ObjectiveTo investigate the therapeutic effects of direct-acting antiviral agents (DAAs) combined regimens for hepatitis C virus (HCV) patients in Dehong Prefecture, Yunnan Province from 2022 to 2024, to analyze the characteristics of treatment failure patients, so as to provide a basis for discovering more effective treatment regimens in the future. MethodsData on HCV prevention and treatment in Dehong Prefecture was extracted from the China Disease Control and Prevention Information System. A total of 617 patients with HCV antiviral therapy were included, and the differences in variable characteristics among patients with different genotypes were analyzed using comparative statistical tests, including basic socio-demographic characteristics, biochemical testing indicators, and information on previous treatment and current treatment. In addition, the cure rate of HCV patients with diverse characteristics was compared, and the potential causes of treatment failure were explored simultaneously. ResultsThe cure rate of HCV was 96.8%, and statistically significant differences were observed in aspartate transaminase (AST) and alanine transaminase (ALT) levels, previous antiviral therapy history and initial treatment regimens among patients with different HCV genotypes (all P<0.05). Among the multi-type combination regimens, the cure rate of sofosbuvir (SOF)-containing regimens was 97.00%, that of velpatasvir (VEL)-containing regimens was 95.45%, and the cure rate of other treatment regimens, including the regimens with ribavirin (RIB) intervention, was 93.10%. Among the patients with treatment failure, 45.00% had genotype 3, 40.00% had abnormal abdominal ultrasound results, and all presented with elevated baseline AST test levels. ConclusionThe clinical treatment of HCV patients should consider the differences in genotype and biochemical test results. DAAs combined regimens for HCV have achieved a high cure rate in Dehong Prefecture and are applicable to HCV patients with diverse clinical characteristics, providing research evidence for wider application.

OBJECTIVE To compare the efficacy of the novel Huoxue plaster and the original powder in the treatment of chronic soft tissue injury, and to provide experimental basis for the development and clinical application of hospital preparations. METHODS According to the different drug administration, mice were assigned to the blank group, the matrix group, the positive control group(voltaren group), the original powder raw product group, the original powder product group and the novel plaster group respectively. The writhing inhibition rate, licking time, analgesic rate and pain threshold were measured by the writhing test, formaldehyde pain test, electrical stimulation test and hot plate test. The purpose of these was to assess disparities in the drugs for analgesic purposes. The mice ear swelling test and capillary permeability test were used to determine the swelling degree, swelling inhibition rate and exudation inhibition rate to compare the differences in anti-inflammatory effects. A rat model of chronic soft tissue injury was established. The changes of calf circumference, soft tissue injury appearance score, hemorheology and histopathological observation and inflammatory factor content were compared before and after the reform of prescription and dosage form. RESULTS The novel Huoxue plaster had a significant inhibitory effect on the inflammatory pain induced by acetic acid and formaldehyde in mice, and there was no significant difference compared with the original powder. The analgesic effect of 60 min after administration was better than that of 90 min and 120 min after administration, and there was no significant difference compared with the original powder. The novel Huoxue plaster and the original powder had no significant effect on hot plate pain threshold. The novel Huoxue plaster had a significant anti-inflammatory effect, which could reduce the degree of ear swelling induced by xylene and reduce the inflammatory exudation of capillaries induced by acetic acid, and there was no significant difference compared with the original powder. The novel Huoxue plaster could significantly reduce the circumference and injury symptom index of the swollen leg in rats with chronic soft tissue injury, improve blood circulation and histomorphology, and significantly reduce the contents of PGE2, TNF-α and IL-1β in the injured soft tissue, and there was no significant difference compared with the original powder. CONCLUSION The novel Huoxue plaster has significant analgesic and anti-inflammatory effects, and can be used to treat chronic soft tissue injury. The efficacy of the novel Huoxue plaster is basically the same as that of the original powder.

Background: Peste des petits ruminants (PPR) is a contagious and fatal disease of sheep and goats. PPR virus (PPRV) infection induces endoplasmic reticulum (ER) stress-mediated unfolded protein response (UPR). The activation of UPR signaling pathways and their impact on apoptosis and virus replication remains controversial. Objectives: To investigate the role of PPRV-induced ER stress and the IRE1-XBP1 and IRE1-JNK pathways and their impact on apoptosis and virus replication. Methods: The cell viability and virus replication were assessed by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, immunofluorescence assay, and Western blot. The expression of ER stress biomarker GRP78, IRE1, and its downstream molecules, PPRV-N protein, and apoptosis-related proteins was detected by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. 4-Phenylbutyric acid (4-PBA) and STF-083010 were respectively used to inhibit ER stress and IRE1 signaling pathway. Results: The expression of GRP78, IRE1α, p-IRE1α, XBP1s, JNK, p-JNK, caspase-3, caspase-9, Bax and PPRV-N were significantly up-regulated in PPRV-infected cells, the expression of Bcl-2 was significantly down-regulated. Due to 4-PBA treatment, the expression of GRP78, p-IRE1α, XBP1s, p-JNK, caspase-3, caspase-9, Bax, and PPRV-N were significantly downregulated, the expression of Bcl-2 was significantly up-regulated. Moreover, in PPRV-infected cells, the expression of p-IRE1α, p-JNK, Bax, and PPRV-N was significantly decreased, and the expression of Bcl-2 was increased in the presence of STF-083010. Conclusions PPRV infection induces ER stress and IRE1 activation, resulting in apoptosis and enhancement of virus replication through IRE1-XBP1s and IRE1-JNK pathways.

Objective:To investigate the value of preoperative breast MRI combined with axillary ultrasound in predicting lymphovascular invasion (LVI) of breast invasive ductal carcinoma.Methods:The clinical, pathological and imaging features of 160 female patients [age 25-74(49±10)years] with breast invasive ductal carcinoma from March 2014 to December 2017 in Shanxi Cancer Hospital were retrospectively analyzed. According to the LVI status determined by postoperative pathology, 160 patients were divided into LVI positive group (56 cases) and LVI negative group (104 cases). The clinical characteristics, pathological characteristics and imaging features of LVI positive group and LVI negative group were compared by the independent t test, Mann-Whitney U test or χ 2 test. Multivariate logistic regression analysis was performed to identify independent predictors for predicting LVI and construct a predictive model. The receiver operating characteristic (ROC) curve and area under the curve (AUC) was used to evaluate the discrimination of the prediction model, and the Hosmer-Lemeshow test was used to evaluate its calibration. Results:There was no significant difference in age, menopausal status, estrogen receptor, progesterone receptor, human epidermal growth factor 2, Ki67 index and molecular subtype between LVI positive group and negative group ( P>0.05). Tumor size, peritumoral edema, adjacent vessel sign, multifocality or multicentricity, peritumoral maximum-apparent diffusion coefficient (ADC), peritumour-tumour ADC ratio, MRI axillary lymph node status and ultrasound axillary lymph node status between LVI positive group and LVI negative group showed significantly statistical difference ( P<0.05). Variables with significant difference in the univariate analysis were entered into multivariate logistic regression analysis to explore predictors for LVI. Peritumoral edema (OR=3.367, 95%CI 1.382-8.201, P=0.008), multifocality or multicentricity (OR=4.026, 95%CI 1.268-12.776, P=0.018), high peritumoral-tumor ADC ratio (OR=7.321, 95%CI 2.226-24.079, P=0.001) and positive ultrasound axillary lymph node (OR=6.779, 95%CI 2.819-16.303, P<0.001) were independent predictors for predicting LVI. A logistic regression model was constructed using the above four indicators, and ROC showed AUC of this model for predicting LVI was 0.882, superior to any of the single indicator ( P<0.05); its sensitivity was 80.36% and specificity was 84.62%. Hosmer-lemeshow test showed that the prediction model had good calibration ( P=0.503). Conclusion:The combined prediction model constructed by preoperative breast MRI and axillary ultrasound could help to predict the LVI status of breast invasive ductal carcinoma.

Objective:To investigate the clinical characteristics and correlation of sleep disturbances(SD)with cognitive impairment-associated cerebral small vascular disease(CSVD-CI)in elderly patients.Methods:In this cross-sectional study, 261 elderly CSVD-CI patients admitted to the Department of Neurology, Second Hospital of Tianjin Medical University between December 2019 and December 2021 were continuously enrolled.The Pittsburgh Sleep Index Scale(PSQI)was used to evaluate the overall sleep quality.Those with a PSQI score ≥7 was assigned to the CSVD-CI with sleep disturbances(CSVD-CI-SD)group, while those with a PSQI score <7 was assigned to the CSVD-CI without SD(CSVD-CI-NSD)group.The Montreal Cognitive Assessment(MoCA)was used to evaluate the cognitive function of patients with CSVD-CI, and scores on the overall cognitive function and various cognitive domains were compared between the CSVD-CI-SD group and the CSVD-CI-NSD group.Results:There were no significant differences between the CSVD-CI-SD group and the CSVD-CI-NSD group in sex ratio, age, education level and comorbidities( P>0.05). Compared with the CSVD-CI-NSD group, patients in the CSVD-CI-SD group took longer to fall asleep, had worse sleep efficiency, a shorter sleep duration, more obvious SD at night, worse sleep quality, more use of sleeping drugs, and more obvious daytime dysfunction(all P<0.05). Compared with the CSVD-CI-NSD group, the total MoCA score, attention score and orientation score in the CSVD-CI-SD group were significantly decreased( P<0.01). Correlation analysis results showed that the total MoCA score and attention in the CSVD-CI-SD group were negatively correlated with SD at night( r=-0.198, r=-0.115, P<0.05 for both), and orientation was negatively correlated with sleep quality( r=-0.170, P<0.05). Conclusions:The prevalence of SD is high in CSVD-CI patients, with CSVD-CI-SD patients showing more obvious overall cognitive, attention and orientation impairment in MoCA.Additionally, the total MoCA score and attention are negatively correlated with nighttime SD, and orientation is negatively correlated with sleep quality in CSVD-CI-SD patients.

Objective:To analyze the longitudinal characteristics of CD4 +T lymphocytes (CD4) among the adult HIV/AIDS on antiretroviral therapy (ART) and the related factors. Methods:A retrospective cohort of adult HIV/AIDS starting ART in Dehong Dai and Jingpo Autonomous Prefecture (Dehong) in 2007-2016 was followed up to December 31, 2018. Group-based trajectory models were utilized to identify CD4 subgroups based on immune recovery (whether and when CD4 reached the average level of >500 cells/μl). The demographics and information at ART baseline were described, and the related factors were analyzed with polytomous logistic regression. The SAS 9.4 software was used for statistical analysis.Results:A total of 7 605 adults with HIV/AIDS were included, of which the median ( P 25, P 75) age at ART were 36 (30,43) years old, 61.0% were male, 42.5% were Han nationality, and 60.8% with the education of primary school or below. The follow-up duration M ( P 25, P 75) was 6.1 (4.1,8.1) years. HIV/AIDS in Dehong showed four CD4 trajectory subgroups from low to high: below the average level, primary recovery to a normal level, full recovery to a moderate level, and normal steady level, accounting for 34.4%, 39.8%, 20.6%, and 5.2%, respectively. When compared with corresponding control groups, age <35 years at ART, female, education of middle school or above, sexual transmission, no opportunistic infection, CD4 ≥200 cells/μl, baseline regimen with tenofovir (TDF) and time from HIV diagnosis to ART <1 year were the related factors facilitating the higher CD4 subgroups. Conclusions:The various CD4 immune recoveries of HIV/AIDS were changing patterns after ART. Starting ART with a high CD4 level was beneficial to CD4 recovery to normal level during the follow-up period. Early initiation of ART and exceptional attention to CD4 immune recovery should be encouraged after the ART.

Gene-environment interactions underlie cancer susceptibility and progression. The human body is exposed to and affected by the microenvironment seiscasts of various microorganisms and their metabolites, such as the microenvironment of gut microbiota. The relative abundance of some intestinal microbes in lung cancer patients was significantly different from that in the control group. These studies suggest that gut microbiota may be associated with lung cancer through some ways. At the same time, gut microbiota is relatively manageable environmental variables compared to the external environment we are exposed to, as they are highly quantifiable and relatively stable in the individual. Just as some measures of diagnosis, intervention and treatment of lung cancer targeting gut microbiota have achieved some results in clinical practice. In this review, we mainly discuss the role of gut microbiota and its metabolites in the progression and treatment of lung cancer through certain ways, such as regulation of metabolism, inflammation, and immune response. Finally, based on current research progress, it is inferred that research on gut microbiota may be an effective approach to the precise and personalized medical treatment of lung cancer.
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Objective:To explore the effect of high-voltage electrical burn on platelet function and rheological behavior in rats and the interventive effect of Xuebijing.Methods:A total of 280 Sprague Dawley rats of clean grade (aged 8-10 weeks, male and female unlimited) were divided into sham injury group, simple electrical burn group, electrical burn+ saline group, and electrical burn+ Xuebijing group according to the random number table, with 70 rats in each group. Rats in sham injury group were not conducted with electrical current to cause sham injury. Rats in the other three groups were given electrical current with output voltage of 2 kV and current intensity of (1.92 ± 0.24) A for 3 s, which caused high-voltage electrical burn wounds, each with an area of 1 cm×1 cm distributed in the left forelimb at the current inlet and the right hindlimb at the current outlet respectively. Rats in sham injury group and simple electrical burn group were not treated after injury. At post injury minute 2 and on post injury day (PID) 1, 2, 3, 4, 5, and 6, rats in electrical burn+ saline group and electrical burn+ Xuebijing group were intraperitoneally injected with 6 mL/kg saline and 6 mL/kg Xuebijing, respectively. Survival conditions of rats were recorded during the experiment. At 15 min before injury and at post injury hour (PIH) 1, 8, 24, 48, 72, and on PID 7, 10 rats in each group were respectively selected according to the random number table to sacrifice after collection of 5 mL blood under the direct vision of heart. Blood in the volume of 0.05 mL from each rat was taken to make blood smear, and platelet aggregation number was counted under 400 fold field of view using multiple projection microscope. The remaining blood samples were centrifuged to collect supernatant, and the content of platelet-derived growth factor (PDGF), thrombopoietin (TPO), and platelet activating factor (PAF) was detected by enzyme-linked immunosorbent assay. Data were statistically analyzed with analysis of variance for factorial design and Student-Newman-Keuls method.Results:All rats in sham injury group and simple electrical burn group survived during the experiment. One rat in electrical burn+ saline group died on PID 6, and one rat on PID 5 and one rat on PID 6 died in electrical burn+ Xuebijing group. The levels of all indexes among the 4 groups were close at 15 min before injury. The serum content of PDGF, TPO, and PAF and platelet aggregation number of rats in the three electrical burn groups at all time points after injury were higher or more than those in sham injury group, and the first three indexes reached the peak at PIH 8. The serum platelet aggregation number of rats in simple electrical burn group reached the peak at PIH 48, and that in electrical burn+ saline group and electrical burn+ Xuebijing group reached the peak at PIH 72. Among them, the serum content of PDGF of rats in electrical burn+ Xuebijing group at PIH 48, 72 and on PID 7 ((12.8±4.0), (11.6±4.4), (11.0±3.6) ng/mL, respectively) was close to that in sham injury group ((10.4±2.0), (10.4±2.5), (9.8±3.3) ng/mL, respectively, P>0.05). The serum content of TPO of rats in electrical burn+ Xuebijing group at PIH 24, 72 and on PID 7 ((200±52), (192±36), (193±32) ng/mL, respectively) was close to that in sham injury group ((182±30) , (184±41), (183±33) ng/mL, respectively, P>0.05). The serum content of PDGF, TPO, and PAF and platelet aggregation number of rats in electrical burn+ Xuebijing group at every time point after injury was generally lower or less than that in electrical burn+ saline group and simple electrical burn group. Conclusions:Application of Xuebijing treatment after high-voltage electrical burn can decrease the content of PDGF, TPO, and PAF in the serum and reduce the number of platelet aggregation, thereby inhibit platelet activation and improve platelet rheology.

Objective To delineate the expressions of ubiquitin-specific proteinase 49 (USP49)and FK506 binding protein 51 (FKBP51) in the spinal dorsal horns and their roles in rats with diabetic neuropathic pain (DNP).Methods Male SD rats were fed with high glucose and high fat diet with an intraperitoneal injection of 1％ streptozocin to establish DNP rat models.DNP rats were allocated into DNP group,control shRNA group (KC group) and knockdown USP49 group (KD group,n=10);saline,Ad-scrambled shRNA (3×108 PFU/mL) and Ad-USP49-shRNA (3×108 PFU/mL) were intrathecally injected into the rats of the three groups.Another 10 normal rats were chosen as control group (C group).Thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were measured one d before model establishment,one and 7 d after model establishment,one,three and 7 d after intrathecal injection.The mRNA and protein expressions of USP49,FKBP51 and glucocorticoid receptor α (GRα)in dorsal horn neurons were detected by real time-PCR and Western blotting.Results (1) TWL showed no significant difference among the four groups one d before model establishment (P＞0.05);three and 7 d after intrathecal injection,TWL in KD group was significantly prolonged as compared with that in the DNP group,and significantly shortened as compared with that in C group (P＜0.05).(2) MWT showed no significant difference among the four groups one d before model establishment (P＞0.05);three and 7 d after intrathecal injection,MWT in KD group was significantly higher as compared with that in the DNP group,and significantly lower as compared with that in C group (P＜0.05).(3) As compared with DNP group,KD group had significantly decreased mRNA expressions of USP49 and FKBP51,and statistically increased mRNA GRα expression (P＜0.05).(4) As compared with DNP group,KD group had significantly decreased protein expressions of USP49 and FKBP51,and statistically increased protein GRα expression (P＜0.05).Conclusion Specific knockdown of USP49 expression is associated with improvement of heat hyperalgesia and mechanical hyperalgesia in DNP rats,which may be attributed to the de-ubiquitination ofFKBP51 by USP49.

Objective To investigate the effect of emotional resilience group training on perceived stress,anxiety and depression in patients with gastrointestinal cancer.Methods 325 cases of patients with gastric cancer were divided into experimental group(n=163) and control group(n=162) by random digital table method.Two groups of patients were treated with chemotherapy and routine treatment and the experimental group was trained once a week for 8 weeks of emotional resilience group training.Chinese version perceived stress(CPSS),SDS and SAS were used to evaluate the effect of intervention before and after intervention.Results After 8 weeks of emotional elastic group training,the CPSS score((39.98±4.82) vs (33.96±5.02)),SAS score((48.83±4.58) vs (42.12±4.01)) and SDS score((49.23±4.12) vs (45.21±3.27))were lower than those before the intervention (all P＜ 0.05).The difference of CPSS ((-6.02 ± 3.74) vs (-0.19±2.78)),SAS((-6.71±3.86) vs (-0.39±5.62)) and SDS((-4.02±2.03) vs (-0.62±2.31)) before and after the intervention of the two groups were statistically significant(t=-9.325,-9.529,-6.132,P＜0.01).Conclusion Emotional resilience group training can effectively reduce the level of perceptual stress in patients with gastrointestinal cancer,and improve depression and anxiety.