Objective To analyze the clinical characteristics and risk factors of extreme thrombocytosis caused by piperacillin sodium and tazobactam sodium injection, and provide reference for medical treatment and pharmaceutical care of such patients. Methods Extreme thrombocytosis of a patient treated with piperacillin sodium and tazobactam sodium injection was found by clinical pharmacists, who participated in clinical diagnosis and treatment by analyzing of the adverse drug reaction, optimization of the medical treatment and pharmaceutical care. Results After correlation analysis, the patient's extreme thrombocytosis was likely to be an adverse reaction caused by the piperacillin sodium and tazobactam sodium injection. The medication was immediately discontinued, and antiplatelet therapy with aspirin was administered. Two weeks later, the patient's platelet count had significantly decreased compared to before. Conclusion Clinical pharmacists participated in patients’ clinical diagnosis and treatment, carried out pharmaceutical care and assisted physicians in adjusting treatment plans, which ensured the safety and effectiveness of patients' clinical drug therapy.

ObjectiveTaking the cuproptosis/oxidative stress pathway as the entry point， this study investigated the effect and mechanism of Liangyi Paste on hepatic lipid deposition in naturally aged mice fed with a high-fat diet. MethodsAfter adaptive feeding， 80 ten-week-old male C57BL/6 mice were used. Thirty of them were randomly divided into three groups （10 mice per group）： The 12-month-old control group （12MCON）， the 15-month-old control group （15MCON）， and the 15-month-old group with a high-fat diet （15MHFD）. The 12MCON and 15MCON groups were continuously fed a standard diet， while the 15MHFD group started receiving a high-fat diet at 12 months of age. Tissue samples were collected at the corresponding time points for each group. The remaining 50 mice were randomly divided into five groups （10 mice per group）： the 20-month-old control group （20MCON）， the model group， and the low-， medium-， and high-dose Liangyi Paste groups （2.91 ， 5.82 ， 11.64 g·kg^-1·d^-1， respectively）. The 20MCON group was continuously fed a standard diet， while the other groups started receiving a high-fat diet at 15 months of age. At 18 months of age， the Liangyi Paste groups were administered the corresponding doses of Liangyi Paste by gavage， while the 20MCON and model groups were given an equal volume of saline by gavage. After 8 weeks of continuous gavage （when the mice reached 20 months of age）， tissue samples were collected. Hepatic TG levels were measured using assay kits； liver histology and lipid deposition were observed via hematoxylin-eosin （HE） and oil red O staining； reactive oxygen species （ROS） were detected by enzyme-linked immunosorbent assay （ELISA）； Cu²⁺， superoxide dismutase （SOD）， and malondialdehyde （MDA） levels were measured by colorimetry； mRNA and protein expression of genes related to cuproptosis and oxidative stress pathways were analyzed by Real-time polymerase chain reaction（Real-time PCR） and Wes automated protein expression system. ResultsCompared with 12MCON， the 15MCON group showed significantly increased hepatic TG， Cu²⁺， ROS， and MDA levels （P<0.01）， decreased SOD （P<0.01）， hepatocyte swelling， and disordered arrangement. The mRNA and protein levels of ferredoxin 1 （FDX1）， dihydrolipoamide S-acetyltransferase （DLAT）， heat shock protein 70 （HSP70）， dihydrolipoamide dehydrogenase （DLD）， pyruvate dehydrogenase E1 subunit-β （PDHB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and peroxisome proliferator-activated receptor γ （PPARγ） were significantly elevated （P<0.05， P<0.01）. Compared with 15MCON group， the 15MHFD and 20MCON groups exhibited further increases in TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， and aggravated hepatocyte swelling and disorder. There were increased lipid droplets with mild vacuolization in the 15MHFD group， and no significant lipid deposition was observed in the 20MCON group. FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and protein levels were significantly increased （P<0.05， P<0.01）. Compared with 20MCON group， the model group demonstrated markedly elevated TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， severe hepatic steatosis， and upregulated expression of FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and proteins （P<0.05， P<0.01）. All abnormalities were significantly reversed after Liangyi Paste treatment. ConclusionLiangyi paste can ameliorate hepatic lipid deposition in naturally aged mice with a high-fat diet by modulating the cuproptosis/oxidative stress pathway.

Objective:To investigate the association between the triglyceride-glucose(TyG)index and the incidence and mortality of cardiovascular disease(CVD)in a large population-based cohort.Methods:Participants aged 40-79 years without a history of CVD at baseline were drawn from the CHi-nese Electronic health Records Research in Yinzhou(CHERRY)study between January 1,2010,and May 31,2020.The TyG index was calculated using baseline triglyceride and fasting blood glucose.Cox proportional hazards models were used to assess the association between the TyG index and the composite outcome of CVD(incidence and mortality),adjusting for age,gender,education,region,smoking sta-tus,body mass index,systolic blood pressure,and total cholesterol.Hazard ratios(HR)and 95％confi-dence intervals(CI)were calculated.Nonlinear associations between the TyG index and CVD were fur-ther evaluated using restricted cubic splines,and subgroup analyses by gender and age were conducted to explore potential differences.Results:A total of 226 406 individuals were included,with a mean age of(55.0±9.7)years at baseline,46.8％of whom were men,and a median TyG index of 8.68.Over a median follow-up of 7.99 years,9 815(4.34％)participants experienced CVD incidence or mortality.After adjusting for age,gender,education,region,smoking status,body mass index,systolic blood pressure and total cholesterol,the risk of CVD increased with higher TyG index levels(P＜0.001).The risk in the highest TyG quartile(TyG＞9.10)was 42％higher than in the lowest quartile(TyG ≤8.32)(HR=1.42,95％CI:1.34-1.51).Individuals under 60 years had a higher HR for CVD compared with those aged 60 years and above(HR:1.71 vs.1.27,P＜0.05).Restricted cubic spline analysis revealed a reverse L-shaped association between the TyG index and CVD risk in the overall population(P＜0.001 for nonlinear trend),with risk increasing after the TyG index exceeded 8.67.However,the threshold varied by gender,with a lower threshold in women(8.51)than in men(8.67).Conclusion:A significant nonlinear relationship was revealed between the TyG index and CVD risk,with a threshold effect.The risk of CVD increased once the TyG index surpassed a certain threshold,with a lower threshold in women than in men.These findings suggest that cardiovascular risk prediction and interven-tions based on the TyG index should be gender-stratified,and early intervention for individuals under 60 years old might have important public health implications.

Objective:To investigate the role of ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) in renal tubular epithelial-mesenchymal transition (EMT) in diabetic nephropathy (DN).Methods:Renal tissue specimens from 24 DN patients (DN group) confirmed by medical history, clinical laboratory tests, and pathological diagnosis at the Third Hospital of Hebei Medical University and 15 adjacent normal renal tissues (control group) from 2018 to 2023 were collected. Immunohistochemical staining was performed to detect the expression of EBP50, E-cadherin, and Vimentin proteins. Additionally, 10 healthy volunteers were enrolled as a normal group, and fasting blood glucose, serum creatinine, blood urea nitrogen, and 24 h urinary protein levels were compared between DN patients and the normal group.Results:Fasting blood glucose, serum creatinine, blood urea nitrogen, and 24 h urinary protein levels were significantly higher in the DN group than in the normal group (all P<0.01). Periodic acid-schiff (PAS) staining revealed significant thickening of the glomerular basement membrane, increased extracellular matrix, vacuolar degeneration of renal tubules, and elevated extracellular matrix in the renal interstitium in the DN group. Immunohistochemistry showed higher expression of EBP50 and E-cadherin proteins in the control group than in the DN group (all P<0.01), while Vimentin expression was lower in the control group ( P<0.01). Conclusions:EBP50 is involved in the EMT process of renal tubules in DN and is associated with tubular injury.

Immune checkpoint inhibitor-related pneumonitis(CIP)is a relatively common immune-related adverse event.The current treatment for CIP mainly relies on glucocorticoids,with 70％～80％of patients being controlled by conventional glucocorticoid therapy.However,steroid-unresponsive CIP is often se-vere and can be life-threatening.There is no standard treatment protocol for steroid-unresponsive CIP,highlighting a significant unmet clinical need.This paper reviews the diagnosis,treatment progress,and exploratory research of steroid-unresponsive CIP to provide evidence-based guidelines and directions for clinical and translational research.

Objective:To investigate the role of ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) in renal tubular epithelial-mesenchymal transition (EMT) in diabetic nephropathy (DN).Methods:Renal tissue specimens from 24 DN patients (DN group) confirmed by medical history, clinical laboratory tests, and pathological diagnosis at the Third Hospital of Hebei Medical University and 15 adjacent normal renal tissues (control group) from 2018 to 2023 were collected. Immunohistochemical staining was performed to detect the expression of EBP50, E-cadherin, and Vimentin proteins. Additionally, 10 healthy volunteers were enrolled as a normal group, and fasting blood glucose, serum creatinine, blood urea nitrogen, and 24 h urinary protein levels were compared between DN patients and the normal group.Results:Fasting blood glucose, serum creatinine, blood urea nitrogen, and 24 h urinary protein levels were significantly higher in the DN group than in the normal group (all P<0.01). Periodic acid-schiff (PAS) staining revealed significant thickening of the glomerular basement membrane, increased extracellular matrix, vacuolar degeneration of renal tubules, and elevated extracellular matrix in the renal interstitium in the DN group. Immunohistochemistry showed higher expression of EBP50 and E-cadherin proteins in the control group than in the DN group (all P<0.01), while Vimentin expression was lower in the control group ( P<0.01). Conclusions:EBP50 is involved in the EMT process of renal tubules in DN and is associated with tubular injury.

Objective:To analyze the reasons for the low results obtained by the determination of isosorbide dini-trate tablets content using the methods in the Chinese Pharmacopoeia and to improve the content determination method.Methods:The content of isosorbide dinitrate in 10 tablets was determined by high-performance liquid chromatography(HPLC)using a Phenomenex Luna C18 column(4.6 mm ×250 mm,5 μm)for separation,with a mobile phase of methanol-water(54∶46),a flow rate of 1.0 mL·min-1,and a UV detector set at a wavelength of 230 nm.The average content of 10 tablets was taken as the result of the content determination.Results:Isosor-bide dinitrate showed good linearity in the range of 49.22 to 1 230.5 μg·mL-1(r=0.999 96);the relative stand-ard deviation was 0.11％,the recovery rate was 96.0％,and the RSD was 1.5％(n=9).Conclusion:This method simplifies the experimental operations and steps,can eliminate the interference factors introduced by the original method,and improves the accuracy of the detection results.

Immune checkpoint inhibitor-related pneumonitis(CIP)is a relatively common immune-related adverse event.The current treatment for CIP mainly relies on glucocorticoids,with 70％～80％of patients being controlled by conventional glucocorticoid therapy.However,steroid-unresponsive CIP is often se-vere and can be life-threatening.There is no standard treatment protocol for steroid-unresponsive CIP,highlighting a significant unmet clinical need.This paper reviews the diagnosis,treatment progress,and exploratory research of steroid-unresponsive CIP to provide evidence-based guidelines and directions for clinical and translational research.

Objectives:To summarize the disease characteristics of thoracolumbar adhesive spinal arach-noiditis.Methods:The clinical data of 35 patients with thoracoland lumbar adhesive spinal arachnoiditis treated in our hospital from May 2012 to July 2023 were retrospectively analyzed,including 26 males and 9 females,aged 34 to 80 years(56.0±10.4 years).There were 17 cases secondary to thoracolumbar fracture,12 cases of lumbar disc herniation or combined with lumbar spinal stenosis,3 cases of thoracic spinal stenosis,and 3 cases of intradural tumor.14 cases were primarily characterized by persistent burning pain in the trunk or lower limbs,or accompanied by limb spasms.Another 17 cases mainly presented with numbness and weakness.Additionally,13 cases experienced urinary dysfunction,and 4 cases lost the ability to walk.Com-puted tomography myelography(CTM)and MRI were used to determine the location and imaging features of thoracolumbar adhesive spinal arachnoiditis.The treatment plans of patients were recorded,and the visual analogue scale(VAS)for lumbar and leg pain and Oswestry disability index(ODI)were observed before treat-ment,at 3 months after treatment and final follow-up.The McCormick grading was used to assess the recov-ery of patients who underwent surgery at the final follow-up.Results:The lesions were located in the tho-racic spinal cord in 11 cases,the conus medullaris in 7 cases,the cauda equina in 14 cases,and long seg-ments from the thoracic spinal cord to conus medullaris or cauda equina in 3 cases.11 patients received conservative treatment,and the VAS score was 7(7,8)and ODI was 54％(32％,64％).Only 3 patients showed mild alleviation of pain symptoms after conservative treatment,with a final follow-up VAS score of 7(6,8)and an ODI of 50％(32％,64％).24 patients underwent surgical treatment,and 9 of whom showed no significant improvement in symptoms at the final follow-up,with preoperative and final follow-up VAS scores of 8(8,9)and ODI of 72％(60％,85％),and McCormick grade Ⅲ;5 patients had a significant long-term im-provement in symptoms after operation,who could walk independently or with the aid of assistive devices and recovered to some extent in bowel and bladder functions,with preoperative VAS score of 7(6,8)and ODI of 58％(33％,68％)improving to 4(3,4)and 32％(19％,35％)respectively at final follow-up,and McCormick grade Ⅰ;3 patients recovered to grade Ⅰ postoperatively,and worsened to grade Ⅱ between 2 and 6 months;6 patients recovered to grade Ⅰ to Ⅱ postoperatively,with symptoms worsening to preoperative level(grade Ⅲ)between 2 weeks and 2 years;1 patient was implanted with electrical spinal cord stimulation de-vice,who was recovered in symptoms(grade Ⅱ).Conclusions:Conservative treatment for thoracolumbar adhesive spinal arachnoiditis is relatively limited in efficacy.While surgical treatment can achieve significant clinical improvement in some patients,its effects vary significantly among individuals.Some patients show no significant improvement in symptoms after surgery,and there are even cases where symptoms recur or worsen over time.

Objective:To analyze the reasons for the low results obtained by the determination of isosorbide dini-trate tablets content using the methods in the Chinese Pharmacopoeia and to improve the content determination method.Methods:The content of isosorbide dinitrate in 10 tablets was determined by high-performance liquid chromatography(HPLC)using a Phenomenex Luna C18 column(4.6 mm ×250 mm,5 μm)for separation,with a mobile phase of methanol-water(54∶46),a flow rate of 1.0 mL·min-1,and a UV detector set at a wavelength of 230 nm.The average content of 10 tablets was taken as the result of the content determination.Results:Isosor-bide dinitrate showed good linearity in the range of 49.22 to 1 230.5 μg·mL-1(r=0.999 96);the relative stand-ard deviation was 0.11％,the recovery rate was 96.0％,and the RSD was 1.5％(n=9).Conclusion:This method simplifies the experimental operations and steps,can eliminate the interference factors introduced by the original method,and improves the accuracy of the detection results.