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.

Neovascular age-related macular degeneration(ARMD)is a condition where various causes induce the formation of choroidal neovascularization(CNV)in the macula, leading to macular hemorrhage, accumulation of fluid, and development of fibrosis, resulting in a large, dark spot in the center of the visual field, causing severe central vision loss in over 90% of patients. Endothelial progenitor cells(EPCs)are a heterogeneous group of cells that play a crucial role in neovascularization. Under pathological stimulation, EPCs are mobilized into the systemic circulation, migrate toward the avascular zone, and promote the restoration of blood vessels and endothelialization in the damaged area. Toll-like receptors(TLRs)are pattern recognition receptors and type Ⅰ transmembrane proteins that are mainly expressed in monocytes, dendritic cells, and other immune cells, recognizing the surface of pathogens and transmitting signals to cells, participating in the innate immune response and adaptive immune response. Studies have shown that most TLRs are involved in the development of neovascularization, and EPCs can express TLRs. Therefore, exploring the role of EPCs/TLRs in the pathogenesis of ARMD can help us understand the disease and may provide new insights for targeted therapy in the future.

Objective To analyze the short-term clinical efficacy and influencing factors of ustekinumab monoclonal antibody(UST)in the treatment of Crohn′s disease(CD).Methods Retrospective cohort study was used to collect the clinical data of CD patients treated with UST in the 10th People′s Hospital affiliated to Tongji University from December 2020 to October 2022.The main analysis is the short-term clinical efficacy and influencing factors of UST treatment for CD at weeks 8 and 16,And analyze the endoscopic response rate of some patients.Results A total of 91 CD patients who first used UST were included.The 8-week clinical response rate of UST treat-ment for CD was 61.5%,and the clinical response rate was 45%;The clinical response rate at 16 weeks was 71.4%,and the clinical response rate was 54.9%.56 cases underwent endoscopic re-examination in our hospital,and the endoscopic response rate at 16 weeks was 41.1%.Univariate analysis showed that fistula(including anal fistula,personal history of anal fistula,and intestinal skin fistula)is associated with clinical remission in Crohn′s disease patients at 8/16 weeks.Further multivariate COX regression analysis showed that the presence of a history of anal fistula surgery was an independent protective factor affecting clinical remission in CD patients treated with UST at 8 weeks(HR = 0.04,95%CI:0.00～0.38;P = 0.005)and 16 weeks(HR = 0.04,95%CI:0.01～0.34;P = 0.003)compared to those without fistula;Narrow lesions are an independent risk factor for 16 week clinical remission in CD patients compared to non-narrow and non-penetrating lesions(HR = 1.75,95%CI:1.08～2.84;P = 0.023).No patients were found to have stopped medication due to serious adverse reactions.Conclusions UST can improve the clinical remission and response of CD patients at 8/16 weeks,and has good short-term clinical efficacy.CD patients with a personal history of anal fistula are recommended to use UST monoclonal antibodies,while patients with stenotic lesions should be cautious in using UST monoclonal antibodies.Whether the patient has undergone surgical treatment in the past,as well as whether UST has been used on the first or non-first line,has no significant impact on clinical remission.

Aging is a necessary process for organisms.The antioxidant capacity in the body decreases, which induces the activation of inflammasomes, autophagy dysregulation, protein misfolding in the lens, resulting in lens opacification. With the increase of age, the secretion of melatonin and glutathione(GSH)gradually decreased, and the pro-oxidant/pro-inflammatory factors increased, which created ideal conditions for the formation of age-related cataract(ARC). A series of changes such as oxidative stress, inflammation and autophagy dysregulation accompany the occurrence of aging, which is also the basis of various diseases. Melatonin has antioxidant, anti-inflammatory, regulation of autophagy and circadian rhythm effects, and has shown benefits in age-related macular degeneration(ARMD), diabetic retinopathy(DR), and glaucoma. Although phacoemulsification and lens implantation have developed maturely, they consume a lot of medical resources. This article reviews the research of melatonin in ARC, which may prevent/delay the formation of ARC, thereby reducing the economic burden of patients and reducing the loss of medical resources.

Objective To investigate the effect of Galangin on pyroptosis of bone marrow derived macrophages(BMDMs).Methods BMDMs were cultured in vitro and divided into blank control group,model group and Galangin group with different concentrations.Lipopolysaccharide(LPS)and adenosine triphosphate(ATP)were used to construct the pyroptosis model.The effect of different concentrations of Galangin on the proliferation of BMDMs was detected by cell counting Kit-8(CCK-8).The level of cysteinyl aspartate specific proteinase-1 p10 subunit(caspase-1 p10),interleukin-1β(IL-1β)in supernatant and intracellular nucleotide NOD-like receptor protein 3(NLRP3)were detected by Western blotting.IL-1β in supernatant was detected by enzyme-linked immunosorbent assay(ELISA).The cell death was observed by propidium iodide(PI)staining.High-throughput sequencing was used to compare the gene expression in the model group and Galangin groups at 20 μmol/L.Results There was no statistically significant difference between the 5,10,20,40,60,80 μmol/L Galangin groups on the proliferation level of BMDMs(all P>0.05),indicating that no significant effect of Galangin at 5,10,20,40,60,80 μmol/L was observed on the proliferation of BMDMs.So we selected Galangin at 5,10,20 μmol/L and treatment for 1,2 and 4 hours as the effects of different concentrations and time on the pyroptosis of BMDMs.Compared with blank control group,the expression of caspase-1 p10 and mature IL-1β protein and IL-1β in supernatant in model group were significantly increased(all P<0.05).Compared with model group,the expression of caspase-1 p10 and mature IL-1β protein and IL-1β in supernatant of Galangin at 5,10 and 20 μmol/L were significantly decreased[IL-1β protein expression(gray value):0.155±0.006,0.113±0.006,0.111±0.007 vs.1.000±0.000,caspase-1 p10 protein expression(gray value):0.207±0.044,0.160±0.008,0.082±0.008 vs.1.000±0.000,IL-1β(μg/L):99.80±10.36,85.21±8.78,26.53±4.56 vs.494.10±35.47,all P<0.05].There was no significant difference between the different concentration groups(all P>0.05),but with the extension of treatment time of Galangin,the inhibitory effect was enhanced.The inhibitory effect of Galangin at 20 μmol/L for 4 hours was the most obvious[IL-1β protein expression(gray value):0.186±0.004 vs.1.000±0.000,caspase-1 p10 protein expression(gray value):0.247±0.009 vs.1.000±0.000,IL-1β(μg/L):173.80±10.56 vs.653.80±76.02,all P<0.05].Treatment with 20 μmol/L Galangin for 4 hours could reduce the number of pyroptotic cell deaths(number of view:23.00±3.61 vs.67.67±15.63,P<0.05)and inhibited the expression of NLRP3 protein(gray value:0.178±0.025 vs.0.406±0.066,P<0.05).High-throughput sequencing showed that,compared with the model group,Galangin down-regulated the genes of Nlrp3,Nod2,IL-1β and up-regulated genes of Skp2(also known as Fbxl1),Fbxl20,Fbxl4,Fbxo32 and Fbxw7.Conclusion Galangin inhibited pyroptosis mediated by NLRP3 inflammasome in macrophages.

Cross-Sectional Studies ; Urodynamics ; China

Objective To explore the therapeutic effect of lignans extracted from Eucommia Ulmoides Oliver on diabetes encephalopathy(DE)rats and the effects on nuclear factor E2 related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway.Methods A rat model of DE was established,and 48 successfully established DE rats were randomly divided into model group,and low-and high-dose lignans groups(200 and 400 mg/kg),and metformin(200 mg/kg)group,with 12 rats in each group.Another 12 healthy rats served as control group.Each group of rats was giv-en corresponding drug intervention once a day for 6 consecutive weeks.Cognitive and memory abilities,serum levels of IL-6,TNF-α,MDA and SOD,and mRNA and protein levels of Nrf2 and HO-1 in the hippocampus were measured in all groups.Pathological changes of the hippocampus were observed after HE staining.Results Compared with the control group,significantly longer escape latency and increased serum levels of IL-6,TNF-α and MDA,while lower times of crossing original platform,shorter residence duration of original platform quadrant,decreased serum SOD level,and reduced mRNA and protein levels of Nrf2 and HO-1 in the hippocampus were observed in the model group(all P＜0.05).Low-and high-dose lignans treatment reversed all above indica-tors when compared with model group(P＜0.05).What's more,the effects of high-dose lignans treatment were more significant than low-dose treatment in escape latency,serum levels of IL-6,TNF-α and MDA,times through the original platform,residence duration of the original platform quadrant,serum SOD level,and mRNA Nrf2 and HO-1 in the hippocampus(6.07±0.70 vs 4.76± 0.52,30.96±2.96 s vs 23.49±2.60 s,77.02±6.51 U/ml vs 61.71±6.75 U/ml,0.69±0.06 vs 0.49± 0.05,0.74±0.07 vs 0.57±0.06,P＜0.05).Conclusion Eucommia lignans can improve the cogni-tive ability,enhance the antioxidant capacity,inhibit inflammatory response and protect the hippo-campus of DE rats,and the mechanism may be related to the activation of Nrf2/HO-1 signaling pathway.

Objective:To explore the value of quantitative parameters of cortical and cancellous bone in the first lumbar vertebrae (L1) based on CT spinal bone quantification system for evaluating the severity of chronic obstructive pulmonary disease (COPD) in males.Methods:A total of 88 male patients with COPD diagnosed at the Second Affiliated Hospital of Shandong First Medical University from August 2021 to December 2022 were retrospectively analyzed. According to the 2023 edition of global initiative for chronic obstructive lung disease (GOLD), the patients were classified as GOLD Ⅰ (29 cases), GOLD Ⅱ (36 cases), and GOLD Ⅲ-Ⅳ (23 cases). And then 29 males with normal lung function during the same period were recruited. People with normal lung function and COPD patients of GOLD Ⅰ-Ⅱ were classified as non-severe COPD group (94 cases), COPD patients of GOLD Ⅲ-Ⅳ were classified into the severe COPD group (23 cases). On the CT images of L1, the CT spine bone quantification system was used to automatically segment cortical and cancellous bone. The total volume, cortical volume, cancellous volume, average cortical thickness, cortical bone average CT value and cancellous bone average CT value of L1 vertebral body were measured using the system respectively. Single factor analysis of variance was used to compare the differences of various parameters among normal lung function and COPD patients with different lung function grades. The efficacy of various parameters in evaluating the severity of COPD were calculated using the receiver operating characteristic curve.Results:The overall differences in L1 vertebral total volume, cancellous volume and cortical bone average CT value among people with normal lung function and COPD patients of GOLD Ⅰ, Ⅱ, and Ⅲ-Ⅳ were statistically significant ( F=3.60, 4.26, 5.39, P=0.016, 0.007, 0.002), and showed a downward trend as the severity of COPD progressed. There were no statistically significant difference in cortical volume, average cortical thickness and cancellous bone average CT value of L1 ( P>0.05). The area under the curve (AUC) for distinguishing severe and non-severe COPD was 0.64 (95%CI 0.54-0.72), 0.65 (95%CI 0.56-0.74) and 0.75 (95%CI 0.66-0.83) for the total vertebral volume, cancellous volume and cortical bone average CT value of L1 respectively. The AUC of cortical bone average CT value was the highest, with a cutoff value of 217 HU/mm 3, a sensitivity of 69.6% and a specificity of 80.9%. Conclusion:Male COPD patients have reduced bone mass compared to the same age male population. The L1 quantitative parameters measured based on the CT spinal bone quantification system can effectively evaluate the severity of lung function in male COPD patients. Among them, the cortical bone average CT value has the highest diagnostic efficacy.

Objective:To investigate the effect of liquiritin on the apoptosis of amygdala cell and the expression of apoptosis-related factors Bax and Bcl-2 protein in rats with post-stroke depression (PSD).Methods:Sixty rats were randomly divided into normal control group, stroke group, PSD group, citalopram group, liquiritin group, and normal saline control group ( n=10 in each group). The middle cerebral artery was occluded with a suture method to induce focal cerebral ischemia, and the PSD model was established by chronic and unpredictable mild stress stimulation and orphanism. At the same time every week after the model was made, the weight of rats in each group was measured and the depression behavior was evaluated, including sucrose water test and open field test. At 6 weeks after the model was made, TUNEL staining was used to detect the apoptosis of amygdala cell, immunofluorescence staining was used to detect the expression of Bax and Bcl-2 in the amygdala, and Western blot analysis was used to detect the protein expression of Bax and Bcl-2 in the amygdala. Results:Compared with the liquiritin group, citalopram group and normal control group, the body weight and sucrose solution preference of rats in the stroke group, PSD group and normal saline control group were decreased, and the horizontal and vertical movements in open field test were decreased; the differences were statistically significant (all P<0.01). TUNEL staining results showed that compared with the liquiritin group, citalopram group and normal control group, the number of apoptotic cells was significantly increased in the stroke group, PSD group, and normal saline control group; the difference was statistically significant (all P<0.01). The results of immunofluorescence staining showed that compared with the liquiritin group, citalopram group and normal control group, the number of bcl-2 immunoreactive cells in amygdala of the stroke group, PSD group and normal saline control group was significantly decreased, while the number of Bax immunoreactive cells was significantly increased; the difference was statistically significant (all P<0.01). Western blot analysis showed that compared with the liquiritin group and citalopram group, the expression of bcl 2 protein in amygdala of the stroke group, PSD group and normal saline control group was significantly decreased, while the expression of Bax protein was significantly increased; the difference was statistically significant (all P<0.01). Conclusion:Liquiritin can alleviate the symptoms of PSD, and its mechanism may be related to inhibiting the apoptosis of amygdala cells and regulating the expression of apoptosis-related factors.

Objective:To observe the changes of protein expression of apoptosis signal pathway in prefrontal cortex of rats with post-stroke depression(PSD) after lateral ventricle injected of brain-derived neurotrophic factor precursor(proBDNF).Methods:Among 55 healthy adult female SD rats, 25 rats were randomly selected as PSD group, and the other 30 rats were randomly divided into normal group ( n=10), depression group ( n=10) and stroke group ( n=10). The middle cerebral artery occlusion(MCAO) model was established by thread occlusion in the stroke group, the chronic stress depression model in the depression group was established by the combination of chronic unpredictable mild stress(CUMS) and the solitary feeding method.And the rats in the PSD group were established MCAO model first, then they were received CUMS stress and solitary rearing one week later so as to establish PSD model.Two weeks after the establishment of the model, 15 rats in PSD group were randomly divided into proBDNF group, rats in tPA group and NS control group.One week after buried tube of lateral ventricle, rats in tPA and proBDNF were injected into the lateral ventricle for one week.The protein expressions of c-Jun N-terminal kinase(JNK), p-JNK, p53, p-p53 and Bax in prefrontal cortex of rats in each group were detected by Western blot at the 4th and 8th week after modeling.SPSS 17.0 software was used for data analysis, one-way ANOVA was used for comparison between groups, and SNK- q was used for pairwise comparison. Results:The expressions of p-p53, p53, p-JNK, JNK and Bax in prefrontal cortex of normal group, depression group, stroke group and PSD group were significantly different at the end of 4th and 8th week after MCAO modeling ( F=3.426-90.355, all P<0.05). Post-hoc analysis showed that, compared with the normal group, the expressions of p-JNK (0.378±0.042) and Bax (0.478±0.054) in the prefrontal cortex of PSD rats increased significantly at the end of the 4th week(both P<0.05), and the expressions of p-JNK(0.411±0.056), p-p53 (0.286±0.083) and Bax (0.471±0.008) in the prefrontal cortex of PSD group increased significantly at the end of the 8th week(all P<0.05). After lateral ventricle injection of proBDNF, there were significant differences in the expression of p-p53, p53, p-JNK, JNK and Bax among proBDNF group, tPA group and NS group ( F=16.915-287.039, all P<0.01). Post-hoc analysis showed that, compared with NS group, the expressions of p-JNK (0.35±0.01)and p-p53 (0.31±0.01)in prefrontal cortex of proBDNF group increased significantly(both P<0.05). After lateral ventricle injection of proBDNF, there were significant differences in body weight, sucrose preference rate, horizontal movement distance among proBDNF group, tPA group and NS group ( F=18.741-76.305, all P<0.01), and compared with tPA group and NS group, behavioral indexes of proBDNF group (body weight (224.36±3.23) g, sucrose preference rate (69.83±1.72)%, horizontal movement distance (57.93±2.09) blocks, vertical movement distance (19.79±1.81)) decreased significantly(all P<0.05). Conclusion:The proBDNF promotes the activation of apoptosis signal pathway in the rats with PSD.