This article reports a case with the chief complaint of “hepatosplenomegaly to be investigated” and a confirmed diagnosis of Niemann-Pick disease type B after various tests， and a literature review was conducted to summarize the heterogeneous manifestations of liver involvement in type B Niemann-Pick disease， in order to improve the clinical management of difficult and rare liver diseases.

POEMS syndrome is a rare plasma cell dysplasia. Its clinical manifestations include polyneuropathy, monoclonal protein, increased extravascular volume load, endocrinopathy, organomegaly and skin changes. The complex and atypical symptoms at presentation make early diagnosis challenging due to multiple system involvement. Peripheral neuropathy, limb numbness, is the most common initial symptom of this disease. However, case reports of increased extravascular volume load are rare. This article collected and analyzed the clinical data of two groups of patients with different initial symptoms (increased extravascular volume load and limb numbness). The clinical characteristics and treatment responses were summarized.

Objective To study the application effect of Glisson hepatic pedicle priority approach marked by APR triangle in laparoscopic anatomic right hemihepatectomy(LARH).Methods The clinical data of 66 patients underwent LARH in the Affiliated Hospital of Tangshan Vocational and Technical College were retrospectively analyzed.According to the surgical approaches,the patients were divided into the extrathecal group and the APR group.The 35 patients of the extrathecal group underwent LARH via Glisson hepatic pedicle extrathecal approach.The 31 patients of the APR group were treated with LARH through the Glisson hepatic pedicle priority approach marked by APR triangle.The clinical data including perioperative indexes,postoperative complications,oxidative stress and liver function indexes of patients in the two groups were statistically analyzed,and the differences between the two groups were compared.Results The operative time and intraoperative blood loss of patients in the APR group were significantly shorter/less than those in the extrathecal group,with statistically significant differences(P<0.05).There was no significant differences in the intraoperative blood transfusion ratio,drainage tube indwelling time,first exhaust time,postoperative hospitalization time or postoperative complications of patients between the two groups(P>0.05).The levels of malondialdehyde(MDA),cortisol(Cor)and superoxide dismutase(SOD)at each time point after surgery of patients in the two groups were significantly different from those before surgery(P<0.05),and the levels of MDA,Cor and SOD at each time point after surgery of patients in the APR group were significantly better than those in the extrathecal group(P<0.05).The levels of albumin(ALB),total bilirubin(TBil),aspartate aminotransferase(AST)and alanine aminotransferase(ALT)at each time point after surgery of patients in the two groups were significantly different from those before surgery(P<0.05).Moreover,the levels of ALB,TBil,AST and ALT at each time point after surgery of patients in the APR group were significantly better than those in the extrathecal group(P<0.05).Conclusion Compared with the Glisson hepatic pedicle extrathecal approach,the Glisson hepatic pedicle priority approach marked by APR triangle in LARH has shorter operation time,less bleeding and less oxidative stress reaction,which is beneficial to the recovery of liver function after surgery.

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

Objective: To evaluate the prognostic value of Mayo MASS and R2-ISS staging systems in patients newly diagnosed with multiple myeloma (MM) . Methods: A total of 371 patients newly diagnosed with MM in Jiangsu Province Hospital were included in the study. Cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization (cIg-FISH) was performed to detect cytogenetic abnormality. Clinical characteristics were combined to analyze the disease stage and evaluate the prognosis. Results: There were 37 (10.0%), 264 (71.0%), and 70 (18.8%) patients in R-ISS stage Ⅰ, Ⅱ, and Ⅲ, respectively. The median progression-free survival (PFS) times were 37, 25, and 14 months (P<0.001). The median overall survival (OS) times were not reached (NR), 66, and 30 months (P<0.001). There were 71 (19.1%), 140 (37.7%), and 160 (43.2%) patients in Mayo MASS stages Ⅰ, Ⅱ, and Ⅲ, and the median PFS times periods were 43, 27, and 19 months (P<0.001), and the median OS times were NR, NR, 35 months, respectively (P<0.001). There were, 23 (6.2%), 69 (18.6%), 222 (59.8%), and 57 (15.4%) patients in R2-ISS stages Ⅰ, Ⅱ, Ⅲ, and Ⅳ, respectively. The median PFS times were 47, 31, 25, and 15 months (P=0.001), and the median OS times were NR, NR, 49, and 55 months, respectively (P<0.001) . Conclusion: Based on the R-ISS staging system, Mayo MASS, and R2-ISS prognostic staging system incorporated 1q21+, which allows a better stratification. However, the proportion of stage Ⅲ patients in Mayo MASS and R2-ISS staging systems is relatively high, which is considered related to the high incidence of 1q21+ and ISS Ⅲ in the Chinese population.
Humans ; Prognosis ; Multiple Myeloma/diagnosis* ; In Situ Hybridization, Fluorescence ; Neoplasm Staging ; Retrospective Studies

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

Objective:This study aimed to investigate the influence of FGFR3 gene mutations on the clinical characteristics and prognosis of patients with newly diagnosed multiple myeloma (NDMM) .Methods:A total of 198 patients with NDMM admitted to the Department of Hematology in Jiangsu Province Hospital between January 2016 and February 2023 were retrospectively analyzed. Next-generation sequencing and cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization were performed for all patients. The prognostic significance of FGFR3 mutation and clinical features were analyzed using the Log-rank test and Cox proportional hazards model.Results:Among 198 patients, 28 carried the FGFR3 gene mutation. These patients had significantly lower serum albumin levels, higher β 2-microglobulin levels, advanced Revised International Staging System stages, more frequent occurrence of t (4;14) , and shorter median progression-free survival (PFS) time (28 months vs 33 months, P=0.024) and overall survival (OS) time (54 months vs undefined, P=0.028) than patients without FGFR3 mutation. Additionally, patients carrying either FGFR3 mutation or t (4;14) had lower PFS (30 months vs 38 months, P=0.012) and OS (54 months vs undefined, P=0.017) than those without. The Cox proportional hazards model identified FGFR3 mutation as an independent risk factor for PFS and OS. Conclusion:FGFR3 gene mutation was an unfavorable independent prognostic predictor for NDMM.

Objective: To establish a survival prediction model based on the independent prognostic factors of long-term prognosis after laparoscopic liver resection(LLR) for intrahepatic cholangiocarcinoma(ICC). Methods: The clinical and pathological data of 351 consecutive patients with ICC who received radical LLR in 13 Chinese medical centers from August 2010 to May 2021 were collected retrospectively. There were 190 males and 161 females,aged(M(IQR)) 61(14)years(range:23 to 93 years). The total cohort was randomly divided into a training dataset(264 cases) and a validation dataset(87 cases). The patients were followed up by outpatient service or telephone,and the deadline for follow-up was October 2021. Based on the training dataset,the multivariate Cox proportional hazards regression model was used to screen the independent influencing factors of long-term prognosis to construct a Nomogram model. The Nomogram model's discrimination,calibration,and clinical benefit were evaluated through internal and external validation,and an assessment of the overall value of two groups was made through the use of a receiver operating characteristic(ROC) curve. Results: There was no significant difference in clinical and pathological characteristics and long-term survival results between the training and validation datasets(all P>0.05). The multivariate Cox analysis showed that CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis were independent prognostic factors for ICC patients after LLR(all P<0.05). The survival Nomogram was established based on the independent prognostic factors obtained from the above screening. The ROC curve showed that the area under the curve of 1, 3 and 5-year overall survival rates of patients in the training dataset were 0.794(95%CI:0.721 to 0.867),0.728(95%CI:0.618 to 0.839) and 0.799(95%CI:0.670 to 0.928),and those in the validation dataset were 0.787(95%CI:0.660 to 0.915),0.831(95%CI:0.678 to 0.983) and 0.810(95%CI:0.639 to 0.982). Internal and external validation proved that the model exhibited a certain discrimination,calibration,and clinical applicability. Conclusion: The survival Nomogram model based on the independent influencing factors of long-term prognosis after LLR for ICC(including CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis) exhibites a certain differentiation,calibration,and clinical practicability.
Bile Duct Neoplasms/surgery* ; Bile Ducts, Intrahepatic/pathology* ; CA-19-9 Antigen ; Cholangiocarcinoma/diagnosis* ; Female ; Humans ; Laparoscopy ; Lymphatic Metastasis ; Male ; Nomograms ; Prognosis ; Retrospective Studies

Objective:To evaluate the predictive value of the UK Myeloma Research Alliance Risk Profile(MRP)score based on clinical outcomes in elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:Patients aged ≥65 years with NDMM in our hospital from March 2018 to September 2021 were divided into three groups with low, medium and high risk according to MRP scores.Their therapeutic efficacy, adverse effects, and survival were analyzed.Results:A total of 63 NDMM patients were enrolled with median age of 69 years(65-84 years)and median follow-up of 13.3(1.2-43.4)months.Based on MRP score, there were 22 patients in the low-risk group, 13 cases in medium-risk group, 28 patients in the high-risk group.The median progression-free survival(PFS)time of the three groups was 38.4, 25.1 and 21.2 months respectively, and the estimated 2-year PFS rate was 83.9%, 60.0%, and 45.6%, respectively(all P=0.177). The estimated 2-year overall survival(OS)rate was 100.0%, 90.0%, 74.6%, respectively(all P=0.049). Among patients with grade 2 or above hematological adverse events, there were 20 cases(71.4%), 7 cases(53.8%)and 8 cases(36.4%)in the high-, medium-and low-risk groups, with statistically significant differences( χ2=6.154, P=0.046). Among patients with grade 3 or higher non-hematological adverse events, there were 17 cases(60.7%), 5 case(38.5%)and 5 cases(22.7%)in the high-, medium-and low-risk groups, with statistically statistical significance( χ2=7.389, P=0.025). The patients experiencing interruption, delay or replacement of chemotherapy regimen were 6 cases(46.2%)and 19 cases(67.9%)in the medium-and high-risk groups, which were higher than in the low-risk group(31.8%, χ2=6.543, P=0.038). Conclusions:It is feasible to conduct MRP score in elderly NDMM patients.The MRP score can be used to predict the adverse events of chemotherapy, etc, and has certain value for the prognosis evaluation of patients.

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*