Most patients with differentiated thyroid cancer have a good prognosis after radioiodine-131 therapy,but a small number of patients are insensitive to radioiodine-131 therapy and even continue to develop disease.At present,some targeted drugs can improve progression-free survival in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC),such as sorafenib and levatinib,have been approved for the treatment of RAIR-DTC.However,due to the presence of primary and acquired drug resistance,drug efficacy in these patients is unsatisfactory.This review introduces the acquired drug resistance mechanism of sorafenib in the regulation of mitogen-activated protein kinase(MAPK)and phosphatidylinositol-3-kinase(PI3K)pathways and proposes related treatment strategies,in order to provide a reference for similar drug resistance mechanism of sorafenib and effective treatment of RAIR-DTC.

Objective To investigate the clinical characteristics of survival in patients with high-risk myelodysplastic syndromes(HR-MDS)and provide a reference for the clinical prognosis of patients with HR-MDS.Methods General data,blood routine test,bone marrow smear with histopathology,cytogenetics,and other clinical data of 200 patients diagnosed with HR-MDS at Xiyuan Hospital of China Academy of Chinese Medical Sciences,during the period of January 2016-September 2022,were retrospectively analyzed.The included patients were categorized into the arsenic-containing herbal combination combined with demethylating agents(HMAs)treatment group and the arsenic-containing Chinese medicine compound combined with androgen treatment group.The influence of clinical indices on the survival characteristics of each group was analyzed.Results Comparison of the impact of clinical indicators on survival in 200 patients with HR-MDS who were treated with arsenic-containing herbal compounds in combination with HMAs or androgens showed that high-risk vs.very high-risk(P=0.018),hemoglobin(Hb)<80 g/L vs.Hb≥80 g/L(P=0.035),platelet(PLT)counts<50×109 L-1 vs.PLT counts≥50×109 L-1(P<0.001),and the difference in median progression-free survival(PFS)time between myelodysplastic syndromes converted to leukemia(MDS-AML)and non-MDS-AML(P=0.003)were statistically significant.Comparison of survival effects of clinical indicators in 68 patients with HR-MDS who were treated with arsenic-containing Chinese medicine compound combined with HMAs showed that the difference in median PFS between PLT count<50×109 L-1 and PLT count≥50×109 L-1(P<0.001)and the difference in median PFS between<5 and≥5 courses of chemotherapy(P=0.018)were statistically significant.Comparison of survival effects of clinical indicators in 132 patients with HR-MDS who were treated with arsenic-containing Chinese medicine compound combined with androgens showed that Hb<80 g/L and Hg≥80 g/L(P=0.028),PLT count<50×109 L-1 and PLT count≥50×109 L-1(P=0.002),and the mean differences in PFS between MDS-AML and non-MDS-AML(P=0.024)were statistically significant.Conclusion The clinical characteristics of long-surviving patients treated with arsenic-containing herbal combination in combination with HMAs included PLT counts≥50×109 L-1 and≥5 courses of chemotherapy.The clinical characteristics of long-surviving patients treated with arsenic-containing herbal combination in combination with androgens included Hg≥80 g/L,PLT count≥50×109 L-1,and non-MDS-AML.

Objective To explore the action mechanism of tauroursodeoxycholic acid(TUDCA)promoting intracellular clearance of Burkholderia pseudomallei(B.pseudomallei)in RAW264.7 macrophages.Methods After TUDCA of different concentrations were used to treat RAW264.7 cells pre-infected with B.pseudomallei for 8 h or not,flow cytometry was applied to detect the apoptosis of the infected and control cells.In addition,another endoplasmic reticulum stress(ERS)inhibitor 4-PBA was used to detect the apoptosis and proliferation of host cells after B.pseudomallei infection with Annexin-V/PI double staining and MTT cell proliferation assay.Furthermore,after transfected with CHOP siRNA,Western blotting and flow cytometry were employed to detect the effect of TUDCA on the expression levels of Caspase-3 and Caspase-12 and the changes in apoptotic rate after B.pseudomallei infection,respectively.Finally,the effect of TUDCA on intracellular multiplication of infected RAW264.7 cells were observed to estimate the CFU value in the presence and absence of CHOP siRNA.Results Under different concentrations of TUDCA,100 or 200 μmol/L TUDCA significantly reduced B.pseudomallei-induced apoptosis in RAW264.7 cells(P＜0.05).Meanwhile,both TUDCA and 4-PBA treatment could decrease the apoptosis induced by B.pseudomallei infection by ERS(P＜0.05).Further,the expression levels of Caspase-3 and Caspase-12 were obviously increased after B.pseudomallei infection compared with uninfected groups,but their expression levels in the siCHOP group was significantly lower than that in the siC group.Besides,flow cytometry also showed that TUDCA could reduce apoptosis induced by B.pseudomallei infection(P＜0.05),but no significant effect of TUDCA on apoptosis was observed under CHOP knockdown.Finally,intracellular CFU assay indicated that TUDCA treatment promoted the host cell clearance of B.pseudomallei(P＜0.05),but no such effect was observed in siCHOP group.Conclusion In B.pseudomallei infected RAW264.7 cells,TUDCA promotes the intracellular clearance of the bacteria by inhibiting ERS-induced apoptosis.

Objective To investigate the effects of the Bushen Quhan Huashi Prescription(mainly composed of Drynariae Rhizoma,Eucommiae Cortex,Dipsaci Radix,Notopterygii Rhizoma et Radix,Zingiberis Rhizoma Recens,Coicis Semen,and Achyranthis Bidentatae Radix)in combination with Methotrexate on the disease activity and serum core-binding factor a1(Cbfa1)level of patients with ankylosing spondylitis(AS)of kidney deficiency and governor-vessel cold type.Methods Ninety AS patients with kidney deficiency and governor-vessel cold type were randomly divided into a trial group and a control group,with 45 patients in each group.The control group was given Methotrexate treatment,and the trial group was treated with Bushen Quhan Huashi Prescription on the basis of treatment for the control group.The course of treatment in the two groups lasted for 3 months.The changes of Bath ankylosing spondylitis disease activity index(BASDAI)scores,Bath ankylosing spondylitis function index(BASFI)scores and serum levels of Cbfa1,type I collagen carboxy-terminal peptide(CTX-Ⅰ)and Dickkopf1 protein(DKK1)of the two groups were observed before and after treatment.After treatment,the clinical efficacy and the incidence of adverse effects were compared between the two groups.Results(1)After 3 months of treatment,the total effective rate of the trial group was 97.78%(44/45)and that of the control group was 82.22%(37/45).The intergroup comparison by chi-square test)showed that the therapeutic efficacy of the trial group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the disease activity scores of BASDAI and BASFI in the two groups of patients were significantly decreased compared with those before treatment(P＜0.05),and the trial group's reduction of BASDAI scores and BASFI scores were significantly superior to those of the control group,and the differences were statistically significant(P＜0.01).(3)After treatment,the serum levels of serological indicators of Cbfa1,CTX-Ⅰ,and DKK1 in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease of Cbfa1,CTX-Ⅰ and DKK1 levels in the trial group was significantly superior to that in the control group,the differences being all statistically significant(P＜0.01).(4)During the treatment,the incidence of adverse reactions in the trial group was 6.66%(3/45)and that in the control group was 11.11%(5/45),and the difference of the incidence of adverse reactions between the two groups was not statistically significant(P＞0.05).Conclusion Bushen Quhan Huashi Prescription combined with Methotrexate exerts certain effect in treating AS patients with kidney deficiency and governor-vessel cold type,and the therapy can effectively control the disease activity and reduce the level of serum Cbfa1 expression in the patients.

The clinical data of one child with metanephric stromal tumor (MST) and BRAF V600E gene mutation admitted to the First Affiliated Hospital of Zhengzhou University in June 2022 was analyzed retrospectively.Literature was reviewed.The patient, a 2-year-old girl, was diagnosed with a tumor in the left abdomen.The maximum diameter of the tumor was 10.5 cm.A radical nephrectomy was performed on the left kidney, and postoperative pathology revealed MST.Microscopically, the tumor had no envelope and exhibited expansive growth.The tumor cells were fusiform or stellate, and nuclear division was visible in the cell-rich region.Dysplastic blood vessels were seen inside the tumor.The tumor cells around the blood vessels and invaginated renal tubules were arranged like onion skin.CD34 was detected positive by immunohistochemical staining, and BRAF V600E mutation was also detected positive by fluorescent polymerase chain reaction.A total of 21 relevant case reports were retrieved, including 16 in English and 5 in Chinese.Fifty-eight MST patients, including the one in this report were analyzed.These patients were aged 2 days to 15 years, with a median age of 2 years.Except for 2 patients with unknown sex, the ratio of male to female was about 1.4∶1.0.Most MST patients were asymptomatic, with an average tumor size of 5.3 cm.The tumor cell CD34 showed positive expression in different degrees.Eight patients received the BRAF V600E mutation detection, and the results were all positive.Fifty-eight patients underwent nephrectomy and were followed up for 0-156 months, of which 7 patients were assisted with radiotherapy and chemotherapy.During the follow-up, 1 patient died, and 1 patient had a relapse.MST is a rare benign renal stromal tumor. BRAF V600E mutations are detected in a variety of malignancies.This paper is the first to report MST with BRAF V600E mutation in China and points out the importance of molecular detection of BRAF mutation for accurate diagnosis of MST.

Objective To investigate the characteristics of imaging signs of giant cell tumor(GCT)of the hand and foot bones.Methods The clinical,X-ray,CT and MRI images of 18 cases of GCT of hand and foot bones diagnosed by pathology were analyzed retrospectively.And compared with 54 cases of long bone GCT imaging manifestations.Results Among the 18 GCT cases of hand and foot bones,there were 8 cases of hand,10 cases of foot,including 12 cases of short tubular bone and 6 cases of tarsal bone.All lesions were dilatant osteolytic bone destruction involving the joint surface,in which the short tubular bone GCT showed central growth,the tumor occupied the entire wide diameter of the bone,the lesion range was long,consistent with the bone axis,easy to invade the surrounding soft tissue,sclerotic edge,bone ridge,lobed and periosteal reaction were rare,and prone to recurrence after surgery.The GCT of tarsal bone and short tubular bone showed eccentric growth,and there was statistical difference(P<0.05).The probability of pathological fracture in GCT of long bone was significantly greater than that of short tubular bone.There was no significant difference between the two groups in swelling growth,involvement of bone end and ethmoid sign of bone cortex.Conclusion Compared with long bone GCT,hand and foot bones are rare occurrence site of GCT,which is more aggressive than long bone GCT and prone to recurrence after surgery.Full attention should be paid to its imaging characteristics to provide more accurate image information for clinical treatment strategies.

Objective To investigate the infection status and changing trend of hepatitis C virus(HCV)infection in hospitalized patients in medical institutions,and provide reference for formulating HCV infection prevention and control strategies.Methods HCV infection surveillance results from cross-sectional survey data reported to China Healthcare-associated Infection(HAI)Surveillance System in 2020 were summarized and analyzed,HCV positive was serum anti-HCV positive or HCV RNA positive,survey result was compared with the survey results from 2003.Results In 2020,1 071 368 inpatients in 1 573 hospitals were surveyed,738 535 of whom underwent HCV test,4 014 patients were infected with HCV,with a detection rate of 68.93％and a HCV positive rate of 0.54％.The positive rate of HCV in male and female patients were 0.60％and 0.48％,respectively,with a statistically sig-nificant difference(x2=47.18,P＜0.001).The HCV positive rate in the 50-＜60 age group was the highest(0.76％),followed by the 40-＜50 age group(0.71％).Difference among all age groups was statistically signifi-cant(x2=696.74,P＜0.001).In 2003,91 113 inpatients were surveyed.35 145 of whom underwent HCV test,resulting in a detection rate of 38.57％;775 patients were infected with HCV,with a positive rate of 2.21％.In 2020,HCV positive rates in hospitals of different scales were 0.46％-0.63％,with the highest in hospital with bed numbers ranging 600-899.Patients'HCV positive rates in hospitals of different scales was statistically signifi-cant(X2=35.34,P＜0.001).In 2020,12 provinces/municipalities had over 10 000 patients underwent HCV-rela-ted test,and HCV positive rates ranged 0.19％-0.81％,with the highest rate from Hainan Province.HCV posi-tive rates in different departments were 0.06％-0.82％,with the lowest positive rate in the department of pedia-trics and the highest in the department of internal medicine.In 2003 and 2020,HCV positive rates in the depart-ment of infectious diseases were the highest,being 7.95％and 3.48％,respectively.Followed by departments of orthopedics(7.72％),gastroenterology(3.77％),nephrology(3.57％)and general intensive care unit(ICU,3.10％)in 2003,as well as departments of gastroenterology(1.35％),nephrology(1.18％),endocrinology(0.91％),and general intensive care unit(ICU,0.79％)in 2020.Conclusion Compared with 2003,HCV positive rate decreased significantly in 2020.HCV infected patients were mainly from the department of infectious diseases,followed by departments of gastroenterology,nephrology and general ICU.HCV infection positive rate varies with gender,age,and region.

Aim To investigate the therapeutic effect of the MW-9 on ulcerative colitis(UC)and reveal the underlying mechanism, so as to provide a scientific guidance for the MW-9 treatment of UC. Methods The model of lipopolysaccharide(LPS)-stimulated RAW264.7 macrophage cells was established. The effect of MW-9 on RAW264.7 cells viability was detected by MTT assay. The levels of nitric oxide(NO)in RAW264.7 macrophages were measured by Griess assay. Cell supernatants and serum levels of inflammatory cytokines containing IL-6, TNF-α and IL-1β were determined by ELISA kits. Dextran sulfate sodium(DSS)-induced UC model in mice was established and body weight of mice in each group was measured. The histopathological damage degree of colonic tissue was assessed by HE staining. The protein expression of p-p38, p-ERK1/2 and p-JNK was detected by Western blot. Results MW-9 intervention significantly inhibited NO release in RAW264.7 macrophages with IC50 of 20.47 mg·L-1 and decreased the overproduction of inflammatory factors IL-6, IL-1β and TNF-α(P<0.05). MW-9 had no cytotoxicity at the concentrations below 6 mg·L-1. After MW-9 treatment, mouse body weight was gradually reduced, and the serum IL-6, IL-1β and TNF-α levels were significantly down-regulated. Compared with the model group, MW-9 significantly decreased the expression of p-p38 and p-ERK1/2 protein. Conclusions MW-9 has significant anti-inflammatory activities both in vitro and in vivo, and its underlying mechanism for the treatment of UC may be associated with the inhibition of MAPK signaling pathway.

Objective:To investigate the relationship between the number of removed lymph nodes(RLN)and patient prognosis during radical surgery for extensive cervical cancer(CC).Methods:Clinical data of 21416 pa-tients with CC who underwent radical hysterectomy between January 1,2004 to August 31,2018 in the Chinese Cervical Cancer Clinical Study was retrospectively reviewed.Restricted cubic spline(RCS)was used to analyze the dose-response relationship between the number of RLN and prognosis.The patients were divided into three groups according to the RCS and RLN number:1-17 group(8733 cases),18-26 group(8189 cases),and≥ 27 group(4494 cases).Kaplan-Meier survival analysis and Log-Rank tests were used to compare the OS rates and DFS rates between groups at 3 and 5 years.Multivariate Cox proportional hazards model was used to analyze the prognostic mortality risk.Results:① RCS results showed a U-shaped nonlinear dose-response relationship be-tween the number of RLN and prognosis(P＜0.01).When the number of RLN was less than 26,the risk of death decreased as the number of RLN increased,and the risk was lowest when the number of RLN was 26.②There were statistically significant differences(P＜0.05)in age,histological type,tumor diameter,nerve invasion,uterine invasion,vaso-lymph node space invasion,cervical invasion,number of lymph node metastasis,whether preopera-tive adjuvant therapy was received,postoperative adjuvant therapy,and whether postoperative adjuvant therapy was standardized among the 3 groups(P＜0.05).③Kaplan-Meier survival curve analysis showed that the 5-year OS of the 1-17 group,18-26 group,and ≥ 27 group were 90.23％,92.28％,and 91.61％,respectively,and the 5-year DFS were 85.32％,87.90％,and 87.18％,respectively.The differences between the three groups were sta-tistically significant(P＜0.01).④The results of multivariate Cox regression analysis showed that RLN number in the range of 1-17 was a significant risk factor for the 3-and 5-year OS and DFS,when compared to the 18-26 RLN group(HR＞1,P＜0.05).Conclusions:RLN number may be one of the prognostic indicators of CC.When the number of RLNs is between 18-26,the prognosis of the patient may be better.The number of RLN in the range of 1-17 may increase the risk of recurrence or death in CC patients.

Objective:To investigate the relationship between the number of removed lymph nodes(RLN)and patient prognosis during radical surgery for extensive cervical cancer(CC).Methods:Clinical data of 21416 pa-tients with CC who underwent radical hysterectomy between January 1,2004 to August 31,2018 in the Chinese Cervical Cancer Clinical Study was retrospectively reviewed.Restricted cubic spline(RCS)was used to analyze the dose-response relationship between the number of RLN and prognosis.The patients were divided into three groups according to the RCS and RLN number:1-17 group(8733 cases),18-26 group(8189 cases),and≥ 27 group(4494 cases).Kaplan-Meier survival analysis and Log-Rank tests were used to compare the OS rates and DFS rates between groups at 3 and 5 years.Multivariate Cox proportional hazards model was used to analyze the prognostic mortality risk.Results:① RCS results showed a U-shaped nonlinear dose-response relationship be-tween the number of RLN and prognosis(P＜0.01).When the number of RLN was less than 26,the risk of death decreased as the number of RLN increased,and the risk was lowest when the number of RLN was 26.②There were statistically significant differences(P＜0.05)in age,histological type,tumor diameter,nerve invasion,uterine invasion,vaso-lymph node space invasion,cervical invasion,number of lymph node metastasis,whether preopera-tive adjuvant therapy was received,postoperative adjuvant therapy,and whether postoperative adjuvant therapy was standardized among the 3 groups(P＜0.05).③Kaplan-Meier survival curve analysis showed that the 5-year OS of the 1-17 group,18-26 group,and ≥ 27 group were 90.23％,92.28％,and 91.61％,respectively,and the 5-year DFS were 85.32％,87.90％,and 87.18％,respectively.The differences between the three groups were sta-tistically significant(P＜0.01).④The results of multivariate Cox regression analysis showed that RLN number in the range of 1-17 was a significant risk factor for the 3-and 5-year OS and DFS,when compared to the 18-26 RLN group(HR＞1,P＜0.05).Conclusions:RLN number may be one of the prognostic indicators of CC.When the number of RLNs is between 18-26,the prognosis of the patient may be better.The number of RLN in the range of 1-17 may increase the risk of recurrence or death in CC patients.