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.

Isolated vertigo due to vascular mechanisms manifests as vertigo, dizziness or imbalance only. Due to the lack of focal neurological symptoms or signs, it is often misdiagnosed as peripheral vestibular disease, resulting in serious adverse consequences. This article reviews the lesion location, cerebrovascular basis, clinical evaluation, and imaging examination of isolated vertigo caused by vascular mechanisms.

Objective:To explore the in vitro anticancer effect of bleomycin (Ble) combined with cisplatin (DDP) on human gastric cancer cells.Methods:CCK-8 experiment was conducted to detect the effect of Ble and DDP alone or in combination on the proliferation of gastric cancer cells; Flow cytometry was used to detect changes in cell apoptosis and changes in reactive oxygen species. Cell scratch test was employed to detect cell migration; Western blot experiment was conducted to detect protein expression.Results:The results of CCK-8 showed that 20 μM DDP could inhibit the proliferation of six types of gastric cancer cells by 40%, while the effect of 20 μM Ble was only about 20%. When used in combination, the inhibitory rate on six types of gastric cancer could reach over 60%, with the strongest inhibitory effect on AGS cells. When 10 μM Ble and 10 μM DDP were combined, the proportion of AGS apoptotic cells reached 75.68%, higher than that of the two drugs treated with 20%, respectively 20 μM processing effect. When 10 μM Ble and 10 μM DDP were used in combination, the number of migrating and invading cells was significantly reduced, and the inhibition rate reached 50%. Compared with single use, the difference was statistically significant ( P<0.05). Flow cytometry results showed that the combination of Ble and DDP promoted cancer cell apoptosis by up-regulating the level of reactive oxygen species in cells; Western blot results showed that the expression of p-JAK2 and p-STAT3 decreased after Ble and DDP were combined, indicating that the JAK2/STAT3 signal pathway was inhibited. Conclusions:The combination of Ble and DDP can inhibit the proliferation and migration of gastric cancer cells, promote the apoptosis of gastric cancer cells, and play a synergistic anti-cancer effect. Its mechanism may be related to the up-regulation of ROS levels in cells, thereby inhibiting the activation of the JAK2/STAT3 pathway.

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.

Objective:To evaluate the status of T, B and NK lymphocytes in peripheral blood of patients with chronic hepatitis B virus(HBV) infection and low-level viremia after nucleos(t)ide analogue (NA) treatment and to provide ideas for solving low-level viremia.Methods:This retrospective study involved 344 patients with chronic HBV infection who had been treated with NAs. They were divided into two groups: low-level viremia group (LLV group) and complete virological response group (CVR group). Clinical data including basic information, biochemistry and coagulation test results, HBV DNA, peripheral blood lymphocyte counts, PD1 and CD28 expression by T lymphocytes, and perforin and granzyme B expression by NK lymphocytes were collected and compared between the two groups. Propensity matching analysis was performed to verify the accuracy of the results.Results:Among the 344 cases, 162 were in the LLV group and 182 in the CVR group. There were no significant differences in disease diagnosis, alanine aminotransferase (ALT), aspartate aminotransferase (AST) or albumin (ALB) level between the two groups ( P>0.05), but the differences in gender and age were statistically significant ( P<0.05). The differences in the counts and percentages of peripheral blood CD3 +, CD4 + and CD8 + T lymphocyte and CD4 + /CD8 + ratios between the two groups were not statistically significant ( P>0.05), but the expression of PD1 and CD28 by peripheral blood CD3 +, CD4 + and CD8 + T lymphocytes was higher in the LLV group than in the CVR group ( P<0.05). The count of peripheral blood CD19 + B lymphocytes in the LLV group was higher than that in the CVR group ( P>0.05), and the percentage of peripheral blood CD19 + B lymphocytes was also higher in the LLV group ( P<0.05). The count of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of perforin in the LLV group were lower than those in the CVR group ( P>0.05). The percentage of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of granzyme B in the LLV group were lower than those in the CVR group ( P<0.05). After propensity score matching, 108 cases in the LLV group and 108 cases in the CVR group showed no significant differences in basic information ( P>0.05); the percentage of CD4 + T lymphocytes and CD4 + /CD8 + ratio in peripheral blood T lymphocyte subsets were higher in the LLV group than in the CVR group, while the percentage of CD8 + lymphocytes was lower in the LLV group ( P<0.05); the expression of PD1 and CD28 by CD3 +, CD4 + and CD8 + T lymphocytes remained higher in the LLV group ( P<0.05); the differences in the counts and percentages of peripheral blood CD19 + B lymphocytes as well as CD16 + CD56 + NK lymphocytes between the two groups were not statistically significant ( P>0.05); no significant difference in the expression of perforin by CD16 + CD56 + NK lymphocytes was found between the two groups ( P>0.05), and the expression of granzyme B remained lower in the LLV group ( P<0.05). Conclusions:Abnormal number and function of T lymphocytes and decreased function of NK lymphocytes might be related to the development of LLV in patients with chronic HBV infection after treatment. Therefore, in addition to adjusting NAs, targeting of T and NK lymphocytes might also be a feasible measure for future LLV 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.

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 investigate the effect of arthroscopy-assisted latissimus dorsi transfer (LDT) on posterosuperior massive rotator cuff tear (psMRCT) and analyze factors related to the outcome.Methods A retrospective case cohort study was conducted to analyze 31 patients with psMRCT admitted from January 2013 to December 2015.There were 13 males and 18 females,aged 52-67 years [(58.4 ± 4.5) years].The mean duration of symptoms was (1.9 ± 0.9) years.All patients received arthroscopy assisted LDT combined with rotator cuff repair.Postoperative rehabilitation training was carried out according to the standard procedures.Before operation and at the last follow-up,X-ray films were taken to measure the acromiohumeral talus,and magnetic resonance imaging was obtained to check the integrity of repaired tissue.Visual analog scale (VAS),active range of motions,Constant-Murley score and Fudan University Shoulder Score (FUSS) were measured to assess the shoulder joint function,and complications were documented.Furthermore,subgroup analysis was made according to "concomitant subscapularis tendon tear or not","concomitant pseudoparalysis or not","Goutallier Ⅲ/Ⅳ level fatty infiltration","complete or partial rotator cuff repair",and " Hamada Ⅰ/Ⅱ level acromiohumeral distance".Pearson correlation analysis was performed to detect the relationship of subgroup factors with postoperative Constant-Murley score and FUSS score.Results All patients were followed up for (38.8 ± 13.0) months.No complications including fever,infection,adhesion or neural malfunction were reported.Mean acromiohumeral distance increased from preoperative (5.4 ± 0.9) mm to (7.0 ± 1.0) mm at the last follow-up (P ＜ 0.05).MRI image showed intact fixation of rotator cuff and transferred latissimus dorsi tendon.At the last follow-up,VAS score decreased from preoperative (4.8 ± 1.4)points to (0.6 ± 0.7)points;the active range of motions was restored significantly;the Constant-Murley score improved from (32.9 ± 9.5) points to (67.4 t 6.7) points;the FUSS score increased from (53.3 ± 9.1) points to (85.1 ± 4.8) points (all P ＜ 0.01).Pearson Correlation analysis indicated that,among subgroup factors,only partial rotator cuff repair was significantly inversely associated with ConstantMurley score (P ＜ 0.05) and FUSS score (P ＜0.01),and the Constant-Murley score and FUSS score of patients with complete repair were significantly higher than those of patients with partial repair (P ＜ 0.05 and P ＜ 0.01,respectively).Conclusions For psMRCT,the effect of arthroscopy-assisted LDT is confirmed,which can relieve pain,restore range of motion and improve shoulder function.Preoperative pseudoparalysis,subacapularis tendon tear,Goutallier Ⅳ level fatty infiltration and Hmada Ⅱ level acromiohumeral distance do not significantly influence postoperative outcome.The torn rotator cuff tear should be repaired as possible.

To summarize professor 's own experience on the acupuncture sensation. Professor puts forward his opinion through the sensation of acupuncture on himself, from the aspects of the expression, the material basis, the distinction and the clinical significance of acupuncture sensation, etc. Professor thinks that the production and conduction direction of acupuncture sensation have their material basis and objectively exist, based on which, professor puts forward the amount of acupuncture stimulation and the total amount of acupuncture stimulation. Professor believes that the amount of acupuncture stimulation is the main basis for the individual reinforcing and reducing of acupuncture. The amount of acupuncture stimulation is related to the depth and intensity of acupuncture, the time of the needle retention, the number of needles, etc. The reinforcing and reducing of acupuncture are relative to the deficiency and excess of the disease, and they are the reaction of acupuncture for body. The tolerance degree of the individual to the stimulation of acupuncture is also the main factor affecting the reinforcing and reducing.