Elemene Antitumor Drugs Development Based on "Molecular Compatibility Theory" and Clinical Application: A Retrospective and Prospective Outlook / 中国结合医学杂志

Elemene, derived from Curcuma wenyujin, one of the "8 famous genuine medicinal materials of Zhejiang province," exhibits remarkable antitumor activity. It has gained wide recognition in clinical practice for effectiveness on tumors. Dr. XIE Tian, introduced the innovative concept of "molecular compatibility theory" by combining Chinese medicine principles, specifically the "monarch, minister, assistant, and envoy" theory, with modern biomedical technology. This groundbreaking approach, along with a systematic analysis of Chinese medicine and modern biomedical knowledge, led to the development of elemene nanoliposome formulations. These novel formulations offer numerous advantages, including low toxicity, well-defined composition, synergistic effects on multiple targets, and excellent biocompatibility. Following the principles of the "molecular compatibility theory", further exploration of cancer treatment strategies and methods based on elemene was undertaken. This comprehensive review consolidates the current understanding of elemene's potential antitumor mechanisms, recent clinical investigations, advancements in drug delivery systems, and structural modifications. The ultimate goal of this review is to establish a solid theoretical foundation for researchers, empowering them to develop more effective antitumor drugs based on the principles of "molecular compatibility theory".

Accuracy of digital guided implant surgery: expert consensus on nonsurgical factors and their treatments / 口腔疾病防治

@#The standardized workflow of computer-aided static guided implant surgery includes preoperative examination, data acquisition, guide design, guide fabrication and surgery. Errors may occur at each step, leading to irreversible cumulative effects and thus impacting the accuracy of implant placement. However, clinicians tend to focus on factors causing errors in surgical operations, ignoring the possibility of irreversible errors in nonstandard guided surgery. Based on the clinical practice of domestic experts and research progress at home and abroad, this paper summarizes the sources of errors in guided implant surgery from the perspectives of preoperative inspection, data collection, guide designing and manufacturing and describes strategies to resolve errors so as to gain expert consensus. Consensus recommendation: 1. Preoperative considerations: the appropriate implant guide type should be selected according to the patient's oral condition before surgery, and a retaining screw-assisted support guide should be selected if necessary. 2. Data acquisition should be standardized as much as possible, including beam CT and extraoral scanning. CBCT performed with the patient’s head fixed and with a small field of view is recommended. For patients with metal prostheses inside the mouth, a registration marker guide should be used, and the ambient temperature and light of the external oral scanner should be reasonably controlled. 3. Optimization of computer-aided design: it is recommended to select a handle-guided planting system and a closed metal sleeve and to register images by overlapping markers. Properly designing the retaining screws, extending the support structure of the guide plate and increasing the length of the guide section are methods to feasibly reduce the incidence of surgical errors. 4. Improving computer-aided production: it is also crucial to set the best printing parameters according to different printing technologies and to choose the most appropriate postprocessing procedures.

Expression and distribution of brain⁃derived neurotrophic factor in different cerebrum regions of yak and cattle / 解剖学报

Objective To clarify the expression and distribution of brain⁃derived neurotrophic factor (BDNF) in the cerebrum of plateau yaks and cattle, and to explore the relationship between BDNF function and the adaptability of altitude hypoxia. Methods Five yaks and five cattles were selected.The content and distribution of BDNF in frontal lobe, temporal lobe, parietal lobe, occipital lobe, cerebrum white matter and hippocampus of yak and cattle were analyzed by Real⁃time PCR, Western blotting and Immunohistochemistry. Results Real⁃time PCR result showed that BDNF mRNA expression in the cerebrum of yaks and cattles was highest in temporal cortex, followed by hippocampus, parietal cortex, occipital cortex and frontal cortex, and lowest in white matter. Western blotting results showed that the content of BDNF protein in the cerebrum of yaks was the highest in temporal cortex,followed by hippocampus. The content of BDNF protein in other tissues was parietal cortex, frontal cortex and cerebrum white matter, and the content of BDNF protein was the lowest in occipital cortex. The content of BDNF protein intlecerebrum of cattles was the highest in the temporal cortex, followed by the hippocampus. The content of BDNF protein in other tissues was parietal cortex, occipital cortex and frontal cortex in descending order, and the protein content in cerebrum white matter was the lowest. Immunohistochemical results showed that the positive expression of BDNF protein in the cerebrum of yaks and cattles was basically similar, mainly distributed in the granulosa cells and glial cells in the frontal cortex, temporal cortex, parietal cortex and occipital cortex, glial cells in cerebrum white matter, pyramidal cell layer and polyform cell layer in the hippocampus. There was the small amount of distribution in Martinotti cells and the molecular layer of hippocampus in the cerebral cortex. Conclusion BDNF mRNA and protein are distributed and expressed in different brain regions of yaks and cattles, but the expression level different, which is speculated to be closely related to the specific functions of different cerebrum regions. The expression level of the cerebrum of yak is higher than that of cattle except occipital cortex, suggesting that it is related to the altitude hypoxic environment. BDNF may play an important role in enhancing hypoxic tolerance and protecting internal environmental homeostasis in the process of animal adaptation to hypoxic environment.

Retinal microstructure and developmental characteristics in Zebrafish / 解剖学报

Objective To study the microscopic structure and morphological characteristics of Zebrafish eyeball and retina at different developmental stages, and to lay a foundation for visual research model. Methods Select eight groups of zebrafish at different ages, with six fish in each group, 48 fish in total. Optical microscopy and transmission electron microscopy were used to observe the eyeball structure of Zebrafish at different developmental stages, and the thickness of retinal each layer was measured to analyze the temporal and spatial development pattern. The morphological characteristics of various cells in the retina and the way of nerve connection were observed from the microscopic and ultrastructural aspects, especially the structural differences between rod cells and cone cells. Results The retina of Zebrafish can be divided into ten layers including retinal pigment epithelial layer, rod cells and cone cells layer, outer limiting membrane, outer nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, nerve fiber layer, inner limiting membrane. Rod cells had a smaller nucleus and a higher electron density than cone cells. Photoreceptor terminals were neatly arranged in the outer plexiform layer, forming neural connections with horizontal cells and bipolar cells, and several synaptic ribbons are clearly visible within them. In Zebrafish retina, ganglion cell layer and inner plexiform layer are the earliest developed. With the growth and development of Zebrafish, the thickness of rod cells and cone cells layer and retinal pigment epithelial layer gradually increases, and the retinal structure was basically developed in about 10 weeks. Conclusion The retinal structure of Zebrafish is typical, with obvious stratification and highly differentiated nerve cells. There are abundant neural connections in the outer plexiform layer. The ocular development characteristics of Zebrafish are similar to those of most mammals.

Validation studies on migraine diagnostic tools for use in nonclinical settings: a systematic review / Estudos de validação de ferramentas de diagnóstico de enxaqueca (migrânea) para uso em ambientes não clínicos: uma revisão sistemática

Abstract Background Migraine underdiagnosis and undertreatment are so widespread, that hence is essential to diagnose migraine sufferers in nonclinical settings. A systematic review of validation studies on migraine diagnostic tools applicable to nonclinical settings can help researchers and practitioners in tool selection decisions. Objective To systematically review and critically assess published validation studies on migraine diagnostic tools for use in nonclinical settings, as well as to describe their diagnostic performance. Methods A multidisciplinary workgroup followed transparent and systematic procedures to collaborate on this work. PubMed, Medline, and Web of Science were searched for studies up to January 17, 2022. The QUADAS-2 was employed to assess methodological quality, and the quality thresholds adopted by the Global Burden Disease study were used to tail signaling questions. Results From 7,214 articles identified, a total of 27 studies examining 19 tools were eligible for inclusion. There has been no high-quality evidence to support any tool for use of migraine diagnosis in nonclinical settings. The diagnostic accuracy of the ID-migraine, structured headache and HARDSHIP questionnaires have been supported by moderate-quality evidence, with sensitivity and specificity above 70%. Of them, the HARDSHIP questionnaire has been the most extensively validated. The remaining 16 tools have provided poor-quality evidence for migraine diagnosis in nonclinical populations. Conclusions Up till now, the HARDSHIP questionnaire is the optimal choice for diagnosing migraine in nonclinical settings, with satisfactory diagnostic accuracy supported by moderate methodological quality. This work reveals the crucial next step, which is further high-quality validation studies in diverse nonclinical population groups.

Resumo Antecedentes O sub-diagnóstico e o subtratamento da enxaqueca são tão difundidos que, portanto, é essencial para diagnosticar os portadores de enxaqueca em ambientes não-clínicos. Uma revisão sistemática dos estudos de validação das ferramentas de diagnóstico da enxaqueca aplicáveis a ambientes não-clínicos pode ajudar os pesquisadores e profissionais nas decisões de seleção de ferramentas. Objetivo Revisar sistematicamente e avaliar criticamente estudos de validação publicados sobre ferramentas de diagnóstico da enxaqueca para uso em ambientes não-clínicos, bem como descrever seu desempenho diagnóstico. Métodos Um grupo de trabalho multidisciplinar seguiu procedimentos transparentes e sistemáticos para colaborar neste trabalho. PubMed, Medline e Web of Science foram pesquisados por estudos até 17 de janeiro de 2022. O QUADAS-2 foi empregado para avaliar a qualidade metodológica, e os limites de qualidade adotados pelo estudo da Global Burden Disease foram usados para responder a questões de sinalização. Resultados De 7.214 artigos identificados, um total de 27 estudos examinando 19 ferramentas foram elegíveis para inclusão. Não houve evidência de alta qualidade para apoiar qualquer ferramenta para o uso de diagnóstico de enxaqueca em ambientes não clínicos. A precisão diagnóstica do ID-Migraine, questionário de dor de cabeça estruturada e questionário HARDSHIP foram apoiados por evidências de qualidade moderada, com sensibilidade e especificidade acima de 70%. Deles, o questionário HARDSHIP foi o mais amplamente validado. As 16 ferramentas restantes forneceram provas de má qualidade para o diagnóstico de enxaqueca em populações não-clínicas. Conclusões Até agora, o questionário HARDSHIP é a escolha ideal para o diagnóstico da enxaqueca em ambientes não-clínicos, com precisão diagnóstica satisfatória apoiada por uma qualidade metodológica moderada. Este trabalho revela o próximo passo crucial, que é a realização de mais estudos de validação de alta qualidade em diversos grupos populacionais não-clínicos.

Trichostatin C attenuates TNFα-induced inflammation in endothelial cells by up-regulating Krüppel-like factor 2 / 药学学报

Krüppel-like transcription factor 2 (KLF2) plays a key regulatory role in endothelial inflammation, thrombosis, angiogenesis and macrophage inflammation and polarization, and up-regulation of KLF2 expression has the potential to prevent and treatment atherosclerosis. In this study, trichostatin C (TSC) was obtained from the secondary metabolites of rice fermentation of Streptomyces sp. CPCC 203909 as a KLF2 up-regulator by using a high throughput screening model based on a KLF2 promoter luciferase reporter assay. TSC significantly inhibited the adhesion of tumor necrosis factor-α (TNFα) induced monocytes (THP-1) to human umbilical vein endothelial cells (HUVECs). Western blot results showed that TSC decreased TNFα induced the protein expression increase of vascular cell adhesion molecule-1 (VCAM-1), and thereby inhibited endothelial inflammation. The results of histone deacetylase (HDAC) overexpression and molecular docking experiments showed that TSC upregulated the expression of KLF2 by inhibiting subtypes of HDAC 4/5/7. In conclusion, this study suggests that TSC up-regulates the expression of KLF2 through inhibiting HDAC 4/5/7 and thus inhibits TNFα induced endothelial inflammation, and it has the potential to prevent and treat atherosclerosis.

Stability and taste evaluation of two kinds of oral solvent after extemporaneous compounding / 药学学报

A flavoring agent and a suspension agent were prepared for extemporaneous compounding. The stability of the two agents before and after drug loading was investigated, and the taste of the suspension after extemporaneous compounding was evaluated by electronic tongue technology. The two agents remained stable under the conditions of influence factor test, accelerated test and long-term test. The appearance properties of the two agents did not change. The relative density of the flavoring agent was maintained at 1.053-1.075, and the pH was stable at 4.2-4.5. The relative density of the suspension agent was maintained at 0.999-1.022, and the pH was stable at 4.0-4.5. Seven kinds of drugs, including warfarin sodium tablets and spironolactone tablets, were mixed with these two oral solvents, and the content uniformity and stability were detected respectively. The results showed that the preparations could be evenly dispersed and the physical and chemical properties were stable. The results of taste evaluation showed that in captopril group and chloral hydrate group, the flavoring agent had the best effect on taste correction. In warfarin sodium group, rifampicin group, spironolactone group, vitamin B1 group and vitamin B2 group, the blending agents had the best effect on taste correction.

Chemical constituents from the fruits of Alpinia oxyphylla and their neuroprotective effects / 药学学报

Fourteen compounds were isolated from the ethyl acetate fraction of 90% EtOH extracts of the dried fruits of Alpinia oxyphylla by silica gel, MCI, RP-18, Sephadex LH-20, TLC and semi-preparative HPLC column chromatography. Their structures were identified by HR-ESI-MS, UV, IR, NMR, ECD and X ray single crystal diffraction spectroscopic data as: (2R,5R,7R,10S)-2,7-dihydroxyl-eudesmane-3(4),11(12)-diene (1), α-rotunol (2), diketone I (3), (1S,4S,5R,7S)-1-hydroxyl-eremophilane-9(10),11(12)-diene-8-one (4), cyperusol A1 (5), (6R,9S,10S)-10-hydroxyl-11,12,13-trinor-cadinane-4(5)-ene-3-one (6), (2E,4E)-6-hydroxy-2,6-dimethylhepta-2,4-dienal (7), oxyphyllacinol (8), yakuchinone A (9), (5R)-5-hydroxy-1,7-diphenylhept-3-heptanone (10), (5S)-5-hydroxy-7-(4″-hydroxyphenyl)-1-phenylhept-3-heptanone (11), (5S)-5-hydroxy-7-(4″-hydroxyl-3″-methoxyphenyl)-1-phenyl-3-heptanone (12), 7-(4″-hydroxy-3″-methoxyphenyl)-1-phenyl-3,5-heptadione (13), bis-(2-ethylhexyl) terephthalate (14). Compounds 1-6 were sesquiterpenoids in which compound 1 is a new eudesmane sesquiterpenoid and compound 7 was a monoterpenoid. Compounds 8-13 were diarylheptanoids, and compounds 2-6 and 14 were isolated from A.oxyphylla for the first time. The experiments on H2O2 induced SH-SY5Y cells showed that compounds 2, 6, 7, 12 and 13 had neuroprotective effects at low and medium concentrations. In particular, compound 6 showed obvious neuroprotective effect at low, medium and high concentrations whose cell viability was higher than that of the positive control.

Effectiveness of online and offline health education myopia intervention on primary school students / 中国学校卫生

Objective@#To assess the effectiveness of online and offline myopia prevention and control health education interventions using wearable behavior monitoring tools for non myopic elementary school students,so as to provide evidence based medical support for public health practices.@*Methods@#From May to June in 2021, two schools were selected within the same county in Jiangsu Province. School 1 conducted online and offline parental health education ( n =111), while school 2 exclusively conducted offline health education activities, representing the traditional intervention group ( n =122). Students from both schools underwent monitoring through wearable behavior tracking tools, with feedback reports provided (eye distance, eye duration, ambient light, and outdoor exposure time). Both schools relied on activities to carry out health education interventions, and organized the distribution of promotional materials and display boards. The intervention group also established WeChat groups to conduct online "Healthy Parents Action" (answering and providing feedback on health knowledge related to myopia prevention and control, myopia prevention and control, science popularization, etc. raised by parents). Evaluation criteria included myopia rates, post dilation refractive error, and axial length, with a tracking period of two years (from 2021 to 2023). Additionally, the study collected refractive parameters from non myopic students who did not participate in wearable tool monitoring in the 12 classes across the two schools.@*Results@#The baseline results indicated that there were no significant differences between the two groups in terms of refractive parameters and wearable tool monitoring results (including screen time, viewing distance, outdoor exposure time, and homework light exposure)( t/Z/χ 2=1.94,1.17,0.58,0.40,0.80,0.69,0.32, P >0.05). After a two-year follow up, in the first and second year, the myopia rate of the online Healthy Parents Action group (11.4%, 29.7%) were lower than that of the traditional group (26.2%, 50.9%), and the degree of refractive change in the intervention group [0.63(0.38,1.19)D] was lower than that of the traditional group [0.91(0.40,1.50)D], and all the differences were statistically significant( χ 2/ Z =4.93，10.37，2.29， P <0.05). However, there were no significant differences ( P >0.05) in axial length changes between the two groups over the twoyear intervention period. Nevertheless, in the second year, the axial length change in the traditional group [0.35(0.20,0.65)mm] was lower than that in the natural observation group [0.55(0.30,0.75)mm], and this difference was statistically significant ( Z =1.92, P <0.05).@*Conclusions@#Online and offline myopia prevention and control health education can effectively reduce myopia rates. The intervention mode combining wearable behavior monitoring tools with online health education may have better effects, but further large sample and multi center studies are needed to provide additional evidence and confirmation.

Periprosthetic gout flare after total knee arthroplasty: A misdiagnostic case report / 北京大学学报(医学版)

Periprosthetic gout flare is a rare arthritic condition after total knee arthroplasty, but the symptoms of gout may have often been mistaken as acute periprosthetic infection given their similarity. Misdiagnosis as periprosthetic infection can lead to unnecessary surgery, long-term dependence on anti-biotics, and even malfunction of the involved knee joint. Here, we report a case study of a patient with immunodeficiency condition of long-term oral glucocorticoid and diabetes mellitus, who had undergone a knee replacement 8 weeks before. The initial symptoms of fever and joint pain together with the dysfunction of her right knee with elevated inflammatory markers, such as increased serum leukocytes, erythrocyte sedimentation rate, C-reactive protein, and synovial cell counts led to a diagnosis of acute periprosthetic infection. Arthrocentesis and bacterial culture were performed preoperatively. According to the current Musculoskeletal Infection Society (MSIS) criteria for diagnosis of periprosthetic infection, the case was classified as periprosthetic infection and a prosthesis retained debridement surgery was performed. However we got negative culture results in all the pre-operative and intro-operative samples. The symptoms as well as the laboratory inflammatory markers improved shortly after the debridement surgery until the 11th day when all the similar systemic and local symptoms recurred. With a remedial crystal analysis of synovial fluid from the patient, gouty flare was found to be the cause of acute arthritis finally. Accor-dingly, after anti-gout medications were administrated, the symptoms associated with acute arthritis gra- dually subsided, and there was no recurrence during a 24-month follow-up. This article described the cli-nical manifestation, diagnosis and differential diagnosis, treatment of a case of periprosthetic gout. Although relatively rare, gout should be considered as a differential diagnosis in suspected periprosthetic infection. Current criteria for periprosthetic infection can not exclude the diagnosis of periprosthetic gout flare, it is therefore imperative that the analysis of joint aspirate for crystals be conducted to determine the correct course of treatment, or unnecessary surgical procedure may be performed in periprosthetic gout case.

Research Progress in Treatment of Chronic Lymphocytic Leukemia --Review / 中国实验血液学杂志

Chronic lymphocytic leukemia (CLL) is a low-grade lymphoproliferative tumor that occurs frequently in middle-aged and elderly people. Early and precise intervention can effectively improve the clinical prognosis of CLL patients. In the past, chemotherapy was the main treatment plan. With the development of molecular biology and the continuous advent of immune targeting drugs, targeted drugs targeting B cell receptor signaling pathway have shown high clinical application value in the diagnosis and treatment path of CLL. Cellular immunotherapies such as CAR-T also offer hope for patients with relapsed and refractory CLL. Allogeneic hematopoietic stem cell transplantation and multi-drug combination have also shown remarkable results in clinical practice. The purpose of this article is to review the latest research progress in the treatment of CLL.

Expression and Clinical Significance of Exosome Component 4 in Newly Diagnosed Patients with Diffuse Large B-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To explore the expression of Exosome Component 4（EXOSC4） in the tissues of newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) and its clinical significance.@*METHODS@#The expression of EXOSC4 protein in the tissues of 181 newly diagnosed DLBCL patients was analyzed by immunohistochemical staining. Clinical data were collected. The correlation between EXOSC4 protein expression in the tissues of newly diagnosed DLBCL patients and clinical features were analyzed and its prognostic significance.@*RESULTS@#The positive rate of EXOSC4 protein expression was 68.51% in the tissues of 181 newly diagnosed DLBCL patients. These patients were divided into two groups, with 44 cases in high expression group and 137 cases in low expression group. There were no significant differences in age, gender, B symptoms, serum lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group (ECOG) score, Ann Arbor stage, extranodal disease, International Prognostic Index (IPI) score, National Comprehensive Cancer Network IPI (NCCN-IPI) score, and cell origin between the two groups (P>0.05). Cox multivariate regression analysis showed that high EXOSC4 protein expression in tissues was an independent poor prognostic factor for OS and PFS in newly diagnosed DLBCL patients (all P<0.05). K-M survival analysis showed that newly diagnosed DLBCL patients with high EXOSC4 protein expression had significantly shorter overall survival (OS) and progression free survival (PFS) than those patients with low EXOSC4 protein expression (all P<0.05).@*CONCLUSION@#High EXOSC4 protein expression in tissues of newly diagnosed DLBCL patients is an independent poor prognostic factor for survival.

Pulmonary granular cell tumors: a clinicopathological analysis of five cases / 中华病理学杂志

Objective: To investigate the clinicopathological features of pulmonary granular cell tumors (pGCTs) and to improve the diagnostic accuracy of the tumor. Methods: A total of 5 pGCTs were diagnosed from February 2016 to January 2022 at Shanghai Pulmonary Hospital, Tongji University School of Medicine and Fudan University Shanghai Cancer Center, China. Immunohistochemical staining, and analysis of the clinicopathological characteristics were performed. Results: The average age of the pGCTs patients was 46 years (ranging from 24 to 54 years), with 3 females and 2 males. One case occurred in the bronchus with multiple nodules in the lung, 2 cases occurred in the bronchial opening, and 2 cases were solitary nodules in the lung. The maximum diameter of the tumors ranged from 12 to 15 mm (mean size 14 mm). Microscopically, the tumor showed infiltrative growth and consisted of round, oval or polygonal cells. Abundant eosinophilic cytoplasm was noted, and the nucleoli were prominent. None of the 5 cases showed any mitosis or necrosis. Immunohistochemical and histochemical study showed positive staining for S-100 (5/5), SOX10 (5/5), Vimentin (5/5), TFE3 (4/5), PAS (3/5), and amylase-digested-PAS (3/5), while 4 cases were negative for CD68. TFE3 FISH analyses on 2 cases showed that no signal abnormality was detected in these 2 cases. The average proliferation index of Ki-67 was 2.2% (range 0-5%). There was no recurrence in 4 cases of pGCTs with a follow-up time ranging from 2 months to 60 months. Conclusions: pGCTs are very rare tumors, most likely originating from Schwann cells. Immunohistochemical staining is the conventional diagnostic tool for pGCTs diagnosis. Recognition of this entity is essential for pathologists to avoid misdiagnosis and unnecessary treatments.

Application of the WHO Classification of Thoracic Tumors (2021) grading system in invasive pulmonary adenocarcinoma and its correlation with the targeted genes' variations / 中华病理学杂志

Objective: To investigate the applicability of the 2021 WHO classification of thoracic tumors' new grading system for invasive pulmonary adenocarcinoma (IPA) with different clinical stages and its correlation with the characteristics of targeted genes' variation. Methods: A total of 2 467 patients with surgically resected primary IPA in Shanghai Pulmonary Hospital, Shanghai, China from September to December 2020 were retrospectively analyzed. Eligible cases were graded using the new grading system of IPA of the 2021 WHO classification of thoracic tumors. The clinicopathological data and targeted-gene abnormality were collected. The utility of new grading system of IPA in different clinical stages was investigated. The correlation of clinicopathological features and targeted-gene abnormality in different grades of IPA were compared. Results: All 2 311 cases of IPA were included. There were 2 046 cases of stage Ⅰ IPA (88.5%), 169 cases of stage Ⅱ (7.3%), and 96 cases of stage Ⅲ (4.2%). According to the new classification system of IPA, 186 cases (9.1%), 1 413 cases (69.1%) and 447 cases (21.8%) of stage-Ⅰ adenocarcinoma were classified as Grade 1, Grade 2 and Grade 3, respectively. However, there were no Grade 1 adenocarcinomas in stages Ⅱ and Ⅲ cases. Among stage-Ⅱ and Ⅲ IPA cases, there were 38 Grade 2 cases (22.5%) and 131 Grade 3 cases (77.5%), and 3 Grade 2 cases (3.1%) and 93 Grade 3 cases (96.9%), respectively. In stage-Ⅰ cases, no tumor cells spreading through airspace (STAS), vascular invasion or pleural invasion was found in Grade 1 of IPA, while the positive rates of STAS in Grade 2 and 3 IPA cases were 11.3% (159/1 413) and 73.2% (327/447), respectively. There was a significant difference among the three grades (P<0.01). Similarly, the rates of vascular and pleural invasion in Grade 3 IPA cases were 21.3% (95/447) and 75.8% (339/447), respectively, which were significantly higher than those of 1.3% (19/1 413) and 3.0% (42/1 413) in Grade 2 (P<0.01). EGFR mutational rates in Grades 1, 2 and 3 IPA were 65.7% (94/143), 76.4% (984/1 288) and 51.3% (216/421), respectively. The differences among the three grades were statistically significant (P<0.01). No fusion genes were detected in Grade 1 IPA, while the positive rates of ROS1 and ALK fusion genes in Grade 3 were 2.4% (10/421) and 8.3% (35/421), respectively, which were significantly higher than that of 0.5% (7/1 288) and 1.6% (20/1 288) in Grade 2 (P<0.01). In stage-Ⅱ cases, only EGFR mutation rate in Grade 2 adenocarcinoma (31/37, 83.8%) was higher than that in Grade 3 adenocarcinoma (71/123, 57.7%; P<0.01). However, the correlation between the new grade system of IPA and the distribution characteristics of targeted-gene variation cannot be evaluated in stage Ⅲ cases. Conclusions: The new grading system for IPA is mainly applicable to clinical stage-Ⅰ patients. Tumor grades of IPA are strongly correlated with the high-risk factors of prognosis and the distribution features of therapeutic targets. It is of great significance and clinical value to manage postoperative patients with early-stage IPA.

Role of histone posttranslational modifications in the regulation of ovarian function / 生理学报

The ovary is the reproductive organ of female mammals, which is responsible for producing mature eggs and secreting sex hormones. The regulation of ovarian function involves the ordered activation and repression of genes related to cell growth and differentiation. In recent years, it has been found that histone posttranslational modification can affect DNA replication, damage repair and gene transcriptional activity. Some regulatory enzymes mediating histone modification are co-activators or co-inhibitors associated with transcription factors, which play important roles in the regulation of ovarian function and the development of ovary-related diseases. Therefore, this review outlines the dynamic patterns of common histone modifications (mainly acetylation and methylation) during the reproductive cycle and their regulation of gene expression for important molecular events, focusing on the mechanisms of follicle development and sex hormone secretion and function. For example, the specific dynamics of histone acetylation are important for the arrest and resumption of meiosis in oocytes, while histone (especially H3K4) methylation affects the maturation of oocytes by regulating their chromatin transcriptional activity and meiotic progression. Besides, histone acetylation or methylation can also promote the synthesis and secretion of steroid hormones before ovulation. Finally, the abnormal histone posttranslational modifications in the development of two common ovarian diseases (premature ovarian insufficiency and polycystic ovary syndrome) are briefly described. It will provide a reference basis for understanding the complex regulation mechanism of ovarian function and further exploring the potential therapeutic targets of related diseases.

Effects of umbilical moxibustion on phobic behavior and monoamine neurotransmitters in stress-model rats / 中国针灸

OBJECTIVE@#To investigate the effects of umbilical moxibustion therapy on phobic behavior and the contents of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in different brain regions of the stress-model rats and explore the potential mechanism of umbilical moxibustion on phobic behavior.@*METHODS@#Among 50 Wistar male rats, 45 rates were selected and randomly divided into a control group, a model group and an umbilical moxibustion group, 15 rats in each one; and the rest 5 rats were used for preparing the model of electric shock. The bystander electroshock method was adopted to prepare phobic stress model in the model group and the umbilical moxibustion group. After modeling, the intervention with umbilical moxibustion started in the umbilical moxibustion group, in which, the ginger-isolated moxibustion was applied at "Shenque" (CV 8), once daily, 2 cones for 20 min each time, for consecutively 21 days. After modeling and intervention completed, the rats in each group were subjected to the open field test to evaluate the state of fear. After intervention, the Morris water maze test and fear conditioning test were performed to evaluate the changes in learning and memory ability and the state of fear. Using high performance liquid chromatography (HPLC), the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were determined.@*RESULTS@#Compared with the control group, the horizontal and vertical activity scores were lower (P<0.01), the number of stool particles was increased (P<0.01), the escape latency was prolonged (P<0.01), the times of target quadrant were reduced (P<0.01), and the freezing time was prolonged (P<0.05) in the rats of the model group. The horizontal and vertical activity scores were increased (P<0.05), the number of stool particles was reduced (P<0.05), the escape latency was shortened (P<0.05, P<0.01), the times of target quadrant were increased (P<0.05), and the freezing time was shortened (P<0.05) in the rats of the umbilical moxibustion group when compared with the model group. The trend search strategy was adopted in the control group and the umbilical moxibustion group, while the random search strategy was used in rats of the model group. Compared with the control group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were reduced (P<0.01) in the model group. In the umbilical moxibustion group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were increased (P<0.05, P<0.01) when compared with the model group.@*CONCLUSION@#Umbilical moxibustion can effectively relieve the state of fear and learning and memory impairment of phobic stress model rats, which may be related to the up-regulation of contents of brain neurotransmitters, i.e. NE, DA, and 5-HT.

Assessment of intensity of seasonal influenza activity in Beijing-Tianjin-Hebei region, 2019-2021 / 中华流行病学杂志

Objective: To explore the feasibility of moving epidemic method (MEM) in the assessment of seasonal influenza (influenza) activity intensity from the perspective of urban agglomeration, assess influenza activity intensity in the Beijing-Tianjin-Hebei region from 2019 to 2021 and evaluate the reliability of surveillance data and the effectiveness of the MEM model application. Methods: The weekly reported incidence rate (IR) of influenza and the percentage of influenza-like illness (ILI%) from 2011-2021 in Beijing-Tianjin-Hebei region were collected to establish MEM models respectively. The model fitting effect and the reliability of the two data were evaluated for the purpose of establishing an optimal model to assess the influenza activity intensity in Beijing-Tianjin-Hebei region from 2019-2021. A cross-validation procedure was used to evaluate the performance of the models by calculating the Youden's index, sensitivity and specificity. Results: The MEM model fitted with weekly ILI% had a higher Youden's index compared with the model fitted with weekly IR at both Beijing-Tianjin-Hebei region level and provincial level. The MEM model based on ILI% showed that the epidemic threshold in Beijing-Tianjin-Hebei region during 2019-2020 was 4.42%, the post-epidemic threshold was 4.66%, with medium, high and very high intensity thresholds as 5.38%, 7.22% and 7.84%, respectively. The influenza season during 2019-2020 had 10 weeks (week 50 of 2019 to week 7 of 2020). The influenza season started in week 50 of 2019, and the intensity fluctuated above and below medium epidemic level for six consecutive weeks. The high intensity was observed in week 4 of 2020, the threshold of very high intensity was excessed in week 5, and the intensity gradually declined and became lower than the threshold at the end of the influenza season in week 8. The epidemic threshold was 4.29% and the post-epidemic threshold was 4.35% during 2020-2021. Influenza activity level never excessed the epidemic threshold throughout the year, and no epidemic period emerged. Conclusions: The MEM model could be applied in the assessment of influenza activity intensity in Beijing-Tianjin-Hebei region, and the use of ILI% to assess influenza activity intensity in this region was more reliable than IR data. Influenza activity intensity in Beijing-Tianjin-Hebei region was higher during 2019-2020 but significantly lower in 2020-2021.

Serological Characteristics of Subtype A Caused by New A Allele Mutation and a Family Survey / 中国实验血液学杂志

OBJECTIVE@#In this study, the results of forward and reverse blood typing of a male patient diagnosed as bronchiectasis were inconsistent, which were type O and type A respectively. Multiple experiments including genotyping and sequencing and family investigation were carried out to determine the subtype of ABO blood group and explore the serological characteristics of this subtype.@*METHODS@#Standard serological techniques were used to conduct forward and reverse typing, reverse blood typing enhancement test, H antigen identification, absorption-elution test, salivary blood group substances test, and PCR-SSP method for ABO genotyping and exon 6 and 7 sequencing.@*RESULTS@#The proband's blood group was type O by forward typing, but antigen A could be detected by absorption-elution test, anti-A1 could be detected by reverse blood typing enhancement test, it was found that there was substance H but no substance A in saliva, and the serological characteristics were consistent with Ael subtype. Gene sequencing analysis showed that there was a c.625T>G base substitution on the basis of A102, which had never been reported before. Family survey showed that c.625T>G base substitution appeared in three generations of the family.@*CONCLUSION@#In this study, a new subtype A with Ael serological characteristics caused by c.625T>G mutation was identified. c.625T>G base substitution results in the weakening of A antigen, and this mutation can be stably passed down to future generations.

Clinical Characteristics and Nomogram Model of Nosocomial Infection in Patients with Newly Diagnosed Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical characteristics of nosocomial infection in newly diagnosed multiple myeloma(NDMM) patients, and establish a predictive nomogram model.@*METHODS@#The clinical data of 164 patients with MM who were treated in Shanxi Bethune Hospital from January 2017 to December 2021 were retrospectively analyzed. The clinical characteristics of infection were analyzed. Infections were grouped as microbiologically defined infections and clinically defined infections. Univariate and multivariate regression models were used to analyze the risk factors of infection. A nomogram was established.@*RESULTS@#164 patients with NDMM were included in this study, and 122 patients (74.4%) were infected. The incidence of clinically defined infection was the highest (89 cases, 73.0%), followed by microbial infection (33 cases, 27.0%). Among 122 cases of infection, 89 cases (73.0%) had CTCAE grade 3 or above. The most common site of infection was lower respiratory in 52 cases (39.4%), upper respiratory tract in 45 cases (34.1%), and urinary system in 13 cases (9.8%). Bacteria(73.1%) were the main pathogens of infection. Univariate analysis showed that ECOG ≥2, ISS stage Ⅲ, C-reactive protein ≥10 mg/L, serum Creatinine ≥177 μmol/L had higher correlation with nosocomial infection in patients with NDMM. Multivariate regression analysis showed that C-reactive protein ≥10 mg/L (P＜0.001), ECOG ≥2 (P=0.011) and ISS stage Ⅲ （P=0.024） were independent risk factors for infection in patients with NDMM. The nomogram model established based on this has good accuracy and discrimination. The C-index of the nomogram was 0.779（95%CI: 0.682-0.875）. Median follow-up time was 17.5 months, the median OS of the two groups was not reached (P=0.285).@*CONCLUSION@#Patients with NDMM are prone to bacterial infection during hospitalization. C-reactive protein ≥10 mg/L, ECOG ≥2 and ISS stage Ⅲ are the risk factors of nosocomial infection in NDMM patients. The nomogram prediction model established based on this has great prediction value.

Alterations in the intestinal microbiota of preterm infants with neurodevelopmental impairments: a prospective cohort study / 中国当代儿科杂志

OBJECTIVES@#To investigate the difference in intestinal microbiota between preterm infants with neurodevelopmental impairment (NDI) and those without NDI.@*METHODS@#In this prospective cohort study, the preterm infants who were admitted to the neonatal intensive care unit of Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from September 1, 2019 to September 30, 2021 were enrolled as subjects. According to the assessment results of Gesell Developmental Scale at the corrected gestational age of 1.5-2 years, they were divided into two groups: normal (n=115) and NDI (n=100). Fecal samples were collected one day before discharge, one day before introducing solid food, and at the corrected gestational age of 1 year. High-throughput sequencing was used to compare the composition of intestinal microbiota between groups.@*RESULTS@#Compared with the normal group, the NDI group had a significantly higher Shannon diversity index at the corrected gestational age of 1 year (P<0.05). The principal coordinate analysis showed a significant difference in the composition of intestinal microbiota between the two groups one day before introducing solid food and at the corrected gestational age of 1 year (P<0.05). Compared with the normal group, the NDI group had a significantly higher abundance of Bifidobacterium in the intestine at all three time points, a significantly higher abundance of Enterococcus one day before introducing solid food and at the corrected gestational age of 1 year, and a significantly lower abundance of Akkermansia one day before introducing solid food (P<0.05).@*CONCLUSIONS@#There are significant differences in the composition of intestinal microbiota between preterm infants with NDI and those without NDI. This study enriches the data on the characteristics of intestinal microbiota in preterm infants with NDI and provides reference for the microbiota therapy and intervention for NDI in preterm infants.