by thoracoscopic surgery, which is a guarantee for safe margin and avoiding removal of too much normal lung parenchyma. With the development of medical technology and equipment, the methods of locating pulmonary nodules are also becoming less trauma and convenience. There are currently a number of methods applied to the preoperative or intraoperative localization of pulmonary nodules, including preoperative percutaneous puncture localization, preoperative transbronchial localization, intraoperative palpation localization, intraoperative ultrasound localization, and localization according to anatomy. The most appropriate localization method should be selected according to the location of the nodule, available equipment, and surgeon鈥檚 experience. According to the published literatures, we have sorted out a variety of different theories and methods of localization of pulmonary nodules in this article, summarizing their advantages and disadvantages for references.

Objective To comparatively observe the incidence of complications and patency rate within 1 year after implantation of totally implantable venous access port(TIVAP)through internal jugular vein(IJV)between different locations of catheter tip.Methods Data of 2 104 patients with tumors who received TIVAP implantation through IJV were retrospectively analyzed.Patients who underwent TIVAP implantation through the right IJV(group R,n=1 903)were divided into R1(n=376,with catheter tip located at the upper right atrium,i.e.0.5 to 1.0 cm below the cavoatrial junction[CAJ])and R2 subgroups(n=1 527,with catheter tips located between the lower 1/3 of superior vena cava[SVC]and CAJ),while those who underwent TIVAP implantation through the left IJV(group L,n=201)were divided into L1(n=64)and L2 subgroups(n=137),respectively.Patients'basic information,incidence of complication and patency rate of catheter 1 year after TIVAP implantation were collected and compared between subgroups.Results No significant difference of gender,age,clinical diagnosis,tumor stage,nor of incidence of complication including pneumothorax/hemopneumothorax,local skin injury,TIVAP infection,catheter-associated thrombosis,drug extravasation,catheter displacement and arrhythmia was found between subgroups within group R nor L(all P＞0.05).One year after TIVAP implantation,no significant difference of catheter patency rates was found between subgroup R1(94.15%)and R2(93.78%)(χ2=0.069,P=0.793),nor between subgroup L1(98.44%)and L2(89.78%)(Yates'continuity correction χ2=3.563,P=0.059).Conclusion No significant difference of incidence of complications nor catheter patency rate within 1 year after implantation of TIVAP was found between catheter tip location at the upper right atrium or between the lower 1/3 of SVC and CAJ through the right or left IJC.

The typical hallmark of tumor evolution is metabolic dysregulation. In addition to secreting immunoregulatory metabolites, tumor cells and various immune cells display different metabolic pathways and plasticity. Harnessing the metabolic differences to reduce the tumor and immunosuppressive cells while enhancing the activity of positive immunoregulatory cells is a promising strategy. We develop a nanoplatform (CLCeMOF) based on cerium metal-organic framework (CeMOF) by lactate oxidase (LOX) modification and glutaminase inhibitor (CB839) loading. The cascade catalytic reactions induced by CLCeMOF generate reactive oxygen species "storm" to elicit immune responses. Meanwhile, LOX-mediated metabolite lactate exhaustion relieves the immunosuppressive tumor microenvironment, preparing the ground for intracellular regulation. Most noticeably, the immunometabolic checkpoint blockade therapy, as a result of glutamine antagonism, is exploited for overall cell mobilization. It is found that CLCeMOF inhibited glutamine metabolism-dependent cells (tumor cells, immunosuppressive cells, etc.), increased infiltration of dendritic cells, and especially reprogrammed CD8⁺ T lymphocytes with considerable metabolic flexibility toward a highly activated, long-lived, and memory-like phenotype. Such an idea intervenes both metabolite (lactate) and cellular metabolic pathway, which essentially alters overall cell fates toward the desired situation. Collectively, the metabolic intervention strategy is bound to break the evolutionary adaptability of tumors for reinforced immunotherapy.

Objective Taking 41 kinds of Chinese herbal medicines commonly used in Meizhou Hakka as the research object,their inhibitory activities against α-glucosidase and α-amylase were screened and the enzyme inhibition types of the species with the strongest activities were explored.Methods The inhibitory activities of 41 commonly used Hakka herbs in Meizhou against α-glucosidase and α-amylase were evaluated by the p-Nitrophenyl a-D-mannopyranoside(pNPG)method and the 3,5-Dinitrosalicylic acid(DNS)method,using the inhibitory rate of half(IC50)as an index.The inhibitory activity of 95%ethanol extracts of 41 Chinese herbal medicines commonly used in Meizhou Hakka on α-glucosidase and α-amylase were analysed.The enzymatic kinetics method and Lineweaver-Burk curve were used to analyze the inhibitory type of the most active species.Results The results showed that 40 Chinese herbal medicines commonly used in Meizhou Hakka had α-glucosidase inhibitory activity,and 23 medicines had α-amylase inhibitory activity,among which Psychotria asiatica Wall.showed the strongest inhibitory activity with the IC50 values aganist α-glucosidase and α-amylase of 0.17±0.001 mg·mL-1 and 0.09±0.001 mg·mL-1,respectively.The inhibition types were reversible competitive inhibition and reversible non-competitive inhibition,respectively.Conclusion The Psychotria asiatica Wall.Chinese herbal medicines commonly used in Meizhou Hakka has significant inhibitory effect on the activity of glucose metabolism enzymes,which has potential value for further research and development on the prevention and treatment of diabetes mellitus.

Uniportal video-assisted thoracic surgery (UniVATS) is a significant approach of mini-invasive surgery for lung cancer. UniVATS was first used for treatment of lung cancer in 2010. The European consensus and the Chinese consensus were published in 2019 and 2020 respectively. The latest Chinese consensus included the definition of UniVATS, indications for lung cancer treatment, safety and feasibility, surgical skills, learning curve, short-term and long-term results, providing suggestions for the standardization of uniportal video-assisted thoracic surgery, which are essential to improve the quality of surgery and reduce the incidence of related complications. The Chinese consensus also summarized the current status of subxiphoid UniVATS and non-intubated UniVATS for lung cancer. Considering the technical difficulties and challenges, the application of both technologies in clinical treatment has certain limitation. This article aims to give an interpretation of the results of the Chinese consensus and the similarities and to compare the differences with the European consensus, and to provide a reference for the majority of thoracic surgery colleagues.

OBJECTIVE:To provide reference for the better development of intemet pharmaceutical service of hospital pharmacists.METHODS:The questionnaire investigation was carried out on the cognition of pharmacists to intemet pharmaceutical service in 9 third grade class A hospitals.The survey data were analyzed statistically.RESULTS:A total of 600 questionnaires were distributed and 527 questionnaires were collected with recovery rate of 87.8％.Among them,there were 499 valid questionnaires with effective rate of 94.7％.The most selected internet pharmaceutical service contents were medication consultation (94.4％) and medication education (91.6％).93.0％ considered that intemet pharmaceutical service were worthy or very worthy of promotion.The most concerned issues about intemet pharmaceutical service were technical problems (58.5％) and legal liability (55.9％).57.1％ of the surveyed pharmacists considered that they were totally or possibly capable of performing interact pharmaceutical care;37.9％ didn' t get in touch with intemet pharmaceutical care and were not clear about it.The most important qualifications of pharmacists who provided intemet pharmaceutical service were rank of pharmacist's title (67.9％) and working experience (67.7％).It was considered that the most effective measures to ensure the quality of intemet pharmaceutical care were regular pharmaceutical service training (74.3％) and proportionally sampling the quality of pharmaceutical service consultation (67.5％).CONCLUSIONS:Internet pharmaceutical service may become a new direction of the development of pharmaceutical service under new medical reform.The development of intemet pharmaceutical service requires perfect laws and regulations,and pharmacist team with high professional level.

Objective To evaluate the efficacy and safety of tolvaptan therapy for edema in patients with nephrotic syndrome(NS).Methods Twelve patients with NS who had normal serum sodium and blood volume were enrolled.All of them were treated with oral tolvaptan of 15-30 mg per day for 7 days.The diuretic effects were observed and the adverse reactions including electrolyte disorders(especially hypernatremia),low blood volume,thromboembolic complications,and acute kidney injury were closely monitored.Results The average urine volume was significantly increased(F=5.792,P ＜ 0.001)and the body weight was significantly decreased(F=24.086,P ＜ 0.001)from the first day of tolvaptan therapy until the end of the treatment.The average serum sodium levels were significantly increased from the second day of tolvaptan therapy until the end of the treatment(F=2.790,P=0.012),but only 3 case-times(3.6％)among the total 84 case-times of serum sodium tests showed mild hypernatremia(the highest level 146.5 mmol/L)and all the hypernatremia returned back to normal after suspending tolvaptan for one day.There were no significant changes in the serum potassium levels(F=0.477,P=0.849)within the whole treatment course.There was also no significant difference of the blood volume between the level at the end of treatment and the baseline level[(74.3± 3.0)ml/kg vs(74.9±3.0)ml/kg,P=0.855].The thromboembolic complications and acute kidney injury both also did not take place.Conclusions As long as a rational and prudent treatment regimen is applied,tolvaptan has good diuretic effects and safety for treatment of edema in the NS patients with normal serum sodium and blood volume.