OBJECTIVES: To investigate the effect of Qianggu Kangshu Formula (QGKSF) for alleviating osteoclast differentiation in rheumatoid arthritis and the underlying mechanism. METHODS: RAW264.7 cells cultured under hypoxic conditions were treated with RANKL to induce osteoclast differentiation and incubated with normal rat serum or sera from rats medicated with methotrexate (MTX) or QGKSF at low and high doses. Cell viability, TRAP-positive multinucleated cells and F-actin ring formation in the treated cells were assessed with CCK-8 assay, TRAP staining and Phalloidin staining, respectively. Autophagy and autophagosomes in the cells were observed with MDC staining and transmission electron microscopy. ELISA was used to measure IL-6 and TNF-α levels in the culture supernatant, and the expressions of HIF-1α, BNIP3, Bcl-2, Beclin1, LC3-I, LC3-II, P62 and TRAP mRNAs and proteins were analyzed using RT-qPCR and Western blotting. RESULTS: In hypoxia- and RANKL-induced RAW264.7 cells treated with normal rat serum, significant increments of TRAP-positive cells and F-actin ring formation were observed with an enhanced autophagic fluorescence intensity and increased autophagosomes. Treatment of the induced cells with rat sera medicated with MTX and low- and high-dose QGKSF obviously reduced the TRAP-positive cells, F-actin rings and autophagosomes as well as the autophagic fluorescence intensity. RANKL treatment significantly increased IL-6 and TNF-α levels in RAW264.7 cells, which were obviously decreased by treatment with MTX- and QGKSF-medicated sera. RANKL also significantly increased the mRNA and protein expression levels of HIF-1α, BNIP3, Bcl-2, Beclin1, LC3 and TRAP and lowered P62 expressions, and these changes were effectively reversed by treatment with MTX- and QGKSF-medicated sera. CONCLUSIONS QGKSF attenuates RANKL-induced osteoclast differentiation in hypoxic RAW264.7 cells by inhibiting the HIF-1α/BNIP3 autophagy signaling pathway, suggesting its potential for treatment of bone destruction in rheumatoid arthritis.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Osteoclasts/drug effects* ; Autophagy/drug effects* ; Mice ; Signal Transduction/drug effects* ; Rats ; Cell Differentiation/drug effects* ; Arthritis, Rheumatoid/pathology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; RAW 264.7 Cells ; Membrane Proteins/metabolism* ; Mitochondrial Proteins

ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules （DHBY， the prescription for consolidating body resistance） and Fuling Yunhua granules （FLYH， the prescription for treating symptoms） on spontaneous type 2 diabetes mellitus （T2DM） in mice. MethodsAccording to the fasting blood glucose （FBG） level， 12-week-old db/db mice were randomized into six groups： model， DHBY （18.02 g·kg^-1）， FLYH （14.80 g·kg^-1）， sequential administration 1 （SEQ-1， DHBY 18.02 g·kg^-1+FLYH 14.80 g·kg^-1）， sequential administration 2 （SEQ-2， FLYH 14.80 g·kg^-1+DHBY 18.02 g·kg^-1）， and dapagliflozin （Dapa， 1.3 mg·kg^-1）. The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal， the retinal thickness， FBG， hemoglobin A1c （HbA1c）， and insulin were determined， and histopathological changes of the pancreas， liver， kidney， and retina were observed by hematoxylin-eosin （HE） staining. ResultsCompared with the model group， SEQ-1 for 4 weeks lowered the FBG level （P<0.05）， raised the insulin level， decreased the triglyceride （TG） level （P<0.05）， increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels （P<0.05）， rose the insulin level， increased the retinal thickness and the number of optic ganglion cells （P<0.05）， and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal， Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However， the levels of FBG and HbA1c in the SEQ-2 group remained decreasing （P<0.05）. ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy， and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover， SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.

ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules （DHBY， the prescription for consolidating body resistance） and Fuling Yunhua granules （FLYH， the prescription for treating symptoms） on spontaneous type 2 diabetes mellitus （T2DM） in mice. MethodsAccording to the fasting blood glucose （FBG） level， 12-week-old db/db mice were randomized into six groups： model， DHBY （18.02 g·kg^-1）， FLYH （14.80 g·kg^-1）， sequential administration 1 （SEQ-1， DHBY 18.02 g·kg^-1+FLYH 14.80 g·kg^-1）， sequential administration 2 （SEQ-2， FLYH 14.80 g·kg^-1+DHBY 18.02 g·kg^-1）， and dapagliflozin （Dapa， 1.3 mg·kg^-1）. The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal， the retinal thickness， FBG， hemoglobin A1c （HbA1c）， and insulin were determined， and histopathological changes of the pancreas， liver， kidney， and retina were observed by hematoxylin-eosin （HE） staining. ResultsCompared with the model group， SEQ-1 for 4 weeks lowered the FBG level （P<0.05）， raised the insulin level， decreased the triglyceride （TG） level （P<0.05）， increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels （P<0.05）， rose the insulin level， increased the retinal thickness and the number of optic ganglion cells （P<0.05）， and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal， Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However， the levels of FBG and HbA1c in the SEQ-2 group remained decreasing （P<0.05）. ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy， and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover， SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.

Objective To investigate the value of procalcitonin-to-albumin ratio(PAR)for predicting 28-day mortality risk in elderly patients with sepsis for optimizing the diagnosis and treatment strategies.Methods The clinical data of 112 elderly patients diagnosed with sepsis in the intensive care unit were retrospectively reviewed and analyzed.Patients were assigned to survivors group or deaths group based on 28-day outcomes.Clinical characteristics and the results of laboratory tests were collected,including procalcitonin(PCT),albumin,and C-reactive protein(CRP).The normally distributed data were compared between groups using t-test.Mann-Whitney U test was adopted for comparing non-normally distributed data.Cox proportional hazards regression model was used to analyze the effects of multiple variables on survival time.Receiver operating characteristic(ROC)curve analysis was performed to determine the sensitivity and specificity of various variables in predicting mortality risk.Results Mechanical ventilation,APACHE Ⅱ scores,and length of hospital stay(all P＜0.05)were significantly different between survivors group and deaths group.Blood culture results showed that Gram-negative bacteria were predominant pathogen(75.9％),especially Escherichia coli(45.5％).Albumin level was significantly lower(P=0.026),while PCT,CRP,and PAR levels were significantly higher(P＜0.05)in the deaths group compared to those in the survivors group.Multivariate Cox regression analysis revealed that PAR was an independent predictor of 28-day mortality(HR=3.72,95％CI:1.98-4.42,P＜0.001).ROC curve analysis showed that the area under the curve(AUC)of PAR was 0.852 in predicting mortality,with a sensitivity of 81.25％and specificity of 87.82％.Conclusions PAR outperformed PCT or albumin alone in predicting 28-day mortality risk in elderly patient with sepsis.For every 0.1 increase in PAR,the risk of mortality increased by 272％.Early monitoring of PAR can assist clinicians in rapidly identifying high-risk patients and optimizing treatment strategies.

This study analyzed the clinical characteristics,diagnosis,treatment,and outcomes of disseminated Tsalaromycosis marneffei(DTSM)in non-HIV-infected patients.A retrospective analysis was conducted on 20 cases of non-HIV-infected DTSM treated at Guangzhou Chest Hospital between January 2015 and December 2021.Clinical data,including demographic characteris-tics,time to diagnosis,clinical manifestations,comorbidities,treatment details,and outcomes,were collected and analyzed.Among the 20 cases,9 were in males,and 11 were in females;the median age was 46(range:1-70)years.The median time from symptom onset to definitive diagnosis was 12(range:1-24)months,and 16 cases were initially misdiagnosed with mycobacterial disease.More than half the patients exhibited four major clinical features:fever,lymphadenopathy,skin lesions,and bone lesions.Pulmonary imag-ing abnormalities were observed in 19 cases,and an average of(3.6±1.6)lung lobes were involved.The positive detection rate of multi-sample cultures(70%,14/20)was significantly higher than that identified through histopathological examination(25%,5/20)(χ2=8.120,P=0.004).Findings for all five patients with positive next-generation sequencing(NGS)results were further confirmed through pathogen culture or histopathology.After antifungal treatment,14 patients showed clinical improvement and were discharged.In conclusion,non-HIV-infected DTSM is characterized by complex clinical manifestations and extensive pulmonary involvement,thus leading to frequent misdiagnosis and diagnostic delays.Pathogen detection methods,such as multi-sample cultures and NGS,demonstrate superior diagnostic accuracy to histopathological examination.Early identification and standardized antifungal therapy are critical factors in determining patient outcomes.

Objective The study aimed to compare the efficacy and safety of tislelizumab combined with chemotherapy versus pembrolizumab combined with chemotherapy as first-line treatments for advanced lung squa-mous cell carcinoma.Methods We retrospectively reviewed and analyzed the medical records of 116 patients with advanced lung squamous cell carcinoma treated with first-line chemotherapy plus tislelizumab or pembrolizumab in Guangzhou Chest Hospital from September 2020 to April 2024.We focused on analysis of time to treatment failure(TTF)and objective response rate(ORR)as well as disease control rate(DCR)and treatment-related adverse events(TRAEs).Results At a median follow up of 19.7 monyhs,the median TTF was 9.7 months in the tislelizumab group and 7.7 months in the pembrolizumab group(P<0.05).In addition,the ORR in the tislelizumab group was significantly higher than that in the pembrolizumab group(77.6%vs.60.3%,P<0.05),with DCRs of 93.1%and 87.9%,respectively(P=0.342).Regarding safety,the proportions of grade 3 or higher TRAEs and any-grade TRAEs were comparable between the two groups:29.3%and 81.0%in the tislelizumab group,and 32.8%and 87.9%in the pembrolizumab group,respectively.The most common TRAEs in both groups were hematological toxicities.Conclusions Tislelizumab plus chemotherapy demonstrated better efficacy and safety compared to pembrolizumab with chemotherapy as first-line treatment for Chinese patients with advanced lung squamous cell carcinoma.

Objective:To investigate the association between different sleep patterns and anxiety and depression in hemodialysis patients, thereby providing a reference for improving their psychological and sleep conditions.Methods:This study was a cross-sectional survey.A convenience sampling method was used to select patients undergoing regular dialysis at a hemodialysis centre in the Sixth People's Hospital of Huizhou from May 2023 to May 2024. Sleep quality, anxiety and depression symptoms were assessed using the Pittsburgh Sleep Quality Index (PSQI), Self-rating Anxiety Scale for (SAS) and Self-rating Depression Scale (SDS). Potential profiles were analyzed using Mplus 8.3 and mixed-effects Logistic regression was used to explore the association between sleep pattern category and anxiety-depression.Results:A total of 264 valid questionnaires were returned, of which 142 were males and 122 were females, aged (56.61 ± 12.69) years old. The sleep patterns of hemodialysis patients were divided into three potential categories:patients with overall better sleep quality31.4%(83/264), patients with poor sleep using hypnotic medication12.9%(34/264), and patients with poor sleep without hypnotic medication 55.7%(147/264). Significant differences were found in age, education, anxiety and depression across different sleep categories ( χ2 values were 9.75-25.72, all P<0.05). Compared with the group with overall better sleep quality, the risk of anxiety was higher in the group with sleep difficulties without hypnotic medication ( OR=5.409, P<0.05), and the risk of anxiety and depression ( OR=5.010, 6.488, both P<0.05) was higher in the group with sleep disorders using hypnotic medication. Compared with patients with poor sleep without hypnotic medication, patients with poor sleep using hypnotic medication had a higher risk of depression ( OR=6.501, P<0.05). Conclusions:There are three potential categories of sleep patterns in hemodialysis patients and significant correlations between them and anxiety and depression, and precise screening and individualized interventions need to be implemented in the clinic to improve patients' quality of life.

Objective To investigate the value of procalcitonin-to-albumin ratio(PAR)for predicting 28-day mortality risk in elderly patients with sepsis for optimizing the diagnosis and treatment strategies.Methods The clinical data of 112 elderly patients diagnosed with sepsis in the intensive care unit were retrospectively reviewed and analyzed.Patients were assigned to survivors group or deaths group based on 28-day outcomes.Clinical characteristics and the results of laboratory tests were collected,including procalcitonin(PCT),albumin,and C-reactive protein(CRP).The normally distributed data were compared between groups using t-test.Mann-Whitney U test was adopted for comparing non-normally distributed data.Cox proportional hazards regression model was used to analyze the effects of multiple variables on survival time.Receiver operating characteristic(ROC)curve analysis was performed to determine the sensitivity and specificity of various variables in predicting mortality risk.Results Mechanical ventilation,APACHE Ⅱ scores,and length of hospital stay(all P＜0.05)were significantly different between survivors group and deaths group.Blood culture results showed that Gram-negative bacteria were predominant pathogen(75.9％),especially Escherichia coli(45.5％).Albumin level was significantly lower(P=0.026),while PCT,CRP,and PAR levels were significantly higher(P＜0.05)in the deaths group compared to those in the survivors group.Multivariate Cox regression analysis revealed that PAR was an independent predictor of 28-day mortality(HR=3.72,95％CI:1.98-4.42,P＜0.001).ROC curve analysis showed that the area under the curve(AUC)of PAR was 0.852 in predicting mortality,with a sensitivity of 81.25％and specificity of 87.82％.Conclusions PAR outperformed PCT or albumin alone in predicting 28-day mortality risk in elderly patient with sepsis.For every 0.1 increase in PAR,the risk of mortality increased by 272％.Early monitoring of PAR can assist clinicians in rapidly identifying high-risk patients and optimizing treatment strategies.

This study analyzed the clinical characteristics,diagnosis,treatment,and outcomes of disseminated Tsalaromycosis marneffei(DTSM)in non-HIV-infected patients.A retrospective analysis was conducted on 20 cases of non-HIV-infected DTSM treated at Guangzhou Chest Hospital between January 2015 and December 2021.Clinical data,including demographic characteris-tics,time to diagnosis,clinical manifestations,comorbidities,treatment details,and outcomes,were collected and analyzed.Among the 20 cases,9 were in males,and 11 were in females;the median age was 46(range:1-70)years.The median time from symptom onset to definitive diagnosis was 12(range:1-24)months,and 16 cases were initially misdiagnosed with mycobacterial disease.More than half the patients exhibited four major clinical features:fever,lymphadenopathy,skin lesions,and bone lesions.Pulmonary imag-ing abnormalities were observed in 19 cases,and an average of(3.6±1.6)lung lobes were involved.The positive detection rate of multi-sample cultures(70%,14/20)was significantly higher than that identified through histopathological examination(25%,5/20)(χ2=8.120,P=0.004).Findings for all five patients with positive next-generation sequencing(NGS)results were further confirmed through pathogen culture or histopathology.After antifungal treatment,14 patients showed clinical improvement and were discharged.In conclusion,non-HIV-infected DTSM is characterized by complex clinical manifestations and extensive pulmonary involvement,thus leading to frequent misdiagnosis and diagnostic delays.Pathogen detection methods,such as multi-sample cultures and NGS,demonstrate superior diagnostic accuracy to histopathological examination.Early identification and standardized antifungal therapy are critical factors in determining patient outcomes.

Objective:To investigate the association between different sleep patterns and anxiety and depression in hemodialysis patients, thereby providing a reference for improving their psychological and sleep conditions.Methods:This study was a cross-sectional survey.A convenience sampling method was used to select patients undergoing regular dialysis at a hemodialysis centre in the Sixth People's Hospital of Huizhou from May 2023 to May 2024. Sleep quality, anxiety and depression symptoms were assessed using the Pittsburgh Sleep Quality Index (PSQI), Self-rating Anxiety Scale for (SAS) and Self-rating Depression Scale (SDS). Potential profiles were analyzed using Mplus 8.3 and mixed-effects Logistic regression was used to explore the association between sleep pattern category and anxiety-depression.Results:A total of 264 valid questionnaires were returned, of which 142 were males and 122 were females, aged (56.61 ± 12.69) years old. The sleep patterns of hemodialysis patients were divided into three potential categories:patients with overall better sleep quality31.4%(83/264), patients with poor sleep using hypnotic medication12.9%(34/264), and patients with poor sleep without hypnotic medication 55.7%(147/264). Significant differences were found in age, education, anxiety and depression across different sleep categories ( χ2 values were 9.75-25.72, all P<0.05). Compared with the group with overall better sleep quality, the risk of anxiety was higher in the group with sleep difficulties without hypnotic medication ( OR=5.409, P<0.05), and the risk of anxiety and depression ( OR=5.010, 6.488, both P<0.05) was higher in the group with sleep disorders using hypnotic medication. Compared with patients with poor sleep without hypnotic medication, patients with poor sleep using hypnotic medication had a higher risk of depression ( OR=6.501, P<0.05). Conclusions:There are three potential categories of sleep patterns in hemodialysis patients and significant correlations between them and anxiety and depression, and precise screening and individualized interventions need to be implemented in the clinic to improve patients' quality of life.