Objective:To explore the clinical phenotype and genetic etiology for a Chinese pedigree affected with Autosomal dominant polycystic kidney disease (ADPKD).Methods:A pedigree with ADPKD diagnosed at the Department of Gynaecology of the First Affiliated Hospital of Zhengzhou University in December 2020 was selected as the study subject. Clinical data of the pedigree was collected, and whole exome sequencing (WES) was carried out for the proband. Candidate variants were verified by Sanger sequencing of the proband and her relatives. This study was approved by the First Affiliated Hospital of Zhengzhou University (Ethics No. KS-2018-KY-36).Results:Fetal ultrasonography showed increased volume and parenchymal echogenicity in both kidneys. The fetus was found to harbor c. 11098C>T (p.R3700C) and c.11039T>C (p.F3680S) compound heterozygous variants of the PKD1 gene, which were respectively inherited from its mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be likely pathogenic (PM1+ PM2_Supporting+ PP3). Conclusion:The c. 11098C>T (p.R3700C) and c. 11039T>C (p.F3680S) compound heterozygous variants of the PKD1 gene probably underlay the ADPKD in the fetus. Above finding has provided guidance for the genetic counseling and prenatal diagnosis for this pedigree.

Objective To investigate the effect of different doses of rocuronium on the monitoring of recurrent laryngeal nerve during endoscopic thyroidectomy.Methods A total of 116 patients undergoing endoscopic thyroidectomy through areolar approach were selected from October 2021 to October 2022,30 males and 86 females,aged 18-64 years,BMI 18.5-30.0 kg/m2,ASA physical status Ⅰ or Ⅱ.All the patients were divided into three groups by random number table method:rocuronium 0.30 mg/kg group(group R1,n=39),rocuronium 0.45 mg/kg group(group R2,n=39),and rocuronium 0.60 mg/kg group(group R3,n=38).After induction of anesthesia,groups R1,R2,and R3 were injected intrave-nously with rocuronium 0.30,0.45,and 0.60 mg/kg,respectively.When the TOF value was 0,the nerve monitoring tracheal catheter was inserted,and the muscle relaxation was monitored throughout the operation.No muscle relaxants were added before the end of the nerve monitoring.The time and amplitude of recurrent laryngeal nerve electromyography(EMG)from intravenous rocuronium to the first occurrence were recorded.The time of intubation and quality of tracheal intubation(Cooper's score),intraoperative special conditions(hypotension,hypertension,bradycardia,tachycardia,intraoperative movement,etc.),postoperative throat pain,hoarseness,and muscle pain were recorded.Results There was no significant difference in the time of first occurrence of recurrent laryngeal nerve EMG among the three groups.Compared with group R1,the recurrent laryngeal nerve EMG amplitude in groups R2 and R3 was significantly decreased for the first occurrence(P＜0.05).Compared with group R1,the time of intubation in groups R2 and R3 was signifi-cantly shortened(P＜0.05).Compared with group R2,the time of intubation in group R3 was significantly shortened(P＜0.05).Compared with group R1,the quality of tracheal intubation in groups R2 and R3 was significantly higher(P＜0.05).Compared with group R1,the incidence of intraoperative and postop-erative laryngeal pain in groups R2 and R3 was significantly lower(P＜0.05).Conclusion During endo-scopic thyroidectomy,compared with rocuronium 0.30 mg/kg,rocuronium 0.45 and 0.60 mg/kg can not only provide good conditions for tracheal intubation,but also monitor recurrent laryngeal nerve signals,and rocuronium 0.60 mg/kg can be intubated for a shorter time.

Objective:To analyze the clinical characteristics and prognostic factors of high-risk neuroblastoma (HR-NB) patients with skeletal metastasis.Methods:The clinical features of 336 newly treated HR-NB patients with skeletal metastases admitted to the Department of Medical Oncology of Beijing Children′s Hospital, Capital Medical University from January 2007 to December 2018 were analyzed retrospectively.Kaplan-Meier method was used for the survival analysis, and Log- Rank test was used for univariate prognosis analysis.The Cox model was used to analyze the multifactorial prognostic analysis. Results:A total of 336 HR-NB patients were recruited, involving 188 males and 148 females with the median age of onset of at 43 (4-148) months.Skeletal metastases affected the viscerocranium (89 cases, 26.5%), neurocranium (193 cases, 57.4%), vertebrae (298 cases, 88.7%), sternum and ribs (183 cases, 54.5%), pelvis (270 cases, 80.4%), upper limbs (182 cases, 54.2%) and lower limbs (240 cases, 71.4%). The 5-year event-free survival (EFS) rate and overall survival (OS) rate were (30.4±2.7)% and (41.3±2.9)%, respectively.Univariate analysis showed a significantly lower 5-year OS rate in skeletal metastatic HR-NB patients with poor prognostic classification, the morphology of neuroblastoma (stroma-poor) and ganglioneuroblastoma (intermixed), high index of mitosis-karyorrhexis index, lactate dehydrogenase≥587 U/L, serum ferritin≥92 μg/L, MYCN amplification and 1p loss of heterozygosity, and metastases in the viscerocranium, neurocranium, vertebrae, sternum and ribs, pelvis, upper limbs and lower limbs (all P<0.05). The 5-year OS rate of HR-NB patients with all 7 regions of skeletal metastases was only (14.2±5.9)%, which was significantly lower than that in patients with a single region metastasis or multi-region metastases[(66.0±10.2)% vs.(43.6±3.4)%, χ2=45.722, P<0.05]. Cox multifactorial analysis showed that MYCN amplification ( HR=4.165, 95% CI: 2.356-7.363) and the viscerocranium metastasis ( HR=2.560, 95% CI: 1.519-4.315) were the independent risk factors affecting the prognosis of HR-NB patients with skeletal metastases (all P<0.05). Conclusions:The prognosis is extremely poor in HR-NB patients with multiple skeletal metastases at the initial diagnosis.The amplification of MYCN and the viscerocranium metastasis are the poor prognostic factors for HR-NB patients with skeletal metastases.

By reviewing ancient materia medica， prescription and medical books， combined with modern literature， the paper made textual research on the name， origin， producing area， quality evaluation， harvesting and processing methods of Angelicae Pubescentis Radix and Notopterygii Rhizoma et Radix， so as to provide a basis for the selection and use of these two herbs in the development of famous classical formulas. Through textual research， it can be found that Angelicae Pubescentis Radix and Notopterygii Rhizoma et Radix were mixed together in the early history of China， but the distinction was first made during the Southern and Northern dynasties， and since then there have been constant controversies， and it is not until contemporary times that they are distinguished clearly. In the past dynasties， Duhuo and Qianghuo were used as the rectification of names， some aliases and trade names were also seen. Angelica biserrata is the mainstream origin of Angelicae Pubescentis Radix in the past dynasties， and there are many plants belonging to Angelica， Heracleum and Aralia， which are also used as this medicine. However， the origin of Notopterygii Rhizoma et Radix used in the past dynasties is mostly Notopterygium incisum or N. franchetii， which is relatively uniform. The producing areas of Angelicae Pubescentis Radix and Notopterygii Rhizoma et Radix are mostly concentrated in the western and northwestern regions of China， among which Angelicae Pubescentis Radix is mainly produced in Hubei， Chongqing， Sichuan， Shaanxi and other places， and the border area between Hubei and Chongqing is the geo-authentic area. Notopterygii Rhizoma et Radix is mainly produced in Sichuan， Gansu， Qinghai， Shaanxi and others with the western and northern Sichuan and southern Gansu as the geo-authentic areas. Angelicae Pubescentis Radix and Notopterygii Rhizoma et Radix in the past dynasties were harvested in spring and autumn， especially in February and August of the lunar calendar. Angelicae Pubescentis Radix with strong main roots， few branches， firm texture and strong aroma is superior， and Notopterygii Rhizoma et Radix with strong rhizomes， tightly raised knots， purple-brown skin， tight cross-section， strong aroma and silkworm-like shape is superior. The processing methods of Angelicae Pubescentis Radix and Notopterygii Rhizoma et Radix are mostly cut after cutting the reeds， and the raw product is used as medicine. Based on the above research results， it is recommended that the roots of A. biserrata should be used for Angelicae Pubescentis Radix and the roots of N. incisum should be used for Notopterygii Rhizoma et Radix in the development of famous classical formulas， and raw products should be used in the formulas that do not specify processing requirements.

【Objective】 To evaluate the predictive value of isoform [-2] proprostate-specific antigen, p2 PSA (p2PSA) and its derived indexes for prostate cancer in a Chinese cohort with PSA 4-20 ng/mL. 【Methods】 A total of 139 males scheduled for biopsy were enrolled in the prospective study from Nov.2021 to Jun.2022. The total PSA (tPSA), free PSA (fPSA), fPSA/tPSA (f/t) and p2PSA were collected, and the percentage of p2PSA(%p2PSA) and prostate health index(PHI) were calculated. The predictive value of p2PSA and its derived indexes were compared with traditional indexes with receiver operating characteristic (ROC) curve and Logistic analysis. 【Results】 Prostate cancer was found in 54 cases (38.8%). There were significant statistical differences in tPSA(10.68 vs.8.14, P=0.021), f/t(0.13 vs.0.16, P=0.006), p2PSA(30.25 vs.19.81, P<0.001), %p2PSA(21.52 vs.13.15, P<0.001) and PHI(64.3vs.38.2, P<0.001) between prostate cancer patients and non-prostate cancer patients. The area under the ROC curve (AUC) of tPSA, fPSA, %fPSA, p2PSA, %p2PSA and PHI were 0.63, 0.51, 0.63, 0.71, 0.73, and 0.80, respectively. The inclusion of %p2PSA and PHI significantly increased the prediction efficiency of the basic prediction model (AUCbase+PHI=0.81, AUCbase+%p2PSA=0.78, AUCbase=0.67). With 35 as the recommended cut-off value of PHI, the incidence of meaningless puncture was reduced by 25.8%(36/139). 【Conclusion】 The application of p2PSA and its derived indexes have good predictive value for patients with PSA 4-20 ng/mL. The combined detection of %p2PSA and PHI can significantly increase the detection efficiency of prostate cancer and reduce the incidence of meaningless prostate puncture by 25.8%.

Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-89(89Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[89Zr]Zr-des-ferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,＞99％)and specific activity(24.15±1.34 GBq/μmol),and was stable in 5％human serum albumin,and phosphate buffer saline(＞85％RCP at 96 h).The EC50 values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P＞0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[89Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2(-).The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16％ID/g)than BGC823 mice(0.69±0.02％ID/g)and blocking group(0.72±0.02％ID/g).A dosimetry estimation study showed that the effective dose of[89Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these re-sults suggest that Good Manufacturing Practices produced by this immuno-positron emission tomog-raphy probe can detect CLDN18.2-overexpressing tumors.

The Zika virus (ZIKV) and dengue virus (DENV) flaviviruses exhibit similar replicative processes but have distinct clinical outcomes. A systematic understanding of virus–host protein–pro-tein interaction networks can reveal cellular pathways critical to viral replication and disease patho-genesis. Here we employed three independent systems biology approaches toward this goal. First, protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and 20,240 human proteins revealed multiple conserved cellular pathways and protein complexes, including proteasome complexes. Second, an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this process. Third, high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds, including six proteasome inhibitors that suppress both ZIKV and DENV replication. Integrative analyses of these orthogonal datasets pinpoint proteasomes as crit-ical host machinery for ZIKV/DENV replication. Our study provides multi-omics datasets for fur-ther studies of flavivirus–host interactions, disease pathogenesis, and new drug targets.

Objective: To observe the effects of Chinese herbalprescription Tizhi-Pingtiao Powder (TP) based on Five-Yun Six-Qi theory to treat hyperlipidemia (HLP). Methods: This study included 641 HLP patients from Constitution medicine clinic in Dongzhimen hospital from January 2015 to November 2017. The embryonic period’s (ten months) Five-Yun Six-Qi endowments of the enrolled patients were analyzed and TP were prescribedaccordingly, in the absent of lipid-lowering drugs. The curative effect was observed after three months’ TP treatment and reviewed ofeach 3 months, and long-term effects will be observed for 1 year,either take the priscription or not. Curative effect is based on blood lipids maintain normal as well as constitution improved while stopped lipid-lowering drugs. Results: Among the 641 patients who met the inclusion criteria, 379 patients take on complete, and 300 patients (79.2%) were clinically cured (with blood lipid decreased to normal, overall constitution and complication condition improved), 375 patients (99.0%) were completely cured. Among 262 patients without dietary restriction, 143 patients (54.6%) were clinically cured, 240 patients (91.6%) were completely cured. Long-term effects showed that 210 patients stopped the TP after 3 months' treatment, the recurrence rate at the end of the 3rd month, 6th month and 12th month in the patients who were on complete dietary restriction were 4.1%, 48.8% and 76.9%, while the recurrence rate in the patients who had not implemented dietary restriction were 37.1%, 70.8%, 89.9%. A total of 115 patients continued the TP for the other 12 months, the recurrence rate at the end of 3rd month, 6th month and 12th month in the patients who were on complete dietary restriction were 2.5%, 4.8% and 6.0%, while the recurrence rate in the patients who had not implemented dietary restriction were 6.5%, 16.1%, 29.0%. The difference between the four groups was significant. All recrudescent patients could gain recovery in a month after re-taking the herbs. Conclusions Chinese herbal priscription TP combined with dietary modification showed long term effect for HLP and improve the constitution comprehensively.

Objective: To analyze the clinical characteristics of newly treated high-risk group neuroblastoma (NB) patients with bone marrow metastasis and to explore the prognostic factors. Methods: The clinical features (sex, age, stage, risk group, pathological type, metastatic site, etc.) of 203 newly treated high-risk NB patients with bone marrow metastasis admitted to Hematology Oncology Center, Beijing Children′s Hospital from January 2007 to December 2016 were analyzed retrospectively. There were 118 males (58.1%) and 85 females (41.9%). Kaplan-Meier method was used for survival analysis and Cox regression was used to analyze the prognostic factors. Results: The age at onset of the 203 patients was 41 months (9-147 months). The metastatic sites at diagnosis were as follows: bone in 195 cases (96.1%), distant lymph nodes in 104 cases (51.2%), skull and endomeninx in 61 cases (30.0%), orbit in 30 cases (14.8%), pleura in 16 cases (7.9%), liver in 13 cases(6.4%), canalis spinalis in 13 cases (6.4%), other sites in 11 cases (5.4%) and skin and soft tissue in 10 cases (4.9%). In all, 194 cases were enrolled for prognostic analysis. The follow-up time was 36 months (1 day-138 months) , and the 5-years event free survival (EFS) and overall survival (OS) were 36.1% and 39.7%, respectively. A total of 118 patients (60.8%) had events (first relapse or death) with the time to event occurrence was 15 months (1 day-72 months), whereas 112 patients (57.7%) died with the event occurrence to death time was 3 months (1 day-21 months). There was no significant difference in 5-years OS between radiotherapy group and non-radiotherapy group (42.3% vs. 38.3%, χ²=3.671, P=0.055). The 5-years OS in transplantation group was significantly better than the non-transplantation group (44.3% vs. 35.5%, χ²=8.878, P=0.003), and the radiotherapy combined transplantation group also had a better 5-years OS rate than the non-radiotherapy combined transplantation group (45.8% vs. 37.3%, χ²=5.945, P=0.015). Univariate survival analysis showed lactate dehydrogenase ≥ 1 500 U/L, the amplification of MYCN, the metastatic sites of orbit, canalis spinalis and pleura were associated with poor prognosis of newly diagnosed high-risk NB patients (χ²=21.064, 13.601, 3.998, 6.183, 15.307, all P<0.05). The amplification of MYCN and the metastatic sites of pleura were risk factors for prognosis of newly diagnosed high-risk NB patients by Cox regression models (HR=1.896,1.100, 95%CI: 1.113-3.231, 1.020-1.187, both P<0.05). Conclusions The prognosis is unfavorable in high-risk group NB patients with BM metastasis. Radiotherapy combined with transplantation can further improve the prognosis of these patients. The amplification of MYCN and the metastatic sites of pleura were the poor prognostic factors for high-risk NB patients with bone marrow metastasis.

To analyze the clinical characteristics of newly treated high?risk group neuroblastoma (NB) patients with bone marrow metastasis and to explore the prognostic factors. Methods The clinical features (sex, age, stage, risk group, pathological type, metastatic site, etc.) of 203 newly treated high?risk NB patients with bone marrow metastasis admitted to Hematology Oncology Center, Beijing Children's Hospital from January 2007 to December 2016 were analyzed retrospectively. There were 118 males (58.1%) and 85 females (41.9%). Kaplan?Meier method was used for survival analysis and Cox regression was used to analyze the prognostic factors. Results The age at onset of the 203 patients was 41 months (9-147 months). The metastatic sites at diagnosis were as follows: bone in 195 cases (96.1%), distant lymph nodes in 104 cases (51.2%), skull and endomeninx in 61 cases (30.0%), orbit in 30 cases (14.8%), pleura in 16 cases (7.9%), liver in 13 cases(6.4%), canalis spinalis in 13 cases (6.4%), other sites in 11 cases (5.4%) and skin and soft tissue in 10 cases (4.9%). In all, 194 cases were enrolled for prognostic analysis. The follow?up time was 36 months (1 day-138 months), and the 5?years event free survival (EFS) and overall survival (OS) were 36.1% and 39.7%, respectively. A total of 118 patients (60.8%) had events (first relapse or death) with the time to event occurrence was 15 months (1 day-72 months), whereas 112 patients (57.7%) died with the event occurrence to death time was 3 months (1 day-21 months). There was no significant difference in 5?years OS between radiotherapy group and non?radiotherapy group (42.3% vs. 38.3%, χ2=3.671, P=0.055). The 5?years OS in transplantation group was significantly better than the non?transplantation group (44.3% vs. 35.5%, χ2=8.878, P=0.003), and the radiotherapy combined transplantation group also had a better 5?years OS rate than the non?radiotherapy combined transplantation group (45.8% vs. 37.3%, χ2=5.945, P=0.015). Univariate survival analysis showed lactate dehydrogenase ≥1 500 U/L, the amplification of MYCN, the metastatic sites of orbit, canalis spinalis and pleura were associated with poor prognosis of newly diagnosed high?risk NB patients (χ2=21.064, 13.601, 3.998, 6.183, 15.307, all P<0.05). The amplification of MYCN and the metastatic sites of pleura were risk factors for prognosis of newly diagnosed high?risk NB patients by Cox regression models ( HR=1.896, 1.100, 95%CI :1.113-3.231, 1.020-1.187, both P<0.05). Conclusions The prognosis is unfavorable in high?risk group NB patients with BM metastasis. Radiotherapy combined with transplantation can further improve the prognosis of these patients. The amplification of MYCN and the metastatic sites of pleura were the poor prognostic factors for high?risk NB patients with bone marrow metastasis.