Background The subway environment, characterized by dense crowds, relatively enclosed architectural structures, and insufficient ventilation, poses various health hazards. Population health risk attributable to subway hygiene have become an important public health issue. Objective To evaluate the current environmental hygiene of metro line X in Nanjing, and to provide a scientific basis for the prevention and control of harmful factors and the establishment of relevant standards. Methods Station halls, platforms, and carriages of Nanjing metro line X were monitored in March 2023. Six stations were selected by stratified sampling, and monitored once during the morning peak hours (9:00—11:00). Carriage monitoring was conducted after a full day of operation (21:00—22:00). The monitoring indicators included physical factors such as temperature, relative humidity, wind speed, illuminance, and noise (A-weighted); air quality factors such as carbon dioxide (CO₂), carbon monoxide (CO), respirable particulate matter (PM₁₀), fine particulate matter (PM_2.5), ammonia (NH₃), formaldehyde, benzene, toluene, xylene, total volatile organic compounds (TVOC), ozone (O₃), total bacterial count, and total fungi count; hygiene status of the inner surface of the central air conditioning ventilation system, such as dust accumulation, total bacterial count, and total fungi count; supply air, such as PM_10, PM_2.5, total bacterial count, and total fungi count; and surface microorganisms on objects, such as total bacterial count, total fungi count, coliform bacteria, and Staphylococcus aureus. Results were evaluated and discussed according to Hygienic indicators and limits for public places (GB 37488-2019) and Hygienic specification of central air conditioning ventilation systems in public buildings (WS 394-2012). Results The environmental temperature medians (P₂₅, P₂₅) in the platforms and carriages of Nanjing metro line X were 20.7 (19.95, 21.65) ℃ and 21.8 (19.80, 35.80) °C, respectively, which exceeded the standard limits. The relative humidity and noise level in the carriages were 38.80% (24.6%, 46.3%) and 79.50 (76.25, 82.00) dB, respectively, failing to meet the national health standards. The total fungi count in supply air in 22.2% of the monitoring points exceeded the standard value. Coliform bacteria and Staphylococcus aureus were detected on the surfaces of some high-touch objects, with the bathroom faucet being the most severely contaminated. The medians (P₂₅, P₂₅) of temperature [21.8 (19.8, 35.8) ℃], wind speed [0.48 (0.39, 1.02) m·s⁻¹], noise [79.5 (76.25, 82.00) dB, and CO₂ content [0.079% (0.070%, 0.091%)] in the carriages were higher than those in the station halls and platforms (P<0.05). There were significant differences in microclimate, air particulate matter, and air microbial levels between urban and suburban stations (P<0.05); the concentrations of PM₁₀ [0.076 (0.046, 0.079) mg·m⁻³)] and PM_2.5 [0.063 (0.044, 0.068) mg·m⁻³)] in suburban stations were 2 times higher than those of urban stations. The temperature [21.60 (20.45, 21.80) ℃], humidity [45.20% (40.95%, 50.10%)], CO₂ [0.100% (0.100%, 0.825%)], and PM₁₀ concentration [0.070 (0.041, 0.080) mg·m⁻³] in transfer stations were all significantly higher than those in non-transfer stations (P<0.05). The temperature at stations was significantly correlated with the CO₂ content (r_s=0.6107, P<0.001), the concentration of air particulate matter and the content of air microorganisms were positively correlated with the relative humidity (P<0.05), and the air PM₁₀ and PM_2.5 concentrations were positively correlated with the total bacterial count and the total fungi count (P<0.05). There was a significant positive correlation between the total bacterial count and the total fungi count on the inner surface of the air duct (r_s=0.5877, P<0.05). The concentrations of PM₁₀ and PM_2.5 in supply air were positively correlated (r_s=0.9635, P<0.001), and both were also positively correlated with the total bacterial count in supply air (r_s=0.6848 and 0.6511, P=0.002 and 0.003). Conclusion All chemical factors of metro line X in Nanjing meet the national standards, while physical factors (temperature, relative humidity, wind speed, and noise) exceed the standards, and coliform bacteria and Staphylococcus aureus are detected on the surfaces of bathroom faucets and carriage poles. It is advisable to reinforce microclimate management and noise reduction measures in carriages, while ensuring regular cleaning and disinfection of public facilities and equipment.

Objective:According to the international cooperation project of Peking University Cancer Hospital on human genetic resource management practices, combined with the development direction of human genetic resource management laws and regulations, and propose reference suggestions for medical institutions to strengthen human genetic resource management.Methods:Sort out the projects that Peking University Cancer Hospital obtained international cooperation approval on the government platform of the Ministry of Science and Technology from July 2019 to June 2023, analyze the current situation of human genetic resource management in the hospital, summarize the challenges brought by the implementation of new regulations on human genetic resource management in medical institutions, and propose corresponding suggestions.Results:A total of 1276 international cooperation projects on human genetic resources have been approved, including 345 initial declarations and 931 change declarations. Involving 453 studies, including 286 clinical trials of drugs or devices on the market, accounting for 63.13%, and 100 clinical trials of Phase I drugs, accounting for 34.97% of the market studies. On average, there are 3.14 changes per project for listed research, and 1.56 changes per project for non listed research.Conclusions:Regulations on the Management of Human Genetic Resources ( short for Rules) limit the management scope of international cooperation projects involving human genetic resources and delegate management authority to medical institutions. Adjusting the scope of application for international cooperative clinical trial filing may result in some administrative approval projects being transferred to filing. The approval process for international cooperative scientific research projects on human genetic resources has been adjusted. Suggest medical institutions to strengthen the management of samples and intellectual property outside the scope of application of Rules.Strengthen the entire process management of international cooperation in scientific research. Pay attention to and timely communicate the dynamics of human genetic resource management.

This paper discussed how to set the limit of impurities in the quality standard when the impurities in small-molecular innovative drugs were metabolites.Firstly,through the analysis and interpretation of each relevant guideline,in combination with the review cases of FDA and EMA,found out the conditions for qualification of im-purity,and then establ ish the acceptable limit of impurities based on the test results of multiple batches,the incre-ments of production process and storage process.

For two young female patients with extramedullary recurrence of reproductive system after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia. And the characteristics of extramedullary relapse of reproductive system are summarized for exploring possible effective treatments.

Objective:To explore the effect of long non-coding RNA (lncRNA) C10orf25 on the proliferation and invasion ability of prostate cancer cells and the possible role of miRNA-671-5p (miR-671-5p).Methods:Data from the Gene expression omnibus (GEO) database (data updated in January 2023) were used to analyze the differences in the expression levels of C10orf25 in 137 cases of prostate cancer tissues and paracancerous tissues. Prostate cancer C4-2B, DU-145, 22Rv1, PC-3, LNCaP cell lines and immortalized prostate epithelial RWPE-1 cell lines were selected, and then real-time quantitative fluorescence polymerase chain reaction (qRT-PCR) was used to detect the relative expression levels of C10orf25 in cell lines. The 22Rv1 cells with the lowest relative expression level of C10orf25 were selected and divided into the control group (transfected with negative plasmid) and the C10orf25 group (transfected with C10orf25 plasmid); the CCK-8 method was used to detect the proliferation activity of 22Rv1 cells in both groups at day 1, 2, 3, 4, 5 (expressed as absorbance value); the Transwell method was used to detect the invasion ability of 22Rv1 cells. Linc2GO software was used to predict miR-671-5p with binding sites for C10orf25. Dual luciferase reporter gene assay was used to verify the targeting relationship between C10orf25 and miR-671-5p. qRT-PCR was used to detect the relative expression levels of C10orf25 and miR-671-5p. Western blot was used to detect the expression of proteins related to the NF-κB signaling pathway of 22Rv1 cells in the both groups.Results:In the GEO database, the relative expression level of C10orf25 in prostate cancer tissues was lower than that in paracancerous tissues ( P < 0.01). The relative expression levels of C10orf25 in immortalized prostate epithelial cell line RWPE-1 and prostate cancer cell lines C4-2B, DU-145, 22Rv1, PC-3, and LNCaP were 1.00±0.05, 0.63±0.04, 0.42±0.03, 0.18±0.04, 0.81±0.02, 0.50±0.07, and the difference was statistically significant ( F = 43.29, P < 0.05). The proliferation ability of 22Rv1 cells in C10orf25 group was lower than that in the control group from the second day, and the differences were statistically significant (all P < 0.05). The number of invasive cells in the control group and C10orf25 group were (97±11) and (36±9), respectively, and the difference was statistically significant ( t = 4.15, P < 0.01). Linc2GO software prediction results showed that C10orf25 had a binding site for miR-671-5p. The dual luciferase reporter gene assay showed that the relative luciferase activity of miR-671-5p and C10orf25 wild plasmid co-transfecting 22Rv1 cells was lower than that of miR-NC and C10orf25 wild plasmid co-transfecting 22Rv1 cells, and the difference was statistically significant ( P < 0.01); when miR-671-5p or miR-NC was co-transfected with C10orf25 mutant plasmid, the difference in the luciferase activity of 22Rv1 cells was not statistically significant ( P > 0.05). The relative expression levels of miR-671-5p in 22Rv1 cells were 7.33±0.99 and 0.98±0.16, respectively in the control group and C10orf25 group, and the difference was statistically significant ( t = 6.32, P < 0.01). The results of Western blot showed that the expression levels of NF-κB signaling pathway protein p50, matrix metalloproteinase 9, c-myc, and vascular endothelial growth factor protein in 22Rv1 cells in C10orf25 group were lower than those in the control group. Conclusions:The overexpression of C10orf25 may inhibit the proliferation and invasion of prostate cancer cells through the miR-671-5p-NF-κB axis.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

OBJECTIVE To mine the adverse drug reaction （ADR） signals of melphalan， so as to provide reference for clinically safe drug use. METHODS Using OpenVigil 2.1 data platform， relative ADR reports of melphalan from the first quarter of 2004 to the second quarter of 2022 in FAERS database were collected； data mining was conducted using the reported odds ratio （ROR） method and Medicines and Healthcare Products Regulatory Agency （MHRA） method of disproportional method. ADR reports were described and classified according to the system organ class （SOC） and preferred term （PT） in Medical Dictionary for Regulatory Activities （24.0 edition）. RESULTS A total of 17 046 ADR reports related to the target drug melphalan were retrieved， and the number of ADR reports showed a fluctuating upward trend； the majority of patients were male （43.28%）， and were concentrated between the ages of 50-＜75 （35.09%）， with the main reporting country being the United States （23.97%）； ADR report involved a total of 22 842 severe outcomes， mainly including hospitalization or extended hospitalization （24.45%）. Totally 403 ADR signals were detected， involving 23 SOC， mainly including blood and lymphatic system diseases （801 cases， 13.77%）， followed by eye organ diseases （755 cases， 12.97%） and infectious and invasive diseases （716 cases， 12.30%）. The ADR signals ranked high in the number of reported cases included febrile neutropenia， diarrhea， fever and mucositis and other PT； PT such as pneumonia， sepsis， vitreous hemorrhage， chorioretinal atrophy， myelodysplastic syndrome were not recorded in drug instructions. The ADR signals with high signal strength ranking included choroidal dystrophy， chorioretinal atrophy， eyeball atrophy and other PT， and above three types of PT were not included in the drug instructions. CONCLUSIONS ADRs caused by melphalan mainly include blood and lymphatic system diseases， eye organ diseases， and infectious and invasive diseases； before using melphalan， it is necessary to evaluate the drug use of patients， and pay close attention to the patient’s blood indicators and eye toxicity reaction， so as to guarantee the safety of treatment.

OBJECTIVE To excavate the risk signals of adverse drug events （ADEs） of atezolizumab after marketing， so as to provide a reference for rational use of atezolizumab. METHODS Using the FAERS database， the ADEs of atezolizumab were collected from marketing on May 18th 2016 to Mar. 31st 2022. The ADEs risk signals were mined by reported odds ratio （ROR） and medicines and Healthcare Products Regulatory Agency method （MHRA）， and then described and classified by preferred term （PT） and system organ classification （SOC） in the adverse drug reaction glossary of Medical Dictionary for Regulatory Activities （MedDRA） （23.0 edition）. RESULTS A total of 16 051 ADEs reports with atezolizumab as the primary suspected drug were collected， and 401 PT were mined， involving 17 SOC. In 16 051 ADEs reports， the majority of patients were male （51.64%）， with main age distribution of 19 to 64 years old and more than 65 years old. According to the number of reports， ADEs were mainly focusing on pyrexia， disease progression， interstitial lung disease， anaemia， pneumonia， etc. The involved SOC includes kidney and urinary system diseases， benign， malignant and unknown tumors （including cysts and polyps）， endocrine system diseases， etc. According to the signal intensity， the new ADEs not specified in the drug instructions were macular thickening， paraneoplastic neurological syndrome， reactive perforating collagenosis， paraneoplastic dermatomyositis， anti-erythrocyte antibody positive and liver sarcoidosis. CONCLUSIONS In addition to the ADEs mentioned in the drug instructions，when using atezolizumab in clinic，attention should also be closely paid to ADEs of eyes， nervous and skin system， so as to ensure the safety of drug use in patients.

Objective:To explore the feasibility of predicting TP53 mutation risk by immunohistochemical staining (IHC) pattern of P53 in Chinese diffuse large B-cell lymphoma (DLBCL) and its correlation with a prognostic difference.Methods:Between January 2021 and December 2021, 51 DLBCL cases at Beijing Boren Hospital were gathered. These cases had both IHC and next-generation sequencing (NGS) results. IHC classified the P53 protein expression pattern into a loss (<1% ) , diffuse (>80% ) , and heterogeneous (1% -80% ) . The sensitivity and specificity of the predicting TP53 mutation by IHC were assessed by comparing the results of the NGS, and the TP53 high mutation risk group included both loss and diffuse expression of P53. From June 2016 to September 2019, Peking University Cancer Hospital collected 131 DLBCL cases with thorough clinicopathological and follow-up data. From their tumor blocks, tissue microarray blocks were made for IHC evaluation of P53 expression pattern, and prognosis effect of P53 studies.Results:Among 51 cases with both IHC and NGS results, 23 cases were classified as TP53 high mutation risk (7 cases loss and 16 cases diffuse) , 22/23 cases were proved with mutated TP53 by NGS. Only 1 of the 28 cases classified as TP53 low mutation risk was proved with mutated TP53 by NGS. IHC had a sensitivity and specificity of 95.7% and 96.4% for predicting TP53 mutation. NGS identified a total of 26 TP53 mutations with a mutation frequency of 61.57% (13.41% -86.25% ) . In the diffuse group, 16 missense mutations and 2 splice mutations were detected; 6 truncating mutations and 1 splice mutation were detected in the loss group; 1 truncating mutation was detected in the heterogeneous group. Multivariate analysis demonstrated that TP53 cases with high mutation risk have impartial adverse significance for the 131 patients included in survival analysis ( HR=2.612, 95% CI 1.145-5.956, P=0.022) . Conclusion:IHC of P53 exhibiting loss (<1% ) or diffuse (>80% ) pattern indicated TP53 high mutation risk, IHC can predict TP53 mutation with high specificity and sensitivity. TP53 high mutation risk is an independent predictor for adverse survival.

Objective:To analyze the clinical phenotype and molecular pathogenesis of nine patients with hereditary factor Ⅴ (FⅤ) deficiency.Methods:Nine patients with hereditary FⅤ deficiency who were admitted to the Institute of Hematology and Blood Diseases Hospital from April 1999 to September 2019 were analyzed. The activated partial thromboplastin time, prothrombin time, and FⅤ procoagulant activity (FⅤ∶C) were measured for phenotypic diagnosis. High-throughput sequencing was employed for the F5 gene mutation screening, Sanger sequencing was adopted to confirm candidate variants and parental carrying status, Swiss-model was used for three-dimensional structure analysis, and ClustalX v.2.1 was used for homologous analysis.Results:The FⅤ∶C of the nine patients ranged from 0.1 to 10.6. Among them, eight had a hemorrhage history, with kin/mucosal bleeding as the most common symptom (three cases, 37.5%) , whereas one case had no bleeding symptom. There were five homozygotes and four compound heterozygotes. A total of 12 pathogenic or likely pathogenic mutations were detected, of which c.6100C>A/p.Pro2034Thr, c.6575T>C/p.Phe2192Ser, c.1600_1601delinsTG/p. Gln534*, c.4713C>A/p.Tyr1571*, and c.952+5G>C were reported for the first time.Conclusion:The newly discovered gene mutations enriched the F5 gene mutation spectrum associated with hereditary FⅤ deficiency. High-throughput sequencing could be an effective method to detect F5 gene mutations.