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 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 man-agement system,and novel tools and methods with Chinese characteristics.Results:The ChP 2025 edition demon-strates three prominent features in microbiological-related standards:enhanced international harmonization,intro-duced emerging molecular biological technologies,and established a risk-based microbiological quality control sys-tem.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 evaluate the intravascular volume at different levels of edema and disease course by the fractional excretion of filtered sodium(FeNa)of children with primary nephrotic syndrome(PNS).Methods A total of 172 children with newly diagnosed PNS who were hospitalized in the Affiliated Hospital of Xuzhou Medical University from September 2022 to September 2024 were selected and divided into non-e-dema group(n=51),mild edema group(n=43),moderate edema group(n=46)and severe edema group(n=32)according to the degree of edema at the time of admission.A total of 40 healthy children who underwent physical examination during the same period were selected as the healthy control group.Serum creatinine,ser-um sodium were detected before and after treatment.Urine samples were collected to detect urine creatinine,urine sodium,FeNa was calculated and compared according to the results,and the degree of edema was recor-ded.24 h urine samples were collected on the same day to detect 24 h urine protein quantification and 24 h u-rine volume.Results On day 1 to 2 of the course of the disease,about 12%of the PNS children had FeNa<0.2%,indicating insufficient intravascular volume,which was mainly concentrated in the severe edema group.The moderate,severe edema group had a significantly lower FeNa level than the non-edema group,mild edema group,and healthy control group(P<0.01).The moderate edema group had a significant increase in FeNa on days 6 to 7 of the course of the disease,and the severe edema group had a significant increase in Fena on days 11 to 12 of the course of the disease(P<0.01).Conclusion Intravascular volume of PNS children with mod-erate to severe edema is often reduced,and intravascular volume may be insufficient in severe edema.PNS chil-dren with moderate to severe edema have increased intravascular volume with the extension of the course of disease and the improvement of the condition.

Objective:To analyze the individual and cumulative effects of unhealthy lifestyle on the prevalence of hypertension, diabetes and dyslipidemia in old adults in China, and find out the critical lifestyle in the network.Methods:Based on the baseline data of Yunnan Behavior and Disease Surveillance Cohort in 2021, a total of 16 763 older adults aged ≥60 years were included in our study. The unhealthy lifestyle factors including smoking, drinking, unhealthy eating habit, lower physical activity level, abnormal BMI and abnormal waist circumference. We calculated the unhealthy lifestyle score by using the cumulative exposures of each participant. Multiple logistic regression and mixed graphical models were used to describe the association between unhealthy lifestyle and the prevalence of hypertension, diabetes and dyslipidemia.Results:The prevalence of hypertension, diabetes and dyslipidemia were 57.0%, 11.5% and 37.0%, respectively. Most of the unhealthy lifestyles included in the study were risk factors for hypertension, diabetes and dyslipidemia, and the risks of disease increased with the increase of the unhealthy lifestyle score. The participants with the highest score (score: 6) had significantly higher prevalence of hypertension ( OR=3.99, 95% CI: 1.81-8.80), diabetes ( OR=4.64, 95% CI: 1.64-13.15) and dyslipidemia ( OR=4.26, 95% CI: 2.08-8.73) compared with those with lowest score (score: 0). In the network constructed by mixed graphical model, abnormal waist circumference (bridge strength=0.81) and hypertension (bridge strength=0.55) were vital bridge nodes connecting unhealthy lifestyle and hypertension, diabetes and dyslipidemia. Conclusions:The unhealthy lifestyle score was associated with risks for hypertension, diabetes and dyslipidemia. Abnormal waist circumference was the key factor for chronic diseases in old adults.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective:To analyze the characteristics of the apolipoprotein E(Apo E)genotype and cognitive impairment in patients with cerebral microbleeds(CMBs)and positive β-amyloid(Aβ)by using [18F]-AV45 positron emission tomography(PET).Methods:From September 2015 to May 2018, 152 patients with cognitive impairment and CMBs on the susceptibility-weighted imaging(SWI)sequence of head MRI at the neurology department of our hospital, assessed by mini-mental status examination(MMSE)score ≤26 and Montreal cognitive assessment(MoCA)≤25, were consecutively recruited in this retrospective study.After assessment with the inclusion and exclusion criteria, 69 patients aged 68.8±9.3 years were considered eligible for further analysis.Patients were divided into the Aβ-positive group(Aβ + Group, n=37)and the Aβ-negative group(Aβ -Group, n=32)after cognitive assessment, ApoE genotyping and [18F]-AV45 PET examination.Twenty-one healthy elderly controls(HC Group)who took health examination during the same period were enrolled.The results of cognitive assessment and Apo E genotyping were compared between the three groups. Results:The positive rate of the ApoE ε4 allele was 35.6%(32/90), 56.8%(21/37), 18.8%(6/32), and 23.9%(5/21)in the Aβ + , Aβ -and HC groups, respectively, with statistical significant differences between the groups( χ2=12.467, P<0.01). There were significant differences in the positive rate of the ApoE ε4 allele between the Aβ + and HC groups and between the Aβ + and Aβ -groups( χ2=5.880 and 10.407, P<0.05 and P<0.01). The percentage of patients with deep cerebral microbleeds was higher(56.3% or 18/32 vs.8.1% or 3/37, χ2=18.784, P<0.01)and of patients with lobar hemorrhage was lower(12.5% or 4/32 vs.45.9% or 17/37, χ2=9.066, P<0.01)in the Aβ -group than in the Aβ + group, while there was no significant difference in the percentage of patients with mixed cerebral microbleeds between the Aβ -and Aβ + groups( χ2=1.556, P>0.05). There were significant differences in cognitive function between the Aβ + and HC groups, in memory, executive function, visuospatial ability and language between the Aβ + and Aβ -groups, and in executive function, visuospatial ability and attention between the Aβ -and HC groups. Conclusions:Cognitive impairment is more extensive and severe in CMBs patients with Aβ deposition and is associated with positive ApoE ε4.

Objective To analyze the mutations of causal genes in sixteen Chinese patients with suspicious Bartter syndrome,and follow up their treatment results.Methods Mutations were identified by the next generation sequencing and the multiplex ligation-dependent probe amplification (MLPA).Clinical and biochemical features at the first presentation as well as follow-up results were reviewed.Results 15 different CLCNKB gene mutations were identified in sixteen patients with BS,including 11 novel ones.A novel missense mutation and a novel small deletion were found from SLC12A1 gene.A novel gross deletion was found in CLCNKA gene.A recurrent missense mutation was identified from BSND gene.The whole gene deletion mutation of CLCNKB gene was the most frequent mutation (32％),and the rate of gross deletion was up to 50 percent in this group of Chinese patients.The most common clinical manifestations were development retardation (15/16),polydipsia and polyuria (15/16).All of the patients were detected with hypokalemia,hypochloremia and metabolic alkalosis.Indomethacin treatment had significant improvement to the stature and weight restoration.Conclusion The present study has found 19 mutations,including 14 novel ones,which enriches the human gene mutation database (HGMD) and provides valuable references to the genetic counseling and diagnosis of Chinese population.

Objective To screen and identify mRNAs targeted by human cytomegalovirus-encoded miR-US33-1-5p (HCMV miR-US33-1-5p) for understanding the biological functions of HCMV miR-US33-1-5p. Methods Potential target mRNAs of HCMV miR-US33-1-5p were screened out by using hybrid-PCR, a simple and effective method. Dual-Luciferase Reporter Assay System was used to identify the binding abili-ties of HCMV miR-US33-1-5p to 3′-UTRs of these potential target mRNAs. Results Twelve potential mRNAs targeted by HCMV miR-US33-1-5p were screened out in human embryo lung fibroblast cells infected with HCMV. Luciferase activities of 3′-UTRs of seven target mRNAs were significantly down-regulated. Conclusion Proteins encoded by these target mRNAs are involved in virus replication,immune system reg-ulation,protein synthesis,cell cycle regulation,energy metabolism and so on. Identification of mRNAs tar-geted by HCMV miR-US33-1-5p is helpful for further studies on biological functions of miR-US33-1-5p.

Background and purpose:Lung cancer is one of the leading causes of cancer death in the world. The aim of this study was to evaluate whether Fas-670 G>A and Fasl-844 T>C polymorphisms were associated with the risk of lung cancer.Methods:Data from 400 lung cancer patients with speciifc histological diagnosis were collected from 2010 to 2015. Meanwhile, data from matched healthy controls with the same gender and ±5 years were also collected. The genotypes of Fas-670 G>A and Fasl-844 T>C polymorphisms were determined by TaqMan lfuorescent probe method, and the results were analyzed using SPSS 16.0 software.Results:A total number of 386 cases and 394 controls were successfully genotyped. Compared with AA genotypeofFasgene, the GA and GG genotype carriers had no signiifcantly increased risk of lung cancer.The OR values were 1.05 (95%CI: 0.77-1.44) and 0.77 (95%CI: 0.81-1.99) respectively. Compared with TT genotype ofFasl gene, the CT and CC genotype carriers had signiifcantly increased risk of lung cancer. The OR values were 1.37 (95%CI: 1.01-1.86) and 1.74 (95%CI: 1.09-2.77), respectively. Conclusion:Fasl-844 T>C polymorphism may be involved in lung cancer risk but not Fas-670 G>A polymorphism.

Objective To investigate the effect of gefitinib on mucus hypersecretion by inhibiting epidermal growth factor receptor (EGFR) activity in chronic obstructive pulmonary disease (COPD).Methods Human airway epithelail cell lines 16HBE cells were exposed to cigarette smoke extraction (CSE) to establish the COPD model.EGFR activity was inhibited by tyrosine kinase inhibitor gefitinib.The mRNA expressions of EGFR and MUC5AC were detected by real-time PCR.EGFR,p-EGFR and MUC5AC protein levels were determined by Western blot and ELISA.Results EGFR mRNA level was increased by 12.7％ in CSE and 8.6％ in gefitinib group,but had no significant differences among CSE,gefitinib group and control group (all P＞ 0.05).MUC5AC mRNA levels were enhanced by 141.7％,26.4％ in CSE group and gefitinib group respectively,and there were significant differences among CSE,gefitinib group and control group (all P＜0.05).EGFR protein levels were (600.34±64.58) μg/mg,(632.58±72.94) μg/mg,(584.57±67.39) μg/mg,in control,CSE and gefitinib groups,respectively,and there were no significant differences between groups (all P＞0.05).p-EGFR protein levels were (338.62±45.28) μg/mg,(679.43±78.23) μg/mg,(292.74±59.17) μg/mg in control,CSE and gefitinib groups,respectively.MUC5AC protein levels were(72.80±6.25)μg/mg,(187.00±±10.26)μg/mg,(92.57±8.32)μg/mg in control,CSE and gefitinib groups respectively.Compared with control group,p-EGFR and MUC5AC protein levels were increased significantly in CSE group (both P＜0.05),and had no significant differences in p EGFR and MUC5AC protein levels between control group and gefitinib group.Conclusions CSE may lead to mucus hypersecretion through activating the EGFR-mediated signaling pathways.Gefitinib may inhibit mucus hypersecretion by inhibiting EGFR tyrosine kinanse activity.EGFR may serve as a potential target for COPD.