Research advances in immunotherapy for hepatocellular carcinoma / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) has an insidious onset, and most patients are in the advanced stage when attending the hospital and thus lose the opportunity for radical surgical resection, which results in the poor prognosis of patients. With the development of clinical treatment, the treatment of advanced HCC has gradually transitioned from the relatively single and limited treatment options in the past to the new model of comprehensive treatment. In recent years, immunotherapy, represented by immune checkpoint inhibitors (ICIs), has become widely used in clinical practice. At present, a number of clinical studies have been conducted for immunotherapy combined with local and targeted antitumor therapy, and in particular, ICIs combined with targeted therapy have become a research hotspot in the field of HCC treatment. This article reviews the research advances in immunotherapy for the treatment of HCC.

Clinical evaluation of direct drug sensitivity test for blood culture positive broths / 中华检验医学杂志

Objective:To evaluate the clinical performance of direct antimicrobial susceptibility test in blood culture-positive broth, and to provide a basis for optimizing the antibiotic use strategy in clinical bloodstream infection.Methods:A retrospective analysis was conducted on 780 blood culture-positive samples collected in Peking University People′s Hospital from May 2017 to December 2021. The direct antimicrobial susceptibility test was performed by disk diffusion method on blood culture-positive broth. The antimicrobial susceptibility breakpoints were in accordance with Clinical and Laboratory Standards Institute (CLSI) M100 S32 edition document.Results:In this study, a total of 331 strains of Gram-negative bacteria (139 strains of Escherichia coli, 79 strains of Klebsiella pneumoniae, 35 strains of Pseudomonas aeruginosa, 21 strains of Acinetobacter baumannii) and 396 strains of Gram-positive cocci (25 strains of Staphylococcus aureus, 316 strains of coagulase-negative staphylococci, 47 strains of Enterococcussp.) were collected, after excluding 53 cases with two or more isolates. Compared with the routine antimicrobial susceptibility test (AST), the rates of category agreement (CA), major error (ME), and very major error (VME) of Gram-negative bacteria were 86.0% (1368/1 591), 8.7% (139/1 591), and 0.5% (8/1 591), respectively. On the other hand, the CA%, ME%, and VME% of Gram-positive cocci were 89.2% (960/1 076), 7.5% (81/1 076), and 1% (11/1 076), respectively. Regarding the individual antimicrobial agents, the CA% of Escherichia coli was 16/17 for imipenem, 90.1% (109/121) for meropenem, and 70.8% (85/120) for cefepime. For Klebsiella pneumoniae, the CA% of was 10/13 for imipenem, 80.9% (55/68) for meropenem, and 80.3% (53/66) for cefepime. The CA% of meropenem in Pseudomonas aeruginosa and Acinetobacter baumannii were 96.0% (24/25) and 16/16. The CA% of linezolid and cefoxitin in Staphylococcus aureus were 100% (25/25) and 100% (24/24), respectively. The CA% of linezolid, cefoxitin and gentamicin in coagulase-negative staphylococci were 98.9% (269/272), 94.5% (277/293) and 71.6% (194/271) respectively. Finally, for Enterococcus sp., the CA% of vancomycin and ampicillin were 91.5% (43/47) and 94.7% (36/38), respectively. Conclusion:Compared with the conventional AST, the blood culture-positive broth direct AST exhibited high category agreement and low error rates for both Gram-negative bacteria and Gram-positive cocci, which can serve a rapid alternative for AST in cases of clinical bloodstream infection.

Interpretation of performance verification of clinical microbial culture, identification and antimicrobial susceptibility testing systems / 中华检验医学杂志

The professional standard for the health industry of People′s Republic of China,"WS/T 807-2022 Performance verification of clinical microbial culture, identification and antimicrobial susceptibility testing systems", was issued on November 2, 2022 and implemented on May 1, 2023. This professional standard (voluntary standard) is the basis for the formulation and implementation of the microbiological testing performance verification scheme, providing guidines for quality control procedures in the laboratories. The purpose of this document is to standardize and homogenize the performance verification protocols in the field of clinical microbiological testing. This article explains and analyzes the background, preparation, main contents, implementation difficulties and significance of the standard, so as to help clinical microbiological laboratory personnel fully understand and implement the relevant provisions of the standard, promoting industry standardization and discipline development.

Continuous positive airway pressure treatment on blood pressure rhythm in hypertension patients with obstructive sleep apnea / 中华老年医学杂志

Objective:To investigate the effect of continuous positive airway pressure(CPAP)on blood pressure and blood pressure rhythm in hypertensive patients with sleep apnea syndrome.Methods:Hypertensive patients with obstructive sleep apnea syndrome consecutively recruited between 2020 and 2022 were randomly divided into two groups, the CPAP group and the control group.Both groups were routinely treated with antihypertensive drugs, and patients in the CPAP group were additionally treated with CPAP for more than 4 hours at night.24-hour ambulatory blood pressure monitoring was conducted following 12 weeks of treatment, and the blood pressure rhythm was analyzed according to blood pressure results.Results:A total of 104 patients(40-73 years old)were enrolled in the study, with 51 patients(mean age: 57.3±9.1)in the CPAP group(58.8% male)and 53 patients(mean age: 58.3±8.1)in the control group(54.7% male). The results of 24-hour ambulatory blood pressure monitoring showed that, compared with the control group, the CPAP group achieved more effective blood pressure reduction in mean systolic blood pressure(SBP)[(134.6±8.4)mmHg vs.(138.2±5.9)mmHg, t=-2.54, P=0.013], mean DBP[(72.4±9.3)mmHg vs.(77.0±9.0), t=-2.56, P=0.012], mean nighttime SBP[(117.2±5.1)mmHg vs.(122.0±6.2)mmHg, t=-4.283, P<0.01]and mean nighttime DBP[(63.7±6.4)mmHg vs.(66.9±5.1)mmHg, t=-2.812, P<0.01). There was a significant increase in blood pressure dippers in the CPAP group(37.25% vs.18.87%, χ2=4.370, P=0.037). Conclusions:CPAP can significantly reduce 24-hour mean blood pressure and nocturnal blood pressure, and improve blood pressure rhythm in hypertensive patients with sleep apnea syndrome.

Rabdosia serra alleviates dextran sulfate sodium salt-induced colitis in mice through anti-inflammation,regulating Th17/Treg balance,maintaining intestinal barrier integrity,and modulating gut microbiota / 药物分析学报

Rabdosia serra(R.serra),an important component of Chinese herbal tea,has traditionally been used to treat hepatitis,jaundice,cholecystitis,and colitis.However,the chemical composition of R.serra and its effect against colitis remain unclear.In this study,the chemical composition of the water extract of R.serra was analyzed using ultra performance liquid chromatography coupled with a hybrid linear ion trap quadrupole-orbitrap mass spectrometer(UPLC-LTQ-Orbitrap-MS).A total of 46 compounds,comprising ent-kaurane diterpenoids,flavonoids,phenolic acids,and steroids,were identified in the water extract of R.serra,and the extract could significantly alleviate dextran sulfate sodium salt-induced colitis by improving colon length,upregulating anti-inflammatory factors,downregulating proinflammatory fac-tors,and restoring the balance of T helper 17/T regulatory cells.R.serra also preserved intestinal barrier function by increasing the level of tight junction proteins(zonula occludens 1 and occludin)in mouse colonic tissue.In addition,R.serra modulated the gut microbiota composition by increasing bacterial richness and diversity,increasing the abundance of beneficial bacteria(Muribaculaceae,Bacteroides,Lactobacillus,and Prevotellaceae_UCG-O01),and decreasing the abundance of pathogenic bacteria(Turi-cibacter,Eubacterium_fissicatena_group,and Eubacterium_xylanophilum_group).Gut microbiota depletion by antibiotics further confirmed that R.serra alleviated colitis in a microbiota-dependent manner.Overall,our findings provide chemical and biological evidence for the potential application of R.serra in the management of colitis.

Effect evaluation of optimizing blood culture testing process / 中华检验医学杂志

Objective:To evaluate whether the time to positive (TTP), handling time after positive alarm and turnaround time (TAT) of bacteremia blood culture can be shortened by optimizing blood culture workflow.Methods:This study was conducted retrospectively. Positive blood culture samples collected from Peking University People′s Hospital from January 1, 2014 to June 30, 2021 were analyzed in stages. In the traditional process stage of this study (2014), 502 bottles of positive blood culture samples were included in the analysis. In the first stage of process optimization (2016), the working time of staff was increased to 22:00, and 976 positive blood culture specimens were included in the analysis. In the second stage of process optimization (2018), the rapid identification process of MALDI-TOF MS was added, and a total of 1 029 bottles of positive blood culture samples were included. In the third stage of process optimization (2020) with the introduction of the new VIRTUO BACT/ALERT system. The difference of TTP, handling time after positive alarm and TAT of whole process in different stages of traditional process and process optimization were compared. All data were statistically significant when P<0.05 using rank-sum test. Results:In the traditional process stage (2014), the median quartile time of handling time after positive alarm was 55.70 (47.35, 68.45) h. In the first stage of process optimization (2016), the median quartile time of handling time after positive alarm was 47.25 (33.88, 59.96) h, and the handling time after positive alarm in the first stage of process optimization was significantly shorter than that in the traditional process stage ( Z=?10.734, P<0.001). In the second stage of process optimization (2018), the median quartile time for handling time after positive alarm was 47.18(36.41, 59.40) h, and 12.18% of the preliminary identification results of Gram-negative bacilli before 17:00 could be reported to the clinic before audit. In the third stage of process optimization (2020), the median quartile of TTP and TAT were 39.56 (21.52, 62.65) h and 78.16(64.68, 99.72) h respectively in the original BACT/ALERT 3D system. The new VIRTUO BACT/ALERT system had a median quartile of 37.03(21.08, 58.22) h for TTP and 73.41(62.88, 89.48) h for TAT. VIRTUO BACT/ALERT 3D had a significantly shorter TTP than BACT/ALERT 3D ( Z=?2.273, P=0.023), the TAT of VIRTUO BACT/ALERT system was significantly shorter than that of BACT/ALERT 3D system ( Z=?4.040, P<0.001). Conclusion:By improving the blood culture process of microbiology laboratory in many aspects and measures, the processing time of blood culture in each stage can be shortened and clinical benefits can be obtained.

Interleukin-1β mediates the effect of macrophage androgen receptor on hyperphosphate-induced vascular smooth muscle cell calcification / 中华肾脏病杂志

Objective:To investigate whether it is by regulating interleukin 1β ( IL-1β) gene expression that androgen receptor (AR) in macrophages affects hyperphosphate-induced vascular smooth muscle cell calcification. Methods:The chromatin immunoprecipitation (ChIP) experiment was used to determine whether AR was bound to the androgen receptor element (ARE) sequence of IL-1β promoter in THP-1 cells. Whether the AR regulated IL-1β gene expression was detected by luciferase assay experiments. AR of THP-1 cells was silenced and transfected by lentivirus with vector or shRNA. Flow cytometry was used to select positive transfected cells THP-1ARsc (control) and THP-1ARsi (AR silencing) with fluorescent markers. Western blotting was used to detect AR protein levels of THP-1ARsc (control) and THP-1ARsi cells (AR silencing in monocytes). Macrophages MФARsc (control) or MФARsi (AR silencing) were induced by 50 ng/ml phorbol ester. Enzyme-linked immunosorbent assay was used to detect IL-1β expression levels of MФARsc or MФARsi conditioned medium. The human aortic smooth muscle cells (HASMC) were cultured in MФARsc or MФARsi conditioned medium with phosphate (2.5 mmol/L final concentration of sodium dihydrogen phosphate), and Alizarin red S staining was used to analyze HASMC calcification degree. Western blotting was used to detect the expression levels of RUNX2 (osteoblast marker) and SM22α (HASMC marker), and neutralization assay was performed to test IL-1β-mediating effect of macrophages AR on HASMC calcification. Results:AR was bound to ARE sequence of IL-1β promoter and regulated IL-1β gene expression. The expression level of IL-1β protein in conditioned medium of MФARsi cells decreased significantly compared to MФARsc cells ( P<0.001). Compared with MФARsc conditioned medium group, HASMC calcium deposition in MФARsi conditioned medium group decreased significantly, RUNX2 protein decreased and SM22α protein increased (all P<0.05). The degree of HASMC calcification in the MФARsi conditioned medium+IgG antibody group decreased than that in the MФARsc conditioned medium+IgG antibody group significantly, and the degree of HASMC calcification in the MФARsc conditioned medium+IL-1β antibody group decreased significantly than that in the MФARsc conditioned medium+IgG antibody group; while the degree of HASMC calcification in the MФARsi conditioned medium+IgG antibody group and MФARsi conditioned medium+IL-1β antibody group decreased than that in the MФARsc conditioned medium+IL-1β antibody group (all P<0.05). Conclusions:Macrophage AR regulates IL-1β expression by binding to ARE sequence within IL-1β promoter, and IL-1β mediates the effect of macrophage AR on hyperphosphate-induced HASMC calcification.

Cefiderocol: a novel siderophore cephalosporin against multi-drug resistant Gram-negative bacilli infections / 生物工程学报

Antimicrobial resistance is one of the critical public health issues in the world. There is an urgent need to develop effective broad-spectrum antibiotics to treat the infection of multi-drug resistant Gram-negative bacilli. Cefiderocol, developed by the Shionogi Inc. in Japan, is a new type of iron carrier cephalosporin antibiotics, which overcomes the drug resistance of Gram-negative bacilli due to the down-regulation of outer membrane pore protein and the up-regulation of efflux pump, and has good stability to serine- and metallo-carbapenemases. This drug has a broad spectrum and strong antibacterial activity against carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. Cefiderocol can be used to treat complex urinary tract infections (including pyelonephritis), hospital-acquired pneumonia, and ventilator-associated pneumonia. By summarizing the chemical structure, antibacterial mechanism, in vitro antibacterial activity, pharmacokinetics, pharmacodynamics, and clinical treatment of cefiderocol, this review shows the application potential of cefiderocol as a new iron carrier cephalosporin in the treatment of multi-drug resistant Gram-negative bacilli infections.

Transcranial magnetic stimulation at low frequency can promote the recovery of neurological functioning after a stroke / 中华物理医学与康复杂志

Objective:To explore any effect of repeated transcranial magnetic stimulation (rTMS) on the recovery of neurological functioning and the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and inflammatory factors after ischemic stroke.Methods:Sixty-four C57BL/6J mice were randomly divided into a normal control group, a model group, a sham stimulation group and an observation group, each of 16. All mice except those of the normal control group received middle cerebral artery occlusion using the suture method to model an ischemic stroke. After the modeling the observation group was given 1Hz rTMS daily for 7 consecutive days, while the sham stimulation group was given sham rTMS. After the intervention, Zea-Longa scores were used for all of the groups, and the size of the cerebral infarct was measured using triphenyltetrazolium chloride staining. The expression of NLRP3 around the cerebral infarction was detected using immunofluorescence, while that in the brain tissue was measured using Western blotting. The expression of interleukin-1β and IL-18 in the brain tissue was detected using enzyme-linked immunosorbent assays.Results:Compared with the normal control group, a significant increase was observed in the other groups′ average neurological function impairment scores. Expression of NLRP3, IL-1β and IL-18 in the model and sham stimulation groups also increased, with large cerebral infarcts in the cortex and hippocampus. Compared with the sham stimulation and model groups, there was a significant decrease in the average neurological dysfunction scores, the area of cerebral infarction in the cortex and hippocampus, as well as the expression of NLRP3, IL-1β and IL-18 in the observation group.Conclusions:Low-frequency rTMS can promote the recovery of damaged nerve function after an ischemic stroke, at least in mice. It can reduce the size of cerebral infarction, and inhibit neuronal pyroptosis, which is closely related to the down-regulation of NLRP3, IL-1β and IL-18 expression.

Diagnostic value of serum miRNA-9-5p, miRNA-21-5p and miRNA-3923 in cervical cancer / 肿瘤研究与临床

Objective:To investigate the diagnostic value of serum miRNA-9-5p (miR-9-5p), miRNA-21-5p (miR-21-5p) and miRNA-3923 (miR-3923) in patients with cervical cancer.Methods:The data of 100 cervical cancer patients in Shanxi Provincial Cancer Hospital from July 2016 to June 2018 (the experimental group) and 100 healthy subjects (the healthy control group) during the same period were collected. The real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) combined with probe hybridization was used to detect the expression levels of human papillomavirus (HPV) E6/E7 mRNA in paraffin-embedded tissues of patients with cervical cancer and in cervical exfoliated cells of the healthy control people. Ct value ≤ 40 cycles was considered as HPV E6/E7 positive. Serum samples from 3 patients with cervical cancer and 3 healthy people were taken out; microRNA (miRNA) Array was used to detect the expression level of 384 miRNA; the differential expression of miRNA was screened out and cluster analysis was performed, and then the screened miRNAs was verified by using qRT-PCR. Finally, the receiver operation characteristics (ROC) curves of screened miRNAs alone and HPV E6/E7 alone or the combination of three miRNAs and HPV E6/E7 in the diagnosis of cervical cancer were drawn to make comparison of diagnostic efficacy.Results:Among the paraffin-embedded tissues from 100 patients with cervical cancer, there were 65 cases (65%) HPV E6/E7 positive; in the healthy control group, HPV E6/E7 in cervical exfoliated cells of 100 people was negative. A total of 248 differentially expressed miRNAs were detected from the serum samples in 3 patients with cervical cancer and 3 healthy people. The cluster analysis finally identified 16 abnormally regulated miRNAs. qRT-PCR verification confirmed that differences in the expression levels of miR-9-5p, miR-21-5p and miR-3923 in the healthy control group and cervical cancer group were statistically significant (all P < 0.01), and then the three were selected to make diagnosis of cervical cancer. The expression levels of miR-9-5p, miR-21-5p and miR-3923 in HPV E6/E7 positive cervical cancer group were higher than those in the healthy control group (all P < 0.05), expression levels of miR-21-5p and miR-3923 in HPV E6/E7 negative cervical cancer group were increased ( P = 0.008, P = 0.038); expression levels of the three miRNAs in HPV E6/E7 positive group were higher than those in HPV E6/E7 negative group (all P < 0.05). ROC curve analysis showed that the area under the curve (AUC) of miR-3923 was the biggest (0.843), the specificity was the highest (82%, the cut-off value was 2.88) and the sensitivity of miR-21-5p was the highest (85%, the cut-off value was 4.08) when miR-9-5p, miR-21-5p and miR-3923 were respectively applied to diagnose the cervical cancer; AUC (0.924), the sensitivity and the specificity (85%, 94%; the cut-off value was 4.04) of the combination of the three indicators were higher than those of the single indicator in the diagnosis of cervical cancer. AUC was 0.766 when HPV E6/E7 was kused alone to diagnose. The diagnostic efficacy of HPV E6/E7 combined with miR-9-5p, miR-21-5p, miR-3923 respectively was further improved, the corresponding AUC was 0.914, 0.848, 0.932, respectively; the diagnostic efficacy of the combination of the four indicators was the highest (AUC was 0.942). Conclusion:miR-9-5p, miR-21-5p and miR-3923 may be helpful in the diagnosis of cervical cancer.

Difference of clinical characteristics in ocular toxocariasis between adults and children and characteristics of anti-toxocaria antibody in intraocular fluids / 中华眼底病杂志

Objective:To compare the clinical manifestations of ocular toxoplasmosis (OT) in adult and children, and to preliminarily explore the role of intraocular fluid detection in the early diagnosis of OT.Methods:A retrospective study. From January 2018 to October 2019, 60 cases of OT patients with 60 eyes diagnosed in the Department of Ophthalmology of Beijing Chaoyang Hospital Affiliated of Capital Medical University were included in the study. The medical history information of patients was collected in parallel with slit-lamp microscopy, indirect ophthalmoscope examination, and canine toxoplasma antibody detection in aqueous or vitreous fluid. Fifty-eight cases underwent visual inspection; 2 cases did not underwent visual inspection, who were children. The visual acuity examination was carried out using the new version of the standard logarithmic visual acuity chart, which was converted into the logarithmic minimum angle of resolution(logMAR) visual acuity during statistics. According to age, the patients were divided into adult group and child group, with 12 eyes in 12 cases and 48 eyes in 48 cases, respectively. The clinical characteristics and main points of diagnosis and treatment of the two groups of patients were compared and observed. The comparison among the measurement data groups conforming and the normal distribution was performed by the independent t test. The comparison between the measurement data groups of the skewed distribution was performed by the Kruskal- Wallis test. The qualitative data were compared with χ 2 test. Results:Among the adult group and the child group, 7 (58.3%, 7/12) and 34 (70.8%, 34/48) patients with a clear history of contact with dogs and cats were in the adult group and the child group, respectively. The adult group was significantly lower than the child group, however, there was no different statistical significance ( χ 2=0.236, P=0.627). At the first visit, the self-reported blurred vision of the adult group and the child group was 10 (83.3%, 10/12) and 22 (45.8%, 22/48) cases, respectively. In the adult group and the child group, 3 (25.0%, 3/12) and 20 (43.5%, 20/46) eyes with logMAR visual acuity greater than 1.85, 8 (66.7%, 8/12) and 22 (45.8%, 22/46) eyes with logMAR visual acuity less than 0.3. The visual acuity of the adult group was better than that of the child group, and the difference was statistically significant ( Z=2.162, P=0.031). There was no statistically significant difference in the composition ratio of different clinical types of the two groups of eyes ( χ 2=1.908, P=0.385). The incidence of inflammation in the anterior segment of the eye in the adult group and the child group were 25.0% (3/12) and 56.3% (27/48), respectively; there was no statistically significant difference between the two groups ( χ 2=3.750, P=0.053). The concentration of antibodies in the vitreous humor of the affected eye in the adult group and the child group was greater than that of aqueous humor. The antibody concentrations of vitreous humor and aqueous humor were 36.51 (22.58) and 19.94 (21.78) U/ml in the children group; 45.95 (56.44) and 32.20 (38.64) U/ml in the adult group. Comparison of antibody concentrations in the vitreous humor and aqueous humor of the affected eyes in the child group showed statistically significant differences ( Z=-1.984, P=0.047). Conclusions:Compared with children with OT, adult patients with OT have better vision and mild inflammation or hyperplasia of the vitreous cavity. The detection of antibodies related to toxoplasma in the intraocular fluid is helpful for early diagnosis.

Pharmacokinetic interactions between the potential COVID-19 treatment drugs lopinavir/ritonavir and arbidol in rats / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has occasioned worldwide alarm. Globally, the number of reported confirmed cases has exceeded 84.3 million as of this writing (January 2, 2021). Since there are no targeted therapies for COVID-19, the current focus is the repurposing of drugs approved for other uses. In some clinical trials, antiviral drugs such as remdesivir (Grein et al., 2020), lopinavir/ritonavir (LPV/r) (Cao et al., 2020), chloroquine (Gao et al., 2020), hydroxychloroquine (Gautret et al., 2020), arbidol (Wang et al., 2020), and favipiravir (Cai et al., 2020b) have shown efficacy in COVID-19 patients. LPV/r combined with arbidol, which is the basic regimen in some regional hospitals in China including Zhejiiang Province, has shown antiviral effects in COVID-19 patients (Guo et al., 2020; Xu et al., 2020). A retrospective cohort study also reported that this combination therapy showed better efficacy than LPV/r alone for the treatment of COVID-19 patients (Deng et al., 2020).

Analysis of risk factors for vasovagal syncope in children / 中国学校卫生

Objective@#To analyze the related factors of the onset of vasovagal syncope (VVS) in children, and to provide basis for the early prevention, early diagnosis and early treatment of VVS.@*Methods@#A total of 126 children with syncope admitted to Department of Pediatric Cardiology, Second Hospital of Lanzhou University from October 2018 to September 2019 were invited in the study. Totally 73 cases of children diagnosed with VVS by HUTT were selected as VVS group, and 53 HUTT negative children were selected as control group. Related factors were retrospectively investigated, and risk factors for VVS were analyzed by univariate and multivariate regression.@*Results@#The VVS group showed statistically significant difference in age distribution with the control group ( χ 2=19.22, P <0.05). The VVS group showed statistically significant differences of proportion in family history, syncope history, prolonged standing, electrocardiogram abnormalities, and vitamin D deficiency (43.84%，31.51%，47.95%，34.25%， 30.14 %) compared with the control group (15.09%，13.21%，20.75%，15.09%，9.43%) ( χ 2=11.71,5.67,9.79,5.83,7.82, P < 0.05 ). Multivariate Logistic regression analysis showed that age and family historywere risk factors for VVS( χ 2=3.13, 11.06, P < 0.05 ).@*Conclusion@#Age and family history may be risk factors for the onset of VVS. Active attention should be paid to the high risk factors of child patient, early identification and diagnosis can prevent the occurrence and development of VVS in children.

Clinical Observation of Roxadustat in the Treatment of Chronic Kidney Disease Combined with Renal Anemia / 中国药房

OBJECTIVE：To observe the efficacy and safet y of roxadustat in the treatment of chronic kidney disease （CKD） combined with renal anemia. METHODS ：The data of 80 inpatients with CKD combined with renal anemia treated in the nephrology department of the First Affiliated Hospital of Anhui University of Science and Technology during Nov. 2019 to Dec. 2020 were analyzed retrospectively. They were divided into observation group （40 case）and control group （40 case）according to different treatment methods. Control group was given Human erythropoieti n for injection subcutaneously ，100-150 IU/kg every week，3 times a week. Observation group were given Roxadu- stat capsules orally ，100 mg each time for dialysis patients with a bodyweight of 45-＜60 kg，70 mg each time for non- 717060193@qq.com dialysis patients ，3 times a week ；120 mg each time for dialysis patients with bodyweight ≥60 kg and 100 mg each time for non-dialysis patients ，3 times a week. After 4 weeks of treatment ，the dosage of the two groups w as adjusted according to the level of hemoglobin （Hb）. Treatment course of 2 groups were 12 weeks. The levels of anemia indexes （Hb，red blood cell count （RBC），hematocrit（Hct）），iron metabolism indexes （serum iron （Fe），ferritin（Fer），total iron-binding capacity （TIBC），tranfeerrin saturation （TSAT）），lipid metabolism indexes （total cholesterol （TC），triglycerides（TG），high-density lipoprotein （HDL），low-density lipoprotein （LDL））and inflammation index（C-reactive protein （CRP））were detected in 2 groups before treatment and after 12 weeks of treatment. The levels of Hb were observed in high-level CRP subgroup and low-level CRP subgroup ；the occurrence of ADR was recorded in 2 groups during treatment. RESULTS ：Before treatment ，there was no statistical significance in the anemia indexes ，iron metabolism indexes ，lipid metabolism indexes or inflammation index between 2 groups（P＞0.05）. After treatment ，the levels of Hb ，RBC and Hct in 2 groups and the levels of TIBC and HDL in observation group were significantly higher than before treatment. The levels of Fe ，Fer and TSAT in 2 groups and the levels of TC and LDL in observation group were significantly lower than before treatment ；the levels of Hb ，RBC，Hct，TIBC and HDL in observation group were significantly higher than before control group ，while the level of TC was significantly lower than control group （P＜0.05）. The incidence of high reactivity in observation group was significantly higher than control group ，while the incidence of low reactivity was significantly lower than control group （P＜0.05）. There was no statistical significance in the levels of CRP between 2 groups before and after treatment （P＞0.05）. Subgroup comparison results showed that there was no statistical significance in the level of Hb between high-level CRP subgroup and low-level CRP subgroup of 2 groups before treatment （P＞0.05）. After treatment ，the level of Hb in high-level CRP subgroup of observation group was significantly higher than that of high-level CRP subgroup of control group （P＜0.05）. The total incidence of ADR in observation group was significantly lower than control group （P＜0.05），and no severe ADR was observed in 2 groups. CONCLUSIONS ： Roxadustat can effectively improve anemia in CKD patients with renal anemia ，and curative effect is less affected by inflammatory state，and it has good short-term safety.

Research progress of relationship between peritoneal microenvironment and peritoneal metastasis of gastric cancer / 中华消化外科杂志

Peritoneal metastasis is one of the most frequent metastatic patterns of advanced gastric cancer, but the mechanism underlying remains unclear. The 'seed and soil’ theory is now well recognized for peritoneal metastasis of gastric cancer at present. The combination of various cells, extracellular matrix, and ascites components within the abdominal cavity provide a suitable microenvironment for the plantation, infiltra-tion, growth and metastasis of gastric cancer cells. Fully under-standing of peritoneal microenvironment will help to diagnose the peritoneal metastasis of gastric cancer and tumor recurrence, and provide theoretical basis for the development of drugs targeting peritoneal microenvironment. The authors review the main cell formation, ascites and immune microenvironment involved in the formation of the peritoneal microenvironment based on relevant literatures at home and abroad, and investigate the relationship between peritoneal microenvironment and peritoneal metastasis of gastric cancer.

Clinical Analysis of 19 Patients With Pancreatic Tuberculosis / 胃肠病学

Background: Pancreatic tuberculosis is relatively rare in clinical practice, its clinical symptoms and imaging findings are lack of specificity, and is easily confused with pancreatic benign and malignant tumors. Aims: To summarize the clinical characteristics of pancreatic tuberculosis. Methods: Data of 19 patients with pancreatic tuberculosis from April 2010 to June 2019 at Xijing Hospital of Digestive Diseases, Air Force Medical University were retrospectively analyzed. Results: Among the 19 patients with pancreatic tuberculosis, 11 were male and 8 were female, median age was 33 years old. Clinical manifestations were mainly abdominal pain or upper abdominal discomfort, fever, night sweat, etc. Laboratory tests showed anemia in 11 patients, increased erythrocyte sedimentation rate in 13 patients, increased amylase in 7 patients, positive T-spot in 9 patients, positive PPD skin test in 3 patients and elevated bilirubin in 5 patients. Imaging examination showed that pancreatic tuberculosis was mainly located in pancreatic head. Ultrasound of the abdomen showed pancreatic mass, changes of internal echo in 8 patients, and pancreatic cystic or solid mass in 11 patients. CT showed significant enlargement of pancreatic head in 5 patients, solid pancreatic occupying lesion in 7 patients, cystic pancreatic occupying lesion in 4 patients, and enlargement of peripancreatic, mesenteric or retroperitoneal lymph nodes in 6 patients. Fourteen endoscopic ultrasound-guided fine-needle aspiration biopsy were performed in 8 patients; 5 patients underwent ultrasound-guided percutaneous biopsy of the occupying lesion. All the patients were given regular anti-tuberculosis treatment, and no relapse was found during the follow-up. Conclusions: For young patients with pancreatic space-occupying lesion, the possibility of pancreatic tuberculosis should be considered. Biopsy is still the current method of diagnosis, and regular anti-tuberculosis treatment is the main treatment for pancreatic tuberculosis.

Effects of caspase-11 non-canonical inflammasome on Leptospira interrogans-induced secretion of inflammatory cytokines in J774A.1 cells / 中华微生物学和免疫学杂志

Objective:To investigate the effects of caspase-11 non-canonical inflammasome on the Leptospira interrogans ( L. interrogans)-induced secretion of inflammatory cytokines in J774A.1 cells. Methods:Murine mononuclear macrophage cells (J774A.1) were infected with L. interrogans strain 56601. Expression of caspase-11, IL-1β, IL-1α and IL-18 at mRNA level in J774A.1 cells were detected by real-time RT-PCR. The levels of caspase-11, IL-1β, IL-1α and IL-18 in the culture supernatants of J774A.1 cells were detected by ELISA. Results:Real-time RT-PCR showed that caspase-11 expression at mRNA level was 5.12, 14.21, 8.94, 14.06, 18.58 and 0.93 times of that in uninfected cells after 1, 2, 4, 8, 12 and 24 h of L. interrogans infection, and respectively decreased to 0.10, 0.07, 0.10, 0.09, 0.07 and 0.45 times after caspase-11 inhibitor intervention ( P<0.05). Expression of IL-1β, IL-1α and IL-18 at mRNA level was significantly increased after infection ( P<0.05). After the intervention with caspase-11 inhibitor, IL-1β mRNA decreased to 0.05, 0.03, 0.02, 0.05, 0.06 and 0.02 times ( P<0.05); IL-1α mRNA decreased to 0.14, 0.07, 0.15, 0.10, 0.03 and 0.06 times ( P<0.05); IL-18 mRNA decreased to 0.08, 0.10, 0.16, 0.18, 0.10 and 0.07 times ( P<0.05). ELISA results showed that the expression of caspase-11, IL-1β, IL-1α and IL-18 at protein level was significantly increased. After the intervention with caspase-11 inhibitor, caspase-11 level decreased to 43.07, 41.64, 51.96, 86.56, 105.36, and 129.95 pg/ml ( P<0.05); IL-1β level decreased to 15.01, 14.19, 68.02, 31.20, 173.13 and 104.98 pg/ml ( P<0.05); IL-1α level decreased to 12.14, 15.40, 38.01, 21.97, 24.48 and 27.09 pg/ml ( P<0.05); IL-18 level decreased to 96.27, 102.21, 85.34, 116.28, 155.36 and 114.03 pg/ml ( P<0.05). Conclusions:Caspase-11 non-canonical inflammasome was involved in the mediation of IL-1β, IL-1α and IL-18 secretion in mouse mononuclear macrophages after L. interrogans infection.

Analysis of sarcopenia and influencing factors in hospitalized elderly patients / 中华老年医学杂志

Objective:To analyze features of sarcopenia and its influencing factors in hospitalized patients at our department.Methods:This was a cross-sectional study.A total of 180 patients aged 80.3±6.7 years admitted to the geriatrics department of our hospital were consecutively recruited.Patients were divided into the non-sarcopenia group(n=80, 44.4%)and the sarcopenia group(n=100, 55.6%)based on the diagnostic criteria for sarcopenia of the Asian Sarcopenia Working Group.All subjects were evaluated by using the comprehensive geriatric assessment.Differences in comorbidity, physical function, nutrition, cognitive function, psychological characteristics, geriatric syndromes, medication and other aspects were analyzed between the two groups.The correlation of the above factors with sarcopenia was analyzed.Results:Scores on the Charlson comorbidity index and the cumulative illness rating scale were higher in the sarcopenia group than in the non-sarcopenia group(2.6±1.7 vs.2.1±1.1, 11.3±4.1 vs.7.9±1.8, P<0.05). Scores on mini-nutrition assessment and mini-cog, grip, chair-rising test(five times), timed get-up and go test(3 m), walking speed, and short physical performance battery were lower in the sarcopenia group than in the non-sarcopenia group[(12.8±2.1) vs.(11.2±1.7), (2.3±1.0) vs.(4.4±0.9), (21.2±5.8)kg vs.(27.6±6.2)kg, (31.4±15.3)s vs.(13.2±4.0)s, (24.2±9.5)s vs.(12.0±2.9)s, (0.6±0.2)m/s vs.(0.9±0.3)m/s, (6.1±1.9) vs.(9.8±1.3), respectively, P<0.05]. The incidences of geriatric syndromes such as incontinence, visual impairment, hearing impairment, sleeping disorders, oral problems, chronic pain, anxiety, depression and falls were higher in sarcopenia patients than in non-sarcopenia patients.Logistic regression analysis showed that body mass index, walking speed and the number of geriatric syndromes were risk factors for sarcopenia( OR=1.401, 1.286 and 3.654, P<0.05). Conclusions:The incidence of sarcopenia is high in hospitalized elderly patients.Comprehensive geriatric assessment can be used to achieve a more complete understanding of the characteristics and influencing factors for patients with sarcopenia and will help provide a basis for appropriate treatment plans.

Pharmaceutical care for severe and critically ill patients with COVID-19 / 浙江大学学报·医学版

Severe and critically ill patients with coronavirus disease 2019 (COVID-19) were usually with underlying diseases, which led to the problems of complicated drug use, potential drug-drug interactions and medication errors in special patients. Based on ( 6), and -19: , we summarized the experience in the use of antiviral drugs, corticosteroids, vascular active drugs, antibacterial, probiotics, nutrition support schemes in severe and critically ill COVID-19 patients. It is also suggested to focus on medication management for evaluation of drug efficacy and duration of treatment, prevention and treatment of adverse drug reactions, identification of potential drug-drug interactions, individualized medication monitoring based on biosafety protection, and medication administration for special patients.

Relationship between changes in cellular immune function and rehospitalization rate in elderly patients / 中华老年医学杂志

Objective To observe the differences in T-lymphocyte subsets between patients with sepsis,non-sepsis and healthy controls with different ages,and to investigate the effect of cellular immune function on readmission rate.Methods The 337 patients with sepsis,350 patients with non-sepsis and 141 healthy controls were enrolled in this prospective study from general department and intensive care unit(ICU)of emergency department in Beijing Chaoyang Hospital during May 2017 to April 2018.The effects of ages on T lymphocyte subsets and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ)and the effects of T lymphocyte subsets and APACHE Ⅱ on 30-day rehospitalization rate were comparatively studied.Results In patients with non-sepsis,the values of CD3+T,CD4+T,CD8+ T,natural killer(NK)cell count were lower in elderly group than in the non-elderlygroup(956.0±85.8)×10-6/L vs.(1363.3±46.7)×10 6/L,(647.3±59.9)×10-6/L vs.(875.8±33.4) × 10-6/L,(288.9± 31.1)× 10-6/L vs.(451.2±21.2)× 10-6/L and (14.5±0.64)％vs.(15.4±0.6)％,respectively,P＜0.01.In patients with sepsis group,the values of CD3+ T,CD4+T,NK cells count were decreased and APACHE Ⅱ were increased in the elderly group as compared with the non-elderly group.The 30-day readmission rate was higher in elderly patients than in the non-elderly patients(74 cases vs.39 cases,P ＜0.01).Compared with the non-elderly patients,the elderly patients had decreased values of CD3+ T,CD4+ T,CD8+ T,NK cells,CD4+/CD8+ cell count and an increased APACHE Ⅱ (P ＜0.05).Conclusions The cellular immune function is decreased in elderly patients,which is more obvious in elderly patients with sepsis.Age,CD3+ T,CD4+ T,CD8+T and APACHE Ⅱ could be used as an independent predictor for 30 day readmission rate.