Afferent baroreflex failure(ABF)is a rare disease.It refers to the clinical syndrome caused by the impairment of the afferent limb of the baroreflex or its central connections at the level of the medul-la.The recognized causes include trauma,surgery in related areas(radical neck tumor surgery,carotid endarterectomy),neck radiotherapy,brain stem stroke,tumor growth paraganglioma and hereditary diseases,among which the most common cause is extensive neck surgery or radiotherapy for neck cancer.The main manifestations are fluctuating hypertension,orthostatic hypotension,paroxysmal tachycardia and bradycardia.This case is a young man,whose main feature is blood pressure fluctuation,accom-panied by neurogenic orthostatic hypotension(nOH).After examination,the common causes of hyper-tension and nOH were ruled out.Combined with the previous neck radiotherapy and neck lymph node dissection,it was considered that the blood pressure regulation was abnormal due to the damage of carotid sinus baroreceptor after radiotherapy for nasopharyngeal carcinoma and neck lymph node dissection,which was called ABF.At the same time,the patient was complicated with chronic hyponatremia.Com-bined with clinical and laboratory examination,the final consideration was caused by syndrome of in-appropriate antidiuretic hormone(SIADH).Baroreceptors controlled the secretion of heart rate,blood pres-sure and antidiuretic hormone through the mandatory"inhibition"signal.We speculate that the carotid sinus baroreceptor was damaged after neck radiotherapy and surgery,which leads to abnormal blood pres-sure regulation and nOH,while the function of inhibiting ADH secretion was weakened,resulting in higher ADH than normal level and mild hyponatremia.The goal of treating ABF patients was to reduce the frequency and amplitude of sudden changes in blood pressure and heart rate,and to alleviate the on-set of symptomatic hypotension.At present,drug treatment is still controversial,and non-drug treatment may alleviate some patients'symptoms,but long-term effective treatment still needs further study.The incidence of ABF is not high,but it may lead to serious cardiovascular and cerebrovascular events,and the mechanism involved is extremely complicated,and there are few related studies.The reports of rele-vant medical records warn that patients undergoing neck radiotherapy or surgery should minimize the da-mage to the baroreceptor in the carotid sinus in order to reduce the adverse prognosis caused by complica-tions.

Objectives:This study aimed to compare the clinical characteristics between light-chain cardiac amyloidosis(AL-CA)and transthyretin cardiac amyloidosis(ATTR-CA). Methods:A retrospective analysis was conducted in patients diagnosed with AL-CA and ATTR-CA at Peking University Third Hospital from January 2011 to October 2023.There were 35 patients diagnosed with AL-CA(AL-CA group)and 21 patients diagnosed with ATTR-CA(ATTR-CA group).Clinical manifestations,ECG,echocardiography and cardiac magnetic resonance(CMR)results were compared between patients with AL-CA and ATTR-CA. Results:Compared to the AL-CA group,the ATTR-CA group has a higher proportion of males(54.3%vs.90.5%,P=0.005),the proportion of patients with hypertension was lower(42.9%vs.9.5%,P=0.009).In terms of clinical manifestations,edema,proteinuria,renal insufficiency and serous effusion were more common in the AL-CA group,while the incidence of limb numbness was higher in the ATTR-CA group(all P＜0.05).There were significant differences in the incidence of limb lead low voltage(57.1%vs.28.6%,P=0.038)and conduction block(14.3%vs.61.9%,P=0.001)between the AL-CA group and ATTR-CA group on ECG.Although the AL-CA group had a shorter time interval from initial symptoms to diagnosis(6.0[2.0,15.0]months vs.35.0[14.0,56.5]months,P=0.002)and less pronounced left ventricular thickening on echocardiography(interventricular septum thickness:[13.3±2.0]mm vs.[15.7±2.2]mm,P=0.001;left ventricular mass:[198.4±67.8]g vs.[246.6±53.5]g,P=0.009)and CMR(interventricular septum thickness:[16.0±2.1]mm vs.[18.9±3.8]mm,P=0.033;left ventricular mass:[132.9±45.3]g vs.[194.7±50.8]g,P=0.011),the proportion of patients with NYHA grades Ⅲ-Ⅳ(48.6%vs.19.0%,P=0.027)was higher,the levels N-terminal B-type natriuretic peptide precursor and cardiac troponin T levels were higher(both P＜0.05),and the 1-year survival rate was lower in the AL-CA group than in the ATTR-CA group(65.7%vs.100%,P=0.001). Conclusions:AL-CA and ATTR-CA had differences in clinical and ECG manifestations.While the severity of left ventricular hypertrophy was less pronounced in AL-CA compared to ATTR-CA,cardiac function and prognosis were worse in AL-CA than in ATTR-CA.

During the gene editing process mediated by CRISPR/Cas9, precise genome editing and gene knock-in can be achieved by the homologous recombination of double-stranded DNA (dsDNA) donor template. However, the low-efficiency of homologous recombination in eukaryotic cells hampers the development and application of this gene editing strategy. Here, we developed a novel CRISPR/Cas9-hLacI donor adapting system (DAS) to enhance the dsDNA-templated gene editing, taking the advantage of the specific binding of the LacI repressor protein and the LacO operator sequence derived for the Escherichia coli lactose operon. The codon-humanized LacI gene was fused as an adaptor to the Streptococcus pyogenes Cas9 (SpCas9) and Staphylococcus lugdunensis Cas9 (SlugCas9-HF) genes, and the LacO operator sequence was used as the aptamer and linked to the dsDNA donor template by PCR. The Cas9 nuclease activity after the fusion and the homology-directed repair (HDR) efficiency of the LacO-linked dsDNA template were firstly examined using surrogate reporter assays with the corresponding reporter vectors. The CRISPR/Cas9-hLacI DASs mediated genome precise editing were further checked, and we achieved a high efficiency up to 30.5% of precise editing at the VEGFA locus in HEK293T cells by using the CRISPR/SlugCas9-hLacI DAS. In summary, we developed a novel CRISPR/Cas9-hLacI DAS for dsDNA-templated gene editing, which enriches the CRISPR/Cas9-derived gene editing techniques and provides a novel tool for animal molecular design breeding researches.
Humans ; Animals ; Gene Editing ; CRISPR-Cas Systems/genetics* ; HEK293 Cells ; Homologous Recombination ; DNA

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
Female ; Humans ; Uterine Cervical Neoplasms/drug therapy* ; Prospective Studies ; Quality of Life ; Neoplasm Staging ; Chemoradiotherapy ; Chemotherapy, Adjuvant/adverse effects* ; Adjuvants, Immunologic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies

Objective:To evaluate the efficacy by using domestic recombinant human thyroid-stimulating hormone (rhTSH) in patients with differentiated thyroid cancer (DTC) before or after 131I therapy. Methods:From May 2019 to November 2020, a total of 24 patients with DTC (5 males, 19 females, median age 41 years) in Peking Union Medical College Hospital and Affiliated Tumor Hospital of Zhengzhou University were enrolled into the open-label, dose escalation phase Ⅰ study. All patients were divided into 4 domestic rhTSH dose groups: 0.9 mg×1 d (group A), 0.9 mg×2 d (group B), 1.8 mg×1 d (group C), 1.8 mg×2 d (group D) in succession, with 6 patients in each group. Each patient underwent rhTSH phase and thyroid hormone withdrawal (THW) phase. The end point included safety, tolerability, the quality of life (hypothyroidism symptom and sign score (Billewicz score), profile of mood states (POMS)), effectiveness (thyroid-stimulating hormone (TSH) and thyroglobulin (Tg) levels, diagnostic whole-body scan (Dx-WBS)) and pharmacokinetic characteristics (peak time, peak concentration) of rhTSH. Paired t test and Wilcoxon signed rank test were used for statistical analysis. Results:There were no dose-limiting toxicities, serious adverse events, or no grade ≥3 adverse events reported. The quality of life in rhTSH phase was significantly better than those in THW phase, including the lower Billewicz score (-53.00(-53.00, -53.00) vs -39.50(-47.00, -23.00); S=119.50, P<0.001) and the lower POMS score (91.92±12.06 vs 99.67±19.13; t=0.95, P=0.025). Serum TSH level was increased from 0.04(0.02, 0.11) mU/L (baseline) to 150.00(105.20, 173.31) mU/L 24 h after the last rhTSH administration, which was increased along with the elevation of rhTSH doses. In the THW phase, patients′ TSH levels were≥30 mU/L after 23 d (median) of THW, with the median of 73.51(57.22, 106.22) mU/L. Median Tg level of baseline was 0.10(0.10, 0.41) μg/L, which reached a peak of 0.85(0.12, 3.01) μg/L at 48 h after rhTSH administration. The peak Tg level in the THW phase was 0.88(0.15, 8.04) μg/L. The Dx-WBS consistency rate between rhTSH and THW phase was 95.8%(23/24). Conclusion:rhTSH is a safe and effective method to stimulate the serum Tg level and radioiodine uptake in patients undergoing post-operation or post- 131I assessment for DTC, as well as maintain a higher quality of life in comparison to THW phase.

Objective:To investigate the differences in the expression of microRNA (miR)-216a and its target gene SerpinB5 at the tissue level, and the effects of miR-216a on the proliferation of different liver cancer cells by regulating the expression of SerpinB5.Methods:Through bioinformatics prediction and selection of miR-216a that regulated SerpinB5. the expressions in liver cancer and normal tissues were detected by real time polymerase chain reaction (PCR). The miR-216a simulacrum and inhibitor, si-Serpinb5 and pcdna3.1-Serpinb5 to HepG2 and MHCC97H (97H) were transfected with liposomes, respectively. Real time PCR and Wester-Blot were used to detect the expression of miR-216a and SerpinB5 before and after transfection, and CCK8 was used to detect the influence of both on the proliferation of liver cancer cells.Results:The expression of miR-216a in human liver cancer tissues was higher than that in adjacent tissues, and the difference was statistically significant ( P < 0.01). The expression of SerpinB5 in human liver cancer tissues was lower than that adjacent tissues, and the difference was statistically significant ( P < 0.01). In HepG2 and 97H, miR-216a inhibitor and SerpinB5 overexpression group showed down-regulated miR-216a expression, which was statistically different from the control group ( P < 0.01). The proliferation of miR-216a inhibitor and pcdna3.1-serpinb5 group was lower than the control group, with statistically significant differences ( P < 0.01). Conclusions:The high expression of SerpinB5 can inhibit the proliferation of liver cancer cells, suggesting that SerpinB5 may have an anti-oncogene effect. MiR-216a may negatively regulate the expression of SerpinB5 and affect the proliferation of HCC cells.

OBJECTIVE： To compare the cost-effectiveness of long-effect and short-effect granulocyte stimulating factor in prevention and treatment of bone marrow suppression induced by chemotherapy for lung malignancies， and to provide reference for rational drug use in the clinic. METHODS： A retrospective analysis was conducted for 132 cases who used granulocyte stimulating factor to prevent and treat bone marrow suppression induced by chemotherapy for lung malignancies in the Affiliated Tumor Hospital of Zhengzhou University during Jan. 2017 to Jun. 2018. Among them， 60 cases were treated with Recombinant human granulocyte stimulating factor injection （short-effect， group A）， and 72 cases were treated with Polyethylene glycol recombinant human granulocyte stimulating factor injection （long-effect， group B）. Clinical efficacies， the occurrence of bone marrow suppression and ADR were compared between 2 groups. Cost was calculated， and cost-effectiveness analysis was conducted. Sensitivity analysis was conducted by down-regulating 20％ drug price. RESULTS： The total response rates of group A and B were 71.7％ and 75.0％， without statistical significance （P＞0.05）. There was no statistical significance in the incidence and duration of bone marrow suppression or the incidence of ADR （P＞0.05）. Average treatment costs of the two groups were （335.91±180.34） and （1 982.75±603.15） yuan； the cost of group A was significantly lower than that of group B （P＜0.05）. The cost-effectiveness ratio of them were 4.69 and 26.44， while group A as a reference， incremental cost-effectiveness ratio of group B was 494.55. The sensitivity analysis results were in agreement with the cost-effectiveness analysis. CONCLUSIONS： The effectiveness of Recombinant human granulocyte stimulating factor injection is similar to that of Polyethylene glycol recombinant human granulocyte stimulating factor injection for the prevention and treatment of bone marrow suppression induced by chemotherapy for lung malignancies. But the cost-effectiveness ratio of the former is lower than that of the latter.

Objective To investigate the expression of bone marrow γ-H2AX in the patients with multiple myeloma(MM) and its correlation with the prognosis.Methods The patients with newly diagnosed MM in this hospital were selected as the case group,and the patients with non-hemopoietic system tumor without obvious morphological abnormalities by bone marrow smear and biopsy served as the control group.The immunohistochemistry was adopted to detect the expression level of bone marrow γ-H2AX in the cases group and control group,the image-Pro Plus(IPP) semiquantitative analysis was performed.The expression differences were compared between the two groups,moreover the case group was re-divided into the strong expression group and weak expression group according to γ-H2AX expression level.Then the relation ship between γ-H2AX expression level and the prognosis in the patients with MM.Results The bone marrow γ-H2AX expression level in the case group was significantly higher than that in the control group (P＜0.05);the level of γ-H2AX expression in the strong expression group was significantly stronger than that in the weak expression group (P＜0.05).Conclusion The level of γ-H2AX expression was higher among MM patients,and the over expression of γ-H2AX predicts the shorter survival time.

OBJECTIVE: To analyze the clinical features and prognosis of cervical adenocarcinoma (AC) and adenosquamous carcinoma of cervix (ASC). METHODS: The clinical data of 237 patients, including 201 cases of AC and 36 cases of ASC (FIGO stage ⅠB1-ⅡA), who underwent surgery in Qilu Hospital between September 2007 and September 2016 were reviewed. Clinical features of two groups were compared, and Kaplan-Meier survival analysis was performed to evaluate the prognosis. RESULTS: A larger proportion of ASC patients had lymphovascular space invasion compared with AC patients (<0.01), but no significant differences were observed in the age, FIGO stage, size of tumor, depth of stromal invasion, parametrial invasion, lymphatic metastasis and risk grade between two groups (all >0.05). The 5-year overall survival rates of AC and ASC groups were 79.4% and 78.3%, and the 5-year recurrence-free survival rates were 77.4% and 73.0%. Among patients received concurrent chemoradiotherapy, the 5-year overall survival rates were 71.0% and 61.4%, and the 5-year recurrence-free survival rates were 68.8% abd 61.1%, respectively. No significant differences were observed in 5-year overall survival rates and recurrence-free survival rates between AC and ASC patients (all >0.05). CONCLUSIONS Lymphovascular space invasion was more likely to occur in patients with ASC, but there was no significant difference in the prognosis between AC and ASC patients.
Adenocarcinoma ; diagnosis ; mortality ; Carcinoma, Adenosquamous ; diagnosis ; mortality ; Female ; Humans ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Survival Rate ; Uterine Cervical Neoplasms ; diagnosis ; mortality