Humans ; Adolescent ; Acne Vulgaris/therapy* ; Skin Care ; Surveys and Questionnaires ; Cognition ; China ; Skin

Objective To explore the values of peripheral blood inflammatory parameters in predicting the efficacy of immunotherapy and prognosis after immunotherapy in patients with proficient mismatch repair(pMMR)metastatic colorectal cancer(mCRC).Methods The clinical data of 44 inoperable pMMR mCRC patients who received immunotherapy in Zhongshan Hospital(Xiamen Branch),Fudan University from February 2019 to February 2024 were analyzed retrospectively.The pre-treatment peripheral blood inflammatory parameters such as neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),pan-immune-inflammation value(PIV)and systemic immune-inflammation index(SⅡ)were collected.The receiver operating characteristic(ROC)curves were drawn to evaluate the predictive value of inflammatory parameters on the efficacy of immunotherapy.The effects of inflammatory parameters on the prognosis after immunotherapy were evaluated according to the optimal cutoff value obtained by ROC curves.Univariate and multivariate Cox proportional hazard models were used to analyze the risk factors affecting the prognosis of patients with pMMR mCRC.Results NLR,PLR,PIV and SⅡ had some predictive values on the efficacy of immunotherapy in inoperable pMMR mCRC patients,and SⅡ was superior to NLR,PLR and PIV.Compared with NLR≥3.36 group,PLR ≥223.54 group and SⅡ≥769.29 group,the disease control rate(DCR)after immunotherapy was higher in the NLR＜3.36 group,PLR＜223.54 group and SⅡ＜769.29 group(P＜0.01);the progression-free survival(PFS)was longer in the NLR＜3.36 group and SⅡ＜769.29 group(P＜0.05),and the overall survival(OS)was longer in the NLR＜3.36 group,PLR＜223.54 group and SⅡ＜769.29 group(P＜0.05).The univariate analysis showed that Eastern Cooperative Oncology Group Performance Status(ECOG PS)score,NLR and SⅡ were risk factors for the PFS of patients after immunotherapy;the liver metastasis,bone metastasis,NLR,PLR and SⅡ were risk factors for the OS of patients after immunotherapy(P＜0.05).The multivariate Cox proportional risk model analysis showed that SⅡ≥769.29 was an independent risk factor for the prognosis of pMMR mCRC patients after immunotherapy(P＜0.001).Conclusions Peripheral blood NLR,PLR,PIV and SⅡ could predict the efficacy of immunotherapy in pMMR mCRC patients and SⅡ is superior to NLR,PLR and PIV,and SⅡ≥ 769.29 has independent predictive value for poor prognosis in pMMR mCRC patients receiving immunotherapy.

Aim To provide references for clinical trials dose and rational drug use by evaluating mitochondrial toxicity of bentysrepinine on HepG2 cells.Methods Mitochondrial toxicity of bentysrepinine on HepG2 cells was cmomprehensively evaluated by measuring proliferation inhibition rate, lactic acid content in culture supernatant, reactive oxygen species(ROS) content, mitochondrial membrane potential (MMP) variation and the activity of mitochondrial respiratory chain complex enzymes Ⅰ to Ⅳ.Results The half inhibitory concentration of bentysrepinine of HepG2 cells was 359 μmol·L-1.Compared with the control group, bentysrepinine could reduce the MMP, raise the level of lactic acid, increase the content of ROS and lower the activity of mitochondrial respiratory chain complex enzymes Ⅰ to Ⅲ with the concentration of 400 μmol·L-1(196 mg·L-1), showing an obvious mitochondrial toxicity.Compared with lamivudine and adefovir dipivoxil, bentysrepinine exerted no influence on indexes above with the same concentration 100 μmol·L-1.Conclusions Bentysrepinine shows an obvious mitochondrial toxicity on HepG2 cells with the concentration of 400 μmol·L-1.This mitochondrial toxicity is not presented with the concentration of 200 μmol·L-1.It shows that the safety range of bentysrepinine about mitochondrial toxicity is relatively wide.The test plays a guiding role in clinical trial dose design as well as clinical treatment.

Objective To evaluate the diagnostic value of gastrin?17( G?17) and pepsinogen( PG) for gastric cancer. Methods A multicenter cross?sectional study of patients with continuous stomach discomfort from four centers including Changhai Hospital Affiliated to Second Military Medical University, the First Hospital Affiliated to Anhui Medical University, Qinghai Provincial People′s Hospital and the First Hospital Affiliated to Zhejiang University of Chinese Medicine from May 2014 to September 2015 was conducted. Before gastroscopy, fasting serum gatrin?17 and pepsinogen were analyzed by enzyme?linked immunosorbent assay(ELISA). The efficacy of G?17 and PG were evaluated according to endoscopic and pathological results. Results Based on the results of the pathological diagnosis, 1 122 cases were enrolled and divided into chronic atrophic gastritis group ( 548 cases ) , chronic non?atrophic gastritis group ( 370 cases), and gastric cancer group(204 cases). Serum G?17 and PGⅡ levels significantly increased(P<0?05) and PGR significantly decreased( P<0?05) in gastric cancer group compared with other groups. There was no significant difference in PGⅠlevel among three groups. The cut?off value of G?17 to diagnose gastric cancer was 7 pmol/L. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of G?17 for gastric cancer were 59?31%, 70?59%, 68?54%, 30?95% and 88?65% respectively. The cut?off value of PG Ⅰ/PG Ⅱ( PGR ) to diagnose gastric cancer was 7. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of PGR for gastric cancer were 41?18%, 83?01%, 75?40%, 35?00% and 86?39% respectively. The cut?off value of PGⅡto diagnose gastric cancer was 10 μg/L. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of PGⅡfor gastric cancer were 73?53%, 53?05%, 56?77%, 25?82% and 90?02% respectively. If G?17>7 pmol/L and PGR<7 was regarded as the cut?off value of diagnosis of gastric cancer, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 25?00%, 91?29%, 79?23%, 38?93%and 84?56%respectively. If G?17>7 pmol/L and PGⅡ>10μg/L was regarded as the cut?off value, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 48?04%, 79?74%, 73?98%, 34?51% and 87?35% respectively. If PGR<7 and PGⅡ>10 μg/L was regarded as the cut?off value, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 33?82%, 84?86%, 75?58%, 33?17% and 85?23% respectively. Based on logistic regression analysis of the independent variables of high serum G?17 value(>7 pmol/L), low serum PGR value(<7) and high serum PGⅡvalue(>10 μg/L), their OR value were 2?592, 2?237 and 1?864 respectively, and high serum G?17 value showed the highest risk of gastric cancer. Conclusion High serum G?17 and PGⅡ, low PGR are indicators of gastric cancer. Combination of G?17 and PGR has the best diagnostic value for gastric cacer. Gastric cancer can be screened in large scale by combining G?17 and PGR in order to improve the early diagnostic rate of gastric cancer and reduce the mortality of gastric cancer in our country.

Objective To observe the preventive and therapeutic effect of Baimai Ointment on stoke,and explore the principle of promoting blood circulation and removing blood stasis.Method By dermal administration,the crude drug contents of Baimai Ointment given to rats were 0.075,0.150,and 0.300 g/kg respectively.Focal cerebral ischemic model was induced by the middle cerebral artery occlusion (MCAO),and the preventive and therapeutic effect of Baimai Ointment was evaluated.The degree of hematoma absorption in rats was measured to observe the effect on promoting blood circulation and removing blood stasis of Baimai Ointmnent.The acute blood stasis model and carotid thrombosis model were established in rats to study the effects on blood viscosity and thrombosis time.Results Baimai Ointment had no significant prevent effect on stroke in rats.It effectively improved behavior coordination in stroke model rats.It also significantly decreased the area of hematoma on rats,speeded up the repairment of local demage.After administration of Baimai Ointment,blood viscosity of blood stasis model rats was obviously decreased,while thrombosis time was effectively prolonged on carotid thrombosis model.Conclusion Baimai Ointment can significantly improve the behavior coordination in stroke model rats,plays a significant role in treatment,but no significant preventive effect,a preliminary study shows that the possible therapeutic principles may be promoting blood circulation and removing blood stasis.

The adverse reactions caused by traditional Chinese medicine have occurred frequently, but there is a lack of scientific,objective and standardized methods for safety evaluation of traditional Chinese medicine.In the process of preclinical evaluation of traditional Chinese medicine, it is imperative to form a set of scientific, standardized and feasible evaluation system of modem Chinese herbal drug.We established the preclinical safety evaluation system of modem Chinese herbal drug including the quality control system of samples for the preclinical safety evaluation, the toxicity evaluation system of modem Chinese herbal drug and its preparation and the evaluation management system, and standardized each research link of preclinical evaluation of traditional Chinese medicine.Whether from protecting patients' health and increasing the safety of clinical medication, or from enriching and improving traditional Chinese medicine science, developing traditional Chinese medicine and promoting mutual connection of traditional Chinese medicine and international medicine, it has important instructional significance and application value.

Objective To determine the principle of applying lysogenicity in Phage-Biotyping Scheme developed for the subtyping of O1 E1 Tor Vibrio cholerae strains.Methods 118 V.cholerae strains including 76 E1 Tor strains,8 classical strains and 34 serogroup O139 were selected to analyze the lysogenicity and sensitivity to lysogenic phage 919TP as described in the Manuals of cholera prevention and control,the genes of this phage were also determined among the genome sequences of these strains and the phages produced by them.Results All O1 E1Tor Vibrio cholerae 19 strains that produced positive results in lysogenicity,had the lysogenic K139 phage in genome and could both resist to lysogenic phage 919TP and release the K139 family phage.All the O1 E1Tor Vibrio cholerae 22 strains that produced positive results in sensitivity to the lysogenic phage,had no K139 family phage genes and got negative results in lysogenicity.However,the phages of this family were not released from 6 classical strains with positive lysogenicity result.Five serogroup O139 strains were detected releasing temperate phages K139 without the sensitivity to phage 919TP.Conclusions Applying the lysogenicity in Phage-Biotyping Scheme for subtyping O1 E1 Tor Vibrio cholerae strains is based on the ability to produce lysogenic bacteriophage K139.The index of "sensitivity to the lysogenic phage" was also associated with this ability.

Objective To investigate the relationship between serum levels of homocysteine (HCy) and adiponectin (APN) in patients with type 2 diabetes mellitus(T2DM).Methods 65 patients with T2DM (diabetes mellitus group) and 25 healthy controls (control group) matched in the age and sex were recruited in the study.Serum HCy,APN,fasting plasma glucose (FPG),fasting insulin (FINS),total cholesterol (TC) and triglyceride (TG) were simultaneously measured.The homeostatic model assessment for insulin resistance(HOMA-IR) was calculated according to FPG and FINS.All the serum indicators were compared between the two groups.Results Serum level of HCy in T2DM group was (15.74 ± 2.76) μmol/L,which was significantly higher than (6.98 ± 1.94) μmol/L in the healthy control group (t =16.88,P ＜ 0.01).The serum level of APN in T2DM group was (8.14 ± 2.70) mg/L,which was significantly lower than (16.10 ± 1.93)mg/L in the healthy control group (t =13.44,P ＜ 0.01).Serum levels of FPG,HOMA-IR,TC,TG in T2DM group were significantly higher than those in the healthy control group (t =10.62,17.49,6.30,7.52,P ＜ 0.05).Serum level of APN in HCy ≥ 15μmol/L group was significantly decreased compared with HCy ＜ 15μmol/L group.Serum level of HCy was negatively correlated with APN in T2DM group after the influence of FPG,HOMA-IR,TG,TC were corrected in the partial correlation analysis.Conclusion In T2DM group,serum level of HCy was increased,but serum level of APN was decreased,serum HCy was negatively correlated with APN,higher serum level of HCy and lower serum level of APN are related with the process of insulin resistance and T2DM.

OBJECTlVE To study the Iong term toxicity of vinoreIbine tartrate(NVB)on rat immune and hematopoietic systems pathoIogicaIIy. METHODS SD Rats were randomIy divided into 4 groups:normaI controI group and NVB 5.0,10.0,and 20.0 mg·m-2 groups,each group containing 6 maIe and femaIe rats. The rats in NBV groups were administered different concentrations of NVB by intravenous drip on the 1st and 8th days,21 da cycIe,for 4 cycIes. On the 14th day after the Iast administration, white bIood ceIIs(WBC),neutrophiI(Neut),Iymphocytes(Lym),red bIood ceIIs(RBC)and reticuIo-cyte‰(RET‰)were detected by ADVIA2120 hematoIogy anaIyzer. Thymus,sternum marrow,spIeen and mesenteric Iymph nodes were observed by histopathoIogicaI examination. The thymus and spIeen were preciseIy weighed to obtain the reIative organ coefficients. Bone marrow smears were made for counting and cIassification. RESULTS Compared with normaI controI group,WBC,Neut,Lym,RBC and RET% of peripheraI bIood of NVB 5,10 and 20 mg·m-2 groups were decreased(P﹤0.05,P﹤0.01). The Neut vaIue of maIe rats was(2.35±0.56)×109·L-1 in normaI controI group,but was reduced to (1.66±0.44),(0.67±0.22)and(0.20±0.02)×109·L-1(P﹤0.05,P﹤0.01)in NVB 5,10 and 20 mg·m-2 groups. The Neut vaIue of femaIe rats was(1.26± 0.27)× 109 L-1 in normaI controI group,but was reduced to(1.14±0.56),(0.47±0.13)and(0.21±0.08)×109 L-1(P﹤0.05,P﹤0.01)in NVB 5,10 and 20 mg·m-2 groups. The resuIts of counting and cIassification of bone marrow smears showed that the myeIoid ceII ratio decreased(P﹤0.05,P﹤0.01). The myeIoid ceII ratio of maIe rats was(42.7±6.1)% in normaI controI group,but was reduced to(28.8±5.3)%,(22.0±3.2)% and(18.9±3.9)% in NVB 5,10 and 20 mg·m-2 groups. The myeIoid ceII ratio of femaIe rats in normaI controI group was(35.4±3.0)%, but was reduced to(31.2±4.7)%,(22.9±6.7)% and(20.8±4.2)% in NVB 5,10 and 20 mg·m-2 groups. The thymus coefficient was reduced(P﹤0.05,P﹤0.01). The thymus coefficient of maIe rats in normaI controI group was 0.36±0.04,but was reduced to 0.31±0.06,0.18±0.03 and 0.08±0.01 in NVB 5,10 and 20 mg·m-2 groups. The thymus coefficient of femaIe rats in normaI controI group was 0.29±0.06,but was reduced to 0.25±0.06,0.19±0.06 and 0.07±0.01 in NVB 5,10 and 20 mg·m-2 groups. Histopatho-IogicaI examination showed that thymus was atrophiedand bone marrow was suppressed. SpIeen com-pensatory extrameduIIary hematopoietic ceIIs were increased in NVB 5.0,10.0 and 20.0 mg·m-2 groups (maIe and femaIe)to different degrees,but the mesenteric Iymph nodes of NVB groups showed no sig-nificant pathoIogicaI changes. CONCLUSlON NVB has immune and hematopoietic toxicity on SD rats, as is showed by thymic atrophy and bone marrow suppression.

The concept and framework of network toxicology and network toxicology of traditional Chinese medicine has been proposed in this paper. The related tools and technologies have been briefly introduced, and the prospects for network toxicology of traditional Chinese medicine are forecasted.
Animals ; Drug Interactions ; Drugs, Chinese Herbal ; analysis ; toxicity ; Humans ; Medicine, Chinese Traditional