Objective To analyze the predictive value of serum levels of procalcitonin(PCT)and cytokines on the prognosis of patients with COVID-19 at admission.Methods From November 2022 to February 2023,patients diagnosed with COVID-19 who were admitted to Beijing Chest Hospital were enrolled.Chemiluminescence was used to detect serum PCT levels,and flow microsphere array was used to detect serum cytokines IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17A,IL-17F,IL-22,TNF-α,TNF-β,IFN-γ level.ICU admission,mechanical ventilation and in-hospital death were defined as poor prognosis.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.Results A total of 176 patients with complete data were included,including 134 in the PCT-normal group and 42 in the PCT-elevated group,with a median age of 71.50 years and 71.59%males.Patients in the PCT elevated-group had significantly higher rates of ICU admission(38.41%vs.13.11%,P<0.05),mechanical ventilation(76.92%vs.24.59%,P<0.001)and in-hospital mortality(38.46%vs.6.56%,P<0.001)were significantly higher than those in the PCT-normal group.Serum levels of cytokines IL-6(7.40 pg/mL vs.4.78 pg/mL,P = 0.033 4)and IL-8(10.97 pg/mL vs.5.92 pg/mL,P<0.001)were significantly higher in patients with poor prognosis than in those with good prognosis.The area under the curve for PCT,IL-6,and IL-8 to predict poor prognosis in COVID-19 patients was 0.687,0.660,and 0.746,respectively;sensitivity was 52.78%,55.17%,and 72.41%,respectively;and specificity was 81.58%,74.19%,and 74.19%,respectively,as calculated from the ROC curve.When PCT,IL-6 and IL-8 jointly predict the prognosis of COVID-19 patients,the area under the curve is 0.764,the sensitivity is 70.00%,and the specificity is 80.00%.Conclusion Serum PCT and cytokines IL-6 and IL-8 could be used as predictive markers for poor prognosis in patients with COVID-19.

Insomnia is the second most common psychiatric disorder in clinical practice, and more than one-third of adults may experience different forms of insomnia during their lifetime, but the root causes behind insomnia need further clarification. Early evidences from twins and family studies had shown that insomnia can be attributed to genetics. In recent years, with the rapid development of gene sequencing technology, Nature Genetics had published several consecutive articles focusing on insomnia and genes, confirming that genetic factors played an important role in the occurrence and development of insomnia. Therefore, the recent research progresses on insomnia and circadian rhythm, cytokines, neurotransmitters, and other related genes were summarized in this review, which could help to understand the pathogenesis of insomnia and develop precise treatment strategies.

Non-invasive brain stimulation (NIBS) is one of the fastest-growing fields of medicine today. Recent studies have highlighted the potential of NIBS as an innovative, safe, and cost-effective treatment method applied to insomnia. Starting from treatment mechanism and clinical effect, we summarize the current research status of repetitive transcranial magnetic stimulation and transcranial electrical stimulation, the two most common NIBSs used in insomnia treatment, and analyze the existing research limitations and its future development direction, in order to provide references for further promoting the clinical application of NIBS in insomnia treatment.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

Sijunzi decoction (SJZD) is a Chinese classical formula to treat spleen qi deficiency syndrome (SQDS) and has been widely used for thousands of years. However, the quality control (QC) standards of SJZD are insufficient. Chinmedomics has been designed to discover and verify bioactive compounds of a variety of formula rapidly. In this study, we used Chinmedomics to evaluate the SJZD's efficacy against SQDS to discover the potential quality-markers (q-markers) for QC. A total of 56 compounds in SJZD were characterized in vitro, and 23 compounds were discovered in vivo. A total of 58 biomarkers were related to SQDS, and SJZD can adjust a large proportion of marker metabolites to normal level and then regulate the metabolic profile to the health status. A total of 10 constituents were absorbed as effective ingredients that were associated with overall efficacy. We preliminarily determined malonyl-ginsenoside Rb2 and ginsenoside Ro as the q-markers of ginseng; dehydrotumulosic acid and dihydroxy lanostene-triene-21-acid as the q-markers of poria; glycyrrhizic acid, isoglabrolide, and glycyrrhetnic acid as the q-markers of licorice; and 2-atractylenolide as the q-marker of macrocephala. According to the discovery of the SJZD q-markers, we can establish the quality standard that is related to efficacy.

Objective To analyze the dose dependent cardiotoxicity of cyclophosphamide and thus establish the mouse models for understanding the underlying mechanisms . Methods Thirty mice ( 7 -8 weeks old) were randomly divided into 6 groups:control of one course group ,control of two courses group , one course of low dose ( 50 mg/kg) group ,two courses of low dose group ,one course of high dose ( 100 mg/kg) group ,two courses of high dose group . The changes of cardiac function and morphology were analyzed at indicated times by ultrasound and histology respectively . Results Compared with the control groups , injection of low dose cyclophosphamide either with one course or two courses ,and injection of high dose with only one course had no in statically significant changes in hair color ,physical activity ,body weight and cardiac function( P > 0 .05) . Treatment of two courses with high dose resulted in significant decrease of physical activity and body weight ( P < 0 .05 ) . Meanwhile ,cardiac systolic function was significantly decreased( P <0 .05) . Histology study revealed robust cardiac hypertrophy and fibrosis . Conclusions Two courses of intraperitoneal injection of cyclophosphamide at high dose result in obvious cardiotoxicity , especially systolic dysfunction .Intraperitoneal injection of two courses of cyclophosphamide serves as a good strategy to induce cardiotoxicity in mice ,which could be applied for future mechanism study .

Objective To investigate the effect of penehyclidine hydrochloride ( PHC) pretreat?ment on nuclear factor erythroid 2?related factor 2∕heme oxygenase?1 ( Nrf2∕HO?1) signaling pathway in re?nal tissues of rats with rhabdomyolysis?induced acute kidney injury ( AKI) . Methods Thirty?six pathogen?free male Sprague?Dawley rats, weighing 200-220 g, were assigned into 3 groups ( n=12 each) using a random number table: control group (group C), group AKI and PHC pretreatment group (group PHC). Rhabdomyolysis was induced by intramuscular injection of 50% glycerol 10 ml∕kg in bilateral hindlimbs. PHC 0?2 mg∕kg was injected intraperitoneally at 30 min before glycerol was injected intramuscularly in group PHC. At 1 and 6 h after glycerol injection, serum was collected for determination of blood urea nitro?gen ( BUN) and creatinine ( Cr) concentrations, and bilateral kidneys were harvested for pathological ex?amination and for determination of HO?1 activity and expression of Nrf2 mRNA and HO?1 mRNA ( by quan?titative real?time polymerase chain reaction) , Nrf2 in nucleoprotein and total protein and HO?1 in total pro?tein in renal tissues ( by Western blot) . The damage to the renal tubules was scored. Results Compared with group C, the BUN and Cr concentrations in serum and renal tubular damage scores were significantly increased, the expression of Nrf2 in nucleoprotein and total protein and HO?1 in total protein was signifi?cantly up?regulated, and HO?1 activity was significantly increased in AKI and PHC groups, the expression of HO?1 mRNA was significantly up?regulated in group AKI, and the expression of Nrf2 mRNA and HO?1 mRNA was significantly up?regulated in group PHC (P<0?01 or 0?05). Compared with group AKI, the BUN and Cr concentrations in serum and renal tubular damage scores were significantly decreased, the ex?pression of Nrf2 in nucleoprotein and total protein and HO?1 in total protein was significantly up?regulated, and HO?1 activity was significantly increased in group PHC ( P<0?01 or 0?05) . Conclusion The mecha?nism by which PHC pretreatment attenuates rhabdomyolysis?induced AKI may be related to activation of Nrf2∕HO?1 signaling pathway in renal tissues of rats.

Objective To investigate the clinical value of clinical application in diagnosis of prostate cancer (PCa) by prostate biopsy guided by rectal ultrasound contrast guided biopsy.Methods One hundred and ninety-eight patients with prostate in Punan Hospital of Pudong New District of Shanghai were investigated.According to different detection methods, the research objects were divided into two groups, the patients were performed with the ultrasound contrast guided biopsy as the imaging group (n =96), the patients with Doppler ultrasound guided biopsy as the ultrasonic group(n =102).The puncture Results were compared with pathological diagnosis.The positive rate of PCa and number of puncture needle were compared with the two puncture methods.The value of the application of the prostate biopsy guided by rectal ultrasound in diagnosis of prostate cancer was evaluated.Result One hundred and ninety-eight patients were all received pathological diagnosis,78 cases benign lesions, 120 cases were diagnosed as PCa.Thirty-six cases of benign lesions were confirmed by pathological biopsy, 60 case PCa.There were 42 cases of benign lesions in ultrasonic group, 60 case PCa.The positive rate of PCa in the imaging groupwas 62.5％ (60/96), the ultrasonic group was 58.82％ (60/102).There was no difference in Pca positive rate between the ultrasound group and the contrast group(x2 =0.104, P=0.747).The positive number of Pca in the imaging group was 28.50％ (17/60), the difference was statistically significant higher than that of the common group(18.80％ (11/60), P =0.001).The average of the patients in the imaging group was 8.19 needle,less than the ultrasonic group per capita 11.31 needle less.When f/tPSA less than or equal to 0.15, Pca positive rate of the contrast group was 46.55％ (27/55), higher than the ultrasonic group(9.30％ (4/43)), the difference was statistically significant (P =0.001);when f/tPSA more than 0.15, the positive rate of Pca in the contrast group was 92.11％ (35/38), less than the ultrasound group (94.92 (56/59)), the difference was not statistically significant (P =0.89).Anal pain, hematuria and hematochezia in contrast group (7.29％ (7/96), 2.08％ (2/96), 10.42％ (10/96)) were significantly less than the ultrasound group(22.55％ (23/102), 8.82％ (9/102), 23.53％ (24/102)), the difference was statistically significant (P =0.003,0.039,0.014).Conclusion Under the guidance of ultrasound contrast, rectal biopsy has important diagnostic value for prostate cancer.Under the premise of reducing the number of puncture needle,can improvethe positive rate of Pca, reduce the pain of patients and the occurrence of complications after puncture.When f/tPSAless than or equal to 0.15,puncture positive rate in contrast group is higher than the ultrasonic group, puncture effect is better.

Objective To evaluate the effect of penehyclidine hydrochloride pretreatment on rhabdomyolysis-induced acute kidney injury (AKI) in rats.Methods Forty-two pathogen-free male SpragueDawley rats,weighing 200-220 g,aged 2 months,were randomly divided into 3 groups using a random number table:control group (group C,n =6),AKI group (n =18),and penehyclidine hydrochloride group (group PH,n =18).The model of rhabdomyolysis-induced AKI was established by injecting 50％ glycerol 10 ml/kg into the lateral muscle of bilateral hindlimbs in AKI and PH groups.The equal volume of normal saline was given in group C.Penehyclidine hydrochloride 0.2 mg/kg was injected intraperitoneally at 30 min before administration of glycerol in group PH.Six rats were selected at 1 h after administration of normal saline in group C,or at 1,6 and 24 h after administration of glycerol,blood samples were collected from the inferior vena cava for determination of the serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations by enzymic colorimetric method.The animals were sacrificed,and kidney specimens were obtained for pathologic examination and for determination of the expression of DJ-1 and phosphatase tensin homolog deleted on chromosome 10 (PTEN) encoding protein (by immuno-histochemistry and Western blot).The damage to the renal tubules was scored.Results Compared with group C,the serum BUN and Cr concentrations and renal tubular damage score were significantly increased,the expression of D J-1 was down-regulated,and the expression of PTEN protein was up-regulated in group AKI (P＜0.05 or 0.01).Compared with group AKI,the serum BUN and Cr concentrations and renal tubular damage score were significantly decreased,the expression of DJ-1 was up-regulated,and the expression of PTEN protein was down-regulated in group PH (P＜0.05 or 0.01).Conclusion Penehyclidine hydrochloride pretreatment can reduce rhabdomyolysis-induced AKI probably by up-regulating the expression of DJ-1 and down-regulating the expression of PTEN protein in rats.

Aim To develop a simple,rapid and ac-curate analysis method for determination of chiral ibu-profen in Beagle dog plasma.Method The plasma sample was submitted to liquid - liquid extraction u-sing hexane /isopropanol (95 ∶5,V/V),with ketopro-fen as the internal standard (IS).The separation was accomplished in a Lux 5u Cellulose-3 (250 mm·4.6 mm,5 μm)column,and the mobile phase consisted of methanol and a mixture of 1 mmol·L -1 ammonium acetate-methanol-formic acid (90 ∶1 0 ∶0.2,V/V/V) with the volume ratio of 82 ∶1 8 at a flow rate of 0.8 mL· min -1 .The mass spectrometer consisted of an ESI interface operating at negative ionization mode and the detection was performed using multiple reaction monitoring at the transitions of m /z 205.2 /1 61 .2 for ibuprofen and m /z 253.1 /209.2 for ketoprofen (IS). Method validation included the evaluation of the matrix effect, extraction recovery, linearity, lower LOQ, within-run and between-run precision,stability and di-lution effect.Results The calibration curve was line-ar across the concentration range of 0.2 ~50 mg·L -1 for each ibuprofen enantiomer with a lower LOQ of 0.2 mg·L -1 .The within-run and between-run precision (RSD%)was in the range 1 .01 % ~1 3.1 % for each ibuprofen.The pharmacokinetic parameters for orally single dose of (S +)and racemic ibuprofen in Beagle dogs were as follows: Cmax , T1 /2 , AUC(0-t) were (82.98 ±1 4.83 )mg·L -1 ,(3.21 7 ±0.7298)h, (362.0 ±58.67)h·mg·L -1 for (S +)ibuprofen and 70.62 /74.48 mg·L -1 ,1 .520 /5.432 h ,1 77.8 /649.6 h·mg·L -1 for (R -)/(S +)ibuprofen,re-spectively.Conclusions A simple,rapid,accurate, high sensitivity and repeatability method has been suc-cessfully developed,which can analyze the concentra-tions of (R -)/(S +)ibuprofen in Beagle dog plasma simultaneously.The method could be applied for the investigation of pharmacokinetics of ibuprofen enanti-omers in Beagle dogs.