Although cisplatin is a widely used chemotherapeutic agent, it is severely toxic and causes irreversible hearing loss, restricting its application in clinical settings. This study aimed to determine the molecular mechanism underlying cisplatin-induced ototoxicity. Here, we established in vitro and in vivo ototoxicity models of cisplatin-induced hair cell loss, and our results showed that reducing STING levels decreased inflammatory factor expression and hair cell death. In addition, we found that cisplatin-induced mitochondrial dysfunction was accompanied by cytosolic DNA, which may act as a critical linker between the cyclic GMP-AMP synthesis-stimulator of interferon genes (cGAS-STING) pathway and the pathogenesis of cisplatin-induced hearing loss. H-151, a specific inhibitor of STING, reduced hair cell damage and ameliorated the hearing loss caused by cisplatin in vivo. This study underscores the role of cGAS-STING in cisplatin ototoxicity and presents H-151 as a promising therapeutic for hearing loss.
Cisplatin/toxicity* ; Animals ; Nucleotidyltransferases/antagonists & inhibitors* ; Membrane Proteins/antagonists & inhibitors* ; Signal Transduction/drug effects* ; Mice ; Hair Cells, Auditory, Inner/pathology* ; Antineoplastic Agents/toxicity* ; Mice, Inbred C57BL ; Hearing Loss/metabolism* ; Male ; Ototoxicity/metabolism*

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective To establish a HPLC method for simultaneous determination of neochlorogenic acid,chlorogenic acid,cryptochlorogenic acid,puerarin,polydatin,isochlorogenic acid A,isochlorogenic acid C,resveratrol,glycyrrhizic acid and emodin in Yinhua Pinggan Granules.Methods The analysis was performed on Thermo Acclaim-C18 column(250 mm×4.6 mm,5 μm)by gradient elution of acetonitrile-0.1%phosphoric acid solution at a flow rate of 1.0 mL·min-1.The detection wavelength was set at 327 nm for detecting neochlorogenic acid,chlorogenic acid,cryptochlorogenic acid,polydatin,isochlorogenic acid A,isochlorogenic acid C and resveratrol,at 252 nm for detecting puerarin,glycyrrhizic acid and emodin.The column temperature was 30℃and the injection volume was 10 μL.Results Good resolution of 10 constituents of Yinhua Pinggan Granules was obtained.The linear ranges of neochlorogenic acid,chlorogenic acid,cryptochlorogenic acid,puerarin,polydatin,isochlorogenic acid A,isochlorogenic acid C,resveratrol,glycyrrhizic acid and emodin were 1.744-17.44,10.75-107.5,1.863-18.63,14.62-146.2,4.784-47.84,1.208-12.08,4.427-44.27,1.971-19.71,3.624-36.24 and 4.142-41.42 μg·mL-1,respectively.The results showed good linear relationships(r≥0.999 4).The average recoveries ranged from 99.17%to 102.97%(RSD≤2.65%).The content ranges of ten constituents in five batches were 1.065-3.238,20.11-25.14,1.785-2.973,23.60-35.55,7.157-9.469,1.224-2.421,6.430-7.879,1.354-2.006,4.907-8.052,4.387-9.484 mg·g-1,respectively.Conclusion This method is simple and accurate,which can be used for the quality control and evaluation of Yinhua Pinggan Granules.

A case of secondary Burkitt lymphoma of prostate was reported. A 39-year-old patient was admitted to the hospital with no apparent cause for impaired urination with frequent/urgent urination. CT scan of the whole abdomen showed irregular soft tissue mass of the prostate, involving the bladder and rectum, and mild obstructive hydronephrosis of the renal pelvis and ureter. Biopsy of the prostatic mass was performed, and the pathological findings were consistent with Burkitt lymphoma. PET-CT examination showed multiple lesions and lymph node enlargement throughout the body, secondary prostate lymphoma was diagnosed. After diagnosis, the patient was treated with R-DA-EPOCH chemotherapy and followed up for 9 months. Prostate lymphoma is rare and needs to be combined with clinical manifestations and laboratory tests to determine whether it is primary or secondary, but also to distinguish from prostate diseases such as prostatitis and poorly differentiated prostate cancer.

Although olaparib has demonstrated substantial clinical benefits as maintenance therapy in BRCA mutation-carrying women with newly diagnosed advanced ovarian cancer, its effectiveness in patients without BRCA mutations remains poorly investigated. This study aims to provide the first evidence on the efficacy of mono-olaparib maintenance therapy in such context. Using real-world data from 11 high-volume tertiary care centers in China, a retrospective cohort study was conducted to assess the efficacy and safety of olaparib as first-line maintenance therapy in patients with BRCA wild-type ovarian cancer. The primary objective was 1-year progression-free survival rate. Safety was also evaluated. Fifty patients with a median age of 54 years were included, and all of them tested negative for BRCA mutations but positive for homologous recombination deficiency (HRD). The 1-year PFS rate was 75.2% (95% CI, 63.4 to 89.2), and the median PFS was 21.0 months (95% CI, 13.8 to 28.2). All the patients received olaparib at a starting dose of 300 mg twice daily, and none experienced serious adverse events (AEs). Eight (16%) patients had dose adjustment, but none discontinued olaparib treatment due to AEs. We provide the first evidence that mono-olaparib could be a safe and effective maintenance treatment option for patients newly diagnosed with HRD-positive/BRCA wild-type ovarian cancer.
Humans ; Female ; Phthalazines/adverse effects* ; Piperazines/administration & dosage* ; Middle Aged ; Ovarian Neoplasms/genetics* ; Retrospective Studies ; Adult ; Aged ; Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage* ; China ; Maintenance Chemotherapy ; BRCA2 Protein/genetics* ; Antineoplastic Agents/adverse effects* ; Progression-Free Survival ; BRCA1 Protein/genetics*

Objective:To observe any effect of electroacupuncture (EA) on the expression of phosphorylated extracellular signal-regulated protein kinase (p-ERK1/2) and phosphorylated cyclic adenosine monophosphate response element binding protein (p-CREB) in the spinal dorsal horns of diabetics experiencing neuropathic pain.Methods:Eight rats were randomly selected from 30 healthy male Sprague-Dawley rats as the normal group (N), and the remaining twenty-two rats were treated with a single high-dose intraperitoneal injection of streptozotocin (STZ) to establish a neuropathic pain model. The rats modeled successfully were randomly divided into a model group (M, n=8) and an EA group ( n=8). In the EA group, electroacupuncture was applied at the bilateral Hou san li and Kunlun acupoints starting on the 15th day after the STZ injection. The daily sessions lasted 30 minutes for 1 week. Body weight (BW), fasting blood glucose (FBG) and paw withdrawal latency (PWL) were observed before the STZ injection and on the 7th, 14th, and 21st days afterward. The expression of p-ERK1/2 and p-CREB in the dorsal horns of the rats′ spinal cords was detected using western blotting. The count of p-CREB-positive cells in the dorsal horns and their co-localization with neurons was detected using immunofluorescence. Results:In comparison with the N group, the average BW of the M group on the 7th, 14th and 21st days after the STZ injection was significantly lower, while the average FBG was significantly higher. There was no significant difference between the M and N groups in the average PWL on the 7th day after the STZ injection, but it had decreased significantly in the M group on the 14th and 21st days. Compared with the M group, the average PWL of the EA group was significantly longer on the 21st day after the injection. The expression of p-ERK1/2 and p-CREB protein in the spines of the M group was significantly higher than in the N group. p-CREB positive cells were more numerous in the M group compared with the N group, while in the EA group they were fewer. P-CREB was co-located with neurons in the spinal dorsal horn.Conclusion:EA can alleviate neuropathic pain effectively, perhaps by inhibiting the expression of p-ERK1/2 and p-CREB in the dorsal horns of the spinal cord.

December 2019 witnessed the outbreak of COVID-19 in Wuhan city and its rapid spread to other parts of China, and overseas as well. Tongji Hospital, as a designated hospital for treatment of critically ill patients, shoulders the diagnosis and treatment tasks of numerous critically ill patients of such a disease. For the purpose of handling their medical records and effectively preventing the nosocomial infection of the disease, the hospital puts in place both the electronic signature system of patients based on a Wechat applet and a paperless medical record total solution based on the data center. These measures overcome the challenges incurred by patients’ signature on paper-based records and medical records archiving during the epidemic. On the other hand, they can not only downsize the paper-based medical records, minimize the risk of infection caused by paper-based medical records via contacts, but also effectively save the hospital of its operating costs and improve its efficiency of clinical work.

Objective To investigate the effects of piperazine ferulate tablets combined with Huangqi injection on β2-microglobulin,NGAL and clinical efficacy in patients with acute renal failure.Methods A total of 56 patients with acute renal failure from June 2012 to October 2015 in our hospital were collected and randomly divided into the experimental group and the control group with 28 cases in each group.All patients before the treatment of conventional care,diuretics and vasodilators to increase the patient's serum protein and vitamins,so that patients with the body's pH,moisture and electrolyte balance,and gave hemodialysis and low molecular heparin anticoagulant therapy.Patients in the control group were treated on the base of the conventional therapy withastragalus injection 20mL/time,one time a day,intravenous drip,treatment of four weeks; patients in the experimental group were treated on the base of the control group with piperazine ferulate tablet 200mg/time,three times/day,treatment of four weeks.After treatment,compared patients' β2 microsphere protein,NGAL and KIM-1 levels.Results There was no significant difference in the survival rate between the two groups.Compared with before treatment,β2 microsphere protein,NGAL and KIM-1 levels in two groups were lower(P<0.05);Compared with control group,β2 microsphere protein,NGAL and KIM-1 levels in the experimental group were lower(P<0.05).Conclusion Piperazine ferulate tablets combine with astragalus injection in the treatment of patients with acute renal failure have a better clinical curative effect,speculate that the mechanism is relate to reduce β2 microsphere protein,NGAL and KIM-1 levels.

[Abstract ] Objective Difficulties with the preparation of gastric cancer stem cells (CSCs) have been a main obstacle to the studies of gastric cancer .This article addresses the technology of the serum-free medium suspension cultivation of the MKN-45 gastric cancer cell line and screening of stem cells from the cell line based on the biomarkers of gastric CSCs . Methods MKN-45 cells were cultured in serum-free medium for 8 weeks and those in the logarithmic phase cultivated with hoechst 33342 followed by detection of the side cells by flow cytometry .When the side population cells reached 25%, all the cell microspheres were collected , hatched with CD133 and CD44, and subjected to fluorescence-activated cell sorting.The CDl33 +and CD44 +cells were selected as gastric CSCs . Results About 40%of the MKN-45 gastric CSCs were alive , prolif-erated, and formed floating cell balls .Side population cells constitu-ted 3.4% of the MKN-45 cells and 26.9% of the cell balls.The CDl33 +and CD44 +cells made up 11.2% of the MKN-45 cells and 90.3%of the cell balls. Conclusion Cell balls rich in CSCs can be successfully obtained by serum-free medium suspension culti-vation and CSCs can be screened out with hoechst 33342 and surface markers , which may serve as an experimental ground for the stud-ies of gastric CSCs .

Objective To evaluate the safety and efficiency of combined finasteride and metformin on benign prostatic hyperplasia (BPH) with type 2 diabetes mellitus(T2DM).Methods Totally 106 patients with BPH plus T2DM received finasteride and metformin treatment for over 12months.Before and after treatment,the side effects and following parameters were measured:prostatic volume (PV),prostate-specific antigen(PSA),international prostate symptom score (IPSS),quality of life (QOL),the maximum flow rate of urinary (Qmax),residual urine(RU),body mass index (BMI),cholesterol (TG).Results There were obvious changes in the following:PV decreased from (56.40±18.75)ml to(42.40± 19.68) ml,PSA decreased from(3.65± 1.08) μg/L to (1.76±0.66)μg/L,IPSS decreased from(22.58±9.45)to(16.67±7.56),QOL decreased from(4.22± ±0.87) to (2.36 ± 0.74),Qmax increased from(8.32±2.42)ml/s to(15.48±3.61)ml/s,RU decreased form(68.36±19.25)ml to(36.42±13.91)ml,BMI decreased from(28.52±3.73)kg/m2 to (19.76± 1.88)kg/m2,TG decreased from (2.52 ± 0.43) mmol/L to (1.38 ± 0.52) mmol/L.The changes of PV,PSA,IPSS,QOL,Qmax,RU,BMI and TG were statistically significant (all P＜0.05).Conclusions Long term combined finasteride and metformin treatment for BPH plus T2DM is effective and safe.And the two drugs may be improve the efficacy each other.