ObjectiveTo investigate the therapeutic efficacy， influencing factors， and safety of a treatment regimen based on coblopasvir hydrochloride capsules/sofosbuvir tablets in patients with chronic hepatitis C virus （HCV） infection in a real-world setting. MethodsA total of 253 patients who attended The Third People’s Hospital of Kunming from September 1， 2021 to May 31， 2024 were enrolled， among whom there were 86 patients with compensated liver cirrhosis （CLC group） and 167 patients with chronic hepatitis C （CHC group）. The patients were treated with coblopasvir hydrochloride capsules （60 mg）/sofosbuvir tablets （400 mg） with or without ribavirin tablets for 12 weeks， and they were followed up for 12 weeks after drug withdrawal. The primary outcome measures were the rate of sustained virologic response at week 12 after treatment （SVR12） and safety， and the secondary outcome measures were the changes in liver function， renal function， blood routine， and liver stiffness measurements （LSM） after 4 weeks of treatment， after 12 weeks of treatment， and at 12 weeks after drug withdrawal. The independent-samples t test and the Mann-Whitney U test were used for comparison of continuous data between two groups， and the Friedman test was used for comparison between multiple groups， while the Bonferroni method was used for paired comparison within each group； the chi-square test was used for comparison of categorical data between two groups. The Logistic analysis was used to investigate related influencing factors. ResultsThe 253 patients with chronic HCV infection had a mean age of 49.38±8.65 years， and there were 151 male patients （59.7%）. Of all patients， 33.99% （86/253） had liver cirrhosis， 25.69% （65/253） had hypertension， 10.67% （27/253） had HIV infection， 8.70% （22/253） had diabetes， 3.95% （10/253） had liver cancer， 1.98% （5/253） had chronic hepatitis B， and 7.91% （20/253） were treatment-experienced patients. As for genotype distribution， 2.77% （7/253） had genotype 1， 12.65% （32/253） had genotype 2， 66.01% （167/253） had genotype 3， 16.60% （42/253） had genotype 6， and 1.98% （5/253） had unknown genotype. The patients had an overall SVR12 rate of 92.09%， with an SVR12 rate of 93.02% in the CLC group and 91.02% in the CHC group. The multivariate logistic regression analysis showed that age （odds ratio ［OR］=1.086， 95% confidence interval ［CI］： 1.007 — 1.170， P=0.032） and HCC （OR=9.178， 95%CI： 1.722 — 48.912， P=0.009） were independent influencing factors for sustained virologic response. Compared with baseline data， the CLC group had significant reductions in alanine aminotransferase （ALT） （χ²=107.103， P0.05）， aspartate aminotransferase （AST） （χ²=90.602， P0.05）， and LSM （χ²=42.235， P0.05） after 12 weeks of treatment， while the CHC group had significant reductions in total bilirubin （χ²=15.113， P0.05）， ALT （χ²=202.237， P0.05）， AST （χ²=161.193， P0.05）， and LSM （χ²=37.606， P0.05）. The incidence rate of serious adverse events was 1.58%， and none of the patients withdrew from drug therapy； the patients with such events were relieved after active symptomatic treatment. The incidence rate of all adverse events was 23.72%， among which fatigue （17.39%） and nausea （2.37%） were the most common adverse events， and these events often disappeared within 2 weeks or were gradually relieved after symptomatic treatment. ConclusionCoblopasvir hydrochloride capsules/sofosbuvir tablets with or without ribavirin tablets has good efficacy and safety in the treatment of chronic HCV infection.

High-performance phototheranostics with combined photothermal therapy and photoacoustic imaging have been considered promising approaches for efficient cancer diagnosis and treatment. However, developing phototheranostic materials with efficient photothermal conversion efficiency (PCE), especially over the second near-infrared window (NIR-II, 1000-1700 nm), remains challenging. Herein, we report an ultraefficient NIR-II-activated nanomedicine with phototheranostic and vaccination capability for highly efficient in vivo tumor elimination and metastasis inhibition. The NIR-II nanomedicine of a semiconducting biradical oligomer with a motor-flexible design was demonstrated with a record-breaking PCE of 87% upon NIR-II excitation. This nanomedicine inherently features extraordinary photothermal stability, good biocompatibility, and excellent photoacoustic performance, contributing to high-contrast photoacoustic imaging in living mice and high-performance photothermal elimination of tumors. Moreover, a whole-cell vaccine based on a NIR-II nanomedicine with NIR-II-activated performance was further designed to remotely activate the antitumor immunologic memory and effectively inhibit tumor occurrence and metastasis in vivo, with good biosafety. Thus, this work paves a new avenue for designing NIR-II active semiconducting biradical materials as a promising theranostics platform and further promotes the development of NIR-II nanomedicine for personalized cancer treatment.

Acetaminophen (APAP) overdose is a major cause of liver injury. Neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) is an E3 ubiquitin ligase that has been implicated in the pathogenesis of numerous liver diseases; however, its role in APAP-induced liver injury (AILI) is unclear. Thus, this study aimed to investigate the role of NEDD4-1 in the pathogenesis of AILI. We found that NEDD4-1 was dramatically downregulated in response to APAP treatment in mouse livers and isolated mouse hepatocytes. Hepatocyte-specific NEDD4-1 knockout exacerbated APAP-induced mitochondrial damage and the resultant hepatocyte necrosis and liver injury, while hepatocyte-specific NEDD4-1 overexpression mitigated these pathological events both in vivo and in vitro. Additionally, hepatocyte NEDD4-1 deficiency led to marked accumulation of voltage-dependent anion channel 1 (VDAC1) and increased VDAC1 oligomerization. Furthermore, VDAC1 knockdown alleviated AILI and weakened the exacerbation of AILI caused by hepatocyte NEDD4-1 deficiency. Mechanistically, NEDD4-1 was found to interact with the PPTY motif of VDAC1 through its WW domain and regulate K48-linked ubiquitination and degradation of VDAC1. Our present study indicates that NEDD4-1 is a suppressor of AILI and functions by regulating the degradation of VDAC1.

Objective:To explore the characteristics of attentional bias to emotional faces of depressed college students with alexithymia.Methods:Using self-rating depression scale (SDS) and the twenty-item Toronto alexithymia scale(TAS-20), 25 low alexithymic-currently depressed undergraduates (LA-CD group), 33 low alexithymic-non depressed undergraduates(LA-ND group) and 23 high alexithymic-currently depressed undergraduates(HA-CD group) were selected from 885 valid questionnaires.Using eye tracking system, emotional face pictures were selected as stimulus materials, and the relative gaze time(attention bias score) of experimental participants was analyzed by statistical methods such as covariance analysis and adjustment analysis to explore the attentional bias of depressed college students with alexithymia.Results:(1) Under the low level of alexithymia, there was significant difference in attentional bias between college students in depression group (-0.23±0.18) and non-depressed group (0.06±0.11) ( F=55.876, P<0.01). (2) There were significant differences in relative attention bias among LA-CD group (-0.234±0.150), HA-CD group(-0.070±0.153) and LA-ND group (0.064±0.149) ( F(2, 78)=27.685, P<0.01). According to Bonferroni test, compared to the LA-CD group, the HA-CD group and LA-ND group showed less negative attentional bias.(3) The interaction between total SDS score and total TAS-20 score showed significant difference.Alexithymia played a regulatory role between total SDS score and attentional bias( β=0.333, t=3.345, P<0.01). Conclusion:Both the depressed college students with high alexithymia and the non-depressed college students with low alexithymia show less negative attentional bias.Alexithymia plays a regulatory role between depression and attentional bias.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy-lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.

Objective To discuss the effect of arthroscopic latissimus dorsi transfer with rotator cuff repair for posterosuperior irreparable massive rotator cuff tear (iMRCT).Methods From September 2014 to December 2015,data of 13 iMRCT including 4 male and 9 female who underwent arthroscopic latissimus dorsi transfer with rotator cuff repair were retrospectively analyzed.The age was ranged from 54 to 65,with a mean age of 58.5±4.3.The mean duration of symptom was 2.1±0.6 years.During operation,complete or partial rotator cuff repair was performed,followed by complete repair of injured subscapularis tendon and tenotomy or tenodesis of the long head of biceps tendon.An arc incision was then made in the axillary fossa to harvest latissimus dorsi tendon from its humeral insertion.The tendon was then introduced into subacromial space and fixed at the footprint of greater tuberosity arthroscopically.X-ray and MRI were conducted prior to and one day after the surgery and at the last follow-up.Pain visual analog scale (VAS) and active range of motion in all planes as well as Constant-Murley score and Fudan University shoulder score (FUSS) were documented before the surgery and at the last follow-up.Results All 13 patients accomplished the follow-up,with a duration from 17 to 22 months and a mean period of 19.6±0.9 months.No complications occurred.No re-tear was identified.The mean acromiohumeral distance increased from 5.4± 1.1 mm to 7.0±0.6 mm.The mean VAS decreased from 4.8± 1.3 to 0.5± 0.7.The mean 0° abduction external rotation,90° abduction external rotation,flexion,as well as abduction increased from 17.3°± 10.5°,12.4°±7.8°,89.2°±41.2°,87.3°±40.7° to 41.2°±12.5°,56.5°±16.6°,120.5°±25.1°,and 113.5°±25.4° respectively.Constant-Mur ley score and FUSS increased from 33.5±9.9 and 50.9±7.6 to 62.8±8.1,and 81.7±7.0,respectively.The improvement in all measurements was significant.Condclion For posterosuperior iMRCT,arthroscopic latissimus dorsi transfer with rotator cuff repair can decrease shoulder pain and improve shoulder function.

Objective To explore the attentional bias to emotional faces on individuals in the remitted phase of recurrent depression through eye-tracking study.Methods Center for epidemiologic studies depression scale (CES-D) and Hamilton depression scale (HAMD) were used to the diagnosis of 24 normal individuals and 21 depressed individuals and 24 individuals in the remitted phase of recurrent depression.Emotion face pictures were chosen as experiment material and discuss the mechanism of the attentional bias of individuals in the remitted phase of recurrent depression through the analysis of eye movement index.Results First fixation duration bias score on happy expression picture of individuals in the remitted phase of recurrent depression((52.60±0.06) ％) was less than normal controls ((59.26±0.09) ％) and the depression group((53.27±0.07)％),(F(1.66)=12.32,7.23,P＜0.05).Gaze Duration Bias score on sad expression picture of individuals in the remitted phase of recurrent depression ((59.17±0.08) ％) was more than normal controls((49.67±0.07) ％),(F(1.66) =4.29,P＜0.05).Conclusion Individuals in the remitted phase of recurrent depression show no original direction bias to sad and happy expression pictures.Original attentional avoidance and total attentional maintenance to sad expression picture exist in individuals in the remitted phase of recurrent depression.

Genetic factors are important causes of male infertility and account for about 30%infertility cases.Therefore, it is necessary to carry out molecular and genetic detections in the diagnosis and treatment of male infertility.Here the most commonly used techniques for molecular and genetic diagnosis of male infertility in recent years are discussed , including chromosomal abnormities analysis , Y chromosome microdeletions detection , gene mutation screening and sperm quality and function examination.

Objective To investigate the impacts of sirolimus (SRL)on the survival time of graft and the differentiation and proliferation of regulatory T cell (Treg ) of spleen in mouse heterotopic heart transplantation model. Methods Male BALB /c → C57BL/6 mice cervical heterotopic heart transplantation model was established by Cuff method. The mice were divided into 3 groups randomly with 10 mice in each group. The control group received no treatment of special medicine after operation. Mice in SRL group were gavaged with SRL 10 mg/(kg·d)at 1-14 d after operation. Mice in ciclosporin (CsA)group were gavaged with CsA 30 mg/(kg·d) at 1-14 d after operation. The survival time of cardiac grafts were recorded. The spleen was procured after asystole of cardiac graft or 14 d after operation. Mononuclear cells were isolated and the proportion of CD4 +CD25 +Treg in CD4 +T cell (CD4 +CD25 +Treg%)were detected by flow cytometry and reverse transcription polymerase chain reaction (RT-PCR)was used to examine the expression of Foxp3 messenger ribonucleic acid (mRNA ) semi-quantitatively. Results Compared with the control group,the survival time of cardiac grafts prolonged significantly in SRL and CsA group (all in P <0.01 ),but no significant difference was observed between SRL and CsA group (P>0.05 ). Compared with the control group,CD4 +CD25 +Treg% significantly decreased in the spleen of CsA group and significantly increased in SRL group (all in P<0.01 ). And significant difference was observed between SRL and CsA group (P<0.01). Expression of Foxp3 mRNA of T lymphocyte in the spleen of SRL group was significantly higher than those in control and CsA group (P<0.01). And expression of Foxp3 mRNA in control group was significantly higher than that in CsA group (P<0.01 ). Conclusions In mouse heart transplantation model,SRL can prolong the survival time of graft and promote the proliferation and growth of CD4 +CD25 +Treg to facilitate the establishment of immune tolerance.

ObjectiveTo explore the relationship of postoperative systemic inflammatory response syndrome(SIRS) and preoperative midway through the urine and perioperative renal pelvis urine of percutaneous nephrostolithotomy(PCNL).Methods Participants included 450 patients with urinary calculus who underwent PCNL,preoperative midway through the urine and perioperative renal pelvis urine of PCNL was collected.ResultsOf 450 cases,preoperative midway through the urine germiculture positive 100 cases (22.2％,100/450 ),perioperative renal pelvis urine germiculture positive 85 cases (18.9％,85/450),46 cases ( 10.2％,46/450) occurred SIRS after PCNL.Decompression of perioperative renal pelvis urine germiculture positive 20 cases(23.5％,20/85) preoperative midway through the urine germiculture positive,perioperative renal pelvis urine the bacteria cultures negative 80 cases (21.9％,80/365 ) preoperative midway through the urine germiculture positive(P ＞0.05),preoperative midway through the urine germiculture positive 15 cases ( 15.0％,15/100) in SIRS,preoperative midway through the urine the bacteria cultures negative 31 cases ( 8.9％,31 /350) in SIRS (P ＞ 0.05 ).Decompression of perioperative renal pelvis urine germiculture positive 18 cases (21.2％,18/85) in SIRS,perioperative renal pelvis urine the bacteria cultures negative 28 cases (7.7％,28/365) in SIRS (P ＜ 0.05 ).ConclusionPreoperative midway through the urine has no correlation with the occurrence of SIRS,perioperative renal pelvis urine germiculture positive can predict the occurrence of SIRS,giving corresponding antibiotic treatment can improve the security of PCNL.