Objective:To investigate the predictive value of neutrophil to lymphocyte ratio (NLR) for hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS).Methods:Consecutive patients with AIS without performing intravenous thrombolysis and mechanical thrombectomy admitted to the Cerebrovascular Disease Treatment Center, the Affiliated Brain Hospital of Nanjing Medical University from December 2015 to December 2020 were enrolled. The clinical, imaging and laboratory examination data were collected. HT was defined as the first imaging examination of AIS patients without finding bleeding signs, but the imaging reexamination after hospitalization found intracranial hemorrhage. Multivariate logistic regression analysis was used to determine the independent correlation between NLR and HT. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of NLR for HT. Results:A total of 805 patients with AIS were included. The median age was 67 years (interquartile range, 63-71 years), the median National Institutes of Health Stroke Scale (NIHSS) score was 4 (interquartile range, 2-9), the median NLR was 3.84 (interquartile range, 2.66-5.30). Seventy-ywo patients (8.9%) had HT. There were significant differences in age, baseline systolic blood pressure, baseline NIHSS score, time from onset to admission, time from onset to blood collection, time from onset to imaging reexamination, NLR, atrial fibrillation, history of previous stroke and transient ischemic attack and stroke etiology between the HT group and the non-HT group (all P<0.05). Multivariate logistic regression analysis showed that NLR was an independent risk factor for HT in patients with AIS after adjusting for confounding factors (odds ratio 1.355, 95% confidence interval 1.099-1.672; P=0.005). The ROC curve analysis showed that the area under the curve of NLR predicting HT was 0.852, and the optimal cut-off value was 4.75. Its sensitivity and specificity of predicting HT were 88.3% and 71.8% respectively. Conclusion:High NLR is an independent risk factor for HT in patients with AIS during hospitalization, and had better predictive value for HT risk.

Objective:To investigate the effect of exosomes (Exo) secreted by brain vascular endothelial cell bEnd.3 after ischemic preconditioning (IPC) on neurons suffering from oxygen and glucose deprivation (OGD).Methods:bEnd.3 was exposed to OGD for 3 h to simulate IPC in vivo. After 48 h of reoxygenation, the Exo (IPC Exo) in the conditioned medium were extracted and identified by Western blot and transmission electron microscopy. IPC Exo were incubated with primary cultured mouse cortical neurons for 24 h. Confocal microscope was used to observe whether Exo could be uptaked by primary cultured mouse cerebral cortical neurons. The primary cultured cortical neurons were divided into control group, OGD group, OGD+ IPC Exo (5 μg/ml, 10 μg/ml, 20 μg/ml) groups and sham OGD group (treated with Exo secreted by bEnd.3 cultured under normoxia conditions). The cell viability was detected by CCK-8 and cell survival/death detection kit.Results:Transmission electron microscopy showed that the extract of bend.3 culture medium showed typical morphology of Exo, i. e., a double concave disc-shaped vesicle with a diameter of 30-100 nm. Western blot analysis showed that the extract of bEnd.3 medium highly expressed Exo markers Alix and Tsg101. Confocal microscopy showed that Exo could be uptaked by primary cultured mouse cortical neurons, and the uptake of Exo was widely distributed in the cytoplasm and synapses. Compared with the OGD group, the addition of 10 and 20 μg/ml IPC Exo could significantly increased the neuronal viability ( P<0.05), while the addition of sham Exo had no neuroprotective effect. Conclusion:Exo released by cerebral vascular endothelial cells after IPC have protective effect on neurons suffering from OGD.

Objective To explore the correlation between different body mass indexes and incidence of digestive carcinoma.Methods The retrospective cohort study was conducted.The data of 95 177 participants (75 909 males and 19 268 females) aged (51± 12)years with the range of 18-98 years who participated health examination at the Kailuan General Hospital,Kailuan Linxi Hospital,Kailuan Zhaogezhuang Hospital,Kailuan Tangjiazhuang Hospital,Kailuan Fan' gezhuang Hospital,Kailuan Jinggezhuang Hospital,Kailuan Lyujiatuo Hospital,Kailuan Linnancang Hospital,Kailuan Qianjiaying Hospital,Kailuan Majiagou Hospital and Kailuan Branch Hospital from July 2006 to December 2015 were collected.According to definition of body mass indexes from Chinese guideline for prevention and control of adult overweight and obesity,all the 95 177 participants were allocated into the 3 groups,including 37 660 with BMI＜24 kg/m2 in the normal BMI group,39 793 with with 24 kg/m2 ≤BMI＜ 28 kg/m2 in the overweight group and 17 724 with BMI≥28 kg/m2 in the obesity group.All participants received the same-order health examinations by the fixed team of doctors in 2006,2008,2010,2012 and 2014 at the same place.Epidemiological investigation,anthropometric parameters and biochemical indicators were collected.Observation indicators:(1) comparisons of clinical characteristics among the 3 groups;(2) incidence of digestive carcinoma in the participants;(3) risk factors analysis affecting new-onset digestive carcinoma;(4) comparisons of the fitting degree of BMI on new-onset digestive carcinoma model;(5) stratified analysis of risk factors affecting new-onset digestive carcinoma at different locations.Measurement data with normal distribution were represented as Mean±SD,and comparisons among groups were analyzed using the one-way ANOVA.Measurement data with skewed distribution were described as M (range),and comparisons among groups were analyzed using the Kruskal-Wallis test.Count data were described as case number and percentage,and comparisons among groups were analyzed using the chi-square test.The cumulative incidence was calculated by the Kaplan-Meier method,and comparisons of incidences among groups were done by the Log-rank test.The incidences of digestive carcinomain patients with different BMI were calculated by person-year incidence (incidence density).The hazard ratio (HR) and 95％ confidence interval (CI) of different BMI (continuous variable and classification variable) on new-onset digestive carcinoma were estimated by the COX proportional hazards regression models.Restrictive cubic spline regression was used to calculate the dose-response relation between the continuous variable and the risks of digestive carcinoma.The fitting degree of BMI on new-onset digestive carcinoma model was calculated by the likelihood ratio test and akaike information criterion (AIC).Results (1) Comparisons of clinical characteristics among the 3 groups:age,sex (male),systolic pressure,diastolic pressure,waistline,total cholesterol (TC),triglyceride (TG),fasting plasma glucose (FPG),C reactive protein,cases with smoking,drinking,physical exercise,positive HBsAg,high salt intake,malignant tumor in immediate family were (51± 13)yeas,28 607,(125±20) mmHg (1 mmHg=0.133 kPa),(80± 11) mmHg,(81±9) cm,(4.9± 1.1) mmol/L,1.05 mmol/L(range,0.75-1.49 mmol/L),(5.3±1.6) mmol/L,0.58 mmol/L (range,0.20-1.60 mmol/L),11 962,6 845,5 676,711,.3 640,1 298 in the normal BMI group and (52±12)years,32 928,(133±21) mmHg,(85±11) mmHg,(89±8)cm,(5.0±1.2) mmol/L,1.39 mmol/L (range,0.99-2.08 mmol/L),(5.6± 1.7)mmol/L,0.84 mmol/L (range,0.33-2.07 mmol/L),12 364,7 413,6 322,839,4 401,1 463 in the overweight group and (51 ± 12) years,14 374,(139 ± 21) mmHg,(88 ± 12) mmHg,(96 ± 9) cm,(5.1 ± 1.2) mmol/L,1.67 mmol/L (range,1.18-2.51 mmol/L),(5.7± 1.8) mmol/L,1.22 mmol/L (range,0.53-2.82 mmol/L),5 092,2 818,2 847,355,2 235,704 in the obesity group,showing statistically significant differences among groups (F=90.60,x2 =576.34,F=2 768.38,3 570.80,22 319.30,256.99,x2 =9 108.21,F=507.11,x2 =3 219.47,52.78,64.38,13.36,0.76,130.39,9.74,P＜0.05).(2) Incidence of digestive carcinoma in the participants:all the 95 177 participants were followed up for 845 085 person-year,1 215 were diagnosed as new-onset digestive carcinoma,with a total person-year incidence of 1.44 thousand person / year.Of 1 215 patients,413 had colorectal-anal cancer,306 had liver cancer,234 had gastric cancer,113 had esophageal cancer,91 had the pancreatic cancer,36 had gallbladder carcinoma or cholangiocarcinoma,25 had intestinal cancer.Three patients had intestinal cancer complicated with colorectal-anal cancer.The person-year incidence of digestive carcinoma was 1.46 thousand person / year,1.37 thousand person / year and 1.53 thousand person / year in the normal BMI group,overweight group and obesity group,respectively.The cumulative incidences of digestive carcinoma in the normal BMI,overweight,obesity group were respectively 11.8‰,10.1‰ and 12.1‰,showing a statistically significant difference among 3 groups (x2=6.13,P＜0.05).There was no statistically significant difference between the normal BMI group and obesity group (x2 =1.07,P＞0.05),and statistically significant differences between the overweight group and normal BMI group and obesity group,respectively (x2=3.90,4.10,P ＜ 0.05).(3) Risk factors analysis affecting new-onset digestive carcinoma.Results of COX proportional hazards regression models showed that continuous BMI was not related factor affecting new-onset digestive carcinoma after adjustment of age,gender,systolic pressure,TC,TG,FPG,smoking,drinking,physical exercise,positive HBsAg,high salt intake,malignant tumor in immediate family (HR=0.99,95％CI:0.98-1.01,P＞0.05).After adding BMI as classification variable in the COX model,risk of new-onset digestive carcinoma in the overweight group was reduced compared with normal BMI group (HR =0.88,0.88,95％CI:0.78-1.01,0.77-0.98,P＜0.05) and risk of new-onset digestive carcinoma in the obesity group was not affected (HR=1.03,1.04,95％CI:0.88-1.20,0.89-1.22,P＞0.05).Results of restrictive cubic spline regression showed a "U" shaped relationship between BMI and incidence risk of digestive carcinoma and the lowest incidence of digestive carcinoma in patients with BMI as 25-27 kg/m2.(4) Comparisons of the fitting degree of BMI on new-onset digestive carcinoma model:multivariate model was constructed after adding risk factors of age,gender,systolic pressure,TC,TG,FPG,smoking,drinking,physical exercise,positive HBsAg,high salt intake,malignant tumor in immediate family,and-2Log L and AIC were 27 175.05 and 27 203.05 for the multivariate model.Then BMI variable was added into the multivariate model,and the-2Log L and AIC of the multivariate model+BMI model were 27 169.53 and 27 201.53,respectively,with a statistically significant difference compared with normal BMI group (x2 =5.52,P＜0.05).(5) Stratified analysis of risk factors affecting new-onset digestive carcinoma at different locations.Results of COX proportional hazards regression models showed risks of new-onset digestive carcinoma in the overweight and obesity groups were reduced compared with normal BMI group (HR=0.57,0.42,95％CI:0.38-0.84,0.23-0.79,P＜0.05) in the esophageal cancer model.Risks of new-onset digestive carcinoma in the overweight group were reduced compared with normal BMI group (HR=0.72,95％CI:0.55-0.93,P＜0.05) and risk of new-onset digestive carcinoma in the obesity group was not affected (HR=1.10,95％CI:0.82-1.47,P＞0.05) in the liver cancer model.Conclusions Participants in the overweight group have the lowest incidence of digestive carcinoma,especially in the esophageal cancer and liver cancer model.Incidence of digestive carcinoma is the lowest with BMI as 25-27 kg/m2.

Background: Microsporum canis is a zoonotic disease that can cause dermatophytosis in animals and humans. Objectives: In clinical practice, ketoconazole (KTZ) and other imidazole drugs are commonly used to treat M. canis infection, but its molecular mechanism is not completely understood.The antifungal mechanism of KTZ needs to be studied in detail. Methods: In this study, one strain of fungi was isolated from a canine suffering with clinical dermatosis and confirmed as M. canis by morphological observation and sequencing analysis.The clinically isolated M. canis was treated with KTZ and transcriptome sequencing was performed to identify differentially expressed genes in M. canis exposed to KTZ compared with those unexposed thereto. Results: At half-inhibitory concentration (½MIC), compared with the control group, 453 genes were significantly up-regulated and 326 genes were significantly down-regulated (p < 0.05). Quantitative reverse transcription polymerase chain reaction analysis verified the transcriptome results of RNA sequencing. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the 3 pathways of RNA polymerase, steroid biosynthesis, and ribosome biogenesis in eukaryotes are closely related to the antifungal mechanism of KTZ. Conclusions The results indicated that KTZ may change cell membrane permeability, destroy the cell wall, and inhibit mitosis and transcriptional regulation through CYP51, SQL, ERG6, ATM, ABCB1, SC, KER33, RPA1, and RNP genes in the 3 pathways. This study provides a new theoretical basis for the effective control of M. canis infection and the effect of KTZ on fungi.

Objective To explore the predictive value of serum uric acid on new-onset cholelithiasis.Methods The retrospective cohort study was conducted.The data of 97 469 subjects who participated health examination at the Kailuan General Hospital Affiliated to the North China University of Science and Technology,Kailuan Linxi Hospital,Kailuan Zhaogezhuang Hospital,Kailuan Tangjiazhuang Hospital,Kailuan Fan'gezhuang Hospital,Kailuan Lyujiatuo Hospital,Kailuan Jinggezhuang Hospital,Kailuan Linnancang Hospital,Kailuan Qianjiaying Hospital,Kailuan Majiagou Hospital and Kailuan Branch Hospital from June 2006 to December 2015 were collected.Epidemiological investigation,anthropometric parameters and biochemical indicators were collected.All the subjects were allocated into 4 groups according to squartiles of serum uric acid:24 140 with serum uric acid ＜232 μmol/L in the Q1 group,24 473 with 232 μmol/L≤ serum uric acid ＜282 μmol/L in the Q2 group,24 382 with 282 μmol/L≤ serum uric acid ＜338 μmol/L in the Q3 group and 24 474 with serum uric acid ≥ 338 μmol/L in the Q4 group.Observation indicators:(1) comparisons of clinical characteristics among the 4 groups;(2) incidence of cholelithiasis in the 4 groups;(3) effects of serum uric acid on the new-onset cholelithiasis:① the dose-response relationship between serum uric acid and the risk of cholelithiasis,② comparisons of the fitting degree of serum uric acid on the cholelithiasis model,③ effects of different serum uric acid levels on incidence of cholelithiasis after stratification by sex,④ serum uric acid of different gender on the boxplots,⑤ effects of different serum uric acid levels on the incidence of cholelithiasis after stratification by age.Measurement data with normal distribution were expressed as (x)±s,and comparisons among groups were analyzed using the one-way ANOVA.Measurement data with skewed distribution is expressed by M (Q),and comparisons among groups were analyzed using the nonparametric Krustal-willis test.Count data were represented by percentage,and comparisons among groups were analyzed using chi-square test.The incidences of cholethiasis in 4 groups of different serum uric acid were calculated by person-year incidence.Restrictive cubic spline regression was used to calculate the dose-response relation between the continuous variable and the risks of new-onset cholelithiasis and 95％ confidence interval (CI).COX regression model was used to analyze the hazard ratio (HR) and 95％ CI of different serum uric acid levels on new-onset cholelithiasis.Likelihood ratio test and akaike information criterion (AIC) were used to calculate the fitting degree of serum uric acid on new-onset cholelithiasis model.Boxplots were used to describe serum uric acid in different genders.Results (1) comparisons of clinical characteristics among the 4 groups:sex (male),age,body mass index (BMI),systolic pressure,diastolic pressure,fasting plasma glucose (FPG),total cholesterol (TC),triglyceride (TG),high sensitive C-reactive protein,diabetes,hypertension,smoking,drinking and physical exercise were 15 162,(50± 11) years,(24±3)kg/m2,(123±21)mmHg (1 mmHg=0.133 kPa),(82± 12)mmHg,(5.6±2.0) mmol/L,(4.8±1.2) mmol/L,1.14 mmol/L (range,0.81-1.63 mmol/L),0.70 mmol/L (range,0.23-2.23 mmol/L),2 537,9 415,4575,2380,2 649 in the Q1 group,19 079,(51±12) years,(25±3)kg/m2,(130±21)mmHg,(83±12) mmHg,(5.5 ± 1.7) mmol/L,(4.9 ± 1.2) mmol/L,1.20 mmol/L (range,0.86-1.76 mmol/L),0.71 mmol/L (range,0.28-1.98 mmol/L),2 287,10 124,6 918,3 649,3 288 in the Q2 group,21 132,(52±13)years,(25±3)kg/m2,(132±21)mmHg,(84±12)mmHg,(5.5±1.6)mmol/L,(5.0±1.2) mmol/L,1.29 mmol/L (range,0.91-1.94 mmol/L),0.80 mmol/L (range,0.30-2.06 mmol/L),2 027,10 755,8 259,4 730,3 958 in the Q3 group,22 651,(53± 14) years,(26± 3) kg/m2,(134± 21) mmHg,(85±12)mmHg,(5.4±1.5)mmol/L,(5.1±1.2)mmol/L,1.54 mmol/L (range,1.05-2.35 mmol/L),1.02 mmol/L (range,0.43-2.50 mmol/L),1 981,12 082,9 562,6 209,4 758 in the Q4 group,respectively,with statistically significant differences among the 4 groups (x2 =7 624.63,F=279.93,961.91,330.84,271.40,38.25,353.18,H =3 406.30,912.23,x2 =108.15,590.49,2567.07,2 209.21,760.15,P＜0.05).(2)Incidence of cholelithiasis in the 4 groups:97 469 participants were followed up for 592 922 person-year,4 270 participants had new-onset cholelithiasis,with a total person-year incidence of 7.20 thousand person / year.The person-year incidence were respectively 6.34 (971/153 205 * 1 000),6.91 (1 034/149 686 * 1 000),7.44 (1 090/146 549 * 1 000),8.19 (1 175/143 482 * 1 000) thousand person / year in Q1,Q2,Q3 and Q4 group.(3) Effects of serum uric acid on the new-onset cholelithiasis.① The dose-response relationship between serum uric acid and the risk of cholelithiasis:restricted cubic spline regression showed a linear relationship between continuous serum uric acid,logarithmic transformated serum uric acid and the risk of cholelithiasis (x2 =11.74,8.01,P＜0.05).② Comparisons of the fitting degree of serum uric acid on the cholelithiasis model:adjusted for sex,age,BMI,TC,TG,diabetes,hypertension,smoking,drinking and physical exercise,risks of new-onset cholelithiasis increased in Q3 and Q4 groups compared with Q1 group (HR=1.10,1.12,95％CI:1.01-1.20,1.03-1.23,P＜0.05).The-2Log L and AIC value of multivariate model,serum uric acid+multivariate model were 92 532.39,92 550.39 and 92 525.35,92 549.35,respectively,with a statistically significant difference (x2=7.04,P ＜ 0.05).③ Effects of different serum uric acid levels on incidence of cholelithiasis after stratification by sex:in female participants,adjusted for age,BMI,TC,TG,diabetes,hypertension,smoking,drinking and physical exercise,risk of new-onset cholelithiasis in Q1 group was not statistically significant different from that in Q2,Q3,Q4 group (HR=1.06,1.15,1.09,95％CI:0.88-1.28,0.93-1.34,0.91-1.31,P＞0.05).In male participants,adjusted for age,BMI,TC,TG,diabetes,hypertension,smoking,drinking and physical exercise,risks of new-onset cholelithiasis in Q2,Q3 and Q4 groups were increased compared with Q1 group (HR=1.17,1.24,1.30,95％CI:1.06-1.30,1.12-1.37,1.18-1.44,P＜0.05).④ Serum uric acid of different gender on the boxplots:in female participants,the level of serum uric acid was (249 ± 61) μmol/L,(235±50)μmol/L,(231±56) μmol/L,(250±66) μmol/L,(266±75) μmol/L,(281±81) μmol/L,(298±76) μmol/L,(379±86)μmol/L respectively in the group of 18-27 years old,28-37 years old,38-47 years old,48-57 years old,58-67 years old,68-77 years old,78-87 years old,88-97 years old after stratified by 10 years old.In male participants,the level of serum uric acid was respectively (310±76)μmol/L,(298 ±75) μmol/L,(298±74) μmol/L,(294±74) μmol/L,(302±78) μmol/L,(311 ±80) μmol/L,(322±80) μmol/Land (330±75)μmol/L after participants stratified by 10 years old.⑤ Effects of different serum uric acid levels on the incidence of cholelithiasis after stratification by age:in participants with age ≤ 60 years old,adjusted for sex,BMI,TC,TG,diabetes,hypertension,smoking,drinking and physical exercise,risk of new-onset cholelithiasis in the Q2 and Q3 groups were not increased compared with Q1 group (HR=1.05,1.10,95％CI:0.94-1.17,0.99-1.23,P＞0.05),however,risk of new-onset cholelithiasis was increased in the Q4 group (HR =1.15,95％CI:1.02-1.28,P＜0.05).In participants with age ＞ 60 years old,adjusted for sex,BMI,TC,TG,diabetes,hypertension,smoking,drinking and physical exercise,risk of new-onset cholelithiasis in the Q2 groups was not increased compared with Q1 group (HR=1.16,95％CI:0.99-1.36,P＞0.05),however,risks of new-onset cholelithiasis were increased in the Q3 and Q4 groups (HR =1.19,1.21,95％CI:1.02-1.40,1.04-1.41,P＜ 0.05).Conclusion Elevated serum uric acid is an independent risk factor for the new-onset cholelithiasis.

Objective To investigate the safety,feasibility and clinical application effect of upper arm totally implantable venous access port (TIVAP) inserted by the combination of oncologists and nurses in patients with tumor.Methods A total of 34 patients,who needed long-term transfusion treatment,were included in this study with upper arm TIVAP from March 2017 and December 2017.There were 20 males and 14 females.The median age was 63 (35 ～ 83) years.Upper arm TIVAP was implanted by both doctors and nurses into the patients with tumor,and the TIVAP related success rate,complications and patients satisfaction were recorded.Results 34 patients all succeeded in TIVAP implantation with the operation success rate of 100％.The average operation time was about 40 minutes (30 to 60 minutes) from the disinfecting cloth to the end of the suture.The operations of all patients were successful.After the operation two patients died of cancer progression,one patient had soft tissue infection around capsular bag,None of the patients had other complications such as blocked infusion,catheter shift,port reversal,and so on,and the incidence of complication was 2.94％ (1/34).Conclusions Upper arm TIVAP has the advantages of safe puncture,shorter operation time,few intra-operative and post-operative complications and higher feasibility for operation by both oncologist and nurse,which can supplement the limitations and deficiencies of the chest wall port and PICC in a certain extent,therefore is a good choice for clinical application.

【Objective】 To investigate the feasibility of prostatic exosomal protein (PSEP) detection kit in the diagnosis of histological prostatitis (HP) in patients with benign prostatic hyperplasia (BPH), and to explore the correlation between PSEP and other clinical parameters. 【Methods】 A total of 104 patients with BPH or BPH plus HP treated during Nov.2021 and Nov.2022 were involved. The patients were instructed to fill out the International Prostate Symptom Score (IPSS) scale independently before surgery. Clinical data such as prostate volume, residual urine volume, free prostate specific antigen (fPSA), total prostate specific antigen (tPSA), and fPSA/tPSA were collected. Preoperative midstream morning urine was collected for PSEP detection. 【Results】 The sensitivity and specificity of PSEP in the diagnosis of BPH were 93.51% and 70.37%, respectively, which were highly consistent with the postoperative pathological diagnosis results (Kappa=0.663). Serum PSEP level was positively correlated with tPSA level (r=0.242, P=0.040). 【Conclusion】 PSEP has a high clinical diagnostic value in the diagnosis of HP, which can provide a reliable basis for the diagnosis of HP in BPH patients and improve the diagnosis rate.

By reviewing the historical materia medica， medical books and modern literature， this paper has systematically sorted out and verified the name， origin， quality and other aspects of Ophicalcitum. After herbal textual research， it is shown that before the Qing dynasty， the mineral medicine was mostly recorded in the name of Huarushi， but now it is called Huaruishi， and there is another mixed name Baiyunshi. The light white spots described in the historical materia medica are consistent with the characteristics of marble with sparkling star-like luster， combined with the color like sulfur， color are green， black spots and other serpentine features， it is deduced that it is serpentine marble， consistent with the present-day Ophicalcitum， and Ophicalcitum in the Song dynasty has a high content of serpentine. The main producing areas are Henan， Shaanxi， Shanxi and Sichuan， Jiangsu， Zhejiang， Hebei and other places are also available. Successive generations of materia medica on the quality evaluation of Ophicalcitum is less， the modern to neat and firm in the texture， sandwiched with yellow-green mottled for the best. Ophicalcitum is acidic， astringent and neutral in nature， belonging to the liver meridian， with the efficacy of treatment of gold sores and blood flow， internal leakage of cataracts， dropping afterbirth， now describing its efficacy as removing blood stasis and stopping bleeding. In ancient times， the earliest processing method was burning， followed by calcination by sulphur， calcination， quenching with vinegar and other methods. In modern times， it has been simplified to open calcination， processing with vinegar and the addition of water quenching. The gravimetric method and ethylenediaminetetraacetic acid titration were used to detect the contents of CO₃^2- and CaCO₃ in Ophicalcitum， respectively， and it was found that the gap in CaCO₃ content among commercially available products was wide， and the content of CaCO₃ in sample S13 and sample S18 was the same， but their compositions were different， and according to the contents of CO₃^2- and CaCO₃， the dolomite and calcite contents could be calculated， of which the higher the calcite content the more obvious the sparkling star-like luster. Raman spectroscopy and X-ray diffraction（XRD） were used to detect the physical phase composition of the powder of the samples， and Raman spectroscopy was used for the rapid non-destructive testing of the striped part， which showed that Ophicalcitum was mainly composed of dolomite， calcite， serpentine， olivine and pyroxene， with serpentine dominanting the striped part. In summary， the 2020 edition of Chinese Pharmacopoeia stipulates that the content of CaCO₃ in Ophicalcitum is not less than 40%， which is difficult to control its quality， and it is suggested to increase the detection of CO₃^2- content. This study can provide a scientific basis for the traceability of Ophicalcitum and better guide the clinical medication and rational utilization of resources.

A series of chemotherapeutic drugs that induce DNA damage, such as cisplatin (DDP), are standard clinical treatments for ovarian cancer, testicular cancer, and other diseases that lack effective targeted drug therapy. Drug resistance is one of the main factors limiting their application. Sensitizers can overcome the drug resistance of tumor cells, thereby enhancing the antitumor activity of chemotherapeutic drugs. In this study, we aimed to identify marketable drugs that could be potential chemotherapy sensitizers and explore the underlying mechanisms. We found that the alcohol withdrawal drug disulfiram (DSF) could significantly enhance the antitumor activity of DDP. JC-1 staining, propidium iodide (PI) staining, and western blotting confirmed that the combination of DSF and DDP could enhance the apoptosis of tumor cells. Subsequent RNA sequencing combined with Gene Set Enrichment Analysis (GSEA) pathway enrichment analysis and cell biology studies such as immunofluorescence suggested an underlying mechanism: DSF makes cells more vulnerable to DNA damage by inhibiting the Fanconi anemia (FA) repair pathway, exerting a sensitizing effect to DNA damaging agents including platinum chemotherapy drugs. Thus, our study illustrated the potential mechanism of action of DSF in enhancing the antitumor effect of DDP. This might provide an effective and safe solution for combating DDP resistance in clinical treatment.
Female ; Male ; Humans ; Cisplatin/pharmacology* ; Disulfiram/pharmacology* ; Testicular Neoplasms/drug therapy* ; Fanconi Anemia/drug therapy* ; Alcoholism/drug therapy* ; Drug Resistance, Neoplasm ; Cell Line, Tumor ; Substance Withdrawal Syndrome/drug therapy* ; Apoptosis ; Antineoplastic Agents/therapeutic use* ; Cell Proliferation

Adipose tissue is a promising target for treating obesity and metabolic diseases. However, pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization, especially in obese subjects. We have previously shown that during cold exposure, connexin43 (Cx43) gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple cells. We reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose tissue. Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic efficacy of the β ₃-adrenergic receptor agonist Mirabegron and FGF21. Additionally, combing those molecules with the Cx43 gap junction channel activator danegaptide shows a similar enhanced efficacy. In light of these findings, we propose a model in which connecting adipocytes via Cx43 gap junction channels primes adipose tissue to pharmacological agents designed to engage it. Thus, Cx43 gap junction activators hold great potential for combination with additional agents targeting adipose tissue.