Aim: To establish a method for the determination of pantoprazole sodium and its related substances. Methods: A column packed with octadecylsiance bonded silica gel (250 mm × 4. 6 mm, 5 pjn) was used. The 0. 01 mol/L monopotassium phosphate solution( adjusted with phosphoric acid to pH 7. 0) -acetonitrile were adopted as the mobile phase, a gradient elution was programmed as follows: 0→30 min(90:10-60:40), 30→45 min(60: 40→15: 85); the detection wavelength was 289 nm; the column temperature was 40 ℃; the flow rate was 1. 0 mL/min. Results: Pantoprazole sodium, the intermediates and its related substances could be well separated. A good linear relationship was obtained over the range of 6. 96-48. 72 μg/mL( r =0. 999 9). The limit detection and quantisation of pantoprazole sodium were 8.51 ng and 17.0 ng, respectively. Conclusion: This method can be applied to control the related substances of pantoprazole sodium and determine pantoprazole sodi-um.

OBJECTIVE To investigate the protective effect of total saponins from stems and leaves of Panax ginseng (GSLS) on cisplatin (CDDP)-induced kidney damage in mice and its possible mechanism. METHODS Thirty-two male ICR mice were randomly divided into normal control group, CDDP group, and GSLS(150 and 300)+CDDP groups. GSLS was administered to mice by oral gavage once a day for 7 d. On the 7th day, a single injection of CDDP 20 mg·kg-1 was given 1 h after GSLS 150 and 300 mg·kg-1 before GSLS 150 and 300 mg·kg-1 continued to be given for 3 d. Blood urea nitrogen (BUN) and creatinine (CRE) , catalase (CAT) in renal tissue, reduced glutathione (GSH), tumor necrosis factorα(TNF-α) and interleukin 1β(IL-1β) of cisplatin induced mice were detected after 72 h. HE and PAS staining were used to observe the renal histopathological changes;While TUNEL and Hoechst33258 staining were employed to observe apoptosis in kidney tissues. RESULTS Compared with normal control group, CDDP group had a significant reduction in relative body mass (P<0.05), and the level of GSH and CAT in kidney tissues (P<0.05). The level of CRE, BUN, TNF-α, and IL-1βin serum and renal indexes significantly increased (P<0.05, P<0.01), especially BUN and CRE that respectively doubled and quadrupled. CDDP group developed glomerulus swelling, renal tubular expansion and epithelial cell necrosis. Trans?parent tube type of tube cavity appeared, the nucleus pycnosis disappeared, but renal interstitial edema and inflammatory cell infiltration appeared. There was a large amount of glycogen deposition and high expressions of TUNEL positive cells and Hoechst33258 positive cells. Compared with CDDP group, the levels of BUN and CRE in GSLS treatment group significantly decreased (P<0.05, P<0.01) in serum, glycogen deposition was reducted and apoptosis of renal tubular epithelial cells decreased in kidney tissues (P<0.05). The level of TNF-α, IL-1β(P<0.05) and the degree of renal tissue necrosis were significantly reduced (P<0.05) in CDDP+GSLS 300 group, but there was a significant increase in the level of CAT and GSH (P<0.05). CONCLUSION GSLS can protect against mouse kidney injury induced by cisplatin. The mechanism may be related to oxidation, reduced inflammation reaction and resistance to apoptosis.

Objective To investigate differences in Rab protein expressions in McCoy cells with acute versus persistent Chlamydia trachomatis (Ct) infection.Methods Cultured McCoy cells were infected with different amounts (400,500,550 μl/well) of Ct strain D suspensions,then cultured with the medium containing 100 U/ml penicillin G (persistent Ct infection groups) or that without penicillin G (acute Ct infection groups).Ct-uninfected McCoy cells receiving no penicillin G treatment served as the blank control group,and those receiving penicillin G treatment as the penicillin group.Mter 48-hour culture,McCoy cells were lysed,proteins were collected,and total RNA was extracted from the cells.Enzyme-linked immunosorbent assay (ELISA) was conducted to measure protein levels of Rab4A,Rab6A,Rab10,Rab11A and Rab14,and fluorescence-based quantitative PCR to quantify mRNA expressions of Rab4A and Rab14 (expressed as 2-ΔΔα).Results Protein levels of Rab4A,Rab6A,Rab10,Rab11A and Rab14 were all significantly lower in the acute than in the persistent Ct infection groups (all Z =3.621,P ＜ 0.001),and lower in the persistent and acute Ct infection groups than in the blank control group (all P ＜ 0.008 3),but insignificantly different between the blank control group and penicillin group (all P ＞ 0.05).In addition,the expressions of Rab4A and Rab14 mRNAs were consistent with those of their proteins in these groups.Conclusion The transcriptional and expression levels of Rab proteins are higher in McCoy cells persistently infected with Ct than in those acutely infected with Ct.

Objective To investigate clinical and pathological features of pseudoepitheliomatous keratotic and micaceous balanitis (PKMB).Methods The clinical and pathological features as well as treatment of PKMB were retrospectively analyzed in 5 male patients collected from Janumy 2008 to December 2013.Results The age at onset of PKMB varied from 56 to 67 years in these 5 patients,and none of the patients had received prepucectomy.Indurated keratotic plaques were observed in the glans of penis and inner lamina of the prepuce with no tenderness on palpation,whose surfaces were covered with grayish yellow,adherent and hard micaceous crusts.Histopathological study revealed obvious hyperkeratosis complicated by parakeratosis,epidermal pseudoepitheliomatous hyperplasia,thickened spinous layer,and normal cell polarity in the epidermis,as well as telangiectasis and mild to moderate lymphocytic infiltration in the upper dermis.Immunohistochemical examination showed positive nuclear staining of epidermal cells for human papillomavirus (HPV) in 2 cases.Two patients took small doses of prednisone,but achieved no obvious improvement.Oral isotretinoin had resulted in a favorable outcome in another two cases,but relapse occurred after dose reduction,and thick crusts still appeared after topical application of glucocorticoid cream and tacrolimus cream,or carbon dioxide laser treatment and photodynamic therapy.Conclusions PKMB is a chronic and obstinate disease,and should be diagnosed based on pathological findings.Its treatment is difficult,and tretinoin has some effects,but relapse often occurs after drug withdrawal and maintenance treatment is needed.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among reproductive-age women, characterized by obesity, insulin resistance, chronic low-grade inflammation, and hyperandrogenemia. Studies have revealed that women with PCOS may experience an increased risk of various adverse pregnancy outcomes, such as gestational diabetes, hypertensive disorders of pregnancy, miscarriages, and preterm births. Preterm birth is an important cause of adverse outcome among perinatal infants. However, due to the complexity of its pathogenesis, the current intervention treatment of preterm birth often yields unsatisfactory results. Recent studies have discovered that women with PCOS have a higher risk of preterm birth than those without, suggesting that PCOS is a risk factor for preterm birth. This article reviews the research progress of PCOS-related preterm birth to offer new insights into the prevention and treatment of preterm birth in women caused by PCOS.

Objective To compare the efficacy and safety of Iamivudine-interferon sequential therapy and lamivudine monotherapy in HBeAg-positive chronic hepatitis B (CHB) patients.MethodsA total of 172 patients with HBeAg-positive CHB were randomized to sequential group (n=83) or lamivudine group (n=89).Sequential group were administrated with lamivudine 100 mg/d and 5 million units interferon alpha 2b subcutaneous injection every other day for 24 weeks were added since week 25 of treatment.Lamivudine group were administrated with lamivudine 100 mg/d for 48 weeks.All subjects were followed up for 24 weeks after drug withdrawal.Measurement data with homogeneity of variance were analyzed by using t test and data with heterogeneity of variance were analyzed by using rank sum test.The comparison of rates was done by chi square test or Fisher exact test.ResultsThe baseline hepatitis B virus (HBV) DNA levels of patients in sequential group and lamivudine group were (7.8±1.0) and (7.9±1.1) lg copy/mL,respectively (P＞0.05),and the baseline alanine aminotransferase (ALT) levels were (210.5 ± 150.1 ) and (211.9 ± 160.9) U/L,respectively (P＞0.05).At the end of treatment,higher ALT levels [(78.4±146.1) vs (36.1±32.4) U/L,P＜0.05)] and HBV DNA levels [(4.5±1.5) vs (3.8±1.3) lg copy/mL,P＜0.05)] levels,lower response rates (65.8％ vs 83.5％,P＜0.05),and similar HBeAg loss rates (31.6％ vs 22.2％,P＞0.05) and HBeAg seroconversion rates (27.6％ vs 16.0％,P＞0.05) were found in sequential group compared with lamivudine group.At the end of follow-up,higher ALT levels [(126.0±143.1) vs (82.7±83.0) U/L,P＜0.05)],similar HBV DNA levels [(5.3±1.5) vs (5.0±1.5) lg copy/mL,P＞0.05)],similar HBeAg loss rates (25.0％ vs 32.3％,P＞0.05) and HBeAg seroconversion rates (25.0 ％ vs 26.2 ％,P＞0.05) were found in sequential group compared with lamivudine group.YMDD motif mutation rate in sequential group was lower than lamivudine group at week 48 of treatment (10.5％ vs 26.9％,P＜0.05).ConclusionsLamivudine-interferon sequential therapy and lamivudine monotherapy are both effective in HBeAg-positive CHB patients,while HBV mutations are reduced in patients with sequential therapy.

Objective:The aim of this study was to determine the colonization rate of carbapenem-resistant Enterobacterales (CRE) and identify the proportion and risk factors for bloodstream infection.Methods:This was a retrospective study conducted at the Department of Clinical Laboratory, Peking University People′s Hospital from January 2018 to December 2021. A total of 4 993 patients underwent rectal swab CRE screening for CRE, of which 137 were found to be positive. Clinical and laboratory data of the positive patients were collected, and the following parameters were analyzed: the positive rate of CRE screening in high-risk population, the species of colonized bacteria, antimicrobial resistance and the risk factors of CRE bloodstream infection in colonized patients. Statistical analysis was performed using SPSS 26.0 software. Univariate analysis was conducted using the chi-square (χ 2) test, while multivariate analysis was performed using binary logistic regression. The results were expressed as relative risk (odds ratio, OR) and 95% confidence interval ( CI). A significance level of 0.05 was considered statistically significant. The drug resistance rate of pathogen was analyzed by WHONET 5.6 software. Results:During the study period, a total of 4 991 patients who underwent rectal swab screening were eligible for inclusion, of which 137 patients were screened positive, resulting in a positive rate of 2.7% (137/4 991). The positive rates were higher in the intensive care ward and hematology ward, with rates of 5.5% (27/493) and 3.3% (109/3 321), respectively. A total of 145 colonization strains were isolated from patients with positive CRE screening, including 63 strains of Klebsiella pneumoniae (43.4%, 63/145), 52 strains of Escherichia coli (35.9%, 52/145), 16 strains of Enterobacter cloacae (11.0%, 16/145) and 14 strains of other Enterobacterales (9.7%, 14/145). The metal β-lactamase production type was the main component of CRE positive colonizing bacteria. The antimicrobial resistance of 145 strains to 22 antibacterial agents revealed that amikacin and tigacycline were the most sensitive. Among 137 CRE screening-positive patients, 14 (10.2%, 14/137) developed bloodstream infection. The isolated pathogenic bacteria included 10 Klebsiella pneumoniae strains and 4 Escherichia coli strains, with a predominant serine carbapenemase producing. Notably, the enzyme type and antimicrobial resistance of the bloodstream infection isolates in the same patient were highly consistent with those of the previous screening strains. Comparison was made between patients with positive CRE screening and those with CRE conversion to bloodstream infection. The unifactor analysis revealed significant differences in surgical history, neutropenia, hematopoietic stem cell transplantation, history of antibiotic use before rectal swab screening, screening within 48 hours after admission, and serine carbapenemase production by strains ( P<0.05). The multivariate analysis indicated that surgical history ( OR 24.659, 95% CI 2.540-239.411, P=0.006) and neutropenia ( OR 93.796, 95% CI 6.294-1 397.804, P=0.001) remained significantly associated with the risk of CRE bloodstream infection ( P<0.05). Conclusions:The CRE colonization rate was low in our hospital, but the proportion of patients with positive screening converted to bloodstream infection was high. Surgical history and neutropenia are risk factors for bloodstream infection transmission. Thus, it is essential to enhance monitoring in high-risk areas and susceptible patients.

OBJECTIVE：To provide reference for constructing a patent linking system in line with international standards and balancing the interest conflict between original drug enterprises and generic drug enterprises. METHODS ：The relevant supporting systems of patent link in the United States were introduced ；combined with the development status and relevant systems of drug patent protection at home and abroad ，the existing problems of China ’s drug patent management system were analyzed to put forward suggestions for improvement. RESULTS & CONCLUSIONS ：The United States patent linking system included Orange book system ，generic drug patent declaration system ，generic drug approval waiting period and market monopoly period system of the first generic drug. The innovation and accessibility in the field of pharmaceutical products were facing the dilemma of “commons tragedy ”and“anti commons tragedy ”. There were many problems in China ’s drug patent protection ，such as insufficient R&D and innovation ability inhibited the development of the pharmaceutical industry ，imperfect laws and regulations were not conducive to the settlement of medical professional disputes. It is suggested to establish a digital information database of patented drugs ，standardize the existing generic drug patent declaration system ，promote the coordination between patent litigation cycle and approval waiting period ，increase the independent innovation ability of the pharmaceutical industry ，promote the coordination between pharmaceutical innovation and drug accessibility ，and jointly promote the improvement of intellectual property legislation and the development of medical and health undertakings.

Objective To explore the structure changes of white matter in the first-episode schizo-phrenic patients with never-medicated(FESZ)and the relationship between facial emotion perception and white matter(WM)integrity.Methods Sixty-three schizophrenic patients and thirty health control subjects underwent diffusion tensor imaging(DTI)scans.Voxel-based analysis was used to compared fractional ani-sotropy(FA)map between the two groups.Correlations were analyzed with pearson relative analysis between impaired facial emotion perception tested by facial emotion categorization(FEC)and severity of symptoms measured by the Positive and Negative Syndrome Scale(PANSS).Results (1)Compared with controls, FESZ patients showed overall decreased FA in WM of the body of left ventral frontal lobe((MNI(x,y,z):-18,26,-4;t=4.43)),right supramarginal gyrus((MNI(x,y,z):32,-50,26;t=4.27)),left middle oc-cipital gyral((MNI(x,y,z):-26,-60,0;t=4.89)),right middle occipital gyral((MNI(x,y,z):28,-70, 14;t=4.18)),left fusiform gyrus((MNI(x,y,z):-40,-50,0;t=3.92)),left cerebellum anterior lobe ((MNI(x,y,z):-32,-56,-28;t=4.57)),right parahippocampa gyrus1((MNI(x,y,z):32,-10,-14;t=4.16)),right parahippocampa gyrus2((MNI(x,y,z):16,-6,-14;t=4.56)),left anterior cingulate ((MNI(x,y,z):-2,4,-6;t=4.41)),left extra-nuclear((MNI(x,y,z):-2,-10,-6;t=4.44)),right thalamus((MNI(x,y,z):10,-10,2;t=4.20)),left thalamus((MNI(x,y,z):-22,-28,12;t=4.01)), and right caudate((MNI(x,y,z):14,12,8;t=4.87)).(2)Compared with controls,the patients with schizo-phrenia showed a higher shift point and a steeper slope than control subjects in FEC.Correlational analysis re-vealed that the negative correlations were found between the slope and negative factor(r=-0.298,P=0.036),between positive factor and the FA value in WM of the right middle occipital gyral(r=-0.322,P=0.023)and the left middle occipital gyral(r=-0.288,P=0.043),and between the FA value in the left cere-bellum anterior lobe and shift point(r=-0.393,P=0.005),but the positive correlation was found between disorganized/concrete factor and the FA value in the right parahippocampal gyrus(r=0.429,P=0.002).Con-clusions There are extensive microstructural abnormalities in WM of patients with FESZ.Disrupted WM in-tegrity in these regions may constitute a potential neural pathological basis for the facial emotion perception impairments in schizophrenia.

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.