Cervi Cornu Pantotrichum is a precious animal-derived Chinese medicinal material, while there are often adulterants derived from animals not specified in the Chinese Pharmacopeia in the market, which disturbs the safety of medication. This study was conducted with the aim of strengthening the quality control of Cervi Cornu Pantotrichum and standardizing the medication. To achieve digital identification of Cervi Cornu Pantotrichum from different sources, a digital identification model was constructed based on ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UHPLC-QTOF-MS~E) combined with an adaptive boosting algorithm(Adaboost). The young furred antlers of sika deer, red deer, elk, and reindeer were processed and then subjected to polypeptide analysis by UHPLC-QTOF-MS~E. Then, the mass spectral data reflecting the polypeptide information were obtained by digital quantification. Next, the key data were obtained by feature screening based on Gini index, and the digital identification model was constructed by Adaboost. The model was evaluated based on the recall rate, F_1 composite score, and accuracy. Finally, the results of identification based on the constructed digital identification model were validated. The results showed that when the Gini index was used to screen the data of top 100 characteristic polypeptides, the digital identification model based on Adaboost had the best performance, with the recall rate, F_1 composite score, and accuracy not less than 0.953. The validation analysis showed that the accuracy of the identification of the 10 batches of samples was as high as 100.0%. Therefore, based on UHPLC-QTOF-MS~E and Adaboost algorithm, the digital identification of Cervi Cornu Pantotrichum can be realized efficiently and accurately, which can provide reference for the quality control and original animal identification of Cervi Cornu Pantotrichum.
Animals ; Algorithms ; Antlers/chemistry* ; Boosting Machine Learning Algorithms ; Chromatography, High Pressure Liquid/methods* ; Deer ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Quality Control ; Reindeer ; Tandem Mass Spectrometry/methods* ; Tissue Extracts/analysis*

Continuous manufacturing, as an innovative pharmaceutical production model, offers advantages such as high production efficiency and ease of control compared to traditional batch production, aligning with the future trend of drug production moving toward greater efficiency and intelligence. However, the development of continuous manufacturing technology in wet granulation has been slow. On one hand, this is closely related to its high technical complexity, substantial equipment investment costs, and stringent process control requirements. On the other hand, the long-term use of the traditional batch production model has created strong path dependence, and the lack of mature standardized processes further increases the difficulty of technological transformation. To promote the deep integration of wet granulation technology with continuous manufacturing, this review systematically outlines the current application of wet granulation in continuous manufacturing. It focuses on the development of key technologies such as online detection, process modeling, and process scale-up, with the aim of providing a reference for process innovation and application in wet granulation.
Drug Compounding/instrumentation* ; Technology, Pharmaceutical/methods* ; Drugs, Chinese Herbal/chemistry* ; Models, Theoretical

This study primarily investigates the effect of Liuwei Dihuang Pills on the activation and proliferation of female germline stem cells(FGSCs) in the ovaries and cortex of mice with premature ovarian failure(POF), and how it improves ovarian function. ICR mice were randomly divided into the control group, model group, Liuwei Dihuang Pills group, Liuwei Dihuang Pills double-dose group, and estradiol valerate group. A mouse model of POF was established by intraperitoneal injection of cyclophosphamide. After successful modeling, the mice were treated with Liuwei Dihuang Pills or estradiol valerate for 28 days. Vaginal smears were prepared to observe the estrous cycle and body weight. After the last administration, mice were sacrificed and sampled. Serum levels of estradiol(E_2), follicle-stimulating hormone(FSH), luteinizing hormone(LH), and anti-Müllerian hormone(AMH) were measured by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe ovarian morphology and to count follicles at all stages to evaluate ovarian function. Immunohistochemistry was used to detect the expression of mouse vasa homolog(MVH), a marker of ovarian FGSCs. Immunofluorescence staining, using co-labeling of MVH and proliferating cell nuclear antigen(PCNA), was used to detect the expression and localization of specific markers of FGSCs. Western blot was employed to assess the protein expression of MVH, octamer-binding transcription factor 4(Oct4), and PCNA in the ovaries. The results showed that compared with the control group, the model group exhibited disordered estrous cycles, decreased ovarian index, increased atretic follicles, and a reduced number of follicles at all stages. FSH and LH levels were significantly elevated, while AMH and E_2 levels were significantly reduced, indicating the success of the model. After treatment with Liuwei Dihuang Pills or estradiol valerate, hormone levels improved, the number of atretic follicles decreased, and the number of follicles at all stages increased. MVH marker protein and PCNA proliferative protein expression in ovarian tissue also increased. These results suggest that Liuwei Dihuang Pills regulate estrous cycles and hormone disorders in POF mice, promote the proliferation of FGSCs, improve follicular development in POF mice, and enhance ovarian function.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Cell Proliferation/drug effects* ; Mice, Inbred ICR ; Ovary/cytology* ; Primary Ovarian Insufficiency/genetics* ; Follicle Stimulating Hormone/metabolism* ; Humans ; Anti-Mullerian Hormone/blood* ; Antineoplastic Agents/adverse effects* ; Luteinizing Hormone/metabolism* ; Cyclophosphamide/adverse effects*

Objective To explore the regulatory effect of amylin on the feeding behavior of mice through the ERK pathway of paraventricular nucleus of the hypothalamus(PVN).Methods A total of 54 C57BL/6J mice were randomly divided into multiple groups for experiments.First,immunofluorescence was used to detect the distribution of ERK and calcitonin receptor(CTR)neurons in the brains of 4 mice.A chemical lesion model of PVN neurons was established,and 16 mice were divided into four groups(4 mice per group):control(Ctrl)group,ibotenic acid(IBO)-lesioned group,amylin group,and amylin+IBO group.The number of ERK-positive neurons in the PVN region and food intake were then measured.Subsequently,16 mice were divided into four groups(4 mice per group),Ctrl group,amylin group,ERK antagonist U0126 group,and amylin+U0126 group.The expression level of the immediate early gene c-fos in the PVN was detected by Real-time PCR.Immunofluorescence was used to detect the distribution of p-ERK positive neurons in the brains of 4 saline-treated mice and 4 amylin-treated mice.Finally,18 mice were randomly divided into three groups(6 mice per group)through intracerebroventricular injection,Ctrl group,amylin group,and amylin+receptor antagonist AC 187 group.Then,triple immunofluorescence was used to detect the co-expression of p-ERK,neuronal nitric oxide synthase(nNOS),and CTR-immunopositive neurons in the PVN region,and food intake within 3 hours after treatment was recorded simultaneously.Results ERK-positive neurons were mainly distributed in the suprachiasmatic nucleus(SCN),arcuate nucleus(ARC),and locus coeruleus(LC),while ERK and CTR co-expressing positive neurons were specifically enriched in the PVN(P=0.0012).Lesion of PVN neurons led to a decrease in the number of ERK-positive neurons(P＜0.001)and blocked the anorectic effect of amylin(P＜0.001).Amylin activated the expression of the c-fos gene in the PVN region(P＜0.05),and this effect was inhibited by U0126(P＜0.05).After intracerebroventricular injection of amylin,the number of triple-positive neurons for p-ERK,nNOS,and CTR in the PVN increased(P＜0.05).Addition of AC 187 blocked the activation effect of amylin(P＜0.01)and reversed the anorectic effect of amylin(1 h,P=0.2218;2 h,P=0.2218;3 h,P=0.6974).Conclusion P-ERK neurons in the PVN regulate feeding behavior through an amylin receptor-dependent ERK signaling pathway.

ObjectiveTo investigate the mechanisms of mitochondrial dynamics and metabolic reprogramming in the treatment of diabetic nephropathy （DN） by Shenxiao Tongluo prescription via the peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）/sirtuin-3 （SIRT3）/hypoxia-inducible factor-1α （HIF-1α） signaling pathway. MethodsSixty-five SD rats were randomized into a sham group （10 rats） and a modeling group （55 rats）， and the modeling rats underwent left nephrectomy and intraperitoneal injection of streptozotocin （35 mg·kg^-1） to prepare a DN model. After successful modeling， the rats were randomized into model， empagliflozin （10 mg·kg^-1）， and low-， medium-， and high-dose （7.656， 15.312， 30.624 g·kg^-1， respectively） Shenxiao Tongluo prescription groups. The urine microalbumin （UmAlb）， blood urea nitrogen （BUN）， and serum creatinine （SCr） levels of rats in each group were assessed after continuous gavage for 8 weeks. The corresponding kits were used to measure the levels of lactate， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the kidney tissue. Hematoxylin-eosin staining， Masson staining， and periodic acid-Schiff staining were performed to observe the pathological changes in the kidney tissue. Transmission electron microscopy was employed to observe mitochondrial morphology. Immunohistochemistry was employed to determine the expression levels of dynamin-related protein 1 （DRP1） and pyruvate kinase M2 （PKM2） in the kidney tissue. Western blot was adopted to assess the protein levels of PGC-1α， SIRT3， HIF-1α， dynamin-related protein 1 （Drp1）， optic atrophy 1 （OPA1）， hexokinase 2 （HK2）， and pyruvate kinase M2 （PKM2） in the kidney tissue. ResultsCompared with the sham group， the model group showed elevated levels of UmAlb， BUN， SCr， lactate， and MDA， decreased SOD level （P<0.05）， glomerular hypertrophy， thickening of the mesangial basement membrane， vacuolar degeneration of renal tubular epithelial cells， and infiltration of renal interstitial inflammatory cells， oval mitochondria with disordered， blurred or disappearing cristae， down-regulated protein levels of PGC-1α， SIRT3， and OPA1， and up-regulated protein levels of HIF-1α， DRP1， HK2， and PKM2 （P<0.05）. Compared with the model group， the treatment in all the groups increased the body weight， lowered the levels of GLU， UmAlb， BUN， and MDA， raised the level of SOD， alleviated the pathological damage in the kidney tissue and mitochondrial damage， up-regulated the expression of PGC-1α， SIRT3， and OPA1， and down-regulated the expression of HIF-1α， DRP1， and PKM2 （P<0.05）. Empagliflozin and Shenxiao Tongluo prescription at medium and high doses lowered the levels of SCr and lactate and down-regulated the expression of HK2 （P<0.05）， which had no statistical significance in the low-dose Shenxiao Tongluo prescription group. ConclusionShenxiao Tongluo prescription may regulate mitochondrial dynamics and metabolic reprogramming by activating the PGC-1α/SIRT3/HIF-1α pathway， thereby alleviating oxidative damage in the kidney tissue and delaying the progression of DN.

ObjectiveTo investigate the mechanisms of mitochondrial dynamics and metabolic reprogramming in the treatment of diabetic nephropathy （DN） by Shenxiao Tongluo prescription via the peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）/sirtuin-3 （SIRT3）/hypoxia-inducible factor-1α （HIF-1α） signaling pathway. MethodsSixty-five SD rats were randomized into a sham group （10 rats） and a modeling group （55 rats）， and the modeling rats underwent left nephrectomy and intraperitoneal injection of streptozotocin （35 mg·kg^-1） to prepare a DN model. After successful modeling， the rats were randomized into model， empagliflozin （10 mg·kg^-1）， and low-， medium-， and high-dose （7.656， 15.312， 30.624 g·kg^-1， respectively） Shenxiao Tongluo prescription groups. The urine microalbumin （UmAlb）， blood urea nitrogen （BUN）， and serum creatinine （SCr） levels of rats in each group were assessed after continuous gavage for 8 weeks. The corresponding kits were used to measure the levels of lactate， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the kidney tissue. Hematoxylin-eosin staining， Masson staining， and periodic acid-Schiff staining were performed to observe the pathological changes in the kidney tissue. Transmission electron microscopy was employed to observe mitochondrial morphology. Immunohistochemistry was employed to determine the expression levels of dynamin-related protein 1 （DRP1） and pyruvate kinase M2 （PKM2） in the kidney tissue. Western blot was adopted to assess the protein levels of PGC-1α， SIRT3， HIF-1α， dynamin-related protein 1 （Drp1）， optic atrophy 1 （OPA1）， hexokinase 2 （HK2）， and pyruvate kinase M2 （PKM2） in the kidney tissue. ResultsCompared with the sham group， the model group showed elevated levels of UmAlb， BUN， SCr， lactate， and MDA， decreased SOD level （P<0.05）， glomerular hypertrophy， thickening of the mesangial basement membrane， vacuolar degeneration of renal tubular epithelial cells， and infiltration of renal interstitial inflammatory cells， oval mitochondria with disordered， blurred or disappearing cristae， down-regulated protein levels of PGC-1α， SIRT3， and OPA1， and up-regulated protein levels of HIF-1α， DRP1， HK2， and PKM2 （P<0.05）. Compared with the model group， the treatment in all the groups increased the body weight， lowered the levels of GLU， UmAlb， BUN， and MDA， raised the level of SOD， alleviated the pathological damage in the kidney tissue and mitochondrial damage， up-regulated the expression of PGC-1α， SIRT3， and OPA1， and down-regulated the expression of HIF-1α， DRP1， and PKM2 （P<0.05）. Empagliflozin and Shenxiao Tongluo prescription at medium and high doses lowered the levels of SCr and lactate and down-regulated the expression of HK2 （P<0.05）， which had no statistical significance in the low-dose Shenxiao Tongluo prescription group. ConclusionShenxiao Tongluo prescription may regulate mitochondrial dynamics and metabolic reprogramming by activating the PGC-1α/SIRT3/HIF-1α pathway， thereby alleviating oxidative damage in the kidney tissue and delaying the progression of DN.

Objective To investigate the clinical value of tumor-stroma ratio (TSR) in combination with KRAS, BRAF, NRAS, and microsatellite status for prognostic assessment of patients with colorectal cancer. Methods A total of 51 colorectal cancer cases meeting the inclusion and exclusion criteria were enrolled in this study. TSR levels were evaluated through optical microscopy. The KRAS/NRAS/BRAF mutation profiles and microsatellite status were determined in accordance with genetic testing results. Clinical data, pathological characteristics, and survival outcomes were systematically recorded. Results Among the 51 patients with colorectal cancer, 19 (37.3%) were categorized into the low stromal group and 32 (62.7%) into the high stromal group. Statistically significant differences were observed between the two groups in drug resistance, M stage, TNM stage, neural invasion, and microsatellite status (P<0.05). Compared with patients exhibiting high TSR, those with low TSR demonstrated significantly increased recurrence rates (5 vs. 21 cases, P=0.007), shortened disease-free survival (34.21 vs. 14.34 months, P=0.001), and reduced overall survival (38.79 vs. 23.09 months, P=0.021). Multivariate Cox regression analysis identified N stage, M stage, TNM stage, neural invasion, lymphovascular invasion, and TSR as independent risk factors for disease-free survival. N stage, M stage, neural invasion, lymphovascular invasion, and TSR emerged as independent prognostic factors for overall survival (P<0.05). Although the combined models of TSR with KRAS, NRAS, BRAF, and microsatellite status, respectively, demonstrated overall statistical significance (P<0.05), none of the dummy variables in these models reached individually statistical significance (P>0.05), and therefore cannot be considered independent prognostic factors. Conclusion TSR serves as an independent predictor of poor prognosis in advanced colorectal cancer, with patients exhibiting low TSR demonstrating a significantly higher risk of recurrence and metastasis than those with high TSR. For patients with colon cancer undergoing first-line palliative chemotherapy after postoperative recurrence, histopathological assessment of TSR in primary tumor sites holds prognostic value and may serve as a relevant factor for evaluating treatment resistance in clinical management.

OBJECTIVE: This study aimed to reexplore minimum iodine excretion and to build a dietary iodine recommendation for Chinese adults using the obligatory iodine loss hypothesis. METHODS: Data from 171 Chinese adults (19-21 years old) were collected and analyzed based on three balance studies in Shenzhen, Yinchuan, and Changzhi. The single exponential equation was accordingly used to simulate the trajectory of 24 h urinary iodine excretion as the low iodine experimental diets offered (iodine intake: 11-26 μg/day) and to further deduce the dietary reference intakes (DRIs) for iodine, including estimated average requirement (EAR) and recommended nutrient intake (RNI). RESULTS: The minimum iodine excretion was estimated as 57, 58, and 51 μg/day in three balance studies, respectively. Moreover, it was further suggested as 57, 58, and 51 μg/day for iodine EAR, and 80, 81, and 71 μg/day for iodine RNI or expressed as 1.42, 1.41, and 1.20 μg/(day·kg) of body weight. CONCLUSION The iodine DRIs for Chinese adults were established based on the obligatory iodine loss hypothesis, which provides scientific support for the amendment of nutrient requirements.
Humans ; Iodine/administration & dosage* ; Male ; Female ; China ; Young Adult ; Diet ; Adult ; Nutritional Requirements ; East Asian People

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.