Research report of living donor kidney harvesting in Bama miniature pigs with six gene modified / 器官移植

Objective To summarize the experience and practical value of living donor kidney harvesting in Bama miniature pigs with six gene modified. Methods The left kidney of Bama miniature pigs with six gene modified was obtained by living donor kidney harvesting technique. First, the ureter was occluded, and then the inferior vena cava and abdominal aorta were freed. During the harvesting process, the ureter, renal vein and renal artery were exposed and freed in sequence. The vascular forceps were used at the abdominal aorta and inferior vena cava, and the renal artery and vein were immediately perfused with 4℃ renal preservation solution, and stored in ice normal saline for subsequent transplantation. Simultaneously, the donor abdominal aorta and inferior vena cava gap were sutured. The operation time, blood loss, warm and cold ischemia time, postoperative complications and the survival of donors and recipients were recorded. Results The left kidney of the genetically modified pig was successfully harvested. Intraoperative bleeding was 5 mL, warm ischemia time was 45 s, and cold ischemia time was 2.5 h. Neither donor nor recipient pig received blood transfusion, and urinary function of the kidney transplanted into the recipient was recovered. The donor survived for more than 8 months after the left kidney was resected. Conclusions Living donor kidney harvesting is safe and reliable in genetically modified pigs. Branch blood vessels could be processed during kidney harvesting, which shortens the process of kidney repair and the time of cold ischemia. Living donor kidney harvesting contributes to subsequent survival of donors and other scientific researches.

Phosphatidic acid-enabled MKL1 contributes to liver regeneration: Translational implication in liver failure

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

Casticin Attenuates Stemness in Cervical Cancer Stem-Like Cells by Regulating Activity and Expression of DNMT1 / 中国结合医学杂志

OBJECTIVE@#To explore whether casticin (CAS) suppresses stemness in cancer stem-like cells (CSLCs) obtained from human cervical cancer (CCSLCs) and the underlying mechanism.@*METHODS@#Spheres from HeLa and CaSki cells were used as CCSLCs. DNA methyltransferase 1 (DNMT1) activity and mRNA levels, self-renewal capability (Nanog and Sox2), and cancer stem cell markers (CD133 and CD44), were detected by a colorimetric DNMT activity/inhibition assay kit, quantitative real-time reverse transcription-polymerase chain reaction, sphere and colony formation assays, and immunoblot, respectively. Knockdown and overexpression of DNMT1 by transfection with shRNA and cDNA, respectively, were performed to explore the mechanism for action of CAS (0, 10, 30, and 100 nmol/L).@*RESULTS@#DNMT1 activity was increased in CCSLCs compared with HeLa and CaSki cells (P<0.05). In addition, HeLa-derived CCSLCs transfected with DNMT1 shRNA showed reduced sphere and colony formation abilities, and lower CD133, CD44, Nanog and Sox2 protein expressions (P<0.05). Conversely, overexpression of DNMT1 in HeLa cells exhibited the oppositive effects. Furthermore, CAS significantly reduced DNMT1 activity and transcription levels as well as stemness in HeLa-derived CCSLCs (P<0.05). Interestingly, DNMT1 knockdown enhanced the inhibitory effect of CAS on stemness. As expected, DNMT1 overexpression reversed the inhibitory effect of CAS on stemness in HeLa cells.@*CONCLUSION@#CAS effectively inhibits stemness in CCSLCs through suppression of DNMT1 activation, suggesting that CAS acts as a promising preventive and therapeutic candidate in cervical cancer.

Preliminary report of perioperative monitoring of six-gene-edited pig-to-cynomolgus monkey kidney xenotransplantation / 器官移植

Objective To investigate the establishment of a six-gene-edited pig-to-non-human primate kidney xenotransplantation model. Methods The kidney of humanized genetically-edited pig (GTKO/β4GalNT2KO/CMAHKO/hCD55/hCD46/hTBM) was transplanted into a cynomolgus monkey. The survival of the recipient and kidney condition after blood perfusion were observed. The parenchymal echo, blood flow changes, and size of the kidney were monitored on a regular basis. Routine blood test, kidney function test and electrolyte assessment were carried out. Dynamic changes of urine, feces and body mass were monitored. At the end of life, the transplant kidney, heart, liver, spleen, lung, and cecum were collected for pathological examination. Results The recipient died at postoperative 7 d. After blood flow was restored, the kidney was properly perfused, the organ was soft and the color was normal. At the end of the recipient's life, a slight amount of purulent secretion was attached to the ventral side of the kidney, with evident congestion and swelling, showing the appearance of "red kidney". Postoperatively, the echo of renal parenchyma was increased, blood flow was decreased, the cortex was gradually thickened, and a slight amount of effusion surrounded the kidney and abdominal cavity over time. In the recipient, the amount of peripheral red blood cells, hemoglobin, albumin, and platelets was progressively decreased, and serum creatinine level was increased to 308 μmol/L at postoperative 7 d, whereas the K+ concentration did not significantly change. Light yellow urine was discharged immediately after surgery, diet and drinking water were resumed within postoperative 3 h, and light yellow and normal-shape stool was discharged. The reddish urine was gradually restored to normal color within postoperative 1 d, which were consistent with the results of the routine urine test. A large amount of brown bloody stool was discharged twice in the morning of 2 d after surgery. Omeprazole was given for acid suppression, and the stool returned to normal at postoperative 4 d. The β2-microglobulin level was increased to 0.75 mg/L at postoperative 7 d. The body mass was increased by 1.7 kg. Autopsy pathological examination showed interstitial edema and bleeding of the transplant kidney, a large amount of infiltration of lymphocytes and macrophages, infiltration of lymphocytes in the arteriole wall and arterial cavity, accompanied by arteritis changes, lymphocyte infiltration in the cecal stroma and congestion in the spleen tissues. No significant abnormal changes were observed in other organs. Conclusions The humanized genetically-edited pig-to-non-human primate kidney xenotransplantation model is successfully established, and postoperative survival of the recipient is 1 week.

Satisfaction of Patients with Above-the-knee Amputation following Periprosthetic Joint Infection / 中山大学学报(医学科学版)

ObjectiveThe purpose of this study was to evaluate the functional outcomes and satisfaction in periprosthetic knee infection patients after above-the-knee amputation （AKA）. MethodsA review was performed in 13 patients who underwent AKA due to periprosthetic knee infection from October 2010 to August 2022， there were 7 females and 6 males with the median age of 69 （45~ 73） years. The mean number of surgical procedures between primary total knee arthroplasty and AKA was 2.9 times （range： 1 ~ 6）. Patients were segregated into non-elderly group （including patients <65 years old） and elderly group （involving patients ≥65 years old）. Functional outcomes were evaluated by SF-12 and Barthel activities daily living index （Barthel ADL index）. Patient satisfaction was accomplished through a questionnaire. ResultsFour patients died within 6 months after the amputation. Three patients received surgical procedures for recurrent infections after AKA. In the remaining 9 patients，the median time from AKA to the final follow-up was 4.2 （1.9~8.2） years， three patients received surgical procedures for recurrent infections after AKA. Patients in non-elderly group showed better functional outcomes than elderly patients after AKA （both P<0.05）. All patients in non-elderly group were fitted with a prosthesis. Whereas， elderly patients reported a better satisfaction after AKA than young patients. ConclusionYoung PJI patients seemed to have better function and ambulatory ability with high expectation and demand， which made them feel less satisfied about AKA. Meanwhile，despite poor function outcomes due to the less healthy physical condition， the alleviation of financial and psychological burdens resulting from reinfections and multiple surgeries and the less demand in function and daily activities made elderly patients have a good satisfaction after AKA.

Protective effect and mechanism of Maiwei Yangfei Decoction on pulmonary fibrosis mice based on Nrf2 regulation of oxidative stress / 中国中药杂志

This study explored the effect and mechanism of Maiwei Yangfei Decoction(MWYF) on pulmonary fibrosis(PF) mice. MWYF was prepared, and its main components were detected by ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-MS/MS). Male C57BL/6J mice were randomly divided into a control group, a model group, a pirfenidone(PFD) group, and low-, medium-, and high-dose MWYF groups, with 10 mice in each group. The PF model was induced in mice except for those in the control group by intratracheal instillation of bleomycin(BLM), and model mice were treated with saline or MWYF or PFD by gavage the next day. The water consumption, food intake, hair, and activity of mice were observed daily. The pathological changes in lung tissues were observed by hematoxylin-eosin(HE) staining, Masson staining, and CT scanning. The level of hydroxyproline(HYP) in lung tissues was detected by alkaline hydrolysis. Immunohistochemistry was used to observe the expression of collagen type Ⅲ(COL3) and fibronectin. The mRNA expression levels of α-smooth muscle actin(α-SMA), type Ⅰ collagen α1(COL1α1), COL3, and vimentin were detected by reverse transcription real-time fluorescence quantitative polymerase chain reaction(RT-qPCR). Superoxide dismutase(SOD) and malondialdehyde(MDA) kits were used to detect oxidative stress indicators in lung tissues and serum. The nuclear translocation of nuclear factor E2-related factor 2(Nrf2) protein was detected by immunofluorescence. The protein and mRNA expression levels of Nrf2, catalase(CAT), and heme oxygenase 1(HO-1) in lung tissues were detected by Western blot and RT-qPCR. Twelve chemical components were detected by UPLC-MS/MS. Animal experiments showed that MWYF could improve alveolar inflammation, collagen deposition, and fibrosis in PF mice, increase body weight of mice, and down-regulate the expression of fibrosis indexes such as HYP, α-SMA, COL1α1, COL3, fibronectin, and vimentin in lung tissues. In addition, MWYF could potentiate the activity of SOD in lung tissues and serum of PF mice, up-regulate the expression level of Nrf2, and promote its transfer to the nucleus, up-regulate the levels of downstream antioxidant target genes CAT and HO-1, and then reduce the accumulation of lipid metabolite MDA. In summary, MWYF can significantly improve the pathological damage and fibrosis of lung tissues in PF mice, and its mechanism may be related to the activation of the Nrf2 pathway to regulate oxidative stress.

Ultrasmall iron-quercetin metal natural product nanocomplex with antioxidant and macrophage regulation in rheumatoid arthritis

Oxidative stress, due to the disruption of the balance between reactive oxygen species (ROS) generation and the antioxidant defense system, plays an important role in the pathogenesis of rheumatoid arthritis (RA). Excessive ROS leads to the loss of biological molecules and cellular functions, release of many inflammatory mediators, stimulate the polarization of macrophages, and aggravate the inflammatory response, thus promoting osteoclasts and bone damage. Therefore, foreign antioxidants would effectively treat RA. Herein, ultrasmall iron-quercetin natural coordination nanoparticles (Fe-Qur NCNs) with excellent anti-inflammatory and antioxidant properties were constructed to effectively treat RA. Fe-Qur NCNs obtained by simple mixing retain the inherent ability to remove ROS of quercetin and have a better water-solubility and biocompatibility. In vitro experiments showed that Fe-Qur NCNs could effectively remove excess ROS, avoid cell apoptosis, and inhibit the polarization of inflammatory macrophages by reducing the activation of the nuclear factor-κ-gene binding (NF-κB) pathways. In vivo experiments showed that the swollen joints of mice with rheumatoid arthritis treated with Fe-Qur NCNs significantly improved, with Fe-Qur NCNs largely reducing inflammatory cell infiltration, increasing anti-inflammatory macrophage phenotypes, and thus inhibiting osteoclasts, which led to bone erosion. This study demonstrated that the new metal-natural coordination nanoparticles could be an effective therapeutic agent for the prevention of RA and other diseases associated with oxidative stress.

Establishment of animal models for depression in the elderly and progress on their application / 中华老年医学杂志

Geriatric depression in the elderly is becoming one of the most common psychiatric disorders affecting older people's mental and physical health.However, there is currently no systematic review on animal models for geriatric depression.Therefore, this paper analyzes and summarizes the animal models commonly used in geriatric depression studies and the application of antidepressants in geriatric depression models based on relevant national and international literature of recent years, aiming to provide insights on research approaches and considerations on study methods for geriatric depression.

Exploration on the blended learning reform in organ-systems based curriculum model of the endocrine system / 中华医学教育探索杂志

Since 2016, Binzhou Medical University began to carry out the blended learning reform in the organ-systems based curriculum (OSBC) of the experimental class of clinical medicine. Based on the traditional face-to-face teaching method, the blended learning mode of the integrated course of endocrine system under OSBC has been carried out by using the small private online course (SPOC) of MOOC platform of China universities. Many teaching methods have been adopted and formed, including case-based learning (CBL), problem-based learning (PBL), professional bilingual teaching, scientific research teaching and virtual simulation experiment teaching. The evaluation system for the combination of formative and summary assessment has been also adopted in the whole process to assess the students' academic achievement, and the teaching effect as well. The blended learning mode of the integrated course of the endocrine system under OSBC is still in the exploratory stage. There are some limitations, such as too high requirements for teachers' quality, long preparation time for teaching, and great difficulty in supervising online learning. However, the practice of teaching reform that has been carried out shows that it is effective, feasible, and worth popularizing.

Mechanism study of Dangshen Pingfei Huoxue decoction in treatment of pulmonary fibrosis based on network pharmacology and molecular docking / 中国药理学通报

Aim To explore the potential mechanism of Dangshen Pingfei Huoxue decoction (DPHD) in the treatment of pulmonary fibrosis. Methods The common targets of DPHD and pulmonary fibrosis were obtained. Cytoscape software was used to construct " disease-drug-ingredients-targets " network diagram, and the common targets were imported into the STRING database for protein-protein interaction (PPI) analysis to screen out the core targets. In order to screen out key signaling pathways, the core genes were inputted into the DAVID platform for gene ontology (GO) and kyoto encyclopedia of genes genomes (KEGG) enrichment analysis. Then the molecular docking technology was used to verify the molecular docking between the core components and the key proteins in the signaling pathway. Finally, the molecular docking technology was used to verify the results of network pharmacology. Results A total of 176 active ingredients were obtained, and the top 5 was quercetin, kaempferol, luteolin, naringenin and p-sitosterol, respectively. A total of 116 common targets were obtained. A total of 21 core targets were finally obtained by PPI screening, and the top 5 was AKT1, CCND1, CASP3, MYC and IL1B, respectively. The results of GO enrichment analysis showed that DPHD was mainly involved biological processes of oxidative stress, proliferation and differentiation, transcriptional regulation, drug response and inflammatory response. The results of KEGG enrichment analysis indicated that the mainly signaling pathways included PI3K/Akt, MAPK, cellular senescence, AMPK, and TGF-beta. Molecular docking results showed that the binding energies of the top 5 active components of DPHD and the top 5 core targets were all less than-6.0 kcal • mo

Mechanism of ophiopogonin D in treatment of pulmonary fibrosis based on network pharmacology and experimental verification / 中国药理学通报

Aim To predict the potential mechanism of ophiopogonin D (OPD) against pulmonary fibrosis by network pharmacology, and further verify it by experiment in vivo. Methods This study found that ophiopogon was the most frequently used drug in the treatment of pulmonary fibrosis with deficiency of Qi and Yin through data mining. In order to explore its material basis, network pharmacology analysis was carried out. A model of pulmonary fibrosis was established by bleomycin, and different concentrations of ophiopogonin D were administered to verify the results of the pharmacological network. Results Firstly, through network pharmacology analysis, it was found that mitophagy might be the potential target for ophiopogon to exert anti-pulmonary fibrosis effect. Meanwhile, network topology analysis showed that OPD had the greatest relationship with mitophagy. Animal experiments showed that OPD could relieve pulmonary fibrosis and reduce collagen deposition in mice. At the same time, the detection of mitophagy related proteins showed that the compound could increase the expression of PINK1 and Parkin proteins, reduce the content of P62 protein in lung tissue, and reduce the intracellular ROS level. Conclusions OPD can improve mitochondrial function and play an anti-pulmonary fibrosis role by promoting PINKl/Parkin dependent mitophagy in lung tissue.

The clinical effect of sacubitril valsartan combined with dapagliflozin in heart failure with reduced ejection fraction and non-diabetes patients / 西安交通大学学报(医学版)

【Objective】 To observe the clinical effect of combination therapy of sacubitril valsartan and dapagliflozin in heart failure with reduced ejection fraction (HFrEF) and non-diabetes patients. 【Methods】 This study involved 96 patients with HFrEF and non-diabetes. The patients were randomly divided into control group (50 cases) and observation group (46 cases). On the basis of routine treatment, the control group was treated with sacubitril valsartan, while the observation group was treated with sacubitril valsartan and dapagliflozin. After 1-month and 6-month treatment, we monitored blood pressure, N-terminal pro brain natriuretic peptide (NT-proBNP), high sensitivity troponin T (cTnT), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDd), left atrial diameter (LAD), left ventricular posterior wall thickness (LVPW), Minnesota soda heart failure life quality score (MLHFQ), the incidence of rehospitalization and death, and major adverse cardiovascular events (MACE) in the two groups. 【Results】 After 6 months, systolic blood pressure, cTnT, NT-proBNP, LVEDd, LVPW, and LAD of the observation group were significantly decreased compared with the control group (P0.05). 【Conclusion】 The combination treatment of sacubitril valsartan and dapagliflozin on HFrEF and non-diabetes patients can significantly improve cardiac function, inhibit myocardial remodeling, reduce the incidence of MACE, and improve the prognosis.

Determination of azelaic acid and potassium azeloycinate diglycinate in cosmetics by HPLC / 上海预防医学

ObjectiveAn HPLC method was established for the determination of azelaic acid and potassium azeloycinate diglycinate in cosmetics. MethodsThe samples were extracted with 60 mmol·L-1 sodium hydroxide water solution-methyl alcohol. After centrifugation and filtration， the analysis of azelaic acid and potassium azeloycinate diglycinate was performed with a SVEA C8（250 mm×4.6 mm， 5 μm） column， using 15 mmol‧L-1 potassium dihydrogen phosphate solution （pH=3.0） and acetonitrile for gradient elution at a flow rate of 1.0 mL·min-1.The analytes were detected with UV detector， and quantified by external standard curve. ResultsThe results showed a good linearity in the range of 5‒1 000 μg‧mL-1 with correlation coefficients （r） larger than 0.999. The detection limit of azelaic acid and potassium azeloycinate diglycinate （LOD） was 0.020% and 0.015%， respectively. The spiked recoveries were 87.66% to 108.96% with the relative standard deviation （RSD） of 0.6% to 3.3%. ConclusionThe method is simple， rapid and highly sensitive. It is suitable for the determination of azelaic acid and potassium azeloycinate diglycinate in cosmetics.

The hypothalamus for whole-body physiology: from metabolism to aging

Obesity and aging are two important epidemic factors for metabolic syndrome and many other health issues, which contribute to devastating diseases such as cardiovascular diseases, stroke and cancers. The brain plays a central role in controlling metabolic physiology in that it integrates information from other metabolic organs, sends regulatory projections and orchestrates the whole-body function. Emerging studies suggest that brain dysfunction in sensing various internal cues or processing external cues may have profound effects on metabolic and other physiological functions. This review highlights brain dysfunction linked to genetic mutations, sex, brain inflammation, microbiota, stress as causes for whole-body pathophysiology, arguing brain dysfunction as a root cause for the epidemic of aging and obesity-related disorders. We also speculate key issues that need to be addressed on how to reveal relevant brain dysfunction that underlines the development of these disorders and diseases in order to develop new treatment strategies against these health problems.

Feasibility of radical prostatectomy without biopsy for patients with highly suspected localized prostate cancer diagnosed by mpMRI and 68Ga-PSMA PET/CT / 中华泌尿外科杂志

Objective:To explore the feasibility of radical prostatectomy without biopsy for patients with highly suspected localized prostate cancer diagnosed by multiparametric magnetic resonance imaging (mpMRI) and 68Ga-PSMA PET/CT. Methods:Patients were enrolled in this single-arm prospective study from March 2019 to January 2022 in the Second Hospital of Tianjin Medical University. Eligible patients were aged ≤80 years with an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1. Based on mpMRI and 68Ga-PSMA PET/CT, patients were diagnosed with highly suspected localized prostate cancer with no evidence of distant lymphatic, bone or visceral metastases. Patients were excluded if they had obvious important organs dysfunction, suspected metastatic lesions or history of other malignant tumor. After fully informed of the surgical risks and possibilities of final pathology, patients received laparoscopic or robot-assisted laparoscopic radical prostatectomy. According to final pathological results, the diagnostic accuracy of mpMRI and 68Ga-PSMA PET/CT was evaluated. Pathological features were compared between low 68Ga-PSMA PET/CT maximum standardized uptake value (SUV max) group (SUV max<10) and high SUV max group (SUV max≥10). Baseline characteristics were compared between clinically significant prostate cancer (CsPCa) and clinically insignificant prostate cancer (cisPCa) + high grade prostatic intraepithelial neoplasia (HGPIN) patients. Additional analysis of the correlation between baseline parameters and different subgroups including pathological stage, ISUP grades and risk groups were performed in CsPCa patients. Results:31 patients were enrolled. Median age was 68 (ranging 48-79)years old. Median BMI was 25.6(ranging 21.9-31.4)kg/m 2. Median prostate specific antigen (PSA) was 23.5 (ranging 5.6-94.7)ng/ml. Median prostate volume was 37.6(ranging 16.2-127.9)ml. Median PSA density (PSAD) was 0.56(ranging 0.11-2.86)ng/ml 2. Fifteen cases were scored prostate imaging reporting and data system (PI-RADS) 4 and 16 cases were scored PI-RADS 5. Median 68Ga-PSMA PET/CT SUV max was 13.3 (ranging 4.6-36.7). All surgeries were successfully accomplished without open conversion. Median postoperative hospitalization time was 5 (ranging 4-7)d. No major complication occurred perioperatively. Recovery of urinary continence was within 6 months in all patients. According to the final pathological results, 1(3.2%) patient was confirmed with HGPIN. 30 (96.8%) patients were confirmed with adenocarcinoma, including 26 (86.7%) patients with CsPCa and 4(13.3%) patients with cisPCa. Among prostate cancer cases, the pathological stage of 11(36.7%) was T 2 and 19(63.3%) was T 3. Four(13.3%) cases were with ISUP grade 1, 7(23.3%) cases were with ISUP grade 2, 7(23.3%) cases were with ISUP grade 3 and 12 (40.0%) cases were with ISUP grade≥4.Two(6.7%) cases were in low risk group, 3(10.0%) cases were in intermediate risk group and 25 (83.3%) cases were in high risk group. Twelve(40.0%) patients had positive surgical margins. Standard pelvic lymph node dissection was carried out in 18 (17 prostate cancer and 1 HGPIN) cases. Sixty-two lymph nodes were dissected and none of them was positive. The diagnostic accuracy of mpMRI and 68Ga-PSMA PET/CT was 96.8%(30/31) in prostate cancer. Compared to low SUV max group, patients in high SUV max group had higher ISUP grade ( P=0.003) but there was no significant difference in positive surgical margin, seminal vesical invasion or pathological stage ( P>0.05). Among CsPCa patients, 10 (38.5%) cases were scored PI-RADS 4 and 16(61.5%) cases were scored PI-RADS 5. Median 68Ga-PSMA PET/CT SUV max was 14.3 (range 6.1-36.7). Compared to cisPCa and HGPIN patients, a smaller median prostate volume (34.3 vs. 73.0 ml, P=0.006), higher median PSAD (0.70 vs. 0.13 ng/ml 2, P=0.001), higher rates of PI-RADS 5 patients (61.5% vs. 0, P=0.018) and higher 68Ga-PSMA PET/CT SUV max (14.3 vs. 6.1, P=0.001) were found in CsPCa patients. Subgroup analysis showed no significant difference between SUV max and pathological stage (25.5 vs. 13.9), ISUP grades (15.4 vs. 14.4 vs. 14.0) and risk groups (9.7 vs. 14.9) in CsPCa patients ( P>0.05). Conclusions:The diagnostic accuracy of mpMRI and 68Ga-PSMA PET/CT is high in prostate cancer. With efficient communication, radical prostatectomy without biopsy for patients with highly suspected localized prostate cancer diagnosed by mpMRI and 68Ga-PSMA PET/CT is safe.

Research progress of engineered nanomaterials in the diagnosis and treatment of prostate cancer / 中华泌尿外科杂志

Prostate cancer poses a serious threat to the health of men with an increasing incidence in China. In recent years, great progress has been made in surgical and pharmaceutical treatment, but there are few promising techniques for early diagnosis of prostate cancer or therapeutics for advanced prostate cancer. Engineered nanomaterials have emerged and shown great potential in early diagnosis, precisely targeted therapies and synergistic therapeutics for prostate cancer because of unique physicochemical properties, such as size on the nanoscale, large specific surface area, high drug loading efficiency, fluorescence excitation ability and photothermal/photodynamic effect. This review focused on the new diagnoses and treatment strategies in prostate cancer with engineered nanomaterials, by summarizing the advancement of engineered nanomaterials in improving the sensitivity of molecular biology and imaging diagnosis, targeted guidance in surgery, sensitization of radiotherapy and chemotherapy, and targeted drug delivery.

Efficacy and safety of docetaxel plus hormone therapy in metastatic prostate cancer / 中华泌尿外科杂志

Objective:To evaluate the efficacy and safety of docetaxel plus hormone therapy in metastatic prostate cancer.Methods:From April 2016 to April 2019, 204 cases with bone metastatic prostate cancer in the Second Hospital of Tianjin Medical University were analyzed retrospectively. There were 97 patients responded to hormone therapy including 92 cases with high-burden metastasis (more than 4 bone metastases with one or more beyond the axial skeleton) and 5 cases with low-burden metastasis, with average age of 70 years (range 42-87 years) and median prostate specific antigen (PSA) of 74.1 ng/ml (range 11.0-145.0 ng/ml). Among them, there were 35 patients (36.1%) with a Gleason score of 7 or lower, and 62 patients (63.9%) with a Gleason score of 8 or higher. There were 26 patients suffering from bone pain, with average numerical rating scales(NRS) score of 3.7. In addition, there were 107 patients being resistant to hormone therapy, with average age of 73 years (range 56-83 years), and median PSA of 84.5 ng/ml (range 12.4-490.2 ng/ml), including 32 patients (29.9%) with a Gleason score of 7 or lower, and 75 patients (70.1%) with a Gleason score of 8 or higher. Among them, there were 75 patients suffering from bone pain, with average NRS score of 5.4. All patients received continuous hormone therapy combined with docetaxel (at a dose of 75 mg per square meter of body-surface area every 3w, plus prednisone 5 mg twice a day), and PSA progression-free survival (PSA-PFS), NRS score, pain relief, and adverse events were analyzed. Additional analysis of the correlation between PSA-PFS and subgroups with age, PSA level and Gleason score were performed.Results:For patients with metastatic hormone sensitive prostate cancer (mHSPC), 6 (6.2%) cases only received 1-2 cycles of chemotherapy due to different reasons, and the others received 3-6 cycles(average 4.7)with the median follow-up of 15 months. Of patients who received ≥3 cycles, there were 36 cases presenting PSA progression, with the median PSA-PFS of 22 months, average NRS score decline from 3.9 to 3.0, and pain relief rate of 72.0%(18/25). For patients with metastatic castration-resistant prostate cancer (mCRPC), 9 (8.4%)cases only received 1-2 cycles of chemotherapy, and the others received 3-14 cycles (average 5.6). Of patients who received≥3 cycles, there were 51 cases with PSA progression, with the median PSA-PFS of 11 months, average NRS score decline from 5.6 to 4.4, and pain relief rate of 48.6%(35/72). Subgroup analysis showed a significant correlation between PSA level and PSA-PFS for patients with mCRPC( P=0.026). Age or Gleason score was not significantly correlated to PSA-PFS in mHSPC or mCRPC( P>0.05). For patients with mHSPC, grade 3 or 4 neutropenia occurred in 17 cases(17.5%), nausea and vomiting in 27 cases(27.8%), and fatigue in 25 cases(25.8%). For patients with mCRPC, grade 3 or 4 neutropenia occurred in 24 cases (22.4%), nausea and vomiting in 34 cases(31.8%), and fatigue in 26 cases(24.3%). Allergic reaction and sensory neuropathy toxicity were occasional. Conclusion:Efficacy of docetaxel plus hormone therapy was confirmed in metastatic prostate cancer and adverse events were tolerable.

Expression and significance of HERG protein in Cajal interstitial cells of gallbladder tissue in patients with gallbladder stones / 中华肝胆外科杂志

Objective:To investigate the expression and significance of human ether-a-go-go related gene (HERG) protein in interstitial cells of Cajal (ICC) in patients with gallbladder stones.Methods:The gallbladder tissues of 60 patients with gallbladder diseases who underwent cholecystectomy from January 2018 to December 2020 in the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital were collected, including 36 males and 24 females, aged (46.0±14.0) years. They were divided into two groups according to whether there were gallstones: gallstone group and control group (patients with gallbladder polyps and gallbladder adenomyosis), with 30 cases in each group. Color ultrasound was used to detect and calculate the gallbladder contraction rate. The neck, body and bottom tissues of the gallbladder were excised and sectioned. The expression of HERG protein and CD117 ( marker of ICC) was detected by immunofluorescence staining, immunohistochemistry and Western blot.Results:The gallbladder contraction rate in the gallstone group was (65.8±4.1)%, lower than that in the control group (73.8±5.3)%, with a statistically significant difference ( t=4.14, P<0.001). Immunohistochemistry showed that HERG protein was mainly distributed in the mucosal layer of gallbladder tissue, which was pale brown. The relative expression of HERG protein at the bottom of gallbladder in the gallstone group was (0.293±0.102), lower than that in the control group (0.694±0.059), with a statistically significant difference ( t=3.38, P=0.027). Immunofluorescence staining showed that HERG protein was mainly distributed in ICC of gallbladder epithelium. HERG protein expression in ICC at the bottom of gallbladder in gallstone group was lower than that in control group, while HERG protein expression at the neck and body of gallbladder had no significant difference. Conclusion:There are ICC and HERG protein in gallbladder tissue of patients with gallstone. The decrease of gallbladder contraction rate may be related to the decrease of HERG protein expression in ICC in gallbladder bottom tissue.

Research progress in the proteomics of crystal-cell interaction in pathogenesis of calcium oxalate kidney stones / 国际生物医学工程杂志

Nephrolithiasis/urolithiasis have long been a global public health problem because of their high incidence. The most common chemical component causing nephrolithiasis/urolithiasis is calcium oxalate, which forms stone lesions through the processes of crystalline formation, crystal growth, aggregation, crystal-cell adhesion, and invasion of the interstitial extracellular matrix of the kidney. In these processes, crystal-cell interactions are crucial. Proteomics has been widely used in the study of nephrolithiasis/urolithiasis. In this paper, the progress of proteomics of calcium oxalate crystal-cell interaction in nephrolithiasis/urolithiasis was reviewed with the aim of better understanding the pathogenesis of kidney stones.

Clinical anatomy of cast specimens of the pancreatic duct / 解剖学报

Objective To explore the distribution and structure of pancreatic ducts and lobules in human pancreas and explore their clinical application value. Methods Three human pancreatic specimens were dissected, 2 of which were fresh whole pancreas samples which were collected from the donated human bod)' after dead,UW organ preservation solution was immediately perfused, and the pancreatic duct was rinsed at low pressure. The surface and internal structure of 1 case was observed as a fixed specimen. Paraffin sections were taken for HE staining to observe the structure of lobules and the distribution of catheters in the leaves. Results The gross specimen showed that the pancreas was composed of lobules of different sizes, with thin layers of connective tissue between the lobules. The pancreatic duct had a complete cast structure and could be clearly displayed to the main duct and the branches of the interlobular duct. The diameters of the interlobular ducts varied widely, and finally a main trunk flowed into the main duct. Each trunk was distributed independently, and the distal pancreatic duct formed a lobule-like structure with different sizes of lobules and no interlobular communication. HE staining showed that the pancreatic lobules were surrounded by connective tissue, in which vascular and ductal structures were visible. Intralobular duct could also be observed in the pancreatic lobules. Conclusion The cast specimen of the human pancreatic duct can clearly show the branch distribution of the pancreatic duct, and the study of the morphological of the pancreatic duct and lobular structure is of great reference value for understanding the clinical problems.