COMPERA 2.0 risk stratification has been demonstrated to be useful in patients with precapillary pulmonary hypertension (PH). However, its suitability for patients at risk for post-capillary PH or PH associated with left heart disease (PH-LHD) is unclear. To investigate the use of COMPERA 2.0 in patients with severe aortic stenosis (SAS) undergoing transcatheter aortic valve replacement (TAVR), who are at risk for post-capillary PH, a total of 327 eligible SAS patients undergoing TAVR at our institution between September 2015 and November 2020 were included in the study. Patients were classified into four strata before and after TAVR using the COMPERA 2.0 risk score. The primary endpoint was all-cause mortality. Survival analysis was performed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression model. The study cohort had a median (interquartile range) age of 76 (70‒80) years and a pulmonary arterial systolic pressure of 33 (27‒43) mmHg (1 mmHg=0.133 kPa) before TAVR. The overall mortality was 11.9% during 26 (15‒47) months of follow-up. Before TAVR, cumulative mortality was higher with an increase in the risk stratum level (log-rank, both P<0.001); each increase in the risk stratum level resulted in an increased risk of death (hazard ratio (HR) 2.53, 95% confidential interval (CI) 1.54‒4.18, P<0.001), which was independent of age, sex, estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and valve type (HR 1.76, 95% CI 1.01‒3.07, P=0.047). Similar results were observed at 30 d after TAVR. COMPERA 2.0 can serve as a useful tool for risk stratification in patients with SAS undergoing TAVR, indicating its potential application in the management of PH-LHD. Further validation is needed in patients with confirmed post-capillary PH by right heart catheterization.
Humans ; Aortic Valve Stenosis/complications* ; Aged ; Hypertension, Pulmonary/mortality* ; Male ; Female ; Transcatheter Aortic Valve Replacement ; Aged, 80 and over ; Risk Assessment/methods* ; Proportional Hazards Models ; Kaplan-Meier Estimate ; Retrospective Studies

To improve the current situation of multiple preoperative visits and evaluations for elderly patients and other patients with complex conditions, in December 2022, Peking Union Medical College Hospital established preoperative multidisciplinary evaluation clinic (shorted as joint clinic). The joint clinic established a multidisciplinary team, clarified service targets, and developed standardized clinic workflows to provide patients with a " one-stop" preoperative assessment(physical fitness assessment, nutritional assessment, and frailty assessment, etc.), nutritional optimization intervention, and prerehabilitation education and guidance services. This practice strengthened preoperative risk management, improved preoperative assessment efficiency, and ensured the safety of patients during the perioperative period. As of September 2023, the joint clinic had received a total of 128 patients, of which 86 underwent surgery after preoperative evaluation and prehabilitation optimization. The obesity rate, smoking rate, and number of frailty cases of these patients had decreased from 13.96%, 11.63%, and 18 at the time of visit to 9.30%, 4.65%, and 14 on the day before surgery, respectively. They had recovered well after surgery. This practice had improved the preoperative status of patients and created conditions for high-risk patients to undergo surgery smoothly, so as to provide references for other hospitals to carry out multidisciplinary collaborative preoperative evaluation works.

TROP-2, a tumor-associated antigen, has been implicated in the progression of various epithelial tumors. Due to its favorable expression profile, TROP-2 has emerged as a promising target for antibody-drug conjugates (ADCs) based anti-tumor therapies. Although ADCs have shown efficacy in cancer treatment, their application in solid tumors is hindered by their high molecular weight, poor tumor penetration, and release of cytotoxic molecules. Therefore, a recombinant immunotoxin was developed based on a shark-derived variable domain of immunoglobulin new antigen receptor (VNAR) antibody. VNARs are only one-tenth the size of IgG antibodies and possess remarkable tissue penetration capabilities and high stability. In this study, a shark VNAR phage display library was created, leading to the identification of shark VNAR-5G8 that targets TROP-2. VNAR-5G8 exhibited a high affinity and cellular internalization ability towards cells expressing high levels of TROP-2. Epitope analysis revealed that VNAR-5G8 recognizes a hidden epitope consisting of CRD and TY-1 on TROP-2. Subsequently, VNAR-5G8 was fused with a truncated form of Pseudomonas exotoxin (PE38) to create the recombinant immunotoxin (5G8-PE38), which exhibited significant anti-tumor activity in vitro and in vivo. Overall, this study highlights the promise of 5G8-PE38 as a valuable candidate for cancer therapy.

Objective:To study the expression level of programmed death ligand 1 (PD-L1) in combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and its correlation with the clinical characteristics and prognosis.Methods:The clinical data of 75 patients with cHCC-CCA undergoing surgery in Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2019, including 61 males and 14 females, with a median age of 55 years (36 to 77). Immunohistochemistry was conducted to determine the PD-L1 expression in tumor. The status of PD-L1 expression, clinicopathological data and prognosis of patients were analyzed.Results:In low-differentiated cHCC-CCA tissues, the proportion of PD-L1 expression (21.1%, 8/38) was higher than that in moderately to well-differentiated cHCC-CCA tissues (2.70%, 1/37, χ2=4.366, P=0.037). The median disease-free survival (DFS) and overall survival (OS)of PD-L1 positive patients were 12.3 and 15.1 months, respectively, lower than those of PD-L1 negative patients (14.4 and 23.3 months). The difference of DFS was statistically significant ( χ2=4.052, P=0.044). In multivariate analysis, major vascular invasion (DFS: HR=1.965, 95% CI: 1.119-3.450, P=0.019; OS: HR=1.781, 95% CI: 1.022-3.105, P=0.042) and lymph node metastasis (DFS: HR=2.451, 95% CI: 1.1033-5.814, P=0.042; OS: HR=2.652, 95% CI: 1.120-6.279, P=0.027) were identified as independent prognostic factors affecting DFS and OS. Conclusions:The proportion of PD-L1 positive is higher inthe low-differentiated cHCC-CCA tissue compared to that in moderately to well-differentiated cHCC-CCA. The major vascular invasion and lymph node metastasis are independent factors affecting the prognosis of patients with cHCC-CCA.

Objective:To evaluate the status and influencing factors of psychiatric comorbidities of patients with epilepsy (PWEs) in Hubei province during the outbreak of COVID-19.Methods:From February 23, 2020 to March 5, 2020, a network questionnaire survey (including demographic characteristics, seizures, Generalized Anxiety Disorder Scale-7 score, Patient Health Questionnaire-9 score, Insomnia Severity Index score) was conducted among 570 PWEs who visited the Epilepsy Center of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology during April 1, 2019 and January 20, 2020. SPSS 22.0 software was used for correlation analysis of sociodemographic characteristics, epilepsy related factors, perceived threat to the COVID-19 and psychiatric comorbidity (depression, anxiety and insomnia) of PWEs during the COVID-19 epidemic.Results:A total of 362 valid questionnaires were included for analysis (the response rate was 63.51%,362/570). Thirty-four (9.4%), forty-seven (13.0%) and seventy-one (19.6%) patients suffered from anxiety, depression and insomnia, respectively. Patients with seizure frequency ≥2 times/month before the epidemic ( OR=3.395,95% CI 1.561-7.384, P=0.002), poor subjective quality of life during the epidemic ( OR=10.753,95% CI 1.938-59.654, P=0.024), and moderate to severe worry about bad impact of the epidemic on epilepsy ( OR=3.077, 95% CI 1.382-6.853, P=0.006) were more likely to be anxious. Patients with poor subjective quality of life during the epidemic ( OR=6.188, 95% CI 1.317-29.079, P=0.021) were more likely to be depressed. Patients with COVID-19 related symptoms ( OR=3.609, 95% CI 1.674-7.778, P=0.001), children ( OR=3.090, 95% CI 1.759-5.431, P<0.001), seizure frequency ≥2 times/month before the epidemic ( OR=1.907, 95% CI 1.017-3.575, P=0.044), and moderate to severe worry about unanticipated seizures ( OR=2.555, 95% CI 1.370-4.764, P=0.003) were more likely to suffer from insomnia. Conclusions:During the COVID-19 epidemic, parts of PWEs suffered from anxiety, depression and insomnia. PWEs with poor subjective quality of life, high frequency of epileptic seizures before the epidemic, excessive worry about bad impact of the epidemic on epilepsy and excessive worry about unanticipated seizures were prone to anxiety, depression and insomnia.

Objective:To evaluate the impact of metastatic site on the prognosis in patients with metastatic renal cell carcinoma (mRCC), and it′s value for modifying the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria.Methods:The data of 218 patients pathologically diagnosed with mRCC were analyzed retrospectively in West China Hospital from Jan. 2009 to Dec. 2019. Among all patients, 71.6%(156/218) were male, and 89.0% (194/218) underwent nephrectomy. Most of the patients were pathologically diagnosed with renal clear cell carcinoma (176 patients, 80.7%). Lung (137/218, 62.8%) was the most observed metastatic site, following by bone (47/218, 26.1%), lymph node (37/218, 17.0%) and liver (23/218, 10.6%). All patients were classified into favorable (26 patients, 11.9%), intermediate (126 patients, 57.8%) or poor (37 patients, 17.0%) risk group according to IMDC criteria. Endpoints of this study were progression-free survival (PFS), overall survival (OS) and tumor response. The impact of metastatic sites on patients’ prognosis was analyzed, and those that had significant relationship with prognosis were then added into IMDC criteria and a modifying IMDC model was established. Predictive value of this model was further evaluated by calculating concordance index (C-index).Results:In the whole cohort, median PFS and OS were 13.0 and 33.0 months. Survival analysis suggested that patients with bone ( P=0.004), brain ( P=0.042) and liver ( P=0.046) had significantly shorter OS. Thus, patients were divided into two groups: patients with bone/brain/liver metastasis (82 patients, 37.6%) and patients with other metastatic sites (136 patients, 62.4%). Compared with patients with other metastatic sites, those who with bone/brain/liver metastasis had inferior tumor response by TKIs treatment (disease control rate: 51.2% vs. 73.5%, P=0.004). Multivariate analysis suggested that bone/brain/liver metastasis had negative impact on OS (25.0 vs. 47.0 mo, P=0.039). Furthermore, bone/brain/liver metastasis also showed significant relationship with shorter OS in IMDC low (30.0 vs. 62.0 months, P=0.036), intermediate (31.0 vs. 48.0 months, P=0.048) or high (7.0 vs. 18.0 months, P=0.037) risk group, indicating that metastatic site had predictive value for prognosis of mRCC patients. Based on that, bone/brain/liver metastasis were added into the IMDC criteria, and weighting each parameter was weighted according to its coefficient to patients’ OS. Finally, a modified IMDC scoring system were established. C-index of this modified model was 0.669 (0.599 for current IMDC criteria). Conclusions:Bone/brain/liver metastasis in mRCC patients indicated a shorter OS duration. When adding bone/brain/liver metastasis as a predictive parameter for prognosis of mRCC patients into IMDC criteria, the modified IMDC criteria could offer more accurate prediction for patients’ survival.

Objective:To establish a method of ion chromatography for the determination of sodium, potassium and citric acid in potassium sodium hydrogen citrate granule. Methods:The chromatographic conditions for potassium and sodium were as follows:a Di-onex IonPac CS12A column (250 mm × 4. 6 mm, 5μm), 0. 02 mol·L-1 methane sulfonic acid solution as the mobile phase, the flow rate of 1. 0 ml·min-1 , the suppressor of CSRS 300, the inhibition current of 59 mA, the inhibition type conductivity detector, and the injection volume of 25 μl. The chromatographic conditions for citrate were as follows: a Dionex HPICE-AS1 colunm ( 250 mm × 9. 0 mm,7. 5 μm), 0. 015 mol·L-1sulfuric acid solution as the mobile phase, the flow rate of 0. 6 ml·min-1, the detection wave-length of 220 nm and the injection volume of 10 μl. Results: The linear range of sodium was 0.82-82.49 μg·ml-1(r=0.9999), and the average recovery was 98.9%(RSD =0.55%, n =9). The linear range of potassium was 1.38-137.89 μg·ml-1 (r =1. 0000), and the average recovery was 100. 5% (RSD=0. 53%, n=9). The linear range of citric acid was 0. 021-10. 600 μg· ml-1(r=1. 0000), and the average recovery was 99. 1% (RSD=0. 54%, n=9). Conclusion:The method is simple, rapid and ac-curate, and can be used for the quality control of potassium sodium hydrogen citrate granule.

Objective: To investigate the blood lead level of children living around lead-zinc mining areas, in order to analyze its distribution features of the population. Methods: In August 2016, three natural villiages around lead-zinc mines were selected randomly as survey sites, which were grouped A, B and C according to each distances from the center field, totally 1 379 children from the three villages were selected by cluster random sampling method as the investigation subjects, and their elbow peripheral vein blood samples were collected to determine the blood lead level by graphite furnace atomic absorption spectrometry. The distribution features of blood lead in different district, gender and age groups were compared and analyzed. Results: The median and quartile range of blood lead were 0.066 and 0.058 mg/L respectively. The blood lead levels of 341 children were esceeding 100 μg/L and that account for 24.73%. The median blood lead showed statistical significant differrnce among three groups (P<0.01) , and the medians from high to low were: 0.075 mg/L (A) , 0.065 mg/L (B) and 0.059 mg/L (C) respectively. The average blood lead of male was higher than that of female (P<0.01) . There was significant difference in blood lead levels among different aged groups (P<0.01) , and the high blood lead rate dicreased with the increase of age (P<0.01) . Results of multivariate logistic regression analysis showed that there was a high risk of excessive lead in the blood lead of boys aged 1-6 years from the center of the area. Conclusion The blood lead level of children living around lead-zinc mining areas is relatively high. There are difference in district distribution, gender and age.

OBJECTIVETo investigate the effect of noise on the antioxidant capacity in different regions of brain tissue in guinea pigs.

METHODSThirty male white red-eye guinea pigs were equally and randomly divided into five groups: 1-, 3-, 7-, and 14-day groups after noise exposure and control group. The guinea pigs of the experimental groups were exposed to steady white noise with a sound pressure level at 100 dB for 8 h per day and for 2 consecutive days. The auditory brainstem response (ABR) of guinea pigs, as well as the glutathione (GSH) level, methane dicarboxylic aldehyde (MDA) level, and superoxide dismutase (SOD) activity in the cerebrum, cerebellum, and hippocampus, was determined prior to and 1, 3, 7, and 14 days after noise exposure.

RESULTSAfter noise exposure, the shifts in ABR threshold of the experimental groups were significantly higher than that of the control group (P<0.05). Compared with those in the control group, the SOD activity and GSH level both significantly decreased in the cerebrum tissue of each experimental group after noise exposure (P<0.05) and MDA content significantly increased in the 1-day group (P<0.05). As for cerebellum tissue, the SOD activity and GSH level in the 7-day group were significantly lower than those in the control group (P<0.05), but there was no difference in MDA level between each experimental group and the control group (P>0.05). In comparison with those in the control group, the GSH and MDA levels in the 1-day group after noise exposure were significantly higher, and the GSH and MDA levels in the 3-day group and the MDA level in the 7-day group after noise exposure were significantly lower (all P<0.05).

CONCLUSIONNoise exposure can lead to hearing loss and affect the antioxidant capacity of brain tissue, which indicates that the improvement in antioxidant levels may alleviate noise-induced damage.

Animals ; Antioxidants ; chemistry ; Brain ; metabolism ; Brain Chemistry ; Evoked Potentials, Auditory, Brain Stem ; Glutathione ; chemistry ; Guinea Pigs ; Male ; Malondialdehyde ; chemistry ; Noise ; adverse effects ; Superoxide Dismutase ; chemistry

Objective:To investigate the effect of gemcitabine on myeloid derived suppressor cells (MDSC) in the spleen of B lymphoma cell-bearing mice, and the therapeutic effect of gemcitabine combined with intratumoral injection of dendritic cells (DCs) in treatment of large B lymphoma. Methods: BALB/c mice were inoculated subcutaneously with B lymphoma A20 cells; large tumors were formed 30 d after inoculation. Gr-1~+ CD11b~+ MDSC proportion in the spleen was analyzed by flow cytometry before and after gemcitabine treatment. Splenic MDSC sorted by immunomagnetic beads was further treated with gemcitabine, and then the apoptosis of MDSC was examined by Annexin-V/PI staining. Tumor growth and survival time of A20 tumor-bearing mice were observed after treatment with gemcitabine and intratumoral injection of DCs. Results: Splenic Gr-1~+ CD11b~+ MDSC ratio in A20 cell-bearing mice was 10 times higher than that in the normal mice. Gemcitabine induced apoptosis and necrosis of purified MDSC in vitro in a time-dependent manner. The percentage of MDSC in the spleen of A20 tumor-bearing mice was decreased after injection of a single dose of gemcitabine. Gemcit-abine or intratumoral injection of DCs alone inhibited growth of tumor to a certain degree, with the mean survival periods of mice in the gemcitabine, DCs, and untreated groups being (48.8±3.6) d, (47.2±7.4) d, and (38.8±2.2) d, respectively. Gemcitabine chemotherapy combined with intratumoral DC injection resulted in continuous shrink of the tumors, and 60% of the mice survived for more than 90 d. Conclusion: Gemcitabine can effectively eliminate splenic MDSC in tumor-bearing mice. Gemcitabine chemotherapy and DCs immunotherapy can work synergistically in the treat-ment of huge lymphoma. These results provide an experimental basis for the comprehensive chemotherapy and immunotber-apy of relapsed or refractory lymphoma.