Objective: To systematically analyze the revisions content and technological development trends of microbiological standards in the Chinese Pharmacopoeia (ChP) 2025 Edition, and explore its novel requirements in risk-based pharmaceutical product lifecycle management.
Methods: A comprehensive review was conducted on 26 microbiological-related standards to summarize the revision directions and scientific implications from perspectives including the revision overview, international harmonization of microbiological standards, risk-based quality management system, and novel tools and methods with Chinese characteristics.
Results: The ChP 2025 edition demonstrates three prominent features in microbiological-related standards: enhanced international harmonization, introduced emerging molecular biological technologies, and established a risk-based microbiological quality control system.
Conclusion: The new edition of the Pharmacopoeia has systematically constructed a microbiological standard system, which significantly improves the scientificity, standardization and applicability of the standards, providing a crucial support for advancing the microbiological quality control in pharmaceutical industries of China.

Objective: To compare the effects of aerobic exercise at maximal fat oxidation (FATmax) and FATmax intensity exercise combined with resistance training (RT), and dietary restriction on the body composition, vascular endothelial function and ferroptosis in obese female university students, so as to provide a reference for exploring the mechanisms by which exercise improves vascular endothelial function. Methods: From February to May 2024, 70 obese female university students were recruited from Shanxi University and randomly divided into control group ( n =24), FATmax group ( n =24) and FATmax+RT group ( n =22). From March 4 to May 26, 2024 control group maintained their normal living habits, FATmax group performed aerobic exercise at FATmax intensity three times per week for 60 minutes per session; FATmax +RT group performed combined aerobic and resistance exercise at FATmax intensity three times per week for 60 minutes per session. The daily dietary calorie intake for all groups was determined according to resting energy expenditure. Body composition, vascular endothelial function and ferroptosis were measured before and after the intervention. Results: After 12 weeks of intervention, there were statistically significant differences in body mass, BMI, body fat, waist hip ratio and muscle mass among the three groups ( F =10.93, 5.88, 65.28, 21.14, 2.25, all P < 0.05). Compared with the control group, participants in both the FATmax group and the FATmax+RT group showed significant reductions in body weight, BMI, body fat and waist hip ratio (all P <0.05). Body fat and waist hip ratio in FATmax+RT group were lower than those in FATmax group, and muscle mass was higher than those in FATmax group and control group (both P <0.05). After 12 weeks of intervention, significant differences were observed among the three groups in serum NO, GSH, serum ferritin levels and FMD ( F = 9.14, 9.67, 4.78, 135.70, all P <0.05). Compared with the control group, the serum NO, GSH levels and FMD significantly increased, and the serum ferritin level decreased (all P <0.05) of obese female university students in FATmax group and FATmax+RT group. Serum GSH level and FMD increased and serum ferritin level decreased in FATmax +RT group when compared with FATmax group (all P <0.05). Conclusions With the same exercise training duration and frequency, FATmax intensity aerobic exercise, alone or combined with resistance and dietary restriction, can significantly improve the body composition, vascular endothelial function and inhibit ferroptosis of obese female university students. However, FATmax intensity aerobic exercise combined with resistance training has more pronounced effects.

The relevant laws and regulations regarding the utilization of the deceased as medical research subjects are not yet fully developed in China nowadays. Taking the deceased as research subjects as a starting point， this paper discussed the definition of the deceased and the scope of their interest protection from multiple perspectives. It posited that the scope of interest protection for the deceased encompassed two components： spiritual personality interests and material personality interests represented by the remains. The spiritual personality interests of the deceased included identification information such as name， portrait， reputation， honor， privacy， and personal information， as well as medical and health information. The personal information of the deceased was not directly affected by the individual’s life and death status and remained relatively independent. In terms of ethical review， the research team approached from two perspectives： the remains and the personal information of the deceased. Based on the standard of whether the research subjects involve a human body， research with the remains of the deceased as the medical research subjects was classified as non-clinical research. According to the standard of whether a human body is clinically operated， research with the personal information of the deceased （including medical and health information） as the medical research subjects was recognized as clinical research without human research operation. This approach provided evidence for the application of existing laws and regulations in ethical review and record management. The ethical review of investigator-initiated clinical research conducted in medical and health institutions， as well as the regulatory conditions for exemption from ethical review， were examined. The forms， content， and acquisition of informed consent were summarized， and the risk-benefit characteristics of the research activity were evaluated， with a view to providing a basis for the smooth and compliant implementation of research activities involving the deceased as medical research subjects.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Venous system diseases mainly include varicose veins and venous malformations of lower limbs and the genital system. Most of them are chronic diseases that cause serious clinical symptoms to patients and affect their health and quality of life. Sclerotherapy has become the first-line therapy for venous system diseases. However, there are problems such as incomplete fibrosis and vascular recanalization after sclerotherapy, and improper operation will cause serious adverse consequences. Therefore, exploring a safe and effective sclerotherapy strategy is essential for developing clinically successful sclerotherapy. To solve the above problems, we proposed a new sclerotherapy strategy with a dual mechanism of "vascular damage and plasmin (PLA) system inhibition." We intended to construct a novel cationic surfactant (AEO_x-TA) by reacting tranexamic acid (TA), a parent structure, with fatty alcohol polyoxyethylene ether (AEO_x) by ester bonds. AEO_x-TA could damage vascular endothelium and initiate a coagulation cascade effect to induce thrombus. Furthermore, AEO_x-TA could be degraded by esterase and release the parent drug, TA, which could inhibit the PLA system to inhibit the degradation of thrombus and extracellular matrix and promote the process of vascular fibrosis. In addition, such surfactant-based sclerosants have foam-forming properties, and they can be blended with polyvinyl alcohol (PVA) to prepare a highly stable foam formulation (AEO_x-TA/P), which can achieve a precise drug delivery and prolonged drug retention time, thereby improving drug efficacy and reducing the risk of ectopic embolism. Overall, the novel cationic surfactant AEO_x-TA provides a new avenue to resolve the bottleneck: surfactant sclerosants' efficiency is relatively low in the current sclerotherapy.

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

ADC189 is a novel drug of cap-dependent endonuclease inhibitor. In our study, its antiviral efficacy was evaluated in vitro and in vivo, and compared with baloxavir marboxil and oseltamivir. A first-in-human phase I study in healthy volunteers included single ascending dose (SAD) and food effect (FE) parts. In the preclinical study, ADC189 showed potent antiviral activity against various types of influenza viruses, including H1N1, H3N2, influenza B virus, and highly pathogenic avian influenza, comparable to baloxavir marboxil. Additionally, ADC189 exhibited much better antiviral efficacy than oseltamivir in H1N1 infected mice. In the phase I study, ADC189 was rapidly metabolized to ADC189-I07, and its exposure increased proportionally with the dose. The terminal elimination half-life (T_1/2) ranged from 76.69 to 98.28 hours. Of note, food had no effect on the concentration, clearance, and exposure of ADC189. It was well tolerated, with few treatment-emergent adverse events (TEAEs) reported and no serious adverse events (SAEs). ADC189 demonstrated excellent antiviral efficacy both in vitro and in vivo. It was safe, well-tolerated, and had favorable pharmacokinetic characteristics in healthy volunteers, supporting its potential for single oral dosing in clinical practice.
Humans ; Antiviral Agents/therapeutic use* ; Animals ; Male ; Adult ; Mice ; Female ; Endonucleases/antagonists & inhibitors* ; Influenza, Human/drug therapy* ; Young Adult ; Dibenzothiepins/pharmacology* ; Oseltamivir/pharmacology* ; Middle Aged ; Triazines/pharmacology* ; Thiepins/pharmacology* ; Influenza B virus/drug effects* ; Influenza A Virus, H1N1 Subtype/drug effects* ; Pyridines/pharmacology* ; Morpholines ; Pyridones

The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.

ObjectiveTo investigate the possible mechanism of Huatan Sanjie Formula （化痰散结方， HSF） in treating Graves' disease （GD） from the perspective of thyroid angiogenesis. MethodsThirty-six BALB/c female mice were randomly divided into a normal control group （n=9） and a modeling group （n=27）. Mice in the modeling group were injected with 2.0×10⁹ PFU/ml of Ad-TSHR289 adenovirus into the tibialis anterior muscle to build GD model. Nine weeks after immunization， the successfully modeled mice were randomly divided into model group， methimazole （MMI） group and HSF group， with 9 mice in each group. The MMI group was given 5.2 mg/（kg·d） of methimazole tablets by gavage， while the HSF group was given HSF at a relative crude drug dosage of 7.02 g/（kg·d） by gavage. The normal control group and the model group were given 0.1 ml/10 g of pure water by gavage. All groups were administered intragastrically once a day for a total of 4 weeks. The levels of thyroxine （T4） and thyrotropin receptor autoantibodies （TRAb） in serum were detected by radioimmunoassay， while the pathological changes of the thyroid gland were assessed by HE staining. The vascular morphology of thyroid tissue was observed by CD34 immunohistochemical staining， and the microvessel density （MVD） was counted. The protein expression of vascular endothelial growth factor A （VEGFA） and vascular endothelial growth factor receptor 2 （VEGFR2） in thyroid was detected by Western-blot. ResultsCompared to those in the normal control group， the thyroid volume of the mice in the model group significantly increased with excessive congestion， and the pathology showed significant thyroid follicular hyperplasia， columnar and proliferated epithelial cells， and enlarged follicle size； serum T4 and TRAb significantly increased， as well as the count of thyroid MVD， and the protein expressions of thyroid VEGFA and VEGFR2 （P＜0.01）. Compared to those in the model group， the thyroid glands of the mice in the MMI group and the HSF group were significantly reduced， and the congestion was improved； pathology showed that thyroid follicular hyperplasia and epithelial cell proliferation were reduced， with smooth edges of the follicles and the significantly reduced inward protrusion； serum T4 and TRAb significantly decreased， as well as the thyroid MVD， thyroid VEGFA and VEGFR2 protein expressions （P＜0.05 or P＜0.01）. There was no significant difference in all indicators between the MMI group and the HSF group （P＞0.05）. ConclusionHSF may inhibit thyroid angiogenesis by down-regulating thyroid VEGFA/VEGFR2 signaling pathway， thereby improving goitre and hyperfunction in GD mice.

AIM:To explore the molecular mechanism of Tiaopi Chengqi decoction (TpCqD) improving hyperthermia and high-protein food-induced hyperphagia mice based on transcriptomics. METHODS:C57 mice were randomly divided into a control group, model group, low-dose TpCqD group, high-dose TpCqD group, and domperidone group. The general condition of the experimental mice was observed and the average food intake was counted, and the rate of gastric emptying and intestinal propulsion was determined for each group of mice. H&E staining was used to observe pathological changes in gastric tissue. PAS staining was used to observe glycogen changes in gastric tissue. Pepsin activity was determined by colorimetry. pH value of gastric contents was measured by acid-base titration. Transcriptome sequencing was used to analyze the differential genes in gastric tissue, a volcano map and a cluster heat map were made for the differential genes, and KEGG was used to analyze the signal pathway enrichment of the differential genes. RT-qPCR verified the differential genes obtained by screening. RESULTS:After treatment with TpCqD, the body weight and average food intake of mice with food accumulation increased (P<0.05), and the intestinal propulsion rate and gastric emptying speed of mice with food accumulation accelerated (P<0.05). TpCqD could protect gastric tissue structure and glycogen degradation, increase pepsin activity (P<0.05), and reduce gastric content pH (P<0.05). Transcriptome results showed that TpCqD could regulate the expression of Acox2 and cilp2, regulate fat digestion and absorption, protein digestion and absorption, and pancreatic secretion signals. RT-qPCR showed that compare with model group, TpCqD up-regulated Acox2 (P<0.05) and down-regulated the mRNA level of cilp2 (P<0.05). CONCLUSION:TpCqD ameliorated digestive dysfunction in mice with high-calorie and high-protein diets leading to food accumulation involving the regulation of the fat and sugar metabolism genes Acox2 and cilp2, and pancreatic secretory signaling.