ObjectiveTo observe ovarian microvascular damage in rats with cold coagulation and blood stasis syndrome and to explore the mechanism by which Liangfang Wenjing decoction improves this condition in rats. MethodsFifty SPF female SD rats were randomly divided into a blank group， a model group， low-dose （8.1 g·kg^-1） and high-dose groups （16.2 g·kg^-1） of Liangfang Wenjing decoction， and a 4-phenylbutyric acid （0.1 g·kg^-1） group， with 10 rats in each group. The ice-water bath method was employed to establish the rat model of cold coagulation and blood stasis syndrome. Concurrent with modeling， Liangfang Wenjing decoction was administered continuously for 21 days， once daily. The rats' syndrome manifestations and estrous cycles were recorded. The enzyme-linked immunosorbent assay （ELISA） was used to detect serum reproductive hormone levels and levels of endothelin-1 （ET-1）， nitric oxide （NO）， thrombomodulin （TM）， and von Willebrand factor （vWF） in ovarian tissue. Prothrombin time （PT）， activated partial thromboplastin time （APTT）， thrombin time （TT）， and fibrinogen （FIB） were measured. The ovarian microcirculatory blood perfusion was detected by laser speckle contrast imaging. Hematoxylin-eosin （HE） staining was performed to observe the ovarian histopathology， flow cytometry to detect ovarian apoptosis rate， and transmission electron microscopy to observe the ultrastructure of ovarian microvascular endothelial cells. Western blot was employed to detect the protein expression of endothelial nitric oxide synthase （eNOS）， phosphorylated eNOS （p-eNOS）， Caspase-3， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， glucose-regulated protein 78 （GRP78）， C/EBP homologous protein （CHOP）， inositol-requiring enzyme1α （IRE1α）， p-IRE1α， apoptosis signal-regulating kinase 1 （ASK1）， p-ASK1， c-Jun N-terminal kinase （JNK）， and p-JNK. Immunofluorescence was used to detect ovarian Bax and Bcl-2 expression in microvascular endothelial cells. ResultsCompared with the blank group， the model group showed signs of cold coagulation and blood stasis syndrome， prolonged estrus cycles， and reproductive hormone disorders. Histopathological results revealed a decrease in follicle counts at all stages and disorganized granulosa cell arrangement. Ovarian microcirculatory perfusion was significantly decreased （P<0.01）. PT， APTT， and TT were reduced （P<0.05， P<0.01）， while FIB levels were increased （P<0.05）. In ovarian tissue， NO content was decreased， while ET-1， vWF， and TM levels were increased significantly （P<0.01）. The apoptosis rate of ovarian cells was markedly increased （P<0.01）. Furthermore， p-eNOS/eNOS and Bcl-2 were decreased （P<0.05）， whereas Bax， cleaved-Caspase-3/Caspase-3， GRP78， CHOP， p-IRE1α/IRE1α， p-ASK1/ASK1， and p-JNK/JNK expression showed significant increases （P<0.05， P<0.01）. Compared with the model group， Liangfang Wenjing decoction intervention alleviated the symptoms of cold coagulation and blood stasis， gradually restored the estrus cycle， and improved ovarian histopathology and endothelial cell ultrastructure. Microcirculatory blood perfusion was significantly elevated （P<0.05）. NO content in ovarian tissue was elevated， while ET-1， vWF， and TM levels were significantly decreased （P<0.05， P<0.01）. The p-eNOS/eNOS ratio and Bcl-2 expression were significantly elevated （P<0.05）， while the expression of Bax， cleaved-Caspase-3/Caspase-3， GRP78， CHOP， p-IRE1α/IRE1α， p-ASK1/ASK1， and p-JNK/JNK was significantly decreased （P<0.05， P<0.01）. ConclusionLiangfang Wenjing decoction may regulate the IRE1α/ASK1/JNK signaling pathway to inhibit endoplasmic reticulum stress， attenuate apoptosis， and improve microvascular endothelial injury in ovaries of rats with cold coagulation and blood stasis syndrome.

ObjectiveTo observe the clinical efficacy of Tongfu Xiezhuo enema in treating stage 3-4 chronic kidney disease （CKD） and the effect of the therapy on the neutrophil-to-lymphocyte ratio （NLR） as an inflammation marker. MethodSixty patients diagnosed with stage 3-4 CKD who visited the Nephrology Department of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from December 2022 to June 2023 were included and randomly assigned into observation and control groups in a ratio of 1∶1. The control group received conventional therapy plus Shenkang suppositories， while the observation group received conventional therapy plus Tongfu Xiezhuo enema. After 8 weeks of treatment， the clinical efficacy was assessed based on the changes in traditional Chinese medicine （TCM） symptom scores， renal function indicators， and NLR. Result① Both groups showed decreases in TCM symptom scores after treatment （P<0.01）， and the decreases were more significant in the observation group than in the control group （P<0.05）. The total response rate of TCM symptoms in the observation group was 79.31% （23/29）， which was higher than that （62.96%， 17/27） in the control group （Z=0.604，P<0.05）. ② After treatment， the observation group showed declined serum levels of creatinine （SCr）， blood urea nitrogen （BUN）， and cystatin C （Cys C） and increased glomerular filtration rate （GFR） （P<0.01）， and the control group showed lowered SCr level and increased GFR （P<0.05）. The observation group had lower SCr level and higher GFR than the control group after treatment （P<0.05）. The total response rate of renal function in the observation group was 79.31% （23/29）， which was higher than that （55.56%， 15/27） in the control group （Z=1.127，P<0.01）. ③ The NLR in the observation group decreased after treatment （P<0.05）， and it was lower than that in the control group （P<0.05）. ④ There were no significant differences in safety indicators between the two groups before and after treatment. ConclusionTongfu Xiezhuo enema ameliorated symptoms and improved renal function indicators in the patients with stage 3-4 CKD by reducing the NLR and inhibiting inflammation.

Studies have shown that vertebral artery hypoplasia(VAH)is associated with posterior circulation ischemic stroke,but it is difficult to distinguish VAH from atherosclerotic stenosis in cerebrovascular angiography and other imaging examinations,and there is currently no unified diagnostic standard for intracranial VAH.The authors reviewed the definition and incidence of intracranial VAH from the aspects of autopsy and imaging,and summarized its relationship with posterior circulation ischemic stroke,in order to improve the clinicians'understanding of intracranial VAH.

Objective:To study the value of urine-based multi-dimensional bioinformatics evaluation model (utLIFE model) in early diagnosis and postoperative monitoring of upper urinary tract urothelial carcinoma (UTUC).Methods:Morning urine samples of patients clinically diagnosed with UTUC without bladder cancer from Peking University First Hospital from August 2022 to October 2022 were collected. Urine samples were collected before and after surgery, and DNA was extracted for gene sequencing. The utLIFE model previously constructed by our center was used to calculate the score, based on 155 gene mutation sites and copy number variation, and the score ≥60 was defined as utLIFE positive. The sensitivity of utLIFE model in diagnosis of UTUC was analyzed with postoperative pathology as the gold standard. The utLIFE scores before and after operation were also compared.Results:A total of 53 patients were included in this study, all of whom were confirmed as UTUC by postoperative pathology. The median age of patients was 66 (59, 72) years. Twenty-four cases (45.3%) of UTUC tumors were located in the renal pelvis, 26 cases (49.1%) were located in the ureter, and 2 cases (5.7%)involved both ureter and renal pelvis. There were 27 patients (50.9%) at T 1stage and 26 patients (49.1%) at ≥T 2 stage. Preoperative utLIFE score of 53 patients was 79 (70, 84). The sensitivity of preoperative utLIFE diagnosis of UTUC was 96.2% (51/53). utLIFE showed similar high sensitivity in T 1 stage and ≥T 2 stage [100.0% (27/27) vs. 92.3% (24/26), P=0.236], in N 0 and ≥N 1 stage [ 95.0% (38/40) vs. 100.0% (5/5), P=1.000]. In addition, the sensitivity of preoperative utLIFE was higher than that of urine cytology [ 95.2% (20/21) vs. 23.8% (5/21). P<0.001], fluorescence in situ hybridization (FISH) [ 92.6% (25/27) vs. 55.5% (15/27), P=0.004] and ureteroscopy [ 86.7% (13/15) vs. 60.0% (9/15), P=1.000]. A total of 45 patients postoperative utLIFE samples were collected, and the postoperative utLIFE score was significantly lower than that of preoperative [ 36 (18, 61) vs. 79 (70, 84), P<0.001]. Conclusions:utLIFE, as a non-invasive urine DNA bioinformatics assessment model, is significantly superior to cytology and FISH in early detection and has high sensitivity in diagnosis of UTUC, and can reflect perioperative minimal residual disease levels.

Objective:To investigate the clinical characteristics of de novo malignancies (DNMs) after liver transplantation (LT) and to study the clinical management strategies.Methods:Adult LT recipients who were regularly followed-up in the Organ Transplantation Center, the Affiliated Hospital of Qingdao University from January 2005 to April 2021 were enrolled in this study. The clinical characteristics of DNMs were retrospectively analyzed. Of 601 LT recipients, there were 105 females and 496 males, aged (51.4±9.6) years old. They were divided into the DNMs group ( n=26) and the non-DNMs group ( n=575) according to whether there were DNMs on followed-up. Clinical data including age, sex, basic diseases before LT and operation time were collected. These patients were follow-up in outpatient clinics. Results:Twenty-six patients were diagnosed to develop DNMs after LT, but there were 28 DNMs (of which 2 patients were diagnosed to have DNMs twice). The incidence of DNMs after LT was 4.3% (26/601), the median time from LT to DNMs was 42 (20, 70) months, and the cumulative incidence rates of DNMs were 0.5%, 2.0%, 6.3%, 21.0% and 34.5% at 1, 3, 5, 10 and 15 years after LT, respectively. Among the 28 DNMs, digestive system tumors were most common, with 17 lesions (60.7%), followed by 3 lesions (11.1%) of lung cancer, 2 lesions (7.4%) of lymphoproliferative diseases, and 1 lesion (3.7%) of cervical cancer, thyroid cancer, soft palate cancer, eyelid cancer, laryngeal cancer, and prostate cancer. The follow-up time of 55.9 (36.6, 102.5) months in the DNMs group after LT was longer than the 33.4 (18.5, 58.9) months in the non-DNMs group ( P<0.001). The 1, 5, and 10 year survival rates of patients with DNMs after LT were 96.3%, 83.5%, and 49.8%, respectively. The 1, 5, and 10 year survival rates of patients with non-DNMs after LT were 94.5%, 77.7%, and 75.4%, respectively. There was no significant difference in the cumulative survival rates between the two groups (log rank=0.402, P=0.526). Conclusion:The incidence of DNMs in LT recipients was 4.3%. The majority of them were digestive system tumors. Early diagnosis and treatment of DNMs significantly improved the prognosis and quality of life of these patients.

Objective: To study the early dynamics of the epidemic of coronavirus disease (COVID-19) in China from 15 to 31 January, 2020, and estimate the corresponding epidemiological parameters (incubation period, generation interval and basic reproduction number) of the epidemic. Methods: By means of Weibull, Gamma and Lognormal distributions methods, we estimated the probability distribution of the incubation period and generation interval data obtained from the reported COVID-19 cases. Moreover, the AIC criterion was used to determine the optimal distribution. Considering the epidemic is ongoing, the exponential growth model was used to fit the incidence data of COVID-19 from 10 to 31 January, 2020, and exponential growth method, maximum likelihood method and SEIR model were used to estimate the basic reproduction number. Results: Early COVID-19 cases kept an increase in exponential growth manner before 26 January, 2020, then the increase trend became slower. The average incubation period was 5.01 (95%CI: 4.31-5.69) days; the average generation interval was 6.03 (95%CI: 5.20-6.91) days. The basic reproduction number was estimated to be 3.74 (95%CI: 3.63-3.87), 3.16 (95%CI: 2.90-3.43), and 3.91 (95%CI: 3.71-4.11) by three methods, respectively. Conclusions The Gamma distribution fits both the generation interval and incubation period best, and the mean value of generation interval is 1.02 day longer than that of incubation period. The relatively high basic reproduction number indicates that the epidemic is still serious; Based on our analysis, the turning point of the epidemic would be seen on 26 January, the growth rate would be lower afterwards.

Objective:To investigate the risk factors for Gleason score upgrading after radical prostatectomy in clinical low-risk prostate cancer patients aged≥65 years.Methods:A total of 485 clinical low-risk prostate cancer patients aged≥65 years at five centers of the national multi-center PC-follow database from January 2015 to March 2019 were retrospectively analyzed.Data including age at diagnosis, prostate-specific antigen(PSA), MRI prostate imaging, puncture Gleason score, operation method, puncture method, positive incision margin and capsule penetration were collected.Differences in Gleason scores before and after operation were compared, and the risk factors for Gleason score upgrading after radical resection were evaluated by univariate and multivariate Logistic regression analysis.Results:Of 485 patients with a puncture Gleason score of 3+ 3=6, 261(53.8%)cases had postoperative pathological upgrading, in whom 228(87.4%)cases had Gleason score upgrading of 7, 22(8.4%)had Gleason score upgrading of 8, and 11(4.2%)had Gleason score upgrading of 9 or more.The rate of Gleason score upgrading was elevated with increased preoperative PSA levels, positive pelvic MRI, and higher positive rates of puncture biopsy.The incidences of postoperative capsule penetration(27.2% vs.12.5%, P<0.001)and positive incision margin(25.2% vs.17.4%, P=0.036)had statistically significant differences between the pathologically upgraded group and the pathologically non-upgraded group.Multivariate analysis showed that preoperative PSA level, percentage of positive puncture biopsies, biopsy Gleason score and pelvic MRI were independent predictors of prostate cancer. Conclusions:For clinical low-risk prostate cancer patients aged≥65 years with high risk factors for Gleason score upgrading, repeated biopsies should be carried out when necessary and the treatment plan should be adjusted accordingly.

Objective:To establish a nomogram model for predicting positive resection margins after prostate cancer surgery, and to perform the corresponding verification, in order to predict the risk of positive resection margins after surgery.Methods:A total of 2 215 prostate cancer patients from The First Affiliated Hospital of Naval Medical University, Hospital, Peking University First Hospital, Peking University Third Hospital, Peking University, and First Affiliated Hospital of Xi′an Jiaotong University were included in the PC-follow database from 2015 to 2018, and a simple random sampling method was used. They were divided into 1 770 patients in the modeling group and 445 patients in the verification group. In the modeling group, the age (<60 years, 60 to 70 years, >70 years), PSA (<4 ng/ml, 4-10 ng/ml, 11-20 ng/ml, >20 ng/ml), pelvic MRI (negative, suspicious, positive), clinical stage of the tumor (T 1-T 2, ≥T 3), percentage of positive needles (≤33%, 34%-66%, >66%), Gleason score of biopsy pathology (≤6 points, 7 points, ≥8 points). Univariate and multivariate logistic analysis were performed to screen meaningful indicators to construct a nomogram model. The model was used for validation in the validation group. Results:The results of multivariate analysis showed that preoperative PSA level ( OR=2.046, 95% CI 1.022 to 4.251, P=0.009), percentage of puncture positive needles ( OR=1.502, 95% CI 1.136 to 1.978, P=0.002), Gleason score of puncture pathology ( OR=1.568, 95% CI 1.063 to 2.313, P=0.028), pelvic MRI were correlated ( OR=1.525, 95% CI 1.160 to 2.005, P=0.033). Establish a nomogram model for independent predictors of positive margin of prostate cancer. The area under the receiver operating characteristic (ROC) curve of the validation group is 0.776. The area under the ROC curve of the preoperative PSA level, percentage of puncture positive needles, puncture pathology Gleason score, pelvic MRI, postoperative pathology Gleason score were 0.554, 0.615, 0.556, 0.522, and 0.560, respectively. The difference between the nomogram model and other indicators was statistically significant ( P<0.05). Conclusions:The constructed nomogram model has higher diagnostic value than the preoperative PSA level, percentage of puncture positive needles, Gleason score of puncturing pathology, pelvic MRI, and postoperative pathological Gleason score in predicting positive margin.

Objective To summarize the characteristics of clinical manifestation of bone flare after the treatment with new endocrine therapy in patients with metastatic castration-resistant prostate cancer (mCRPC) in order to evaluate the curative effect of patients properly and determine the reasonable treatment strategy.Methods We retrospectively analyzed the clinical data of two patients with mCRPC performed "bone flare" defined as PSA decline and bone metastases progression in the initial treatment with new endocrine therapy in Urology Department of Peking University First Hospital,and analyzed the clinical characteristics and treatment methods with the relative literature.Case 1,a 79-year-old man,presented with frequent urination and prostate-specific antigen (PSA) was 115.900 ng/ml,was diagnosed as prostate cancer (cT3N0M1) with bone metastasis.After androgen deprivation therapy of 24 months,PSA elevated and multiple bone metastases progressed.The patient was diagnosed with mCRPC and then began the treatment of enzalutamide.Case 2,a 62-year-old man,complained about emaciation and frequent urination,was diagnosed with prostate cancer(cT4N1M1)with bone and lymph metastases.After androgen deprivation therapy of 22 months,PSA elevated and multiple bone metastases progressed.The patient was diagnosed with mCRPC and then began the treatment of abiraterone.Results Case 1 was treated with enzalutamide and 2 months later PSA decreased from 133.400 ng/ml to 5.530 ng/ml,while bone scan showed multiple bone metastases,part of which was newly metastatic lesions.6 months later,the number of metastatic lesions kept stable,and part of lesions presented metabolism decrease.8 months later,the number of metastatic lesions began to decrease.1 year later,the patient started to receive chemical therapy because of the progression of the disease.After 5 cycles of chemotherapy,PSA progression occurred and chemotherapy was stopped.Liver failure and disseminated intravascular coagulation caused death in June 2016.Case 2 was treated with abiraterone and 2 months later PSA decreased from 54.820 ng/ml to 3.580 ng/ml,while bone scan showed multiple bone metastases,part of which was newly metastatic lesions.6 months later,the number of metastatic lesions began to decline.10 months later,the number of metastatic lesions kept stable.The treatment of abiraterone was continued so far and the patient was in a stable condition.Conclusions Enzalutamide and abiraterone,two new endocrine therapy,are determined as preferred methods for the treatment of mCRPC.The bone scanning is required to evaluate the possibility of "bone flare" which is defined as PSA decline and bone metastases progression in the initial treatment.These patients should be evaluated to make appropriate clinical decision.

Objective? To explore the risk factors of incontinence-associated dermatitis(IAD) in intensive care uni(t ICU) patients, so as to provide evidence for early clinical prevention of IAD. Methods? The relevant literature about IAD in ICU patients were retrieved from multiple electronic databases including Cochrane library, PubMed, Ovid Medline, Web of Science, CBM, CNKI, Wanfang Data and VIP from buiding database to November 2018. The Meta-analysis was performed after searching databases, extracting data and assessing quality of included studies using the software of RevMan 5.3. Results? Finally, 14 articles were included with totally 691 case groups, and 1 377 cases in the control group with 2 068 subjects, the incidence of IAD was 20.00%-50.00%. The results of Meta-analysis indicated that feve[r OR=1.79, 95%CI (1.43-2.26), P＜0.05], diabetes[OR=2.73, 95%C(I 1.77-4.21), P＜0.05], the use of antibiotics[OR=2.45, 95%C(I 1.71-3.53), P＜ 0.05], level of albumin[OR=-3.81, 95%C(I -4.61- -3.00), P＜ 0.05], Acute Physiology and Chronic Health EvaluationⅡ(APACHEⅡ) score[OR=1.70, 95%C(I 0.06-3.33), P＜0.05], fecal incontinence[OR=1.80, 95%C(I 1.07-3.03), P＜ 0.05], incontinence frequency (＞ 3 times/day) [OR=1.86, 95%CI(1.56-2.22), P＜ 0.05]and watery stoo[l OR=2.22, 95%CI(1.81-2.73), P＜0.05]significantly associated with the onset of IAD. Through the sensitivity analysis of the combined effect of the fixed effect model and the random effect model, it was found that the combined effect values were close, indicating that the analysis results were robust and credible. Conclusions? According to the present evidence, the risk factors of IAD in ICU patients are fever, diabetes, antibiotics, low albumin level, high APACHE score, fecal incontinence, incontinence frequency (＞ 3 times/day) and watery stool. Medical staff should pay attention to these risk factors in clinical practice, and actively implement targeted preventive measures to reduce the incidence of IAD in ICU patients and improve the quality of nursing practice.