OBJECTIVE To explore the mechanism of Yishen Qingli Huoxue Formula(YQHF)improving renal fibrosis by inhib-iting HIF1-α using data mining,molecular docking,and in vivo and in vitro experiments.METHODS The expression changes of HIF1-α in renal biopsy tissues of patients with chronic kidney disease(CKD)in the GEO database were analyzed.Molecular docking was used to clarify the interaction mode between YQHF effective monomers and HIF1-α.Thirty SD rats were randomized to sham,model,low-dose YQHF,high-dose YQHF,and losartan potassium groups(n=6 per group).Unilateral ureteral obstruction(UUO)was used to induce renal fibrosis.Serum creatinine(Scr)and blood urea nitrogen(BUN)were measured,and kidney sections were stained with HE and Masson to assess pathology and fibrosis.Renal HIF1-α protein expression was quantified by Western blot.A renal fibro-sis cell model was established by inducing NRK-52E cells with TGF-β1,and the cells were divided into control,model,YQHF,HIF1-α inhibitor,HIF1-α inhibitor+YQHF,HIF1-α agonist,and HIF1-α agonist+YQHF groups.Western blot analysis was used to detect the protein expression levels of HIF1-α,COL-1,and α-SMA,and to observe the mechanism of YQHF-containing serum in protecting renal tubular epithelial cells.RESULTS Data mining showed HIF1-α expression in the CKD group was significantly higher than in the control group(P<0.01).Molecular docking indicated YQHF core components had good binding affinity to HIF1-α.In vivo,com-pared with the sham group,HE staining revealed tubular atrophy and inflammatory-cell infiltration,and Masson staining showed in-creased collagen deposition in UUO model rats(P<0.01).Serum creatinine and blood urea nitrogen were also elevated in the model group(P<0.05),together with up-regulated renal expression of COL-1,α-SMA and HIF-1α(P<0.01).After intervention with either high-dose or low-dose YQHF or losartan potassium,these pathological changes were attenuated:collagen deposition decreased(P<0.01),creatinine and BUN fell to varying degrees(P<0.05),and renal COL-1,α-SMA and HIF-1α levels were down-regulated(P<0.01);immunohistochemistry confirmed reduced HIF-1α in UUO kidneys(P<0.01).In NRK-52E cells,TGF-β1 stimulation mark-edly increased COL-1,α-SMA and HIF-1α protein levels(P<0.01).Both YQHF and chloramphenicol alone down-regulated these proteins(P<0.05,P<0.01),and their combination produced stronger inhibition of HIF-1α than YQHF alone(P<0.05).Conversely,the HIF-1α agonist fenbendazole-d3 reversed YQHF's anti-fibrotic effect,re-elevating COL-1,α-SMA and HIF-1α(P<0.01),with no significant difference versus agonist alone.CONCLUSION YQHF may inhibit extracellular matrix deposition and delay renal fi-brosis progression by suppressing HIF1-α accumulation,providing new theoretical evidence for traditional Chinese medicine in treat-ing renal fibrosis.

Objective:To compare the effects of standard cognitive behavioral therapy for insomnia (CBT-I) and enhanced cognitive behavioral therapy for insomnia(CBT-I Plus) in patients with chronic insomnia disorder comorbid anxiety or depressive symptoms.Methods:This prospective study included 148 patients with chronic insomnia disorder and anxiety/depression symptoms who were treated at the Sleep Disorder clinic of Shanghai Mental Health Center between July 2020 and August 2023. Participants (56 males, 92 females; aged 18-65 years, mean age 35.08±10.30 years) were randomly assigned in a 1∶2 ratio to the CBT-I group ( n=54) or CBT-I Plus group ( n=94). The CBT-I Plus group received additional treatments targeting anxiety and depressive symptoms. Treatment lasted 8 weeks, with assessment conducted at baseline, weeks 2, 4, and 8. Depression severity was measured using the 17-item Hamilton Depression Rating Scale (HAMD 17), anxiety severity with the Hamilton Anxiety Scale (HAMA), and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). Paired sample t-tests were used to evaluate within-group changes, repeated-measures ANOVA compared treatment effects between groups, and ANCOVA was employed to adjust for confounding variables. Results:Significant reductions in PSQI, HAMD 17, and HAMA scores were observed in both groups after treatment: CBT-I group: PSQI ((14.15±2.54) vs. (7.50±3.35), t=13.25), HAMD 17 ((14.70±4.09) vs. (7.40±4.61), t=9.33), and HAMA ((14.94±4.11) vs. (5.56±3.67), t=12.38) (all P<0.001).CBT-I Plus group: PSQI ((14.87±3.01) vs. (7.19±3.86), t=18.75), HAMD 17 ((16.84±3.91) vs. (6.84±4.79), t=17.42), and HAMA ((15.57±3.93) vs. (6.10±4.57), t=18.39) (all P<0.001). After adjusting for HAMD 17 scores and medication use, no statistically significant between-group differences were observed in changes in PSQI, HAMD 17, and HAMA scores ( P>0.05). A significant time-by-group interaction was found for the PSQI daytime dysfunction subscale ( F=4.87, P<0.01). Conclusion:Both CBT-I and CBT-I Plus improve sleep and emotional symptoms in patients with chronic insomnia disorder and comorbid anxiety/depression symptoms. However, CBT-I Plus has no significant advantages over standard CBT-I. Further studies are needed to refine the timing and content of interventions.

Head and neck squamous cell carcinoma （HNSCC） is one of the ten most common cancers worldwide and is one of the refractory cancers with a poor prognosis in otorhinolaryngology-head and neck surgery. Cetuximab is widely used in the clinical treatment of HNSCC and has been approved by the FDA as a first-line chemotherapeutic agent. However, its efficacy varies significantly among different individuals. Therefore, exploring the resistance mechanisms of cetuximab in the treatment of HNSCC and screening for sensitive populations are essential for the precision treatment of head and neck cancer. This article summarizes the research progress on cetuximab resistance mechanisms in HNSCC, and the main aspects include: alterations in epidermal growth factor receptor （EGFR） and its ligands, changes in downstream effectors of EGFR, bypass activation and crosstalk, epithelial-mesenchymal transition, epigenetic modifications, and immunosuppression in the tumor microenvironment.
Humans ; Cetuximab/therapeutic use* ; Drug Resistance, Neoplasm ; Squamous Cell Carcinoma of Head and Neck/drug therapy* ; Head and Neck Neoplasms/drug therapy* ; ErbB Receptors/metabolism* ; Tumor Microenvironment ; Epithelial-Mesenchymal Transition ; Molecular Targeted Therapy ; Antineoplastic Agents, Immunological/therapeutic use*

OBJECTIVE To explore the mechanism of Yishen Qingli Huoxue Formula(YQHF)improving renal fibrosis by inhib-iting HIF1-α using data mining,molecular docking,and in vivo and in vitro experiments.METHODS The expression changes of HIF1-α in renal biopsy tissues of patients with chronic kidney disease(CKD)in the GEO database were analyzed.Molecular docking was used to clarify the interaction mode between YQHF effective monomers and HIF1-α.Thirty SD rats were randomized to sham,model,low-dose YQHF,high-dose YQHF,and losartan potassium groups(n=6 per group).Unilateral ureteral obstruction(UUO)was used to induce renal fibrosis.Serum creatinine(Scr)and blood urea nitrogen(BUN)were measured,and kidney sections were stained with HE and Masson to assess pathology and fibrosis.Renal HIF1-α protein expression was quantified by Western blot.A renal fibro-sis cell model was established by inducing NRK-52E cells with TGF-β1,and the cells were divided into control,model,YQHF,HIF1-α inhibitor,HIF1-α inhibitor+YQHF,HIF1-α agonist,and HIF1-α agonist+YQHF groups.Western blot analysis was used to detect the protein expression levels of HIF1-α,COL-1,and α-SMA,and to observe the mechanism of YQHF-containing serum in protecting renal tubular epithelial cells.RESULTS Data mining showed HIF1-α expression in the CKD group was significantly higher than in the control group(P<0.01).Molecular docking indicated YQHF core components had good binding affinity to HIF1-α.In vivo,com-pared with the sham group,HE staining revealed tubular atrophy and inflammatory-cell infiltration,and Masson staining showed in-creased collagen deposition in UUO model rats(P<0.01).Serum creatinine and blood urea nitrogen were also elevated in the model group(P<0.05),together with up-regulated renal expression of COL-1,α-SMA and HIF-1α(P<0.01).After intervention with either high-dose or low-dose YQHF or losartan potassium,these pathological changes were attenuated:collagen deposition decreased(P<0.01),creatinine and BUN fell to varying degrees(P<0.05),and renal COL-1,α-SMA and HIF-1α levels were down-regulated(P<0.01);immunohistochemistry confirmed reduced HIF-1α in UUO kidneys(P<0.01).In NRK-52E cells,TGF-β1 stimulation mark-edly increased COL-1,α-SMA and HIF-1α protein levels(P<0.01).Both YQHF and chloramphenicol alone down-regulated these proteins(P<0.05,P<0.01),and their combination produced stronger inhibition of HIF-1α than YQHF alone(P<0.05).Conversely,the HIF-1α agonist fenbendazole-d3 reversed YQHF's anti-fibrotic effect,re-elevating COL-1,α-SMA and HIF-1α(P<0.01),with no significant difference versus agonist alone.CONCLUSION YQHF may inhibit extracellular matrix deposition and delay renal fi-brosis progression by suppressing HIF1-α accumulation,providing new theoretical evidence for traditional Chinese medicine in treat-ing renal fibrosis.

Objective:To compare the effects of standard cognitive behavioral therapy for insomnia (CBT-I) and enhanced cognitive behavioral therapy for insomnia(CBT-I Plus) in patients with chronic insomnia disorder comorbid anxiety or depressive symptoms.Methods:This prospective study included 148 patients with chronic insomnia disorder and anxiety/depression symptoms who were treated at the Sleep Disorder clinic of Shanghai Mental Health Center between July 2020 and August 2023. Participants (56 males, 92 females; aged 18-65 years, mean age 35.08±10.30 years) were randomly assigned in a 1∶2 ratio to the CBT-I group ( n=54) or CBT-I Plus group ( n=94). The CBT-I Plus group received additional treatments targeting anxiety and depressive symptoms. Treatment lasted 8 weeks, with assessment conducted at baseline, weeks 2, 4, and 8. Depression severity was measured using the 17-item Hamilton Depression Rating Scale (HAMD 17), anxiety severity with the Hamilton Anxiety Scale (HAMA), and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). Paired sample t-tests were used to evaluate within-group changes, repeated-measures ANOVA compared treatment effects between groups, and ANCOVA was employed to adjust for confounding variables. Results:Significant reductions in PSQI, HAMD 17, and HAMA scores were observed in both groups after treatment: CBT-I group: PSQI ((14.15±2.54) vs. (7.50±3.35), t=13.25), HAMD 17 ((14.70±4.09) vs. (7.40±4.61), t=9.33), and HAMA ((14.94±4.11) vs. (5.56±3.67), t=12.38) (all P<0.001).CBT-I Plus group: PSQI ((14.87±3.01) vs. (7.19±3.86), t=18.75), HAMD 17 ((16.84±3.91) vs. (6.84±4.79), t=17.42), and HAMA ((15.57±3.93) vs. (6.10±4.57), t=18.39) (all P<0.001). After adjusting for HAMD 17 scores and medication use, no statistically significant between-group differences were observed in changes in PSQI, HAMD 17, and HAMA scores ( P>0.05). A significant time-by-group interaction was found for the PSQI daytime dysfunction subscale ( F=4.87, P<0.01). Conclusion:Both CBT-I and CBT-I Plus improve sleep and emotional symptoms in patients with chronic insomnia disorder and comorbid anxiety/depression symptoms. However, CBT-I Plus has no significant advantages over standard CBT-I. Further studies are needed to refine the timing and content of interventions.

AIM: To investigate the characteristics of anterior segment structure in first-degree relatives of patients with primary angle-closure glaucoma(PACG).METHODS: A total of 48 first-degree relatives of PACG patients aged 40-60 who were treated in the Affiliated Eye Hospital of Nanchang University from September 2020 to October 2022 were selected as the observation group. Additionally, 40 cases(40 eyes)of healthy individuals without glaucoma and family history of glaucoma at the same age group were collected as the control group. They were divided into younger group(40-49 years old)and elder group(50-60 years old). All subjects were examined with ultrasound biomicroscopy(UBM)and were measured using camera measure software. The parameters mainly included anterior chamber depth(ACD), anterior chamber area(ACA), anterior chamber width(ACW), anterior segment depth(ASD), angle open distance(AOD500), trabecular iris angle(TIA), trabecular iris area(TISA500), lens vault(LV), iris curve(IC), iris thickness(IT500), scleral ciliary process angle(SCPA), and iris ciliary process distance(ICPD).RESULTS: ACD, ACA, AOD500, TISA500 and TIA in the observation group were lower than those of the control group, and LV and IC were higher than those of the control group(all P<0.05). ACD, ACA, AOD500, TISA500, and TIA of the elder group were lower than those in the age-matched control group, while LV and IC were larger than those of the age-matched control group(all P<0.05). ACD, AOD500, TISA500, and TIA of the younger observation group were smaller than those of the age-matched control group, but LV and IC were significantly larger than those of the age-matched control group(all P<0.05). ACD, ACA, AOD500, TISA500 and TIA of the elder observation group were significantly lower than those of the younger observation group, and LV and IC were significantly larger than those of the younger observation group(all P<0.05). There was a difference in the distribution of ACD between the observation group and the control group(P<0.05), and the proportion of moderate to severe shallow anterior chambers was 10 times that of the control group. Correlation analysis showed that TISA500 was positively correlated with ACD and ACA, and negatively correlated with LV and IC, and TISA500 was mainly influenced by LV. IC had a positive correlation with LV and a negative correlation with ACD and ACA.CONCLUSION: First-degree relatives of PACG with normal axial length have a high risk of angle closure. The anterior segment structures of first-degree relatives of PACG are more crowded than normal individuals, and the lens forward shift may be the initial influencing factor for narrow angle.

Objective:To analyze the intraoperative hemodynamic management by hypotension prediction index(HPI)in one patient underwent robot-assisted laparoscopic cystectomy,and to provide the reference for anesthesia monitoring and hemodynamic management in the similar major surgery.Methods:The clinical data,intraoperative hemodynamic data,usage and dosage of vasoactive drugs,and clinical outcomes of one patient underwent robot-assisted laparoscopic cystectomy with HPI-guided intraoperative hemodynamic management were retrospectively analyzed,and the relevant literatures were reviewed.Results:The patient,a 72-year-old female,was admitted due to macroscopic hematuria for 5 months accompanied by dysuria for 3 months.The cystoscope results showed a 7 cm× 7 cm× 5 cm mass on the right side of the bladder trigone and a 4 cm × 3 cm × 3 cm mass near the bladder neck.The positron emission tomography/computed tomography(PET/CT)results showed thickening of the right posterior bladder wall with high metabolism,and the preliminary diagnosis was bladder malignancy.After preoperative anesthesia evaluation,the robot-assisted laparoscopic cystectomy was planned.After entering the operating room,the routine monitoring was conducted,and the monitor equipped with HPI software was used to guide intraoperative hemodynamic management.After routine anesthesia induction,the tracheal intubation was performed by video laryngoscope.The patient experienced intraoperative hypotension(IOH)for six times,the cumulative time of mean arterial pressure(MAP)＜65 mmHg was 13.7 min,accounting for 4.40％of the anesthesia duration,and the time-weighted average of MAP＜65 mmHg was 0.28 mmHg.The time range with HPI≥85 roughly overlapped with and included the period of MAP＜65 mmHg.At 146 time points with HPI≥85,the MAP remained greater than 65 mmHg at 68.5％(100/146)of the points.At 47 time points with MAP＜65 mmHg,HPI≥85 occurred at 97.9％(46/47)of the points.On the first postoperative day,the patient's hypersensitive cardiac troponin I was＜0.01 μg·L-1,and no perioperative adverse events occurred.The patient was discharged on the eighth day.Conclusion:HPI can promptly and accurately predict the occurrence of IOH in the patients undergoing robot-assisted laparoscopic cystectomy.The use of HPI-based hypotension correction strategies during surgery can maintain the time-weighted average of MAP＜65 mmHg at a lower level.

Objective:To explore the effects of body mass index (BMI) on the incidence of nocturnal hypertension in patients with hypertension.Methods:Totally 341 hospitalized hypertensive patients treated at the Affiliated Hospital of Jining Medical University from February to May 2023 were selected by convenience sampling. Patients' general information, clinical data, and 24-hour ambulatory blood pressure results were collected. A binomial Logistic regression analysis was conducted to investigate the factors affecting the occurrence of nocturnal hypertension in these patients. The relationship between BMI and the incidence of nocturnal hypertension was examined using threshold effect tests and smooth curve fitting.Results:The binomial Logistic regression analysis indicated that blood phosphate level was a factor influencing the occurrence of nocturnal hypertension in hypertensive patients ( P<0.05). Smooth curve fitting and threshold effect test results showed that the relationship between BMI and the incidence of nocturnal hypertension was curve-correlated, with a turning point at 24.61 kg/m 2. To the left of the turning point, there was no correlation ( P=0.130) ; to the right, there was a correlation ( P=0.016) . Conclusions:When the BMI of hypertensive patients exceeds 24.61 kg/m 2, the likelihood of nocturnal hypertension increases with rising BMI, providing a precise intervention target for weight management-based patient care in hypertension.

OBJECTIVE: Evidence that long-term exposure to ambient air pollution increases mortality among older adults, particularly those residing in low-level air pollution locations, remains scarce. This study investigated the potential links between long-term low-level air pollution exposure and mortality among Chinese older adults. METHODS: A population-based study with 317,464 individuals aged ≥ 65 years was conducted in Shenzhen, China during 2018 and 2020. Logistic regression models were used to analyze the associations between long-term exposure to air pollution and all-cause mortality, as the primary outcome, as well as non-accidental, cancer and cardiovascular mortality. RESULTS: Significant associations of PM ₁, PM _2.5, PM ₁₀, SO ₂, CO, and O ₃ exposures with a higher risk of all-cause mortality were found. Adjusted odds ratio ( OR) for each 1 µg/m ³ increment was 1.49 [95% confidence interval ( CI): 1.46, 1.53] for PM ₁, 1.30 (1.27, 1.32) for PM _2.5, 1.05 (1.04, 1.06) for PM ₁₀, 5.84 (5.39, 6.32) for SO ₂, 1.04 (1.04, 1.05) for CO, and 1.02 (1.00, 1.03) for O ₃, respectively. Long-term PM ₁, PM _2.5, PM ₁₀, SO ₂, and CO exposures also elevated the risks of non-accidental, cancer and cardiovascular mortality. CONCLUSION Long-term low-level air pollution exposure was associated with an increased mortality risk among Chinese older adults.
Humans ; Aged ; China/epidemiology* ; Male ; Female ; Air Pollution/adverse effects* ; Environmental Exposure/adverse effects* ; Air Pollutants/analysis* ; Aged, 80 and over ; Particulate Matter/adverse effects* ; Cardiovascular Diseases/mortality* ; Mortality ; Neoplasms/mortality* ; East Asian People