Objective To identify the clinical characteristics and prognostic factors of young patients with sporadic rectal cancer liver metastasis(RCLM).Methods The clinical data of young RCLM patients at 45 years or under(n=40,as younger patient group)in Peking University First Hospital from January 2016 to January 2021 were reviewed,meanwhile,elder RCLM patient group were comprised of 82 patients older than 45-year-old in a 1:2 ratio.Proportions of categorical variables were compared between young patients and old patients.The clinicopathologic parameters were analyzed with univariate and multivariate Cox regression models and Kaplan-Meier method for demonstrating survival differences between the maximum diameter of liver metastasis and local therapy.Results One hundred and twenty-two RCLM patients were identified,the 1-,3-and 5-year survival rates of young patient group were 97.5%,47.5%,15.0%,those of elder patient group were 84.1%,26.8%,9.8%,respectively.The differences in BMI(P=0.008),primary tumor with obstruction and bleeding(P=0.006),synchronous rectal cancer liver metastases(P=0.005),the maximum diameter of liver metastasis>3 cm(P=0.019)were statistically significant between the two groups.And univariate and multivariate analyses showed that age(P=0.003),N stage(P=0.007),local therapy for liver metastases(P=0.047)and the maximum diameter of liver metastasis(P=0.030)were independent risk factors for influencing the prognosis of RCLM patients;curative resection or not of primary tumor(P=0.035)and the maximum diameter of liver metastasis(P=0.041)were independent risk factors for influencing the prognosis of young RCLM patients.Kaplan-Maier curve demonstrated survival differences between the maximum diameter of liver metastasis and local therapy for liver metastasis in RCLM patients(log-rank P=0.000).Conclusions Although with later staging of initial tumor station,young RCLM patients may obtain better survival benefit compared with old patients.Higher degree of lymph node metastasis,local therapy for liver metastases and the maximum diameter of liver metastasis>3 cm indicates poor prognosis in RCLM patients,and without curative resection of primary tumor and maximum diameter of liver metastasis are also considered as the independent poor prognostic factors of young RCLM patients.Local therapy for liver metastases appears to play an important role in the treatment strategy of RCLM patients.

Objective To analyze the antigen recognition sites of commercial and homemade antibodies against aquaporin(AQP)9,and to identify the application effect.Methods Western blotting was used to compare the efficacy of three commercial antibodies and self-made antibody in identifying AQP9 genotypes.The antigen recognition sites of four antibodies and their specificities in practical applications were analyzed.Results Western blotting showed that protein bands of three commercial antibodies were detected in both WT and Aqp9-/-mice.The keyhole limpet hemocyanin(KLH)conjugated synthetic peptides corresponding to the three commercial antibodies were derived from rat,human and human,respectively.And The sequences of these three synthetic peptides were different from those of mice.AQP3/7 and AQP9 have similar molecular weight and were expressed in the liver with high homology.An obvious band of self-made antibody was observed at the 27 kD position in WT mice,but no band was observed at the corresponding position in Aqp9-/-mice.Conclusion Commercial antibodies 1 and 3 can be used to assist in the identification of genotypes in Aqp9-/-mice.Homemade antibodies can accurately identify genotypes at the protein level.

Objective We aim to analyse semaglutide related adverse events in real-world,overall and by gender and age subgroups and compare the differences of different gender and age patients in adverse events,in order to supply references for security usage in the clinic.Methods OpenVigil 2.1 was used to search FDA Adverse Event Reporting System for semaglutide related adverse events from the establishment of the databases to April 2023.According to age and gender,patients were divided into 18-64 years old group and≥65 years old group,male group and female group.We selected ten adverse events which we interested(nausea,diarrhoea,vomiting,pancreatitis,cholecystitis,cholelithiasis,hypoglycaemia,diabetic retinopathy,acute kidney injury and thyroid cancer/medullary thyroid cancer)and analyzed overall and each group of semaglutide adverse events.Results A total of 5 330 cases and 15 558 adverse events were collected.2 935 patients aged 18-64 old group years with 8 553 adverse events;2 395 patients aged≥65 years old group with 7 005 adverse events.2 231 male group patients with 6 195 adverse events;3 059 female group patients with 9 277 adverse events.The sex of 40 patients was unknown.Nausea(1 089 cases/7.00％),vomiting(775 cases/4.98％)and diarrhoea(545 cases/3.50％)remained the most common adverse events.The constituent ratio of pancreatitis was significantly higher in patients aged 18-64 years old group than in patients aged 65 years old group(P＜0.05);the constituent ratio of diarrhoeaand cholelithiasis was significantly lower in patients aged 18-64 years old group than patients aged≥65 years old group(P＜0.05).The constituent ratio of diarrhoea,vomiting,pancreatitis,cholecystitis,cholelithiasis,diabetic retinopathy,and acute kidney injurywas significantly higher in male group patients than in female group(P＜0.05).Conclusion Nausea,diarrhoea and vomiting remined the most common adverse events of semaglutide.Male should be more concerned about gastrointestinal,pancreatitis,gallbladder events,retinopathy and acute kidney injury.Elderly patients should be more alert diarrhoea and cholelithiasis.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the value of single-phase gonadotropin releasing hormone(GnRH)stimulation test in the diagnosis of central precocious puberty(CPP)in girls with different levels of body mass index(BMI).Methods A retrospective analysis was performed for the data of 760 girls with breast development before 7.5 years of age who attended the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2023.According to the results of GnRH stimulation test and clinical manifestations,they were divided into a CPP group(297 girls)and a non-CPP group(463 girls).According to the values of BMI,the girls were divided into a normal weight group(540 girls),an overweight group(116 girls),and an obese group(104 girls).The receiver operating characteristic(ROC)curve was used to investigate the value of single-phase GnRH stimulation test in the diagnosis of CPP in girls with different levels of BMI.Results Luteinizing hormone(LH)/follicle-stimulating hormone at 30 minutes after GnRH stimulation had an area under the curve(AUC)of 0.985 in the diagnosis of CPP,which was higher than the AUC at 0,60,and 90 minutes(P<0.05).LH at 30 minutes had a similar diagnostic value to LH at 60 minutes(P>0.05).LH at 30 minutes was negatively correlated with BMI and BMI-Z value(P<0.05).The AUC for diagnosing CPP in normal weight,overweight,and obese girls at 30 minutes LH was 0.952,0.965,and 0.954,respectively(P<0.05).Conclusions The 30-minute GnRH stimulation test has a good value in the diagnosis of CPP in girls with different levels of BMI and is expected to replace the traditional GnRH stimulation test,but the influence of BMI on LH level should be taken seriously.

Objective:To investigate the effects of down-regulation of p21 activated kinase 1(PAK1)on the proliferation,differentiation,and apoptosis of myeloproliferative neoplasm(MPN)cells(6133/MPL)with thrombopoietin receptor MPL mutation at codon 515(MPLW515L)and survival of 6133/MPL mice.Methods:Interference with the protein level of PAK1 in 6133/MPL cells was assessed using lentivirus-mediated shRNA transfection technology.CCK-8 assay was used to detect the effect of down-regulation of PAK1 on the proliferation viability of 6133/MPL cells,and colony-forming ability was measured by cell counting.Flow cytometry was used to detect the PAK1 kinase activity on the ability of polyploid DNA formation and cell apoptosis in 6133/MPL cells.The expression of cyclin D1,cyclin D3 and apoptosis-related protein Bax was detected by Western blot.The infiltration of tumor cells in spleen and bone marrow of 6133/MPL mice were detected by HE staining.Results:Down-regulation of PAK1 inhibited the proliferation and reduced the ability of cell colony formation of 6133/MPL cells.After knocking down PAK1,the content of polyploid DNA in 6133/MPL cells increased from 31.8 to 57.5％and 48.0％,and the proportion of apoptosis increased approximately to 10.8％.Down-regulation of PAK1 led to a reduction of infiltration of tumor cells in liver and bone marrow of 6133/MPL mice,thereby prolonging survival time.Conclusion:Down-regulation of PAK1 can significantly inhibit the growth of 6133/MPL cells,promote the formation of polyploid DNA,induce 6133/MPL cell apoptosis,and prolong the survival time of 6133/MPL mice.

Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P＜0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.

AIM To investigate the effects of total Astragalus saponins on the improvement of sarcopenia in a rat model of type 2 diabetes mellitus(T2DM).METHODS The rats were divided into the normal group for a normal feeding and the model group for the feeding of high-sugar and high-fat diet combined with intraperitoneal injection of STZ to establish a T2DM model.The successful model rats were randomly divided into the model group,the metformin group(0.2 g/kg)and the total Astragalus saponins group(80 mg/kg),and given corresponding doses of drugs by gavage.After 12 weeks administration,the rats had their FBG,postprandial blood glucose(PG2h)and wet weight of skeletal muscle measured;their serum levels of INS,C-peptide(C-P),IGF-1,TNF-α and IL-1β detected by ELISA;their morphological changes of skeletal muscle observed by HE staining;their protein expressions of PI3K,p-Akt,mTOR,S6K1,FoxO1 and Murf1 in skeletal muscle detected by Western blot;and their mRNA expressions of Pi3k,Akt and mtor in skeletal muscle detected by RT-qPCR method.RESULTS Compared with the model group,the total Astragalus saponins group displayed decreased levels of FBG,PG2h,OGTT-AUC,HOMA-IR,TNF-α and IL-1β(P＜0.01);increased levels of INS,C-P,IGF-1 and wet weight of skeletal muscle(P＜0.05,P＜0.01);improved skeletal muscle atrophy and increased protein expressions of PI3K,p-Akt,mTOR and S6K1 in skeletal muscle(P＜0.05,P＜0.01);decreased protein expressions of FoxO1 and Murf1(P＜0.05,P＜0.01);and increased mRNA expressions of Pi3k,Akt and mtor(P＜0.01).CONCLUSION The improvement effects of total Astragalus saponins on sarcopenia in T2DM rats may be associated with the regulation of PI3K/Akt/mTOR and PI3K/Akt/FoxO1 pathways.

AIM: To investigate the effect of repeated intravitreal injection of anti-vascular endothelial growth factor(VEGF)on the vitreomacular interface(VMI)and its related risk factors in patients with diabetic macular edema(DME).METHODS: The clinical data of 31 patients(55 eyes)with DME who received intravitreal injections of Conbercept(3+PRN)in the ophthalmology department of the First People's Hospital of Zunyi from January 2018 to December 2021 were analyzed retrospectively. There were 9 cases(13 eyes)in the group that has changes in VMI and 22 cases(42 eyes)in the other group that has no changes in VMI. The best corrected visual acuity(BCVA), central retinal thickness(CRT), and central choroidal thickness(CCT)of the two groups were compared, and the risk factors of VMI change were analyzed.RESULTS: The patients were followed up for an average of 9.58±8.32mo, received an average of 4.07±2.17 times of anti-VEGF therapy, and the number of intravitreal injections in VMI changed group was more than that in VMI unchanged group(5.77±2.09 times vs. 3.55±1.93 times, P=0.001). At the last follow-up, compared with before treatment, the BCVA of both patients improved significantly after treatment(both P<0.05), while CCT had no significant change(both P>0.05). CRT of patients in the VMI unchanged group decreased significantly(P=0.039), but there was no significant change in patients of VMI changed group(P=0.627). Logistic regression analysis showed that BCVA was a risk factor for VMI change before treatment(P=0.049, OR=6.210, 95%CI 1.006～38.346).CONCLUSIONS: The VMI of DME patients may change during repeated intravitreal injections of anti-VEGF drugs. The worse the BCVA before treatment, the higher the risk of change in VMI, and the patients with VMI change have a poor response to anti-VEGF treatment.

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*