OBJECTIVE: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism. METHODS: B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. RESULTS: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. CONCLUSIONS Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.
Mice ; Animals ; Alocasia/metabolism* ; MAP Kinase Signaling System ; Caspase 3/metabolism* ; Apoptosis ; RNA, Messenger/metabolism*

Background and purpose:Follow-up data of 6 737 patients undergoing surgery for gastric cancer were collected based on hospital registration,and the 1-,3-and 5-years observed overall survival(OS)rates and disease-free survival(DFS)rates were analyzed to provide real-world research evidence for the prevention and control of gastric cancer and policy making in China.Methods:A total of 6 737 gastric cancer patients who underwent surgical treatment at Fudan University Shanghai Cancer center from 2015 to 2020 were included in this study.Clinical information and the follow-up endpoint data were collected through medical records review,telephone visits and death registry data linkage.The last follow-up date was November 30,2023.Kaplan-Meier method was applied in evaluating the 1-,3-and 5-year OS rate and DFS rate,and survival data were described by different subgroups including age group,gender,treatment period,tumor staging,and pathological characteristics.Results:With a median follow-up time of 50.99 months,the 5-year OS rate of surgically resected gastric cancer patients was 70.37%,and 5-year DFS rate in Ⅰ-Ⅲ stage cases was 69.46%.The 5-year OS rates of stage Ⅰ,Ⅱ,Ⅲ and Ⅳ were 94.32%,82.56%,51.01%and 23.97%,respectively.The differences in survival among patients with different age,tumor location,gross classification,Borrmann classification and Laurence classification were significant.Conclusion:Staging is an important factor directly affecting the survival of gastric cancer patients.Screening and early diagnosis and treatment in large population,especially high-risk group,should be strengthened to further improve the patients'survival.

Objective:To explore the value of salivary gland imaging based on deep learning and Delta radiomics in assessing salivary gland injury after 131I treatment in post-thyroidectomy thyroid cancer patients. Methods:A retrospective analysis on 223 patients (46 males, 177 females, age(47.7±14.0) years ) with papillary thyroid cancer, who underwent total thyroidectomy and 131I treatment in Affiliated Hospital of Guilin Medical University between December 2019 and January 2022, was conducted. All patients underwent salivary gland 99Tc mO 4- imaging before and after 131I therapy. The patients were categorized according to salivary gland function based on 99Tc mO 4- imaging results (normal salivary gland vs salivary gland injury), and divided into training and test sets in a ratio of 7∶3. A ResNet-34 neural network model was trained using images at the time of maximum salivary gland radioactivity and those based on background radioactivity counts for structured image feature data. The Delta radiomics approach was then used to subtract the image feature values of the two periods, followed by feature selection through t-test, correlation analysis, and the least absolute shrinkage and selection operator( LASSO) algorithm, to develop logistic regression (LR), support vector machine (SVM), and K-nearest neighbor (KNN) predictive models. The diagnostic performance of 3 models for salivary gland function on the test set was compared with that of the manual interpretation. The AUCs of the 3 models on the test set were compared (Delong test). Results:Among the 67 cases of the test set, the diagnostic accuracy of 3 physicians were 89.6%(60/67), 83.6%(56/67), and 82.1%(55/67) respectively, with the time required for diagnosis of 56, 74 and 55 min, respectively. The accuracies of LR, SVM, and KNN models were 91.0%(61/67), 86.6%(58/67), and 82.1%(55/67), with the required times of 12.5, 15.3 and 17.9 s, respectively. All 3 radiomics models demonstrated good classification and predictive capabilities, with AUC values for the training set of 0.972, 0.965, and 0.943, and for the test set of 0.954, 0.913, and 0.791, respectively. There were no significant differences among the AUC values for the test set ( z values: 0.72, 1.18, 1.82, all P>0.05). Conclusion:The models based on deep learning and Delta radiomics possess high predictive value in assessing salivary gland injury following 131I treatment after surgery in patients with thyroid cancer.

Diabetic kidney disease （DKD） is the main cause of end-stage renal disease. Its high prevalence， mortality rate， and medical cost bring a heavy economic burden to society and families， and DKD has become one of the most important public health problems. Intestinal microecology is the most important and complex micro-ecosystem in the human body， which is involved in important life activities such as material and energy metabolism， immune system regulation， and signal transduction， thereby maintaining the dynamic balance of the human internal environment. The dynamic balance between the intestinal microecology and the body is essentially a Yin-Yang balance. Once this balance is broken， intestinal microbiota imbalance， intestinal mucosal barrier damage， immune dysfunction， and reduction of metabolite short-chain fatty acids （SCFAs） will occur， which play an important role in the progression of DKD. From the perspective of the Yin-Yang theory of traditional Chinese medicine （TCM）， the imbalance of intestinal microecology in DKD is equivalent to the excessive or insufficient constraint of Yin and Yang， or Yin deficiency affecting Yang， or Yang deficiency affecting Yin， or waning and waxing of Yin and Yang. For different pathogenesis changes， "Yin disease treated through Yang"， "treating Yin for Yang"， or "treating Yang for Yin" methods are adopted to regulate intestinal microbiota， inhibit immune inflammation， protect intestinal mucosal barrier， and increase SCFAs through TCM， thereby reconciling Yin and Yang to achieve the condition where "Yin is at peace and Yang is compact". Based on the Yin-Yang theory， this paper intended to interpret the scientific connotation of TCM in the treatment of DKD with intestinal microecology as the target and TCM in the treatment of DKD by regulating intestinal microecology as the breakthrough point to provide a novel insight for the occurrence and development of DKD and the mechanism of TCM.

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.

Purpose::Traumatic brain injury (TBI), currently a major global public health problem, imposes a significant economic burden on society and families. We aimed to quantify and predict the incidence and severity of TBI by analyzing its incidence, prevalence, and years lived with disability (YLDs). The epidemiological changes in TBI from 1990 to 2019 were described and updated to provide a reference for developing prevention, treatment, and incidence-reducing measures for TBI.Methods::A secondary analysis was performed on the incidence, prevalence, and YLDs of TBI by sex, age group, and region ( n =21,204 countries and territories) between 1990 and 2019 using the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Proportions in the age-standardized incidence rate due to underlying causes of TBI and proportions of minor and moderate or severe TBI were also reported. Results::In 2019, there were 27.16 million (95% uncertainty intervals ( UI): 23.36 -31.42) new cases of TBI worldwide, with age-standardized incidence and prevalence rates of 346 per 100,000 population (95% UI: 298 -401) and 599 per 100,000 population (95% UI: 573 -627), respectively. From 1990 to 2019, there were no significant trends in global age-standardized incidence (estimated annual percentage changes: -0.11%, 95% UI: -0.18% --0.04%) or prevalence (estimated annual percentage changes: 0.01%, 95% UI: -0.04% -0.06%). TBI caused 7.08 million (95% UI: 5.00 -9.59) YLDs in 2019, with age-standardized rates of 86.5 per 100,000 population (95% UI: 61.1 -117.2). In 2019, the countries with higher incidence rates were mainly distributed in Central Europe, Eastern Europe, and Australia. The 2019 global age-standardized incidence rate was higher in males than in females. The 2019 global incidence of moderate and severe TBI was 182.7 per 100,000 population, accounting for 52.8% of all TBI, with falls and road traffic injuries being the main causes in most regions. Conclusions::The incidence of moderate and severe TBI was slightly higher in 2019, and TBI still accounts for a significant portion of the global injury burden. The likelihood of moderate to severe TBI and the trend of major injury under each injury cause from 1990 to 2019 and the characteristics of injury mechanisms in each age group are presented, providing a basis for further research on injury causes in each age group and the future establishment of corresponding policies and protective measures.

Objective To observe the effect of Bushen Jianpi Prescription,a prescription with the actions of tonifying the kidney and strengthening the spleen,combined with short-term intensive insulin therapy on dedifferentiation of pancreatic beta-cells in patients with type 2 diabetes mellitus(T2DM)of spleen and kidney deficiency type.Methods Seventy patients with T2DM of spleen and kidney deficiency type were randomly divided into control group and observation group,with 35 cases in each group.The control group was treated with intensive insulin therapy,and the observation group was treated with Bushen Jianpi Prescription on the basis of treatment for the control group.The course of treatment lasted for 2 weeks.The changes of TCM syndrome score,and levels of blood glucose,serum high mobility group protein B1(HMGB1),interleukin 1β(IL-1β),tumor necrosis factor α(TNF-α)and the ratio of proinsulin to insulin(PI/I)in the two groups were observed before and after treatment.Results(1)During the treatment,one case in the control group and 2 cases in the observation group fell off.Eventually,34 cases in the control group and 33 cases in the observation group were included in the efficacy statistics.(2)After treatment,the scores of TCM syndromes in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the levels of fasting plasma glucose(FPG)and 2-hour postprandial plasma glucose(2hPG)in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the level of HMGB1 in the two groups was significantly lower than that before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the serum levels of inflammatory factors of IL-1β and TNF-α in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05).(6)After treatment,the PI/I ratio of the two groups was significantly lower than that before treatment(P＜0.05),and the decrease of the observation group was significantly superior to that of the control group(P＜0.05).Conclusion Bushen Jianpi Prescription combined with short-term intensive insulin therapy can effectively improve the islet function of patients with T2DM of spleen and kidney deficiency type.The mechanism may be related to the relief of high-glucose toxicity and the decrease of the inflammatory factor levels,thus to inhibit the dedifferentiation of pancreatic beta-cells.

Aim To investigate the mechanism of Banxia Baizhu Tianma Decoction(BBTD)in interfer-ing methamphetamine(MA)addiction using network pharmacology.Methods The mechanism of BBTD intervention in MA addiction was analyzed using net-work pharmacology,and MA-dependent SH-SY5Y cell model was further constructed to observe the effects of BBTD on cell model and PI3K-Akt pathway.Results A total of 88 active ingredients and 583 potential tar-gets of BBTD were screened.KEGG analysis showed that BBTD might intervene in MA addiction through PI3K-Akt,cAMP and other pathways.The molecular docking results showed that key active ingredients ex-hibited strong binding ability with core targets of PI3K-Akt pathway.In vitro experiments showed that MA-de-pendent model cells had shorter synapses,tended to be elliptical in morphology,had blurred cell boundaries,showed typical cell damage morphology,and had high intracellular expression of cAMP(P＜0.01)and low expression of 5-HT(P＜0.05).BBTD intervention could counteract the above morphology,cAMP,and 5-HT changes,suggesting that it had therapeutic effects on MA-dependent model cells.Western blot showed that MA modeling elevated the p-PI3K/PI3K(P＜0.05)and p-Akt/Akt(P＜0.01);BBTD inter-vention decreased their relative expression.Conclu-sions Gastrodin and other active ingredients in BBTD have therapeutic effects on MA addiction,and the mechanism may be related to regulation of PI3K-Akt pathway relevant targets.

Objective To explore the efficacy and safety of low-dose tirofiban in stent-assisted coil embolization(SAC)for ruptured intracranial aneurysms.Methods From April 2011 to September 2020,335 patients of ruptured intracranial aneurysms with subarachnoid hemorrhage(SAH)admitted in the First People's Hospital of Changzhou were retrospectively analyzed.All cases underwent stent-assisted coil embolization within 24-48 h and antiplatelet medications.The patients were divided into dual antibody group(89 cases)and tirofiban group(246 cases).Baseline and clinical data of all patients were collected for comparison between groups,including age,sex,hypertension,diabetes mellitus,Hunt-Hess grade at admission,modified Fisher scale score at admission,aneurysm diameter(＞5 mm,≤5 mm),aneurysm location(anterior circulation,posterior circulation),postoperative acute hydrocephalus or intraventricular hemorrhage,postoperative complete embolization rate of ruptured aneurysm.All patients with ruptured intracranial aneurysm with SAH were confirmed by emergency cerebral CT scan after admission.The Raymond grading criteria were used to evaluate the embolization effect after operation:grade Ⅰ refers to no development(complete embolization),grade Ⅱ refers to only aneurysm neck development(incomplete embolization),and grade Ⅲ refers to aneurysm body development,in which Raymond grading Ⅰ orⅡ indicates effective embolization.Tirofiban group:4.2 μg/kg tirofiban was intravenously injected after the coil was placed in the aneurysm lumen and the stent was released,followed by maintenance dose 0.07 μg/(kg·min)for 6-8 h,and aspirin 100 mg and clopidogrel 75 mg were given as sequential dual antiplatelet therapy 2 hours before the tirofiban infusion was stopped.Dual antiplatelet group:a loading dose of aspirin 300 mg and clopidogrel 300 mg was given at least 2 hours before stent implantation,and then transferred to aspirin 100 mg and clopidogrel 75 mg given on the second day after operation.All patients received aspirin(100mg/d)for 6 months and clopidogrel(75 mg/d)for 3 months after operation.The efficacy indicators,safety indicators,adverse events and other complications of the two groups were collected and compared.The efficacy indicators were the incidence of thrombotic events during operation and within 72 hours after operation.The safety indicators were the incidence of intraoperative and early postoperative intracranial hemorrhage(within 48 hours after operation),the incidence of late postoperative intracranial hemorrhage(over 48 hours after operation),and the incidence of intracranial hemorrhage related to external ventricular drainage(symptomatic and asymptomatic).The adverse event was the occurrence of drug-related thrombocytopenia.Other complications were delayed ischemic events.The modified Rankin scale(mRS)score was used to evaluate the clinical prognosis of patients at 180 days after operation.mRS score ≤2 was defined as good prognosis,mRS score＞2 was defined as poor prognosis,of which 6 was defined as death.Results(1)There were no significant differences in baseline and clinical data between the tirofiban group and the dual antibody group(all P＞0.05).(2)There was no significant difference in the proportion of patients with good outcome(75.2％[185/246]vs.74.2％[66/89],P=0.845)and death(10.2％[25/246]vs.12.4％[11/89],P=0.566)at 180 days after operation between the tirofiban group and the dual antiplatelet group.(3)There was no significant difference in the incidence of intraoperative(0.8％[2/246]vs.4.5％[4/89],P=0.075)and postoperative thrombotic events(11.0％[27/246]vs.13.5％[12/89],P=0.527)between the tirofiban group and the dual antiplatelet group.(4)Results about safety comparison between this two antiplatelet regimens showed that the incidence of early postoperative intracranial hemorrhage were lower in the tirofiban group than that in the dual antiplatelet group(2.8％[7/246]vs.10.1％[9/89],P=0.014).There were no significant differences in the symptomatic external ventricular drainage related intracranial hemorrhage(0 vs.2/15,P=0.050),incidences of intraoperative intracranial hemorrhage(1.6％vs.3.4％,P=0.580),late postoperative intracranial hemorrhage(3.3％vs.4.5％,P=0.836),and drug-related thrombocytopenia(0.4％vs.1.1％,P=0.461)between the two groups.Conclusion Low-dose tirofiban infusion in SAC for ruptured aneurysms may prevent perioperative thromboembolic events without high risk of intracranial hemorrhage.

Background and purpose:Effective treatment for cervical cancer patients is one of the global strategies to eliminate cervical cancer.By analyzing the metastasis characteristics and survival status of patients with distant metastasis of cervical cancer from a hospital-based cancer registry data,our study provided real-world evidence for better survival of cervical cancer and finally eliminating cervical cancer.Methods:A total of 572 cervical cancer patients who had metastasis cancer at the initial diagnosis or developed distant metastasis during follow-up in Fudan University Shanghai Cancer Center from 2008 to 2017 were included in this study.Medical records review,telephone visits and death registry data linkage were applied in collecting endpoint data.The first follow-up date was the diagnose date of metastasis,and the last follow-up date was November 1,2020.Kaplan-Meier method was applied in evaluating the 1-,3-and 5-year overall survival(OS)rates for overall and site-specific patients.Results:The median follow-up time was 38.93 months,and 348 cases died during the follow-up.72.55%were single site metastasis,and 27.45%were multiple metastases.Among all metastatic sites,the proportion of lung metastasis was the highest,41.26%,15.21%to bone,and 11.54%to liver.After metastasis,the 1-year,3-year and 5-year OS rates were 62.29%(95%CI:62.25-62.33),33.13%(95%CI:33.08-33.18)and 23.42%(95%CI:23.37-23.47),respectively.In single site metastasis,1-year OS was the highest after metastasis to the lung(72.52%).Besides,there was no significant difference among different metastatic sites,both in 3-year and 5-year OS.Conclusion:The most frequent distant metastatic sites of cervical cancer are lung,bone and liver.The survival rate after metastasis is poor.Further research with systematic treatment strategy is required for better survival.