Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans ; Male ; Azoospermia/diagnostic imaging* ; Deep Learning ; Testis/pathology* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Sperm Retrieval ; Sertoli Cell-Only Syndrome/diagnostic imaging*

Objectives:The ORION-18 study has demonstrated that inclisiran can significantly reduce low-density lipoprotein cholesterol(LDL-C)and has good safety in Asian atherosclerotic cardiovascular disease(ASCVD)patients or ASCVD high-risk population.This subgroup analysis aims to further evaluate the efficacy and safety of inclisiran in Chinese mainland population.Methods:ORION-18 study is a multi-center,randomized,double-blind,placebo-controlled,phase Ⅲ clinical trial among Asian subjects,Chinese mainland subgroup included 232 ASCVD patients or ASCVD high-risk subjects who had already been treated with diet control and maximum tolerated doses of statins treatment(with or without other lipid-lowering treatments)but still had elevated LDL-C levels.Subjects were randomized in a 1:1 ratio to the inclisiran group and the placebo group(n=116 each),and received 300 mg of inclisiran or placebo respectively on day 0,90 and 270.The primary endpoint was the percentage change in LDL-C from baseline to day 330.The secondary endpoints included the time-adjusted percentage change and absolute change in LDL-C from baseline after day 90 and up to day 360,the absolute change in LDL-C from baseline to day 330,and the percentage changes from baseline to day 330 in proprotein convertase subtilisin/kexin type 9(PCSK9),total cholesterol,apolipoprotein B(ApoB),non-high-density lipoprotein cholesterol(non-HDL-C).Other secondary endpoints included the proportion of participants reaching LDL-C levels of<1.8 mmol/L at day 330,the proportion of participants with≥50%LDL-C reduction from baseline to day 330 and the proportion of participants who attained global lipid targets(the LDL-C target was<1.4 mmol/L for ASCVD patients and<1.8 mmol/L for ASCVD high-risk subjects)at day 330.Safety endpoints included adverse events during treatment,aboratory test abnormalities during treatment,serious adverse events,and assessed their severity and relation to treatment.Results:The inclisiran group showed a placebo-corrected percentage change in LDL-C from baseline to day 330 of-61.16%,and an absolute change of-1.73 mmol/L(both P<0.0001).Compared to the placebo group,the inclisiran group's time-adjusted percentage change in LDL-C from baseline between day 90 and day 360 was-58.51%,and an absolute change of was-1.64 mmol/L(both P<0.0001).At day 330,reductions from baseline were observed in the inclisiran group for PCSK9,total cholesterol,ApoB,non-HDL-C,with placebo-corrected percentage changes of-77.44%,-35.65%,-43.43%,-50.90%(all P<0.0001),respectively.At day 330,79.6%(74/93)of patients in the inclisiran group and 7.8%(6/77)in the placebo group achieved LDL-C levels<1.8 mmol/L,69.9%(65/93)of patients in the inclisiran group and 0%(0/77)in the placebo group achieved≥50%LDL-C reduction from baseline,66.7%(62/93)of patients in the inclisiran group and 2.6%(2/77)in the placebo group achieved their global LDL-C targets.The safety profile of inclisiran treatment over 12 months was comparable to that of the placebo,with no occurrence of treatment-related serious adverse events.Conclusions:In ASCVD patients or ASCVD high-risk subjects in Chinese mainland who have received diet control and maximum tolerable dose statins treatment(with or without other lipid-lowering treatments)and still have elevated LDL-C,inclisiran has a definite efficacy and good safety in reducing LDL-C.The efficacy and safety results of inclisiran assessed in Chinese mainland population are consistent with those of the general Asia population.

AIM To investigate the effects of volatile oil from Acorus tatarinowii Schott(A.tatarinowii)on neuroinflammation in a rat model of tic disorders.METHODS The SD rats were randomly divided into the blank group(8 rats)and the model group(40 rats).The rat models of tic disorders established successfully by intraperitoneal injection of iminodiapropionitrile(IDPN)were further divided into the model group,the tiapride group and the high-dose,moderate-dose and low-dose A.tatarinowii volatile oil groups,with 8 rats in each group.The 4-week intragastric treatment of respective drug was initiated the next day after the completion of modeling,and normal saline was dosed upon the blank group and the model group,during which the rats' behavioral changes were assessed by stereotyped behavior and motor behavior score every week.After the administration,the rats had their morphological changes of striatal neurons observed by Nissl staining;their levels of TGF-β,IL-10,TNF-αand IL-1β in serum and striatum detected by ELISA;their striatal protein expressions of CX3CL1 and CX3CR1 detected by Western blot and immunohistochemistry;and their striatal expressions of M1,M2 microglia marker proteins CD86,CD206,SYN and PSD-95 detected by immunofluorescence co-staining.RESULTS Compared with the model group,the A.tatarinowii volatile oil groups demonstrated improved twitch-like behavior;decreased scores of motor behavior and rigid behavior(P＜0.01);alleviated damage of Nissl bodies in neurons;increased serum and striatum levels of TGF-β and IL-10(P＜0.05,P＜0.01);decreased levels of TNF-α and IL-1β(P＜0.01);decreased striatal protein expressions of CX3CL1 and CX3CR1(P＜0.01);increased protein expressions of PSD95 and SYN(P＜0.05,P＜0.01);and decreased CD86/Iba1(P＜0.01)and increased CD206/Iba1(P＜0.01)in terms of the fluorescence intensity.CONCLUSION A.tatarinowii volatile oil contributes an anti-tic effect and improves the neuroinflammation in the brain of the rat model of tic disorders by promoting the transformation of microglia into M2 type via CX3CL1/CX3CR1 signal axis.

AIM To investigate the effects of volatile oil from Acorus tatarinowii Schott(A.tatarinowii)on neuroinflammation in a rat model of tic disorders.METHODS The SD rats were randomly divided into the blank group(8 rats)and the model group(40 rats).The rat models of tic disorders established successfully by intraperitoneal injection of iminodiapropionitrile(IDPN)were further divided into the model group,the tiapride group and the high-dose,moderate-dose and low-dose A.tatarinowii volatile oil groups,with 8 rats in each group.The 4-week intragastric treatment of respective drug was initiated the next day after the completion of modeling,and normal saline was dosed upon the blank group and the model group,during which the rats' behavioral changes were assessed by stereotyped behavior and motor behavior score every week.After the administration,the rats had their morphological changes of striatal neurons observed by Nissl staining;their levels of TGF-β,IL-10,TNF-αand IL-1β in serum and striatum detected by ELISA;their striatal protein expressions of CX3CL1 and CX3CR1 detected by Western blot and immunohistochemistry;and their striatal expressions of M1,M2 microglia marker proteins CD86,CD206,SYN and PSD-95 detected by immunofluorescence co-staining.RESULTS Compared with the model group,the A.tatarinowii volatile oil groups demonstrated improved twitch-like behavior;decreased scores of motor behavior and rigid behavior(P＜0.01);alleviated damage of Nissl bodies in neurons;increased serum and striatum levels of TGF-β and IL-10(P＜0.05,P＜0.01);decreased levels of TNF-α and IL-1β(P＜0.01);decreased striatal protein expressions of CX3CL1 and CX3CR1(P＜0.01);increased protein expressions of PSD95 and SYN(P＜0.05,P＜0.01);and decreased CD86/Iba1(P＜0.01)and increased CD206/Iba1(P＜0.01)in terms of the fluorescence intensity.CONCLUSION A.tatarinowii volatile oil contributes an anti-tic effect and improves the neuroinflammation in the brain of the rat model of tic disorders by promoting the transformation of microglia into M2 type via CX3CL1/CX3CR1 signal axis.

Objectives:The ORION-18 study has demonstrated that inclisiran can significantly reduce low-density lipoprotein cholesterol(LDL-C)and has good safety in Asian atherosclerotic cardiovascular disease(ASCVD)patients or ASCVD high-risk population.This subgroup analysis aims to further evaluate the efficacy and safety of inclisiran in Chinese mainland population.Methods:ORION-18 study is a multi-center,randomized,double-blind,placebo-controlled,phase Ⅲ clinical trial among Asian subjects,Chinese mainland subgroup included 232 ASCVD patients or ASCVD high-risk subjects who had already been treated with diet control and maximum tolerated doses of statins treatment(with or without other lipid-lowering treatments)but still had elevated LDL-C levels.Subjects were randomized in a 1:1 ratio to the inclisiran group and the placebo group(n=116 each),and received 300 mg of inclisiran or placebo respectively on day 0,90 and 270.The primary endpoint was the percentage change in LDL-C from baseline to day 330.The secondary endpoints included the time-adjusted percentage change and absolute change in LDL-C from baseline after day 90 and up to day 360,the absolute change in LDL-C from baseline to day 330,and the percentage changes from baseline to day 330 in proprotein convertase subtilisin/kexin type 9(PCSK9),total cholesterol,apolipoprotein B(ApoB),non-high-density lipoprotein cholesterol(non-HDL-C).Other secondary endpoints included the proportion of participants reaching LDL-C levels of<1.8 mmol/L at day 330,the proportion of participants with≥50%LDL-C reduction from baseline to day 330 and the proportion of participants who attained global lipid targets(the LDL-C target was<1.4 mmol/L for ASCVD patients and<1.8 mmol/L for ASCVD high-risk subjects)at day 330.Safety endpoints included adverse events during treatment,aboratory test abnormalities during treatment,serious adverse events,and assessed their severity and relation to treatment.Results:The inclisiran group showed a placebo-corrected percentage change in LDL-C from baseline to day 330 of-61.16%,and an absolute change of-1.73 mmol/L(both P<0.0001).Compared to the placebo group,the inclisiran group's time-adjusted percentage change in LDL-C from baseline between day 90 and day 360 was-58.51%,and an absolute change of was-1.64 mmol/L(both P<0.0001).At day 330,reductions from baseline were observed in the inclisiran group for PCSK9,total cholesterol,ApoB,non-HDL-C,with placebo-corrected percentage changes of-77.44%,-35.65%,-43.43%,-50.90%(all P<0.0001),respectively.At day 330,79.6%(74/93)of patients in the inclisiran group and 7.8%(6/77)in the placebo group achieved LDL-C levels<1.8 mmol/L,69.9%(65/93)of patients in the inclisiran group and 0%(0/77)in the placebo group achieved≥50%LDL-C reduction from baseline,66.7%(62/93)of patients in the inclisiran group and 2.6%(2/77)in the placebo group achieved their global LDL-C targets.The safety profile of inclisiran treatment over 12 months was comparable to that of the placebo,with no occurrence of treatment-related serious adverse events.Conclusions:In ASCVD patients or ASCVD high-risk subjects in Chinese mainland who have received diet control and maximum tolerable dose statins treatment(with or without other lipid-lowering treatments)and still have elevated LDL-C,inclisiran has a definite efficacy and good safety in reducing LDL-C.The efficacy and safety results of inclisiran assessed in Chinese mainland population are consistent with those of the general Asia population.

Objective To investigate the effect of Polyetheretherketone(PEEK)rod semi-rigid pedicle screw fixation sys-tem in lumbar spine non-fusion surgery.Methods A total of 74 patients with tow-level lumbar degenerative diseases who un-derwent surgery from March 2017 to December 2019 were divided into PEEK rod group and titanium rod group.In the PEEK rod group,there were 34 patients,including 13 males and 21 females,aged from 51 to 79 years old with an average of(62.4±6.8)years old;There were 1 patient of L1-L3 segments,7 patients of L2-L4 segments,20 patients of L3-L5 segments and 6 pa-tients of L4-S1 segments.In the titanium rod group,there were 40 patients,including 17 males and 23 females,aged from 52 to 81 years old with an average of(65.2±7.3)years old;There were 3 patient of L1-L3 segments,11 patients of L2-L4 segments,19 patients of L3-L5 segments and 7 patients of L4-S1 segments.The general conditions of operation,such as operation time,intraoperative blood loss,postoperative drainage was recorded.The visual analogue scale(VAS)for low back pain and Os-westry disability index(ODI)were compared in preoperatively and postoperatively(3 months,12 months and last follow-up)between two groups.The change of range of motion(ROM)was observed by flexion and extension x-ray of lumbar Results All patients successfully completed the operation.The follow-up time ranged from 22 to 34 months with an average of(26.8±5.6)months.The operative time(142.2±44.7)min and intraoperative blood loss(166.5±67.4)ml in PEEK group were lower than those in titanium group[(160.7±57.3)min、(212.8±85.4)ml](P＜0.05).There was no significant differences in postoperative drainage between the two groups(P＞0.05).At the final follow-up visit,in PEEK group and titanium group VAS of low back pain[(0.8±0.4)points vs(1.0±0.5)points],VAS for leg pain[(0.7±0.4)points vs(0.8±0.5)points]and ODI[(9.8±1.6)％vs(12.1±1.5)％]were compared with preoperative[(5.8±1.1)points vs(6.0±1.1)points],[(7.2±1.7)points vs(7.0±1.6)points],[(68.5±8.9)％vs(66.3±8.2)％]were significantly different(P＜0.05).There was no significant difference in VAS scores between the two groups at each postoperative time point(P＞0.05).At 3 months after surgery,there was no difference in ODI between the two groups(P＞0.05).There were significant differences in ODI between PEEK group and titanium rod group at 12 months[(15.5±2.1)％vs(18.4±2.4)％]and at the last follow-up[(9.8±1.6)％vs(12.1±1.5)％](P＜0.05).The total range of motion(ROM)of lumbar decreased in both groups after surgery.At 12 months after surgery and the last follow-up,the PEEK group compared with the titanium rod group,the total range of motion of lumbar was statistically significant(P＜0.05).The range of motion(ROM)of the fixed segments decreased in both groups after surgery.The ROM of the fixed segments in PEEK group decreased from(9.5±4.6)° to(4.1±1.9)° at the last follow-up(P＜0.05),which in the titanium rod group was de-creased from(9.8±4.3)°to(0.9±0.5)° at the last follow-up(P＜0.05).The range of motion(ROM)of upper adjacent segment increased in both groups,there was statistical significance in the ROM of upper adjacent segment between the two groups at 12 months after surgery and the last follow-up,(P＜0.05).There was no screw loosening and broken rods in both groups during the follow-up period.Conclusion The PEEK rod semi-rigid pedicle screw internal fixation system used in lumbar non-fusion surgery can retain part of the mobility of the fixed segment,showing comparable short-term clinical efficacy to titanium rod fu-sion.PEEK rod semi-rigid pedicle screw internal fixation system is a feasible choice for the treatment of lumbar spine degener-ative diseases,and its long-term efficacy needs further follow-up observation.

Quercetin can mediate the activation of mitogen-activated protein kinase(MAPK)signaling pathways to prevent osteoporosis(OP).This paper comprehensively discusses the interrelationship between MAPK and osteoporosis-related cells based on the latest domestic and international research.Additionally,it elucidates the research progress of quercetin in mediating the MAPK signaling pathway for OP prevention.The aim is to provide an effective foundation for the clinical prevention and treatment of OP and the in-depth development of quercetin.

Objective To investigate the effect and mechanism of hypericin on osteoporosis(OP)in rats with chronic obstructive pulmonary disease(COPD).Methods COPD combined with OP rat model was established by cigarette combined with bacteria.The rats were randomly divided into control group,model group(COPD combined with OP model was constructed),experimental-L group(50 mg·kg-1 hypericin was given by intragastric administration after constructing COPD combined with OP model),experimental-H group(100 mg·kg-1 hypericin was given intragastric administration after constructing COPD combined with OP model),positive group(subcutaneous injection of 16 U·kg-1 salmon calcitonin after constructing COPD combined with OP model);each group was given 12 rats for 90 days.The lung function of rats was detected by pulmonary function apparatus;bone mineral density(BMD)was detected by micro-computed tomography(CT);serum bone metabolism and inflammatory factors were detected by enzyme-linked immunosorbent assay(ELISA);Western blot assay was used to detect the relevant indicators of the pathway.Results The levels of forced vital capacity(FVC)in control group,model group,experimental-H group and positive group were(10.42±1.40),(4.10±0.60),(6.75±0.37),(4.18±0.33)mL,respectively;BMD levels were(0.31±0.04),(0.12±0.02),(0.28±0.03),(0.29±0.04)g·mm-3,respectively;bone alkaline phosphatase(BALP)levels were(200.04±20.03),(80.80±6.00),(148.16±14.23),(173.97±23.55)U·L1,respectively;interleukin-1β(IL-1β)levels were(122.60±8.70),(695.59±74.84),(422.41±44.86),(527.90±39.36)pg·mL-1,respectively;phosphorylated p38 mitogen-activated protein kinase(p-P38)protein expression levels were 0.99±0.11,0.36±0.05,0.79±0.08,0.36±0.04,respectively.Compared with the control group,the above indexes in the model group had statistical significance(all P＜0.05);the above indexes in experimental-H group were significantly different from those in model group(all P＜0.05).Conclusion Hypericin can inhibit inflammatory response,improve bone metabolism and biomechanics.

OBJECTIVE: To investigate the toxicity management and efficacy evaluation of BCMA-chimeric antigen receptor T cells(CART) in the treatment of relapsed and refractory multiple myeloma (MM). METHODS: The efficacy and adverse reactions of 21 patients with MM who received BCMA-CART treatment at the First Affiliated Hospital of Wenzhou Medical University from December 2017 to September 2020 were evaluated, and the efficacy assessment and survival analysis for high-risk patients and non-high-risk patients were evaluated. RESULTS: After infusion of BCMA-CART cells in 21 MM patients, the number of effective cases was 17, of which the complete remission (sCR/CR) was 10, and the partial remission (VGPR/PR) was 7. The median OS time for all patients was 19.4 months, and the median PFS time was 7.9 months. The number of patients with extramedullary disease(EMD), high-risk genetics, and ISS stage Ⅲ were 5, 15 and 8, and the effective number was 3, 11 and 6, respectively. The treatment of 3 patients without high-risk factors was effective. The median OS and median PFS of patients with EMD were 14.2 and 2.5 months, respectively, which were shorter than those of patients without EMD (19.4 months and 8.9 months, respectively). The median OS and median PFS of patients with high-risk cytogenetic factors and ISS Ⅲ were not significantly different from those of non-high-risk patients. Cytokine release syndrane (CRS) occurred in 20 patients, of which 14 cases were Grade 1 CRS, while 6 were Grade 2, no CRS of Grade 3 or above occurred. IL-6 receptor inhibitors were used in 9 patients. All CRS were controlled effectively, and no patients had neurological toxicity. CONCLUSION BCMA-CART is a certain curative effect in the treatment of relapsed and refractory multiple myeloma, and the adverse reactions can be well controlled through close monitoring and timely treatment.
B-Cell Maturation Antigen ; Humans ; Immunotherapy, Adoptive/adverse effects* ; Multiple Myeloma/therapy* ; Receptors, Chimeric Antigen ; Remission Induction

Aged ; Antiviral Agents/therapeutic use* ; COVID-19/drug therapy* ; China/epidemiology* ; Cohort Studies ; Female ; Hospital Mortality ; Hospitalization ; Humans ; Male ; Middle Aged ; Patient Acuity ; SARS-CoV-2 ; Treatment Outcome