Di-(2-ethylhexyl) phthalate (DEHP) is currently one of the most widely used plasticizers, widely found in all kinds of items, such as children’s toys and food packaging materials, but also added to wallpaper, cable protective agents and other building decoration materials. DEHP is toxic and absorbed by the human body through respiratory tract, digestive tract and skin contact, which can cause damage to multiple systems, especially the male reproductive system, and testis is an important target organ. Oxidative stress injury is the core mechanism of spermatogenesis disorder caused by DEHP. DEHP exposure can cause oxidative stress or reactive oxygen species (ROS) increase in germ cells, and on this basis, promote cell apoptosis or cause excessive autophagy. The toxicity of DEHP to Leydig cells is mainly to interfere with the synthesis of steroid hormones. For Sertoli cells, ferroptosis and destruction of the blood-testis barrier are common injury mechanisms. In addition, gene methylation caused by DEHP not only affects the spermatogenic process, but also has epigenetic effects on offspring. In this paper, we reviewed the pathological damage, germ cell toxicity and epigenetic effects of DEHP on testis, and focused on the damage and molecular mechanism on testicular spermatogenic cells, Leydig cells and Sertoli cells. Future research is required to elucidate the body’s clearance mechanism and treatment plan after exposure to DEHP and whether DEHP will damage the function of myoid cells. It is hoped that this can provide new ideas for prevention and treatment of male reproductive disorders resulting from long-term exposure to plastic products.

As a unique gene in the genome,FLASH(FADD-like interleukin-1β-converting enzyme asso-ciated huge protein)/CASP8AP2 is involved in multiple cellular processes,including apoptosis,histone gene pre-mRNA processing,transcriptional regulation,and cell cycle progression.Clinical studies have shown that FLASH is a valuable prognostic marker for acute lymphoblastic leukemia,and a crucial factor for the survival of various cancer cells.Therefore,in-depth research into the function of FLASH may offer new perspectives for the treatment of related diseases.Our previous research identified FLASH as a bind-ing partner of p53,demonstrating that FLASH enhances the transcriptional activity of p53.Here we fur-ther investigate the molecular mechanisms of the interaction between FLASH and p53,revealing that the p53-K386R mutation(SUMOylation residue)attenuated its interaction with FLASH(aa 51-200)and FLASH-SIM(SUMO-interacting motif)(aa 1 534-1 806)significantly.However,SUMO can bind to FLASH-SIM directly,instead of FLASH(aa 51-200).Subsequent research shows that overexpression of FLASH in cells enhances global SUMO1 conjugation and p53-SUMO1 conjugation,therefore providing a plausible explanation for the underlying mechanism of FLASH enhancing the transcriptional activity of p53.Since promyelocytic leukemia protein nuclear body(PML NB)serves as subcellular reactors for SUMO conjugation within the cell,and the PML Ⅳ isoform can specifically enhance the SUMO modifica-tion of p53,we have investigated the interaction between FLASH and PML Ⅳ,and elucidated the struc-tural basis of their interaction:both FLASH-N3A(501-802)and FLASH-C2(1 807-1 981)bind to PML Ⅳ(aa 228-633).Further investigations reveal that they can synergistically enhance global SUMO1 modification as well as SUMO1 modification of p53.The interaction between FLASH and tumor suppres-sors p53 or PML Ⅳ enriches our understanding of its function and reveals the potential mechanism of FLASH in tumor development,therefore offering novel insights into cancer diagnosis and treatment.

Aim To establish the fingerprint of raw bupleurum and vinegar bupleurum,investigate the difference in their anti-liver fibrosis effects,and ex-plore the relationship between the chemical composition of raw bupleurum and vinegar bupleurum and their an-ti-liver fibrosis efficacy.Methods The fingerprints of 10 batches of raw bupleuri and 10 batches of bupleuri were established by UPLC method.The liver fibrosis cell model in vitro was established by TGF-β induced LX-2 hepatic stellate cells.The liver fibrosis cell mod-el was analyzed with collagen type Ⅰ(col1a1)and α-smoothmuscleactin.The expression of α-SMA protein was used as the pharmacodynamic index.MetaboAna-lyst5.0 was used to screen the difference markers af-fecting the quality of raw bupledges and vinegar bu-pledges with VIP value＞1 as the criterion.Orthogo-nal partial least squares discriminant analysis(OPLS-DA)was used to screen the main components of raw bupleurum and vinegar bupleurum against liver fibro-sis.Results There were 18 peaks in the UPLC fin-gerprints of raw bupleurum and vinegar bupleurum,and the analysis results showed that there were nine main differences between raw bupleurum and vinegar bupleurum,among which peaks 9,7 and 6 could be considered as bupleurin d,bupleurin a and bupleurin f.The results of spectral effect relationship showed that the main components of bupleurum anti-liver fibrosis were peaks 11,12,14,15 and 18.Conclusions The established fingerprint method of raw bupleurum and vinegar bupleurum is simple and feasible,and the important components of anti-liver fibrosis activity are screened through the spectrum effect relationship,which provides a basis for clarifying the material basis of anti-liver fibrosis effect of raw bupleurum and vine-gar bupleurum.

Objective: To examine the feasibility and surgical approach of removing type D trigeminal schwannoma through nasal cavity and nasal sinus under endoscope. Methods: Eleven patients with trigeminal schwannoma who were treated in the Department of Otorhinolaryngology, Qilu Hospital of Shandong University from December 2014 to August 2021 were analyzed retrospectively in this study. There were 7 males and 4 females, aged (47.5±13.5) years (range: 12 to 64 years). The neoplasm involved the pterygopalatine fossa, infratemporal fossa, ethmoidal sinus, sphenoid sinus, cavernous sinus, and middle cranial fossa. The size of tumors were between 1.6 cm×2.0 cm×2.0 cm and 5.7 cm×6.0 cm×6.0 cm. Under general anesthesia, the tumors were resected through the transpterygoid approach in 4 cases, through the prelacrimal recess approach in 4 cases, through the extended prelacrimal recess approach in 2 cases, and through the endoscopic medial maxillectomy approach in 1 case. The nasal endoscopy and imaging examination were conducted to detect whether neoplasm recurred or not, and the main clinical symptoms during follow-up. Results: All the surgical procedures were performed under endonasal endoscope, including Gross total resection in 10 patients. The tumor of a 12-year-old patient was not resected completely due to huge tumor size and limited operation space. One patient was accompanied by two other schwannomas located in the occipital region and the ipsilateral parotid gland region originating from the zygomatic branch of the facial nerve, both of which were removed concurrently. After tumor resection, the dura mater of middle cranial fossa was directly exposed in the nasal sinus in 2 cases, including 1 case accompanied by cerebrospinal fluid leakage which was reconstructed by a free mucosal flap obtained from the middle turbinate, the other case was packed by the autologous fat to protect the dura mater. The operation time was (M(IQR)) 180 (160) minutes (range: 120 to 485 minutes). No complications and deaths were observed. No recurrence was observed in the 10 patients with total tumor resection during a 58 (68) months' (range: 10 to 90 months) follow-up. No obvious change was observed in the facial appearance of all patients during the follow-up. Conclusion: Type D trigeminal schwannoma involving pterygopalatine fossa and infratemporal fossa can be removed safely through purely endoscopic endonasal approach by selecting the appropriate approach according to the size and involvement of the tumor.
Male ; Female ; Humans ; Child ; Retrospective Studies ; Endoscopy/methods* ; Nasal Cavity/surgery* ; Neurilemmoma/surgery* ; Cranial Nerve Neoplasms/surgery*

AIM:To investigate the neuroprotective effect of 17β-estradiol(E2)on retina light damage in BALB/c and C57BL/6 mice and provide experimental data for the successful construction of a research model for E2 against retinal light damage.METHODS:Totally 40～45 adult female BALB/c or C57BL/6 mice were divided into six groups, 6 for each group: normal control, ovariectomized control, ovariectomized light(mice were stimulated with continuous white light at 10000 lx for 4, 8, 12, 16, and 24h after 14d of ovariectomy), intravitreal administration sham operation, saline and E2 pre-treatment groups(2μL saline or 10-5mol/L E2 were intravitreal injected respectively after 14d of ovariectomy operation and 24h of dark adaptation). The morphological and functional changes of the retina were detected by paraffin section HE staining, TUNEL staining and electroretinogram.RESULTS:In the ovariectomized light group, the thickness of the inner/outer nuclear layer decreased significantly from the 4h stimulation of 10000 lx white light group. Intravitreal administration of E2 significantly inhibited the apoptosis of retinal cells in the two strains of mice(P<0.01)and the decrease of amplitudes of a- and b-waves in max-ERG of C57BL/6 mice(P<0.05).CONCLUSION:The light loss sensitivity of two strains of mice was different under the same light stimulation. E2 had a protective effect on both morphology and function of the retina in BALB/c mice, and had a significant protective effect on retina function in C57BL/6 mice.

Both anti-glomerular basement membrane (GBM) disease and the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are common causes of pulmonary-renal syndrome. Organizing pneumonia (OP), a special pattern of interstitial lung disease, is extremely rare either in AAV or anti-GBM disease. We report an old woman presented with OP on a background of co-presentation with both ANCA and anti-GBM antibodies.
Female ; Humans ; Antibodies, Antineutrophil Cytoplasmic ; Organizing Pneumonia ; Autoantibodies ; Glomerulonephritis ; Anti-Glomerular Basement Membrane Disease ; Pneumonia ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications*

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Human use experience(HUE) is important for the research and development of Chinese medicine. For the sake of more reliable data, the Professional Committee for Clinical Evaluation of Chinese Medicine of Chinese Pharmaceutical Association drafted the Expert Consensus on Human Use Experience Research of Traditional Chinese Medicine. It highlights that the research on HUE should have clear purposes, describe the theoretical basis of traditional Chinese medicine(TCM) for the clinical indications and prescriptions and the clinical value of prescriptions, especially the advantages or characteristics in clinical orientation and target population, evaluate the dosages and number of medicinals of prescriptions, verify the accordance with the preparation process of new Chinese medicine, analyze feasibility of the process for large-scale production and the rationality of the dosage form, and assess the medicinal material resources. Moreover, such research should have reasonable protocol and the collection of clinical data on HUE must comply with medical ethics and avoid conflicts of interest. The collection method should be selected depending on the characteristics of clinical data. Quality control measures should be formulated to ensure the authenticity, accuracy, completeness, reliability, and traceability of clinical data. The definitions on the clinical data should be uniform and clear, and methods should be adopted to avoid bias. The data can be statistically analyzed after the processing. Through the study of HUE, the clinical orientation, target population, commonly used dosage, course of treatment, preliminary efficacy and safety of Chinese medicine prescriptions will be clarified. On this basis, the data on the HUE should be discussed and conclusions will be drawn. Finally, a standardized report will be formed.
Consensus ; Drug Prescriptions ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Reproducibility of Results

Objective: To investigate the independent and joint effects of chronotype and sleep duration on self-rated health in medical students. Methods: A cross-sectional study was conducted in 1 526 medical students selected through proportional stratified cluster random sampling from a medical university in Zhejiang province. A questionnaire survey was conducted to collect the information about their basic demographic characteristics, chronotype, sleep duration, and other lifestyle factors such as midnight snack, sedentary behavior, physical activity, meal time, and self-rated health. The independent and joint effects of chronotype and sleep duration on self-rated health were assessed by logistic regression model after controlling for confounding variables. Results: The numbers of the students with evening chronotype, neutral chronotype, and morning chronotype were 664 (43.5%), 442 (29.0%), and 420 (27.5%), respectively. Among the medical students, 42.8% (653) had poor self-rated health. Compared with those with the morning chronotype, the adjusted ORs for those with neutral chronotype and evening chronotype were 1.69 (95%CI: 1.23-2.31) and 2.43 (95%CI: 1.81-3.26), respectively, trend test P<0.001. Compared with those with sleep duration of 8 h or above per night, the adjusted ORs for those with sleep duration of 7 and ≤6 h per night were 1.40 (95%CI: 1.07-1.84) and 2.38 (95%CI: 1.69-3.37), respectively, trend test P<0.001. In the joint effect, compared with those with the morning chronotype and sleep duration of 8 h or above per night, the adjusted OR for those with evening chronotype and sleep duration of ≤6 h per night was 6.53 (95%CI: 3.53-12.09). Conclusions: Both evening chronotype and insufficient sleep were associated with increased odds of poor self-rated health in medical students, and they had joint effects. Therefore, it is necessary to promote early to bed, early to rise and adequate sleep in medical student to maintain their health.
Humans ; Students, Medical ; Cross-Sectional Studies ; Sedentary Behavior ; Sleep

Objective: To explore the clinical characterist ics and risk factors of hemorrhage complicated by hemoperfusion therapy in patients with acute poisoning. Methods: In January 2021, the clinical data of 196 patients with acute poisoning who received hemoperfusion therapy in the Second Affiliated Hospital of Air Force Military Medical University from January 2018 to December 2020 were analyzed, and the patients were divided into bleeding group and non-bleeding group according to whether the patients were complicated with bleeding. Multivariate logistic regression was used to analyze the independent risk factors for hemorrhage in patients treated with hemoperfusion. Results: A total of 21 patients in the bleeding group and 175 patients in the non-bleeding group were included. There was no significant difference in general data such as gender, age, and body mass index between the two groups (P>0.05) . Organophosphorus pesticides (χ(2)= 4.56, P=0.030) , HA230 perfusion device (χ(2)=4.12, P=0.042) , platelet count (t=-2.33, P=0.009) and activated partial thromboplastin time (t=14.53, P<0.001) at 2 h of perfusion were the influencing factors of hemorrhage in patients with acute poisoning treated with hemoperfusion. Among them, organophosphorus pesticides, 2 h perfusion activated partial thromboplastin time ≥35 s and other factors were independent risk factors forcomplicated bleeding (P<0.05) . Conclusion: Patients with acute poisoning, especially organophosphorus pesticide poisoning, are at greater risk of bleeding during hemoperfusion therapy. Monitoring of changes in activated partial thromboplastin time should be strengthened and the dose of anticoagulants should be adjusted in time to reduce the risk of bleeding.
Hemoperfusion ; Hemorrhage/therapy* ; Humans ; Organophosphorus Compounds ; Pesticides ; Poisoning/therapy* ; Risk Factors