This paper summarizes Professor SHI Zaixiang's clinical experience in treating high fever caused by sepsis using Chaihu Guizhi Ganjiang Decoction （柴胡桂枝干姜汤）. He holds that the key pathogenesis of sepsis involves constrained heat in the shaoyang and internal accumulation of water and fluids. The clinical manifestations such as high fever， chills， and alternating sensations of cold and heat are attributed to pathogenic heat constrained in the shaoyang. Meanwhile， soft tissue edema and serous cavity effusions are due to shaoyang dysfunction and internal water retention. In clinical practice， treating sepsis-related high fever requires addressing both the shaoyang-constrained heat and the associated edema and effusions. The therapeutic approach focuses on harmonizing the shaoyang and resolving internal fluids， using Chaihu Guizhi Ganjiang Decoction as the base formula with flexible modifications. Professor SHI emphasizes that this formula shows a rapid antipyretic effect， particularly in cases where multiple anti-infective treatments have failed.

BACKGROUND:Relatively or absolutely active bone resorption function of osteoclasts is one of the causative factors of osteoporosis. Therefore,how to inhibit the formation of osteoclasts and reduce the bone resorption activity is a key element in the prevention and treatment of osteoporosis. Liquiritin,which is derived from licorice,plays a role in the clinical treatment of bone diseases,but there are fewer studies addressing the application of liquiritin in osteoporosis and the mechanism is unknown.OBJECTIVE:To confirm,through both in vivo and in vitro experiments,that liquiritin inhibits osteoclast differentiation and alleviates bone loss.METHODS:Cell counting kit-8 was used to detect whether Liquiritin exerts toxic or proliferative effects on mouse bone marrow-derived macrophages,and tartrate-resistant acid phosphatase staining was performed to observe the effect of liquiritin in inhibiting osteoclast differentiation. The affinity of liquiritin binding to proteins related to osteoclast differentiation was verified by network pharmacology. RT-PCR and western blot assays were performed to detect the inhibitory effects of liquiritin on osteoclast-specific protein and gene expression as well as relevant signaling pathways. Finally,the mitigating effect of liquiritin on bone loss was verified in the C57BL/6J mouse osteoporosis model.RESULTS AND CONCLUSION:Liquiritin,at concentrations of 20 μmol/L and below,could inhibit the formation and differentiation of osteoclasts. Concurrently,it exhibited a high affinity with osteoclast-specific proteins such as nuclear factor of activated T-cells 1,Cathepsin K,c-Fos,and matrix metalloproteinase 9,and reduced the relative expression levels of these genes and proteins. Liquiritin could also effectively lower the phosphorylation expression level of JNK in the MAPK signaling pathway at the 15th,30th,45th,and 60th minutes,and it could salvage the degradation of nuclear factor-κB inhibitor α in the nuclear factor-κB signaling pathway at the 60th minute. In vivo experiments demonstrated that liquiritin could mitigate bone loss caused by osteoclasts and improve parameters related to trabecular bone. To conclude,liquiritin possesses the capacity to inhibit osteoclast differentiation and alleviate bone loss,thereby exerting a protective role against osteoporosis.

Objective To analyze the clinical characteristics of 3 patients with Wilson's disease who suffered from skin striae atrophicae after treatment with penicillamine,and to conduct literature review to extensively profile ad-verse events of penicillamine-induced skin changes.Methods A retrospective analysis was performed on the clinical data of 3 patients with Wilson's disease who developed skin striae atrophicae after administration of peni-cillamine in the Department of Pediatrics of Peking Union Medical College Hospital from August 2013 to August 2024,and a literature review was performed.Results Three patients with Wilson's disease all developed skin striae atrophicae after taking penicillamine.Among them,2 patients reduced or stopped using penicillamine short-ly after the appearance of striae atrophicae,and their striae atrophicae improved significantly.After taking penicil-lamine again,their skin changes remained stable.A literature research showed that 48 patients with Wilson's disease experienced penicillamine induced skin changes,and no similar reports of striae atrophicae were found.The reported skin changes included elastosis perforans serpiginosa,skin laxity or wrinkled skin,pseudo-pseudox-anthoma elasticum,increased skin fragility,pigmentation and so on.Among them,24 patients reduced or stopped penicillamine,and 18 patients(75％)had improved or maintained stable skin changes.Conclusions Penicillamine can cause various skin changes in patients with Wilson's disease,including striae atrophicae,which can be improved after reducing or discontinuing taking penicillamine.And skin striae atrophicae can main-tain stable even if they taking penicillamine again.

BACKGROUND:Relatively or absolutely active bone resorption function of osteoclasts is one of the causative factors of osteoporosis. Therefore,how to inhibit the formation of osteoclasts and reduce the bone resorption activity is a key element in the prevention and treatment of osteoporosis. Liquiritin,which is derived from licorice,plays a role in the clinical treatment of bone diseases,but there are fewer studies addressing the application of liquiritin in osteoporosis and the mechanism is unknown.OBJECTIVE:To confirm,through both in vivo and in vitro experiments,that liquiritin inhibits osteoclast differentiation and alleviates bone loss.METHODS:Cell counting kit-8 was used to detect whether Liquiritin exerts toxic or proliferative effects on mouse bone marrow-derived macrophages,and tartrate-resistant acid phosphatase staining was performed to observe the effect of liquiritin in inhibiting osteoclast differentiation. The affinity of liquiritin binding to proteins related to osteoclast differentiation was verified by network pharmacology. RT-PCR and western blot assays were performed to detect the inhibitory effects of liquiritin on osteoclast-specific protein and gene expression as well as relevant signaling pathways. Finally,the mitigating effect of liquiritin on bone loss was verified in the C57BL/6J mouse osteoporosis model.RESULTS AND CONCLUSION:Liquiritin,at concentrations of 20 μmol/L and below,could inhibit the formation and differentiation of osteoclasts. Concurrently,it exhibited a high affinity with osteoclast-specific proteins such as nuclear factor of activated T-cells 1,Cathepsin K,c-Fos,and matrix metalloproteinase 9,and reduced the relative expression levels of these genes and proteins. Liquiritin could also effectively lower the phosphorylation expression level of JNK in the MAPK signaling pathway at the 15th,30th,45th,and 60th minutes,and it could salvage the degradation of nuclear factor-κB inhibitor α in the nuclear factor-κB signaling pathway at the 60th minute. In vivo experiments demonstrated that liquiritin could mitigate bone loss caused by osteoclasts and improve parameters related to trabecular bone. To conclude,liquiritin possesses the capacity to inhibit osteoclast differentiation and alleviate bone loss,thereby exerting a protective role against osteoporosis.

BACKGROUND:Osteoporotic vertebral compression fracture is a common fracture secondary to osteoporosis.At present,there is no effective prediction index and method for osteoporotic vertebral compression fracture. OBJECTIVE:To investigate the predictive effect of the comprehensive index of lumbar vertebral body bone strength on osteoporotic vertebral compression fracture. METHODS:233 patients with osteoporosis were divided into a fracture group and a non-fracture group according to whether a vertebral fracture occurred.The demography,body mass index,vertebral bone mineral density and other details were collected.Lateral X-ray films of the lumbar spine were photographed.The vertebral body width,vertebral body length,sacral slope,pelvic tilt,pelvic incidence,lumbar compressive strength index and the lumbar impact strength index were measured,calculated,and analyzed by univariate and multivariate,and the receiver operating characteristic curve was analyzed.The survival analysis was conducted according to the cut-off value. RESULTS AND CONCLUSION:(1)All patients were followed up for 2-4 years,with an average of 3.1 years.During the follow-up period,99 cases(38 cases of L1 vertebral body,61 cases of L2 vertebral body)had fractures(fracture group),and 134 cases(52 cases of L1 vertebral body,82 cases of L2 vertebral body)had no fractures(non-fracture group).Univariate analysis showed that there was no significant difference in age,sex,height,body mass,body mass index and fracture segment between the two groups(P>0.05).(2)Lumbar compressive strength index and lumbar impact strength index in the fracture group were lower than those in the non-fracture group(P<0.05).Pelvic incidence and pelvic tilt in the fracture group were higher than those in the non-fracture group(P<0.05).(3)Multivariate analysis showed that lumbar compressive strength index,lumbar impact strength index and pelvic tilt were risk factors for osteoporotic vertebral compression fractures(P<0.05).(4)Receiver operating characteristic curve analysis showed that the cutoff values of vertebral bone mineral density,lumbar compressive strength index,lumbar impact strength index,pelvic tilt and pelvic incidence were 0.913 5 g/cm2,1.932,0.903,21.5° and 55°,respectively;areas under the curve were 0.630,0.800,0.911,0.633 and 0.568,respectively.(5)According to the survival analysis(with osteoporotic vertebral compression fracture as the end point),the average survival time of the patients with lumbar impact strength index≥0.903 was significantly longer than that of the patients with lumbar impact strength index<0.903(P<0.05).(6)These findings conclude that the comprehensive index of lumbar vertebral body bone strength is more accurate than the bone mineral density of the vertebral body and spine-pelvis sagittal parameters in predicting osteoporotic vertebral compression fractures,which is helpful for early prevention and treatment of osteoporotic vertebral compression fractures.

BACKGROUND:Osteoporosis vertebral compression fracture is a common fracture secondary to osteoporosis,and there is currently a lack of effective predictive indicators and methods for osteoporosis vertebral compression fracture. OBJECTIVE:To investigate the predictive effects of paravertebral muscle degeneration,functional cross-sectional area,and percentage of fat infiltration on osteoporotic vertebral compression fractures. METHODS:The 224 patients with osteoporosis diagnosed from January 2018 to June 2022 were included.They were followed up for more than 2 years.They were divided into fracture group and non-fracture group according to the presence and absence of vertebral fracture.The detailed information of demographics,body mass index,bone mineral density and so on were collected.The functional cross-sectional area and percentage of fat infiltration of bilateral Psoas major muscle and extensor dorsi(Erector spinae muscles muscle and multifidus muscle)at the level of lower endplate of L2 vertebral body were measured and calculated. RESULTS AND CONCLUSION:(1)224 patients were ultimately included,of which 126 had fractures as the fracture group and 98 had no fractures as the non-fracture group.There was no statistically significant difference in age,gender,height,body mass,body mass index,and fracture segment between the two groups(P>0.05).(2)The bone mineral density of the fracture group was significantly lower than that of the non-fracture group(P<0.05).Functional cross-sectional areas of Psoas major muscle and extensor dorsi in the fracture group were significantly lower than those in the non-fracture group(P<0.05).The percentage of fat infiltration of the extensor dorsi in the fracture group was significantly higher than that in the non-fracture group(P<0.05).There was no significant difference in percentage of fat infiltration of Psoas major muscle between the two groups(P>0.05).(3)Receiver operating characteristic analysis showed that the vertebral bone mineral density,percentage of fat infiltration of extensor dorsi,functional cross-sectional area of extensor dorsi and percentage of fat infiltration of Psoas major muscle were 0.903 g/cm2,35.426%,418.875 mm2,and 6.375%,respectively.The areas under curve were 0.634,0.755,0.876,and 0.585,respectively.(4)These findings indicate that paravertebral muscle degeneration is strongly associated with the occurrence of osteoporotic vertebral compression fractures.The functional cross-sectional area of extensor dorsi muscle can effectively predict the occurrence of osteoporotic vertebral compression fractures,which is helpful for early prevention and treatment of osteoporotic vertebral compression fractures.

Objective To develop an ultra-performance liquid chromatography-mass spectrometry(UPLC-MS/MS)method for the simultaneous quantification of dolutegravir,raltegravir,efavirenz,lamivudine and tenofovir in human plasma and to apply it to the therapeutic monitoring.Methods Dolutegravir-D5,raltegravir-D4,efavirenz-D5,lamivudine-13 C-15 N2 and tenofovir-D7 were used as internal standard,respectively.All samples were extracted using the protein precipitation method with acetonitrile and then diluted for analysis.Chromatographic separation was performed on Shim-pack XR-ODS Ⅲ(2.0 mmx50 mm,1.6 μm)column.Mobile phases A and B consisted of 0.1％formic acid in water and acetonitrile respectively.A programmed mobile phase gradient was used at a flow rate of 0.3 mL·min-1 and column temperature of 40 ℃.The tandem mass spectrometer was equipped with an electrospray ionization(ESI)source operating in multiple reaction monitoring(MRM)modes.After methodological validation,it can be used for therapeutic drug monitoring in HIV patients.Results There was good linearity in the validated concentration ranges of 62.5-3 000 ng·mL-1 for dolutegravir,10-500 ng·mL-1 for raltegravir,125-6 000 ng·mL-1for efavirenz,10-500 ng·mL-1 for lamivudine and 10-500 ng·mL-1 for tenofovir with the linear correlation coeffificients of determination(R2)of all higher than 0.998.The accuracy of both intra-day and inter-day studies ranged from 94.0％-109.3％,and the relative standard deviations were less than 7％.The IS-normalized matrix factor and extraction recoveries of all analytes were 95.7％-106.0％and 98.7％-104.5％at all concentrations.All analytes were stable in plasma at a certain storage environment.The trough blood concentrations of dolutegravir,efavirenz,lamivudine and tenofovir were 107.7-2 366.0,740.0-3 410.0,38.5-1 229.3,31.6-224.4ng·mL-1 in HIV patients,respectively.Conclusion The method is highly aceurate,easy to perform,low-cost,and suitable for therapeutic drug monitoring of dolutegravir,raltegravir,efavirenz,lamivudine and tenofovir in HIV patients.

In order to study the biological characteristics and whole-genome sequence of Streptococ-cus equi,a sheep-derived Streptococcus equi preserved in our laboratory was subjected to recovery,biochemical experiments,drug susceptibility tests and animal experiments,and followed by whole genome sequencing and annotation of the gene functions of the genome by using the biogenetic da-tabase.The biochemical identification results showed that this strain could ferment sugars,but the results of nitrate,catalase,V-P test,and M-R test were negative;the drug susceptibility test results showed that this strain was highly sensitive to most antibiotics and was resistant to kanaphylaxis.It was resistant to amikacin and amikacin;animal experiments showed that the lethality rate of this strain to mice was 100％,and the median lethal dose of this strain was measured to be 4.86X 106 CFU/kg.According to the pathological section results of mice,it showed that the lungs,liver,kidneys,and spleen all had varying degrees of lesions.The whole genome sequencing results showed that the total genome length of this strain is 2 272 497 bp,the G+C content was 41.1％,and it was predicted to contain 2 124 CDS regions.The RNA prediction results showed that the number of rRNA and tRNA was 15,and the number of tRNA was 57.There were four prophages and gene islands,and there were 362 pathogenicity-related genes in the VFDB database without CRISPR sequences.This study analyzed the complete genome of Streptococcus equi derived from sheep,and also provided a theoretical basis for the treatment,prevention and control of the disease.

Objective To investigate the predictive value of a nomogram model constructed based on imaging combined with prostate-specific antigen(PSA)and its related parameters for biopsy in patients with PSA levels of 4-10 ng/mL.Methods The serological and imaging data of 191 patients who were detected for PSA and related indicators and underwent the first biopsy of prostate by transrectal ultrasound at Zhongshan City People's Hospital and/or Yunfu Hospital of TCM from January 2018 to December 2023 were analyzed retrospectively.Multivariate Logistic regression identified independent risk factors for prostate cancer,and a nomogram model was developed for patients with PSA levels of 4-10 ng/mL.The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curves,calibration curves,and decision curves.Results The multivariate Logistic regression analysis showed that free PSA,prostate volume,transition zone volume,PSA density,and the prostate imaging-reporting and data system(PI-RADS v2.1)score were independent risk factors for prostate cancer.The model incorporating these significant variables demonstrated the best performance,with an area under the curve(AUC)of 0.750(95%CI:0.678-0.821),sensitivity of 72.7%,specificity of 77.2%,and accuracy of 74.9%.The calibration curve indicated good agreement between the predicted probability and the actual probability of prostate cancer;and the decision curve analysis further confirmed that the model had high clinical utility.Conclusion The constructed nomogram prediction model can effectively estimate the preoperative risk of prostate cancer in patients with PSA levels of 4-10 ng/mL,providing clinicians with an intuitive tool to adjust treatment plans based on the assessed risk,thereby optimizing patient outcomes.

Objective To investigate the predictive value of a nomogram model constructed based on imaging combined with prostate-specific antigen(PSA)and its related parameters for biopsy in patients with PSA levels of 4-10 ng/mL.Methods The serological and imaging data of 191 patients who were detected for PSA and related indicators and underwent the first biopsy of prostate by transrectal ultrasound at Zhongshan City People's Hospital and/or Yunfu Hospital of TCM from January 2018 to December 2023 were analyzed retrospectively.Multivariate Logistic regression identified independent risk factors for prostate cancer,and a nomogram model was developed for patients with PSA levels of 4-10 ng/mL.The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curves,calibration curves,and decision curves.Results The multivariate Logistic regression analysis showed that free PSA,prostate volume,transition zone volume,PSA density,and the prostate imaging-reporting and data system(PI-RADS v2.1)score were independent risk factors for prostate cancer.The model incorporating these significant variables demonstrated the best performance,with an area under the curve(AUC)of 0.750(95%CI:0.678-0.821),sensitivity of 72.7%,specificity of 77.2%,and accuracy of 74.9%.The calibration curve indicated good agreement between the predicted probability and the actual probability of prostate cancer;and the decision curve analysis further confirmed that the model had high clinical utility.Conclusion The constructed nomogram prediction model can effectively estimate the preoperative risk of prostate cancer in patients with PSA levels of 4-10 ng/mL,providing clinicians with an intuitive tool to adjust treatment plans based on the assessed risk,thereby optimizing patient outcomes.