Immunogenicity and influencing factors of hepatitis B vaccination based on different vaccination schedules among chronic kidney disease patients / 中华流行病学杂志

Objective: To explore the immunogenicity and influencing factors of hepatitis B vaccination based on different vaccination schedules among chronic kidney disease (CKD) patients. Methods: CKD patients who participated in randomized controlled trials in four hospitals in Shanxi province and completed three doses of 20 µg vaccination (at months 0, 1 and 6) and four doses of 20 µg or 60 µg vaccination (at months 0, 1, 2, and 6) were surveyed from May 2019 to July 2020.According to the ratio of 1∶1∶1, 273 CKD patients were divided into 3 groups randomly. Quantification of the anti-hepatitis B surface antigen-antibody (anti-HBs) in serum samples was performed using chemiluminescent microparticle immunoassay at months 1 and 6 after the entire course of the vaccinations. The positive rate, high-level positive rate, geometric mean concentration (GMC) of anti-HBs, and the influencing factors were analyzed by χ2 tests, analysis of variance, unconditional logistic regression analysis. Results: A total of 273 CKD patitents were participants.The positive rates in the CKD patients with four doses of 20 µg vaccination (92.96%,66/71) or 60 µg vaccination (93.15%, 68/73) were higher than that in the CKD patients with three doses of 20 µg vaccination (81.69%, 58/71) at month one after the full course of the vaccinations (P<0.05). The GMCs of anti-HBs showed similar results (2 091.11 mIU/ml and 2 441.50 mIU/ml vs. 1 675.21 mIU/ml) (P<0.05). The positive rate was higher in the CKD patients with four doses of 60 µg vaccination (94.83%,55/58) than in those with three doses of 20 µg vaccination (78.79%,52/66) (P<0.05) at month six after the full course of the vaccinations. And the GMC of anti-HBs in the patients with four doses of 60 µg vaccination (824.28 mIU/ml) was significantly higher than those in the patients with 3 or 4 doses of 20 µg vaccination (639.74 mIU/ml and 755.53 mIU/ml) (P<0.05). After controlling the confounding factors, the positive rate in the CKD patients with four doses of 60 µg vaccination were 3.19 (95%CI: 1.02-9.96) and 5.32 (95%CI: 1.27-22.19) times higher than those in the patients with three doses of 20 µg vaccination at months 1 and 6 after the full course of the vaccinations, respectively. The positive rate in CKD patients without immune suppression or hormone therapy was 3.33 (95%CI: 1.26-8.80) and 4.78 (95%CI: 1.47-15.57) times higher than those in the patients with such therapy, respectively. Conclusions: Four doses of 20 µg or 60 µg hepatitis B vaccination could improve the immunogenicity in patients with CKD. And four doses of 60 µg vaccination might play a positive role in maintaining anti-HBs in this population. The immunogenicity in the CKD patients with immune suppression or hormone therapy was poor.

Predictive value of impedance of leadless pacemaker during implantation on trend changes of pacing threshold / 中华心血管病杂志

Objective: To explore the predictive value of the impedance measured during leadless pacemaker Micra implantation on the trend of changes of pacing threshold post implantation. Methods: This is a retrospective cross-sectional study. Patients who received implantation of leadless pacemaker Micra at the Second Xiangya Hospital of Central South University from December 2019 to August 2020 were enrolled. The clinical data and the intraoperative electrical parameters during leadless pacemaker implantation were collected. The impedance and pacing threshold data were analyzed at three time points: immediate release, 5-10 min after release, and after traction test. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to analyze the value of the impedance at immediate release on predicting the trend of changes of pacing threshold post implantation. Results: A total of 21 patients (mean age: (72.2±12.5) years, 12 males) were included. The impedance of 21 patients was (798.1±35.3) Ω immediately after implantation, (800.9±35.6) Ω after 5-10 minutes of release, and (883.6±31.7) Ω after traction test. Impedance was similar between the three time points (P>0.05). The threshold was (0.97±0.11) V/0.24 ms immediately after implantation, (0.95±0.12) V/0.24 ms at 5-10 min after the release, and (0.59±0.06) V/0.24 ms after the traction test. The threshold was significantly lower after the traction test than that immediately after release (P=0.003) and than that at 5-10 minutes after release (P=0.008), suggesting a decreased tendency of the threshold over time. According to the analysis of the ROC curve, the immediate impedance after the release ≥680 Ω could predict the ideal pacing threshold after the traction test (AUC=0.989, 95%CI 0.702-0.964, P<0.001), the prediction sensitivity was 87%, and the specificity was 100%. The pacing threshold would be not ideal with the immediate impedance ≤ 520 Ω (95%CI 0.893-1.000, P<0.001), the sensitivity was 100%, and the specificity was 80%. Conclusions: The impedance immediately after the release has predictive value for the changing trend of threshold post leadless pacemaker Micra implantation. Impedance ≥680 Ω immediately after release is often related with ideal pacing threshold after the traction test. In contrast, the impedance ≤ 520 Ω pacing is often related with unsatisfactory threshold after the traction test, therefore, it is recommended to find a new pacing site to achieve the impedance ≥680 Ω immediately after release during leadless pacemaker Micra implantation.

Application of machine learning in the prediction of college students suicidal ideation / 中国学校卫生

Objective@#To explore the predictive effect of machine learning algorithms on college students suicidal ideation and to analyze the associated factors of college students suicidal ideation.@*Methods@#The mental health data of 21 224 undergraduates was selected from a university in 2021. The independent variables were 37 demographic and internal and external mental health factors. The dependent variable was whether college students had suicidal ideation. Support vector machine, random forest and LightGBM algorithm were used to establish prediction models. The model was used in test set to so as to evaluate the model s prediction effect by using detection rate, F1 score and accuracy rate. Based on the superior model, the highrisk factors of suicidal ideation in college students were analyzed.@*Results@#The detection rates of support vector machine, random forest, and LightGBM models were 61.0% ,64.0%, 69.0%; F1 scores were 0.63, 0.63, 0.64, and accuracy rates were 73.0%, 73.0%, 72.0%, respectively. Based on the superior LightGBM model, risk factors of suicidal ideation in college students included, depression, grade, gender, despair, place of origin, sense of meaning, attitude toward suicide, dependence, family economic situation, hallucinatory delusion symptoms, anxiety, internet addiction, and interpersonal distress.@*Conclusion@#The LightGBM model has a better prediction effect than the support vector machine and random forest models.

Application of machine learning in the prediction of college students suicidal ideation / 中国学校卫生

Objective@#To explore the predictive effect of machine learning algorithms on college students suicidal ideation and to analyze the associated factors of college students suicidal ideation.@*Methods@#The mental health data of 21 224 undergraduates was selected from a university in 2021. The independent variables were 37 demographic and internal and external mental health factors. The dependent variable was whether college students had suicidal ideation. Support vector machine, random forest and LightGBM algorithm were used to establish prediction models. The model was used in test set to so as to evaluate the model s prediction effect by using detection rate, F1 score and accuracy rate. Based on the superior model, the highrisk factors of suicidal ideation in college students were analyzed.@*Results@#The detection rates of support vector machine, random forest, and LightGBM models were 61.0% ,64.0%, 69.0%; F1 scores were 0.63, 0.63, 0.64, and accuracy rates were 73.0%, 73.0%, 72.0%, respectively. Based on the superior LightGBM model, risk factors of suicidal ideation in college students included, depression, grade, gender, despair, place of origin, sense of meaning, attitude toward suicide, dependence, family economic situation, hallucinatory delusion symptoms, anxiety, internet addiction, and interpersonal distress.@*Conclusion@#The LightGBM model has a better prediction effect than the support vector machine and random forest models.

Diagnostic value of 18F-prostate specific membrane antigen PET/CT combined with multiparametric-MRI in identifying the grade group of prostate cancer / 中华泌尿外科杂志

Objective:To investigate the diagnostic value of the combination of 18F-prostate specific membrane antigen (PSMA) PET/CT and multiparametric magnetic resonance imaging (mpMRI) in identifying the grade group of prostate cancer, using parameters derived from the two imaging modalities. Method:Prostate cancer patients diagnosed by histopathology and received 18F-PSMA PET/CT and mpMRI during September 2018 to May 2021 in our hospital were retrospectively studied. The median age was 68(64-75), with the median PSA level of 14.74(7.75-24.19)ng/mL. All patients received mpMRI before biopsy. On biopsy, 6(12.2%) patients had International Society of Urological Pathology grade group(ISUP GG) 1 diseases, 16(32.7%) had ISUP GG 2 diseases, 12(24.5%) had ISUP GG 3 diseases, and 15(10.9%) had ISUP GG 4 or 5 diseases. Patients were then divided into high-grade group (ISUP 4-5) and low-grade group(ISUP 1-3). The median age of patients in high-grade group and low-grade group were 65(62-76) and 71(65-74), respectively. The PSA level in high-grade group and low-grade group were 15.11(6.63-42.86) ng/ml and 12.31(7.94-18.25) ng/ml, respectively. No significant differences were found in age and PSA level between the two groups ( P=0.334, P=0.448). All patients underwent 18F-PSMA PET/CT within 4 weeks after biopsy. The maximum standardized uptake value(SUV max) and the minimum apparent diffusion coefficient(ADC min)were recorded, and the ratio of SUV max/ ADC minwere calculated. The correlation between the above parameters and ISUP grade group were analyzed.The diagnostic value of the parameters was evaluated by the receiver operating characteristic (ROC) curve. Results:The data of 49 patients were analyzed. The average ADC minwas (0.57±0.16)×10 -3 mm 2/s, with the average SUV max and SUV max/ADC min of 15.30±12.54 and (29.69±23.72)×10 3, respectively. Statistical differences were found in SUV max ( P=0.012) and SUV max/ADC min ( P=0.002) between the high- and low-grade groups, while ADC min ( P=0.411) showed no statistical differences between the two groups. Significant positive correlations were found between SUV max(r=0.501, P<0.001), SUV max/ADC min (r=0.527, P<0.001) and ISUP grade group, respectively. There was a negative correlation between ADC min and ISUP grade group (r=-0.296, P=0.039). SUV max/ADC min was the best index to distinguish high-grade group from low-grade group prostate cancer with the area under the curve(AUC) of 0.749. In contrast, the AUC of SUV maxand ADC min were 0.731 and 0.615, respectively. The diagnostic sensitivity and specificity of SUV max/ADC min were 73.3% and 85.3%, respectively, with a critical value of 37.23×10 3. Conclusion:The combination use of 18F-PSMA PET/CT and mpMRI could improve the diagnostic efficiency for prostate cancer, compared to either modality alone. The ratio of SUV max/ADC min has a positive correlation with ISUP grade group, and is a promising index for distinguishing the high-grade prostate cancer from low-grade cancer.

Value of MRI findings for the evaluation of a hernia sac in fetuses with congenital diaphragmatic hernia / 中华放射学杂志

Objective:To explore the value of MRI signs in assessing the presence or absence of hernia sacs in fetuses with congenital diaphragm hernia.Methods:MRI images of 57 patients with congenital diaphragm hernia confirmed by postpartum surgery were analyzed from November 2016 to December 2020 in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, with a gestational age of 20－40 (28±5) weeks. In postpartum surgery, 18 cases were found with hernia sacs (hernia sac group) and 39 cases without hernia sacs (hernia-free group). Seven MRI signs were analyzed, including hernia peripheral enveloping sensation, smooth lung-hernia interface, crescent-shaped lung compression, residual lung tissue on the affected side, heart displacement, effusion above the lung-hernia interface and effusion below the lung-hernia interface. The differences in MRI signs between the hernia sac and hernia-free groups were compared using the χ 2 test or Fisher′s exact probability method. The diagnostic efficacy of each sign was calculated. The MRI signs with statistical differences between the two groups were included in the predictive integration model, and 1 point was scored for each sign, the imaging score of each fetus was calculated, and the efficacy of imaging points in diagnosing the presence or absence of hernia sacs was assessed by the subject manipulation receiver operating characteristics (ROC) curve. Results:There were statistically significant differences in 5 MRI signs between the hernia sac and the hernia-free groups, namely hernia peripheral enveloping sensation (χ2=25.74, P<0.001), smooth lung-hernia interface (χ2=48.20, P<0.001), crescent-shaped lung compression (χ2=57.00, P<0.001), residual lung tissue on the affected side (χ2=12.14, P<0.001) and effusion above the lung-hernia interface (χ2=4.31, P=0.022). Among them, the sign of crescent-shaped lung compression had the highest diagnostic efficacy, and the sensitivity, specificity and accuracy all were 100%. Five statistically significant MRI signs were included in the predictive integration model, and the area under the ROC curve was 0.999, the sensitivity was 100%, the specificity was 94.9%, and the optimal threshold was 2 points. Conclusion:Fetal MRI signs and predictive integration model can effectively identify the presence or absence of hernia sacs in fetuses with congenital diaphragm hernia, which has certain clinical significance.

Analysis and discussion on practical activities of standardized residency training in the department of radiology / 中华医学教育探索杂志

Based on the characteristics of medical imaging specialty, this paper introduces in detail several features of standardized residency training in the Department of Radiology in our hospital, from the aspects of teaching purpose, preliminary preparation and specific implementation, namely, the morning reading and analysis of difficult cases, the analysis of postoperative cases and missed diagnosis cases, and the teaching reading. At the same time, it also deeply analyzes the advantages, existing problems and solutions of this teaching practice. In order to provide reference for improving the teaching quality of the standardized residency training in the Department of Radiology.

Advances on the spectrum of neurological diseases related to the CACNA1A gene / 中华实用儿科临床杂志

The CACNA1A gene encodes a voltage-gated calcium channel of the pore-forming protein, which has important functions in the central nervous system.The CACNA1A gene mutation can lead to a variety of neurological diseases, including familial hemiplegic migraine 1, spinocerebellar ataxia 6, episodic ataxia 2 and early infantile epileptic encephalopathy 42.Overlapping phenotypes could be observed in a small number of patients.This review summarized the clinical and genetic characteristics of the CACNA1A gene mutation.

Changes of corneal parameters in different areas after cataract surgery / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the distribution characteristics of axial sagittal front power(ASF), true net power(TNP), total corneal refractive power(TCRP)and the difference in back-front corneal radius ratio(B/F ratio)after cataract surgery.METHODS: A prospective study. A total of 156 patients(156 eyes)with age-related cataract who attend Weifang Eye Hospital for cataract surgery from December 2020 to May 2021 were collected. Pentacam was performed before operation and 3mo after operation to collect ASF, TNP and TCRP on 2, 4 and 6mm diameters rings and areas on the corneal apex and pupil-centered, as well as B/F ratio.RESULTS: 3mo after operation, there was no statistical difference in ASF on the 2mm diameters ring and area centered on the corneal apex compared with preoperative values(all P&#x003E;0.05), however, the ASF values on the 4 and 6mm diameters rings and areas were significantly different from those before surgery(all P&#x003C;0.05); There was no statistical difference in ASF on the 2mm diameters rings and areas centered on the pupil compared with preoperative values(all P&#x003E;0.05). The postoperative values of TNP and TCRP on the 2, 4 and 6mm diameters rings and areas centered on the corneal apex and centered on the pupil were statistically different before surgery(all P&#x003C;0.05). Preoperative, TCRP values were different between 2mm and 6mm and between 4mm and 6mm on both corneal apex and pupil-centered rings(all P&#x003C;0.0167), TCRP values were all different between 2mm and 6mm diameters areas on corneal apex and pupil-centered(all P&#x003C;0.0167); 3mo after operation, TCRP values were different on corneal apex and pupil-centered rings between 2mm and 6mm and between 4mm and 6mm diameters(all P&#x003C;0.0167). While TCRP values on the corneal apex and pupil-centered areas were only different between 2mm and 6mm diameters(all P&#x003C;0.0167). The preoperative B/F ratio of patients was 81.79%±1.87%, and the postoperative B/ F ratio of patients was 80.68%±2.23%(P&#x003C;0.001).CONCLUSION: Corneal parameters of different diameters of rings and areas centered on the corneal apex and pupil before and after cataract surgery may change and differ, which should be taken into account when selecting the K value for intraocular lens calculation and individualizing the selection of IOLs based on corneal characteristics.

PXR activation impairs hepatic glucose metabolism partly via inhibiting the HNF4α-GLUT2 pathway

Drug-induced hyperglycemia/diabetes is a global issue. Some drugs induce hyperglycemia by activating the pregnane X receptor (PXR), but the mechanism is unclear. Here, we report that PXR activation induces hyperglycemia by impairing hepatic glucose metabolism due to inhibition of the hepatocyte nuclear factor 4-alpha (HNF4α)‒glucose transporter 2 (GLUT2) pathway. The PXR agonists atorvastatin and rifampicin significantly downregulated GLUT2 and HNF4α expression, and impaired glucose uptake and utilization in HepG2 cells. Overexpression of PXR downregulated GLUT2 and HNF4α expression, while silencing PXR upregulated HNF4α and GLUT2 expression. Silencing HNF4α decreased GLUT2 expression, while overexpressing HNF4α increased GLUT2 expression and glucose uptake. Silencing PXR or overexpressing HNF4α reversed the atorvastatin-induced decrease in GLUT2 expression and glucose uptake. In human primary hepatocytes, atorvastatin downregulated GLUT2 and HNF4α mRNA expression, which could be attenuated by silencing PXR. Silencing HNF4α downregulated GLUT2 mRNA expression. These findings were reproduced with mouse primary hepatocytes. Hnf4α plasmid increased Slc2a2 promoter activity. Hnf4α silencing or pregnenolone-16α-carbonitrile (PCN) suppressed the Slc2a2 promoter activity by decreasing HNF4α recruitment to the Slc2a2 promoter. Liver-specific Hnf4α deletion and PCN impaired glucose tolerance and hepatic glucose uptake, and decreased the expression of hepatic HNF4α and GLUT2. In conclusion, PXR activation impaired hepatic glucose metabolism partly by inhibiting the HNF4α‒GLUT2 pathway. These results highlight the molecular mechanisms by which PXR activators induce hyperglycemia/diabetes.

Oxygen Metabolism-induced Stress Response Underlies Heart-brain Interaction Governing Human Consciousness-breaking and Attention / 神经科学通报·英文版

Neuroscientists have emphasized visceral influences on consciousness and attention, but the potential neurophysiological pathways remain under exploration. Here, we found two neurophysiological pathways of heart-brain interaction based on the relationship between oxygen-transport by red blood cells (RBCs) and consciousness/attention. To this end, we collected a dataset based on the routine physical examination, the breaking continuous flash suppression (b-CFS) paradigm, and an attention network test (ANT) in 140 immigrants under the hypoxic Tibetan environment. We combined electroencephalography and multilevel mediation analysis to investigate the relationship between RBC properties and consciousness/attention. The results showed that RBC function, via two independent neurophysiological pathways, not only triggered interoceptive re-representations in the insula and awareness connected to orienting attention but also induced an immune response corresponding to consciousness and executive control. Importantly, consciousness played a fundamental role in executive function which might be associated with the level of perceived stress. These results indicated the important role of oxygen-transport in heart-brain interactions, in which the related stress response affected consciousness and executive control. The findings provide new insights into the neurophysiological schema of heart-brain interactions.

Literature analysis of adverse drug reactions induced by roxadustat / 中国药房

OBJECTIVE To study clinical manifestations and characteristics of adverse drug reactions （ADRs）induced by roxadustat，and to provide reference for rational use of it in clinic . METHODS Retrieved from PubMed ，Web of Science ，Wanfang Med，VIP and CNKI ，clinical trials and case reports （including series studies and case reports ）of ADRs induced by roxadustat were collected ；descriptive method was used to analyze patients ’basic information ，involved systems/organs and main clinical manifestations. The incidence of ADR was compared between roxadustat group and erythropoietin （EPO）group. RESULTS & CONCLUSIONS A total of 17 articles were included ，including 14 clinical trials and 3 case reports . In the clinical trial studies ， there were 4 033 patients using roxadustat ，including 1 972 males（48.9%）and 2 061 females（51.1%），aged from 36 to 80 years. The type of patients in one clinical trial was low -risk myelodysplastic syndrome ，and the others were renal anemia ；they received relevant drugs with dosage of 40-120 mg，mostly three times a week . Roxadustat-induced ADR （1-2 grade）involved systems/ organs mainly included cardiovascular system ，respiratory and thoracic system ，digestive system ，infection and infestation . The major systems/organs involved in serious adverse drug reaction （sADR）were cardiovascular system ，infection and infestation ； there was no statistically significant difference in the incidence of ADR between roxadustat group and EPO group （P＞0.05），but the incidence of sADR in roxadustat group was significantly higher than that in EPO group （P＜0.05）. In the case reports ， pulmonary hypertension ，rhabdomyolysis and fatigue were the clinical manifestations of ADRs induced by roxadustat . During clinical medication ，attention should be paid to the changes in relevant systems/organs of patients . If ADR is found ，timely intervention should be carried out .

Intervention effects and mechanism of Compound yu ’e nasal drops on allergic rhinitis in rats / 中国药房

OBJECTIVE To study the intervention effects and mechanism of Compound yu ’e nasal drops on ovalbumin induced allergic rhinitis in rats . METHODS The allergic rhinitis model of rat was induced with ovalbumin . Model rats were randomly divided into model group ，triamcinolone acetonide group （positive control ，0.026 mg/kg），Compound yu ’e nasal drops high-dose，medium-dose and low -dose groups （134.4、67.2、33.6 mg/kg），12 rats in each group . Another blank control group was set. Except for blank control group ，the corresponding drugs were given by nasal drip twice a day for 14 days. One hour after last administration，the nasal symptom scores of rats were recorded ；the levels of serum immunoglobulin E （IgE），interleukin-2（IL- 2），IL-13 and tumor necrosis factor -α（TNF-α）were measured by enzyme -linked immunosorbent assay . The changes of nasal mucosa in rat were observed by HE staining . The expressions of TNF -α，IL-2 and IL -13 in nasal mucosa were detected by Western blot. RESULTS Compared with blank control group ，nasal symptom score and the levels of serum IgE ，IL-2，IL-13，TNF-α in model group were increased significantly （P＜0.01）；obvious pathological injury was found in nasal mucosa ，and the expressions of TNF -α，IL-2 and IL -13 protein were increased significantly （P＜0.01）. Compared with model group ，Compound yu ’e nasal drops significantly reduced the nasal symptom score ，the levels of serum IgE ，IL-2，IL-13，TNF-α to different extents ，improved pathological injury of nasal mucosa and significantly inhibited the expressions of TNF -α，IL-2 and IL -13 protein（P＜0.05 or P＜ 0.01）. CONCLUSIONS Compound yu ’e nasal drops play significant effects against allergic rhinitis in rats by regulating the balance of t ype 1 helper T cells/type 2 helper T cells ，balancing and inhibiting the secretion of inflammatory cytokines .

A cross-sectional study on the clinical phenotypes of rheumatoid arthritis / 北京大学学报(医学版)

OBJECTIVE@#To explore the characteristics and clinical phenotypes of rheumatoid arthritis (RA) and provide the basis for further understanding, interventions and outcomes of this disease.@*METHODS@#RA patients attended at Peking University People's Hospital from 2018 to 2021 were enrolled in the study. Data collection included demographic data, the sites and numbers of joints involved, extra-articular manifestations (EAM), comorbidities and laboratory variables. Statistical and bioinformatical analysis was performed to establish clinical subtypes by clustering analysis based on the type of joint involved, EAM involvement and other autoimmune diseases overlapped. The characteristics of each subtype were analyzed.@*RESULTS@#A total of 411 patients with RA were enrolled. The mean age was (48.84±15.17) years, and 346 (84.2%) were females. The patients were classified into 4 subtypes: small joint subtype (74, 18.0%), total joint subtype (154, 37.5%), systemic subtype (100, 24.3%), and overlapping subtype (83, 20.2%). The small joint subtype had no medium or large joint involvement, and 35.1% had systemic involvement. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and platelet count (PLT) were lower than those in other subtypes, and the rates of positive rheumatoid factors (RF-IgA and RF-IgG) were significantly higher in the small joint subtype. The total joint subtype had both large and small joint involvement but no systemic involvement. The rate of morning stiffness and positive antinuclear antibodies (ANA) in this subtype were lower than those in other subtypes. In the systemic subtype, interstitial lung disease and secondary Sjögren syndrome were the most common systemic involvements, with prominent levels of disease activity score 28-joint count (DAS28-ESR and DAS28-CRP). The overlapping subtype was commonly combined with Hashimoto's thyroiditis or primary Sjögren syndrome. Female in the overlapping subtype was more common than in other subtypes. This subtype was characterized by hyperglobulinemia, hypocomplementemia and high rate of positive ANA, especially spotting type.@*CONCLUSION@#Based on the clinical features, RA patients could be classified into 4 subtypes: small joint subtype, total joint subtype, systemic subtype, and overlapping subtype. Each subtype had its own clinical characteristics. They help for further understanding and a more individualized treatment strategy of RA.

Bipolar androgen therapy followed by immune checkpoint inhibitors in metastatic castration resistant prostate cancer: A report of 4 cases / 北京大学学报(医学版)

The relationship between androgen and prostate cancer treatment has plagued the field of urologic oncology. To investigate the efficacy and safety of bipolar androgen therapy (BAT) followed by immune checkpoint inhibitor therapy in patients with metastatic castration resistant prostate cancer (mCRPC). In August 2020, Beijing Hospital conducted an investigator-initiated study: Bipolar androgen therapy followed by immune checkpoint inhibitor therapy in metastatic castration resistant prostate cancer. Up to now, the study has included 4 patients who completed the entire cycle of treatment. The mean age of the patients was 74.5 (68 to 82) years old, the mean prostate-specific antigen (PSA) was 20.8 (9.9 to 8.36) μg/L, the mean testosterone was 0.50 (0.00 to 1.81) μg/L, and the Gleason score were 10 and 9, 7, 7 respectively. The pain scale score before treatment was 1.5 (1 to 2). In this study, 4 patients completed the entire cycle of treatment, and the treatment effect of the patients showed great heterogeneity. PSA in case 1 decreased from 24.0 μg/L to 0.47 μg/L, testosterone increased from 0.175 6 μg/L to 2.62 μg/L. PSA in case 2 increased from 9.939 μg/L to 168.536 μg/L, and testosterone increased from 0.0 μg/L increased to 2.85 μg/L. PSA increased from 13.31 μg/L to 39.278 μg/L in case 3, testosterone increased from 0.0 μg/L to 2.54 μg/L. and PSA increased from 36.0 μg/L to 350.2 μg/L in the case 4, testosterone increased from 1.81 μg/L to 3.85 μg/L. Except for one patient who showed significant PSA remission, the PSA levels of the remaining three patients remained high overall. There were no adverse reactions reported in 4 patients. In the follow-up, case 1 continued to use PD-1 monoclonal antibody (median progression free survival time was 10 months). Two patients who had previously been resistant to enzalutamide received enzalutamide again after the whole cycle of treatment, and their PSA decreased again, which indicated that the patient was sensitive to enzalutamide again. BAT had a certain therapeutic effect on mCRPC patients, and the safety was controllable. Its tumor control effect still needed long-term follow-up verification in large-sample clinical trials. BAT has a certain therapeutic effect on mCRPC patient, especially the resensitivity of tumors to enzalutamide can be restored. Immune checkpoint inhibitors may have therapeutic potential in patients with prostate cancer treated with BAT and enzalutamide.

Hepatitis C elimination among drug users in China: challenges, strategies and experiences / 中华肝脏病杂志

The prevalence of hepatitis C among drug users in China is high, and thus it is one of the populations that needs attention to achieve hepatitis C elimination. However, due to the complexities of this population's situation, hepatitis C elimination still faces many challenges, such as difficult screening, low cure rate, poor compliance, and high reinfection rates. Therefore, the existing diagnostic and therapeutic system cannot meet the needs of this population. China has pledged to establish a unified system for drug users that will integrate drug treatment programs, education, medical care, and rehabilitation, creating favorable conditions for integrating hepatitis C diagnosis and treatment and improving the accessibility of drug users. Starting with the current situation and challenges of eliminating hepatitis C among drug users in China, in combination with cases from other countries, this paper discusses the strategy for eliminating hepatitis C and introduces what Hainan Province did to eliminate hepatitis C among drug users.

Outcomes of patients awaiting lung transplantation after the implementation of donation after brain death at a single Chinese center / 医学前沿

Voluntary contribution has become the only source of donor lungs in China since 2015. To elaborate the outcomes of patients awaiting lung transplantation (LTx) after the implementation of donation after brain death, we performed a retrospective study that encompassed 205 patients with end-stage lung disease who registered for LTx at Shanghai Pulmonary Hospital from January 1, 2015 to January 1, 2021. A total of 180 patients were enrolled in the study. The median waiting time was 1.25 months. Interstitial lung disease (ILD) (103/180, 57.2%) and chronic obstructive pulmonary disease (COPD) (56/180, 31.1%) were the most common diseases in our study population. The mean pulmonary artery pressure (mPAP) of patients in the died-waiting group was higher than that of the survivors (53.29±21.71 mmHg vs. 42.11±18.58 mmHg, P=0.002). The mortality of patients with ILD (34/103, 33.00%) was nearly twice that of patients with COPD (10/56, 17.86%) while awaiting LTx (P=0.041). In the died-waiting group, patients with ILD had a shorter median waiting time than patients with COPD after being listed (0.865 months vs. 4.720 months, P=0.030). ILD as primary disease and mPAP > 35 mmHg were two significant independent risk factors for waitlist mortality, with hazard ratios (HR) of 3.483 (95% CI 1.311-9.111; P=0.011) and 3.500 (95% CI 1.435-8.536; P=0.006). Hence, LTx is more urgently needed in patients with ILD and pulmonary hypertension.

Advantages of Chinese Medicine in Treating Dominant Disease： Benign Prostatic Hyperplasia / 中国实验方剂学杂志

China Association of Chinese Medicine organized specialists in andrology of Chinese and western medicine to explore the population and treatment stage of benign prostatic hyperplasia （BPH） with Chinese medicine as the leading therapy. Chinese medicine has great advantages in the treatment of benign prostatic hyperplasia. However， it is necessary to make clear the stage when Chinese medicine or modern medical treatment can be used as the leading therapy， and the conditions under which Chinese and western medicine can be combined to achieve the best treatment efficacy. The specialists agreed Chinese medicine as the leading therapy for the treatment of BPH in the following populations or conditions： the elderly and weak patients with basic diseases， BPH symptoms， and cannot tolerate anesthesia and surgery， the patients with BPH symptoms and cannot tolerate the adverse reactions or the possible adverse reactions of western medicine； the patients with mild ［international prostatic symptom score （IPSS） ≤ 7］ or moderate lower urinary tract symptoms （IPSS ≥ 8） and the quality of life not significantly affected， the patients with bladder detrusor hypofunction， bladder dysfunction and cannot be treated surgically， or with incomplete bladder emptying after surgical treatment； the BPH patients with prostatitis as the main clinical manifestation， the patients with non-acute complications after operation. BPH is one of the dominant diseases in urology and andrology of Chinese medicine， and the symptoms， complications， and prognosis of BPH patients need to be fully considered during the clinical treatment. When Chinese medicine is taken as the leading therapy， it is essential to regularly review the serum level of prostate-specific antigen to exclude the possibility of prostate cancer， and apply Chinese medicine for full treatment course and cycle. At the same time， Chinese and western medicine can be combined to achieve the most effective， convenient， economical， and satisfactory treatment， which can carry forward the advantages of Chinese medicine in treating this disease.

Mechanism of Yiqi Jiedu Prescriptions in Protection of Mitochondria in PC12 Cells Against Hypoxia Injury Based on Energy Metabolism / 中国实验方剂学杂志

ObjectiveTo establish an evaluation method for mitochondrial energy metabolism with Seahorse analyzer and investigate the protective effect of Yiqi Jiedu prescriptions （YQ） on mitochondria in rat adrenal pheochromocytoma （PC12） cells against hypoxia injury. MethodThe PC12 cell injury model was induced in vitro using hypoxic chambers. Five groups were set up， ie， a control group， a model group （model）， high- （25 µmol·L-1）， medium- （5 µmol·L-1） and low-dose （1 µmol·L-1） YQ groups， and a positive drug trimetazidine （TMZ） group， with three replicate wells in each group. The experiment was repeated three times. The established method for energy metabolism analysis was used to assay the activity of mitochondrial complex in cells and screen the optimal dosing concentration. Subsequently， the YQ group and modified YQ groups were set up， and the aerobic respiration and glycolysis function were assayed by the Seahorse analyzer. According to the non-mitochondrial oxygen consumption， proton leakage， basal respiration， maximum respiration， ATP production， and potentially improved respiration， the effects of modified YQ groups on the aerobic respiration of mitochondria damaged by hypoxia were evaluated by principal component analysis （PCA） and variable importance in projection （VIP）. The expression of cytochrome C， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） was detected by Western blot. ResultCompared with the groups of other concentrations， the optimal dosing concentration of carbonyl cyanide-4 （trifluoromethoxy）phenylhydrazone （FCCP） was 2 µmol·L-1. Compared with the model group， the medium-dose YQ group showed enhanced mitochondrial complex activity （P<0.05）. The YQ groups were superior to the model group in improvement （P<0.01）. The combination of ginsenoside and geniposide showed the optimal effect among the modified YQ groups （P<0.01）. VIP analysis revealed that for the improvement of mitochondrial respiratory function， the contribution of geniposide in YQ was the greatest. Compared with the model group， the high-dose YQ group displayed reduced leakage of mitochondrial cytochrome C （P<0.01）， decreased expression of Bax protein （P<0.01）， and increased expression of Bcl-2 protein （P<0.05， P<0.01）. ConclusionA cellular， high-throughput quantitative evaluation method for mitochondrial energy metabolism was established， which demonstrated that YQ could significantly improve the impaired mitochondrial energy metabolism in PC12 cells damaged by hypoxia， and the underlying mechanism might be related to the protection against mitochondrial apoptosis.

Clinical Study of Jiawei Xiaochaihutang Combined with Microwave Ablation in Treatment of Primary Hepatocellular Carcinoma / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Jiawei Xiaochaihutang combined with microwave ablation （MWA） in the treatment of primary hepatocellular carcinoma （HCC） and its influence on tumor microenvironment. MethodA total of 128 patients were randomly divided into control group （64 cases： 2 cases of dropout，2 cases of elimination，and 60 cases of completion） and observation group （64 cases： 3 cases of dropout，2 cases of elimination，and 59 cases of completion）. Both groups were given comprehensive treatment after MWA surgery. Patients in control group took Biejiajian Wan orally （3 g/time，3 times/d）， and those in observation group took Jiawei Xiaochaihutang （1 dose/d）. The treatment lasted for 3 consecutive months. The size of solid tumor before and after treatment was evaluated to record the progression-free survival （PFS）. The alpha-fetoprotein-L13 （AFP-L3），des-γ-carboxy prothrombin （DCP），Golgi protein 73 （GP73），tumor necrosis factor-α （TNF-α），transforming growth factor-β （TGF-β），vascular endothelial growth factor （VEGF） and matrix metalloproteinase-2 （MMP-2） levels，as well as performance status （PS），liver function and syndrome of liver depression and Qi stagnation scores were also detected before and after treatment. In addition， the incidence of side effects of grade Ⅲ and above was compared. ResultThe total effective rate of solid tumor in observation group was 91.53% （54/59），higher than that （76.67%， 46/60） in control group（χ2=4.895，P<0.05）. The PFS in observation group was （7.16±0.95） months， longer than that （6.24±0.89 months） in control group （P<0.01）. The effective rate of traditional Chinese medicine （TCM） syndrome in observation and control groups were 88.14% （52/59）and 70.00% （42/60）， respectively （χ2=5.897，P<0.05）. The observation group （57.63%，34/59） had higher marked effective rate of TCM syndrome than control group （31.67%，19/60） （χ2=8.116，P<0.01）. The AFP-13，DCP，GP73，TNF-α，TGF-β，VEGF and MMP-2 levels and the PS，liver function and syndrome of liver depression and Qi stagnation scores in observation group were lower than those in control group （both P<0.01）. The cumulative incidence of side effects of grade Ⅲ and above in observation and control groups was 16.95% and 33.33%， respectively（χ2=4.261，P<0.05）. ConclusionConsolidation treatment of HCC after MWA surgery with Jiawei Xiaochaihutang relieved symptoms and side effects，improved PS and liver function，regulated tumor microenvironment，inhibited tumor markers and prolonged survival time. The clinical effect was better than that of Biejia decoction pill， and thus it was worthy of clinical use.