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 explore the value of artificial intelligence(AI)-assisted diagnosis platform combined with optical coherence tomography(OCT)in diagnosing blinding eye diseases,so as to provide effectively scientific basis for favorable prognosis of patients with blinding eye diseases.Methods:A total of 72 patients with visual impairment who admitted to the outpatient of hospital were selected.All patients received the detection of AI-assisted diagnosis platform combined with OCT diagnosis.The final diagnosis result of the detection of doctor combined with the relevant ophthalmic examination was used as the"gold standard"to assess respectively the consistence among single AI-assisted diagnosis platform,single OCT,the combination of them and the"gold standard",as well as the sensitivity,specificity and accuracy of them in diagnosing the blinding eye diseases.Results:For the 72 patients,the detection rate of the detection result of doctor combined with the relevant ophthalmic examination was 27.78%(20/72)for blinding eye diseases,and the detection rate of that was 72.22%(52/72)for non-blinding eye diseases.The consistency between AI-aided platform diagnosis and the"gold standard"was general in diagnosing the blinding eye diseases(kappa=0.530).The consistency between OCT and the"gold standard"was favorable in diagnosing that(kappa=0.611).The consistency between AI-assisted platform combined with OCT and the"gold standard"was better(kappa=0.799).The specificity,sensitivity,positive predictive value,negative predictive value,diagnostic accuracy of AI-assisted platform combined with OCT diagnosis were respectively 92.31%,90.00%,81.82%,96.00%and 91.67,and the diagnostic value of the combination was higher than that of single AI-assisted platform and that of single OCT for all of above these indicators.Conclusion:Both the AI-assisted diagnosis platform and OCT can detect blinding eye diseases,and the combined detection of them has higher diagnostic value.

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of～260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

Objective:To observe and analyze the intervention effect of logotherapy on anxiety and depression in patients with chronic glomerulonephritis (CGN).Methods:Selected 102 CGN patients from March 2019 to May 2020 in Beijing Tiantan Hospital Affiliated to Capital Medical University as the research objects, the general information of the patients was collected, and the patients were randomly divided into the observation group and the control group with 51 cases in each group. The control group was given routine nursing intervention for CGN patients, and the observation group was given logotherapy therapy intervention based on the intervention of the control group. The differences in the scores of the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) between the two groups before and after 3 months of intervention.Results:There were no significant differences in SAS and SDS scores before and after intervention in the control group ( P>0.05). The SAS and SDS scores in the observation group after 3 months of intervention were (40.67 ± 4.17), (48.74 ± 5.01) points, which were significantly lower than (51.34 ± 5.04), (55.19 ± 5.49) points in the control group ( t=8.37, 3.32, both P<0.01). Conclusions:The positive psychological intervention of patients with logotherapy can effectively improve the anxiety and depression of patients with CGN.

Objective:To investigate the differences in ametropia among school-age children and between Han and Uygur ethnic groups in the main urban area of Kashgar, and to understand the epidemiological characteristics of myopia among children in Kashgar.Methods:A cross-sectional study was conducted.Random stratified sampling method was used to select the first to third grade students from 6 primary schools in the main urban areas of Kashgar, Xinjiang, from April to June 2018.Visual acuity was examined by the international standard visual acuity chart and refraction was detected by the automatic computer refractometer without cycloplegia.The subjects were classified into low vision (uncorrected visual acuity<0.8 in either eye), hyperopia≥2.00 D, myopia≥-1.00 D, astigmatism≥1.00 D and anisometropia≥1.00 D according to examination results.The percentage of different refraction states and percentage of different ethnic groups among myopic students in the three grades were analyzed.The study protocol was approved by an Ethics Committee of The First People's Hospital in Kashgar ([2021] QSY No.81).Results:A total of 6 108 students were enrolled, among which, there were 3 119 males and 2 989 females, 3 395 Uygur and 2 713 Han people, 2 016 first grade, 2 155 second grade and 1 937 third grade students.The detection rate of low vision was 13.5% (825/6 108) in the whole, 21.5% (584/2 713) in the Han people and 7.1% (241/3 395) in the Uygur people, 8.8% (176/2 016) in the first grade, 11.8% (254/2 155) in the second grade and 20.4% (395/1 937) in the third grade.The detection rate of myopia was 9.9% (606/6 108) in the whole, 17.6% (477/2 713) in the Han people and 3.8% (129/3 395) in the Uygur people, 4.4% (89/2 016) in the first grade, 8.1% (174/2 155) in the second grade and 17.7% (343/1 937) in the third grade.There were significant differences in percentage of low vision, myopia, astigmatism and anisometropia among different grades and between the two nationalities (all at P<0.001), and no significant difference in the percentage of hyperopia was found (P>0.05).Conclusions:The percentage of visual abnormalities and myopia in the first to third grade children in Kashgar is lower than the national average, but the percentage is gradually increasing with age.The percentage of visual abnormalities and myopia among Han pupils is close to the national average, and far higher than that of Uygur pupils.

Objective:To explore the influence of short-time pasteurization (62.5±0.5℃ for 5 s) on the main bioactive components and immune cells in human breast milk.Methods:Fresh breast milk was collected from 53 women whose premature infants were admitted to the neonatal intensive care unit of the Children's Hospital of Fudan University from May 2020 to October 2020. Each sample (20 ml) was divided into unsterilized, Holder pasteurized (62.5 ℃ for 30 min), or short-time pasteurized groups. The concentration of secretory immunoglobulin A (sIgA), lactoferrin (LTF), lysozyme (LZM), and insulin-like growth factor binding protein-3 (IGFBP-3) in breastmilk whey were detected by enzyme-linked immunosorbent assay and the number of viable immune cells (leukocytes, monocytes, T cells, and B cells) in breastmilk by flow cytometry.Results:(1) A total of 87 breast milk samples were collected. The levels of sIgA, LTF, and LZM were the highest in the unsterilized group, followed by the short-time and Holder pasteurized group [0.42 mg/ml (0.33-0.65 mg/ml) vs 0.40 mg/ml (0.28-0.62 mg/ml) and 0.25 mg/ml (0.17-0.37 mg/ml); (3.57±1.06) vs (3.53±1.11) and (0.85±0.58) mg/ml; 128.60 μg/ml (77.18-203.00 μg/ml) vs 121.70 μg/ml (68.66-188.20 μg/ml) and 83.40 μg/ml (47.40-151.40 μg/ml); all P<0.05]. There was no significant difference in the level of IGFBP-3 among the groups. The median retention rates of sIgA, LTF, and LZM in the Holder pasteurized group were all lower than those in the short-time pasteurized group [55.87% (46.01%-71.41%) vs 96.93% (83.03%-115.90%); 21.72% (12.54%-29.42%) vs 97.88% (88.98%-104.30%); 69.26% (49.42%-89.08%) vs 93.80% (74.85%-110.20%); all P<0.05]. No significant difference in the level of preserved IGFBP-3 was observed between the three groups ( P>0.05). (2) The number of viable leukocytes, monocytes, T cells, and B cells in the Holder pasteurized group were lower than those in the unsterilized group [leukocytes: 185.50 (87.00-356.50) vs 1 271.00 (540.50-2 283.00); monocytes: 12.00 (6.00-16.75) vs 266.00 (137.30-518.80); T cells: 1.00 (0.00-2.00) vs 47.50 (28.50-116.00); B cells: 1.00 (0.00-1.75) vs 21.00(10.00-41.50); all P<0.05]. The percentage of viable leukocyte to the total leukocyte and the viable monocytes, T cells, and B cells to the viable leukocytes were lower in the Holder pasteurized group than those in the unsterilized group [24.80%(16.00%-36.80%) vs 74.20%(63.55%-86.45%); 5.91%(4.09%-8.77%) vs 21.90%(17.40%-29.30%); 0.31%(0.00%-1.31%) vs 4.00%(2.69%-6.43%); 0.30%(0.00%-0.86%) vs 1.27%(0.57%-2.85%); all P<0.05]. A similar trend was observed between short-time pasteurization and unsterilized groups (all P<0.05). (3) The percentages of viable monocytes, T cells, and B cells in their subsets were lower in both Holder and short-time pasteurized groups than those in the unsterilized group [2.94%(1.33%-7.14%) vs 9.72%(5.77%-16.00%) and 52.60%(31.35%-68.75%); 0.00%(0.00%-1.61%) vs 0.49%(0.00%-2.53%) and 28.10%(10.55%-57.00%); 0.00%(0.00%-0.83%) vs 0.24%(0.00%-2.47%) and 13.80%(3.27%-41.00%); all P<0.05].The number and percentage of viable leukocytes in total leukocytes and viable monocytes in total monocytes [leukocytes: 279.50(116.80-548.50), 32.20%(20.70%-45.75%); monocytes: 32.00(21.00- 83.75),15.60%(11.10%-19.15%)] were higher than those in the pasteurized group (all P>0.05). The short-time pasteurized group was noted only for a higher percentage of the viable monocytes to viable leukocytes than the Holder pasteurized group (all P<0.05). Conclusions:Compared with the Holder pasteurization, sIgA, LTF, LZM level, and monocyte activity in breast milk can be better preserved by short-time pasteurization.

Objective:To investigate the development and maturation process of intestinal organoids in neonatal mice so as to provide a new model for research on perinatal/neonatal intestinal epithelial development and related diseases.Methods:Intestinal tissue of 3-day-old C57BL/6 mice were collected and cultured for mouse intestinal organoids (MIOs) under standard conditions down to the fifth generation. The morphological changes of MIOs were observed and recorded using inverted phase contrast microscope. Real-time fluorescent quantitative polymerase chain reaction and immunofluorescence technique were used to detect the expression and location of markers of intestinal stem cells and differentiated cells of intestinal epithelium among different generations of MIOs (Selected marker genes: Lgr5 for intestinal stem cells, Tpm2 and Gja1 for fetal intestinal progenitor cells, Villin for intestinal epithelial cells, Lyz1 for Paneth cells, Muc2 for goblet cells, Chga for endocrine cells; Selected marker proteins: villin for intestinal epithelial cells, mucin 2 for goblet cells, chromaffin A for endocrine cells, lysozyme for Paneth cells). One-way analysis of variance and Bonferroni test were adopted for statistical analysis. Results:Two types of MIOs were observed, immature spheroid and mature organoids with crypt-villus structure. Spheroid was the main form in the primary culture. From primary to the second generation, the proportion of spheroids decreased from (96.61±1.36)% to (8.93±1.50)%, and so did the size ( F=12.88, P<0.001). During the second to the fifth generation, mature organoid, as the main form, increased from (91.07±1.50)% to (95.56±2.14)%. The expression of intestinal stem cell marker Lgr5 in the second generation decreased to 0.40±0.06 times of the primary one ( F=76.75, P<0.001) and then increased after this period. The expression of fetal intestinal progenitor markers Tpm2 decreased significantly during the passage (primary generation: 1.00±0.11, the fifth generation: 0.003±0.001, F=148.00, P<0.001); And the expression of Gja1 decreased from primary generation (1.00±0.14) to the second generation (0.06±0.04) ( F=197.10, P<0.001), but kept stable from the second to fifth genetation ( F=2.20, P=0.13). The expressions of gene markers of differentiated cells in intestinal epithelium, including enterocytes, goblet cells, endocrine cells, and Paneth cells, increased after the second generation (the second generation: Villin: 0.46±0.11; Muc2: 0.68±0.29; Chga: 2.53±0.16; Lyz1: 0.98±0.21; the fifth generation: Villin: 1.02±0.05; Muc2: 8.79±0.61; Chga: 4.32±0.45; Lyz1:3.81±0.36; all P<0.05). Immunofluorescence showed that villin, the intestinal epithelial cell marker protein, was distributed along the villus-side of MIOs in primary and the fifth generation culture. Mucin 2 from goblet cell and chromaffin A from endocrine cell expressed at a very low level in the primary generation, while higher in the fifth generation. In the primary culture, lysozyme from Paneth cell was evenly distributed in organoid cells, and high fluorescent dot-shaped expression was observed in the fifth generation. Conclusions:The development and maturation of immature intestinal epithelium can be simulated by continuous culture of neonatal MIOs. MIOs between the primary and second generation could be used as a research model for development of perinatal intestinal epithelium, and the second to the fifth generation as a model for neonatal intestinal diseases studies.

Objective:To evaluate the performance and application of a fast nucleic acid detection system for testing severe acute respiratory syndrome virus 2 (SARS-COV-2).Methods:Clinical samples were collected from February to July 2020 from Beijing Center for Diseases Prevention and Control and the Laboratory Department of China-Japan Friendship Hospital, to evaluate the sensitivity, specificity, anti-interference ability, precision and clinical sample coincidence rate of fast nucleic acid detection system for SARS-CoV-2. The analytical sensitivity was determined by a dilution series of 20 replications for each concentration. Analytical specificity study was performed by testing organisms whose infection produces symptoms similar to those observed at the onset of corona virus disease 2019 (COVID-19), and of the normal or pathogenic microflora that may be present in specimens collected. Potential interference substances were evaluated with different concentration in the interference study. Precision study was conducted by estimating intra-and inter-batch variability. Clinical evaluation was performed by testing 230 oropharyngeal swab specimens and 95 sputum specimens in fast nucleic acid detection system, comparing with conventional real-time fluorescent quantitative PCR (RT-qPCR) and clinical diagnostic results.Results:The analytical sensitivity of SARS-CoV-2 using fast nucleic acid detection system was 400 copies/ml. The result is negative for testing with the organisms that may likely in the circulating area or causing similar symptoms with SARS-CoV-2 and human nucleic acid, indicating that no cross reactivity with organisms. The results of precision test showed that the Coefficient of variation of Ct value of high, medium and low concentration samples was 1.90%-3.92%, and all of them were less than 5% in intra-and inter-batch testing. The results of the samples were still positive after adding the potential interfering substances, indicating that the possible interfering substances in the samples had no effect on the results. 98.46% and 97.85% diagnosis results of fast nucleic acid detection system were consistent with RT-qPCR and clinical diagnostic results, respectively.Conclusion:The fast nucleic acid detection system based on molecular parallel reaction can be used as a selection method for SARS-CoV-2 testing.

Objective:To evaluate the performance and application of a fast nucleic acid detection system for testing severe acute respiratory syndrome virus 2 (SARS-COV-2).Methods:Clinical samples were collected from February to July 2020 from Beijing Center for Diseases Prevention and Control and the Laboratory Department of China-Japan Friendship Hospital, to evaluate the sensitivity, specificity, anti-interference ability, precision and clinical sample coincidence rate of fast nucleic acid detection system for SARS-CoV-2. The analytical sensitivity was determined by a dilution series of 20 replications for each concentration. Analytical specificity study was performed by testing organisms whose infection produces symptoms similar to those observed at the onset of corona virus disease 2019 (COVID-19), and of the normal or pathogenic microflora that may be present in specimens collected. Potential interference substances were evaluated with different concentration in the interference study. Precision study was conducted by estimating intra-and inter-batch variability. Clinical evaluation was performed by testing 230 oropharyngeal swab specimens and 95 sputum specimens in fast nucleic acid detection system, comparing with conventional real-time fluorescent quantitative PCR (RT-qPCR) and clinical diagnostic results.Results:The analytical sensitivity of SARS-CoV-2 using fast nucleic acid detection system was 400 copies/ml. The result is negative for testing with the organisms that may likely in the circulating area or causing similar symptoms with SARS-CoV-2 and human nucleic acid, indicating that no cross reactivity with organisms. The results of precision test showed that the Coefficient of variation of Ct value of high, medium and low concentration samples was 1.90%-3.92%, and all of them were less than 5% in intra-and inter-batch testing. The results of the samples were still positive after adding the potential interfering substances, indicating that the possible interfering substances in the samples had no effect on the results. 98.46% and 97.85% diagnosis results of fast nucleic acid detection system were consistent with RT-qPCR and clinical diagnostic results, respectively.Conclusion:The fast nucleic acid detection system based on molecular parallel reaction can be used as a selection method for SARS-CoV-2 testing.

Recent studies have revealed that human milk harbors stem cells at various stages of differentiation,including pluripotent stem cells,hematopoietic stem cells and mesenchymal stem cells.The stem cellular components of human milk with high interindividual variability are affected by gestational age and lactation stages.The maternal stem cells which pass to the infant through human milk could help boost offspring growth and development.Human milk stem cell with multi-directional differentiation potential may be a new source of stem cell replacement therapy in the future.We hereby review the latest progress in human milk stem cells from these aspects.