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.

Data analysis models may assist the transmission of traditional Chinese medicine （TCM） experience and clinical diagnosis and treatment， and the possibility of constructing a “data-knowledge” dual-drive model was explored by taking gastric precancerous state as an example. Data-driven is to make clinical decisions around data analysis， and its syndrome-differentiation decision-making research relies on hidden structural models and partially observable Markov decision-making processes to identify the etiology of diseases， syndrome elements， evolution of pathogenesis， and syndrome differentiation protocols； knowledge-driven is to make use of data and information to promote decision-making and action processes， and its syndrome-differentiation decision-making research relies on convolutional neural networks to improve the accuracy of local disease identification and syndrome differentiation. The “data-knowledge” dual-driven model can make up for the shortcomings of single-drive numerical simulation accuracy， and achieve a balance between local disease identification and macroscopic syndrome differentiation. On the basis of previous research， we explored the construction method of diagnostic assisted decision-making platform for gastric precancerous state， and believed that the diagnostic and decision-making ability of doctors can be extended through the assistance of machines and algorithms. Meanwhile， the related research methods were integrated and the core features of gastric precancerous state based on TCM syndrome differentiation and endoscopic pathology diagnosis and prediction were obtained， and the elements of endoscopic pathology recognition based on TCM syndrome differentiation were explored， so as to provide ideas for the in-depth research and innovative application of cutting-edge data analysis technology in the field of intelligent TCM syndrome differentiation.

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.

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:To investigate the clinical characteristics, diagnosis and treatment of dermatomyositis with kidney neoplasm.Methods:The data of two patients with dermatomyositis complicated with kidney neoplasm in Tongji Hospital from January to February 2022 were retrospectively analyzed. The first case was a 55-year-old female, who was admitted with the chief complaints of recurrent erythema of upper extremities for 2 months and facial erythema for 1 month. Physical examination: erythema can be seen on upper limbs and face, no tenderness or percussion pain in kidney area. Myositis enzyme profile test showed that anti-Mi-2 antibody and anti-SSA /Ro-52 antibody were positive. Contrast CT showed nodular uneven enhancement in the right kidney with a size of 50 mm×41 mm. The second case was a 58-year-old female, who was admitted with the chief complaints of kidney occupying for a month. Physical examination: flaky erythema on face, no tenderness or percussion pain in kidney area. Myositis enzyme profile test showed that anti-Ro-52 antibody and anti-MDA5 antibody were positive. Contrast CT showed a significantly uneven enhanced mass with a size of about 50 mm×41 mm on left kidney. Both patients were diagnosed with kidney neoplasm before surgery and underwent laparoscopic partial nephrectomy in Tongji Hospital.Results:Both patients received regular oral prednisone after surgery. The pathological presentation of case 1 was papillary renal cell carcinoma, the facial erythema subsided 1 month after surgery, and there was no tumor recurrence for 13 months. The pathological presentation of case 2 was clear cell renal cell carcinoma, facial erythema subsided 2 weeks after surgery, and there was no tumor recurrence for 12 months.Conclusions:The diagnosis of dermatomyositis should be combined with clinical manifestations and laboratory examination, and the possibility of malignant tumor should be excluded due to the high likelihood of concomitant malignancy. For patients with dermatomyositis with kidney neoplasm, the main treatment is still surgery, and supplemented with glucocorticoid therapy.

Objective To summarize the magnetic resonance imaging (MRI) features of the persistcnt perineal sinus (PPS).Methods The retrospective and descriptive study was conducted.The clinical data of 7 patients with PPS who were admitted to the Nanjing University of Traditional Chinese Medicine between July 2010 and January 2017 were collected.Patients received horizontal,anteroposterior axes and coronal scanning of MRI after abdominoperineal resection (APR) of rectal cancer.Two physicians read collectively films and then achieved consistent results if there was a disputed result.Observation indicators:(1) MRI features;(2) treatment and follow-up situations.Patients underwent resection of PPS according to results of MRI examination,and then regular pathological examination.Follow-up using telephone interview was performed to detect sinus recurrence and reoperation up to April 2017.Results (1) MRI features:① Lesion location:lesions of PPS in 7 patients were located at the presacral areas,top side was up to the third sacral plane,and lower side extended down to the pubic area.② Morphology and signal:sinus tract of 7 patients showed irregular flaky and tubular abnormal signals;fibrotic sinus tract wall showed low signals in T1 weighted imaging (T1WI) and T2WI;contents of sinus tract in 7 patients showed low signal in T1WI and high signals in T2WI and T2WI-fat suppression (T2WI-FS).Of 7 patients,uniform signal and mixed signal were respectively detected in 2 and 5 patients.③ Branches and cystic spaces:1 patient had a branch at the tip of the coccyx,extending to the rear of the sacral vertebra.The top of sinus tract in 4 patients enlarged to form a cavity.④ Signs of infection:signs of infection in 3 patients included blurred and exuded fat gaps around the sinus tract,unclear and partially adhesion with pelvic organ;the pelvic floor muscles in 1 patient were thickened and swollen,with a high signal in T2WI-FS;flaky fluid shadows in 2 patients were seen in the posterior sinus,with a high signal in T2WI-FS,showing a tissue edema of anterior sacrum.⑤ Enhancement features:result of MRI examination of 1 patient showed mild and heterogeneous enhancement of sinus.(2) Treatment and follow-up situations:among 7 patients undergoing sinus resection,2 received curettage of superior sinus due to high location,and 5 received successfully operation.All patients underwent postoperatively regular antibiotic therapy.The healing time was 14-78 days,with an average time of 42 days.The postoperative pathological examination showed different degrees of inflammatory cell infiltration.Seven patients were followed up for 2-74 months,with an average time of 40 months.Of 7 patients,sinus in 6 patients was healed,1 had recurrence of sinus and didn't receive therapy.Seven patients didn't undergo debridement or transposition of skin flap again.Conclusion The MRI imaging features of PPS includes flaky and tubular abnormal signal in the the anterior sacrum,low signal in T1WI,high signals in T2WI and T2WI-FS,and the enhanced scanning of sinus duet shows mild and heterogeneous enhancement.

OBJECTIVE:To investigate the effects of Compound changpu yizhi decoction combined with nimodipine on clini-cal symptoms,cognitive function and cerebral blood flow velocity of patients with mild cognitive impairment(MCI)after stroke, and its medication safety. METHODS:84 MCI patients after stroke in our hospital from Feb. 2012 to Oct. 2014 were selected as re-search objects and randomly divided into observation group and control group,42 cases in each group. All patients received basic preventive treatment;control group was additionally given Nimodipine tablet 30 mg,tid,po;based on it,observation group was given Compound changpu yizhi decoction,one dose a day,taking with warm water every morning and evening. They were treated for 3 months. Clinical symptoms of patients were compared by vascular dementia TCM syndrome table before and after treatment, mini-mental state examination(MMSE)was used to compare the cognitive function of patients before and after treatment,cerebral blood flow velocity before and after treatment and incidence of adverse reactions in 2 groups were compared. RESULTS:Before treatment,there was no statistical significance in clinical symptom scores,cognitive function score and blood flow velocity of main artery between 2 groups(P>0.05). Clinical symptom scores of 2 groups were decreased significantly,while cognitive function and cerebral blood flow velocity were increased significantly;there was statistical significance,compared to before treatment (P<0.05). Memory scores,pain scores,complexion scores,tongue scores,pulse scores,additional scores and total scores in observa-tion group were obviously lower than control group;orientation ability scores,recall ability scores,language skills scores and com-prehensive cognitive function scores in observation group were obviously higher than control group;blood flow velocities of anteri-or cerebral artery,middle cerebral artery,posterior cerebral artery,vertebral artery and basilar artery in observation group were obvi-ously faster than control group,with statistical significances(P<0.05). The incidence of ADR in observation group and contral group were 11.90%and 9.52%,there was no statistical significance between 2 groups(P>0.05). CONCLUSIONS:Compound changpu yi-zhi decoction combined with nimodipine helps to relieve clinical symptoms of MCI patients after stroke,improve cerebral blood circulation and cognitive function,with good safety.

BACKGROUND:In the treatment of tibial plateau fractures, because of the variety of fracture, the complexity of anatomical changes, X-ray films or three-dimensional CT scan limited by two-dimensional plane, increases the difficulty in preoperative plan and surgical treatment. The application of three-dimensional (3D) printing technology has attracted attention in the department of orthopedics. OBJECTIVE:To explore the auxiliary role of 3D printing technique in preoperative plan and treatment for tibial plateau fractures. METHODS:Thirty patients with tibial plateau comminuted fractures were enroled in this study and divided into two groups: experimental and control groups, with 15 patients in each group. In the experimental group, patients underwent 3D CT scan, which was stored in DICOM format, and processed by Mimics software. Data were converted into STL format, entered 3D printer, and a 1:1 entity size of the fracture model was made, in accordance with repair plan of 3D fracture model. Operation time and intraoperative blood loss were compared between the two groups. At 12 months after treatment, their outcomes were assessed using Rasmussen evaluation criteria. RESULTS AND CONCLUSION: The 3D printing fracture models of 1:1 ratio identified fracture type and made a repair program before surgery in the experimental group. Operation time and intraoperative blood loss were significantly less in the experimental group than in the control group (P < 0.05). After surgery, patients were folowed up for 12 to 18 months. The healing time was 3-5 months, averagely 4.3 months. At 12 months after treatment, the Rasmussen evaluation criteria results showed that the excelent and good rate was significantly higher in the experimental group than in the control group (P < 0.05). These results suggest that the fracture model of 3D can help to make the operation plan. The treatment of tibial plateau fractures is more precise, personalized and visual.

BACKGROUND:As a noticeable tissue engineering material of polyhy droxyalka noates family, poly (3-hydroxybutyrate-co-4-hydroxybutyrate)(P3HB4HB) exhibitsgood biocompatibility, adhesion and mechanicalproperties, presenting aextensive application future in tissue-engineered research.
OBJECTIVE:To investigate the biocompat ibilityin vitroand ectopic osteogenic differentiationin vivoof P3HB4HB and human bone marrow mesenchymal stem cels.
METHODS:Passage 5human bone marrow mesenchymal stem cels transplanted ontothe three-dimensional P3HB4HB scaffoldwereincubated with osteogenic induction medium (test group)or with no osteogenic induction(control group), respectively. After 5-day incubation, thecelgrowth was assessed by acridine orange staining and scanning electron microscopy; after14-day incubation, both kinds of cel-scaffold composites were subcutaneously implanted into the nude mice. At 16 weeks after implantation, the cel-scaffold composites were removed to observeectopic osteogenic differentiationin vivousing hematoxylin-eosin staining, von Kossa staining and colagen type I immunohistochemical staining.
RESULTS AND CONCLUSION:Acridine orange staining showed that cels adhered wel on the surface of the scaffold;under thescanning electron microscope, induced celsgrew wel on the P3HB4HB scaffold and produced abundant extracelular matrixes. In addition, at 16 weeks after implantation, there were osteoidtissues in the test group, positive for von Kossa staining as wel as colagen type I immunohistochemical staining;furthermore, hematoxylin-eosin staining showednumerous osteoblasts and bone lacunas. In contrast, no bone tissues appeared in the control group. To conclude, P3HB4HB is a suitable material for bone tissue engineering.