AIM:To analyze the compliance rate and possible influencing factors for blood concen-tration of meropenem in patients with central ner-vous system(CNS)infections,and to provide basis for optimizing the administration of meropenem in the patients.METHODS:A retrospective analysis was performed in patients who were treated with meropenem and monitored the concentration(Cmin)from January 2021 to December 2022.The basic clinical data of the patients were recorded,and the achievement of meropenem blood concentration was counted.Univariate and binary logistic regres-sion analysis were used to analyze the influencing factors for the e substandard steady-state blood trough concentration of meropenem.The ROC curve was drawn to predict the clinical characteris-tics.RESULTS:Forty-five cases were included.The median Cmin of meropenem was 4.14(0.82,16.29)mg/L,and 51.11％reached the target range with 4 mg/L.Binary logistic regression analysis showed that serum creatinine value and using mannitol were risk factors for the substandard steady-state blood trough concentration of meropenem(P＜0.05).When serum creatinine value was less than 84 μmol/L,the area under the ROC curve was the largest(0.916),the sensitivity was 0.783,the speci-ficity was 0.955,and the Youden index was 0.738.CONCLUSION:The Cmin compliance rate of merope-nem blood concentration in patients with CNS in-fection is low,especially in patients with hyperfunc-tion of kidney and those who using mannitol.It is necessary to conduct drug concentration monitor-ing to optimize the administration of meropenem in patients with CNS infection.

Objective To establish a ultra performance liquid chromatography(UPLC)fingerprint of extract of Cuscutae Semen,and analyze the relationship between the UPLC fingerprint and antioxidant activity.Methods The fingerprint of 11 batches of extract of Cuscutae Semen were determined by UPLC method,the antioxidant activity of Cuscutae Semen in vitro was determined by 1,1-diphenyl-2-picrylhydrazine radical,2,2-diazo-bis(3-ethylbenzothiazole-6-sulfonic acid)diamine salt,and the correlation between the fingerprints and antioxidant activity was analyzed by orthogonal partial least squares(OPLS)and gray correlation method.The key substances that contributed greatly to the antioxidant activity were selected.Results The extract of Cuscutae Semen contains 21 common peaks,all of which exhibited a similarity of more than 0.97.By comparing with the reference sample,10 peaks were identified,of which peak 5 was neochlorogenic acid,peak 8 was chlorogenic acid,peak 9 was cryptochlorogenic acid,peak 10 was caffeic acid,peak 12 was coumaric acid,peak 15 was hyperin,peak 16 was isoquercitrin,peak 17 was astragaloside,peak 20 was quercetin,and peak 21 was kaempferol.According to the grey correlation degree and OPLS results,the peaks 8,15,16 and 18 were positively correlated with the antioxidant activity,and were thus considered to be main effective components.Conclusion The antioxidant activity of Cuscutae Semen is the result of the combined effect of multiple components.The fingerprint and antioxidant spectrum analysis can provide evidential reference for further research of Cuscutae Semen.

ObjectiveTo explore the practical value of environment-friendly sample release agent combined with ultrasound in the preparation of pathological tissue sections. MethodsFrom February 2013 to December 2022， 2 518 pathological specimens submitted by Foshan Municipal Hospital of Traditional Chinese Medicine were selected as the study objects. Two samples of the same specimen were randomly divided into two groups： the environment-friendly fast group， in which the pathological tissue sections were made by using the environment-friendly sample release agent combined with ultrasound； and the traditional group， in which formaldehyde， ethanol and xylene were used to make slices in the conventional way. The differences of hematoxylin （HE） staining effect， immunohistochemistry （IHC） staining effect and MDM2 gene detection result of atypical lipomatous tumor/highly differentiated liposarcoma （ALT/WDL） tissue sections between the two groups were compared. Results① The wax of the two groups' pathological tissues was dehydrated well and the tissue hardness was moderate. After HE staining， the sections of the two groups were intact， without cracks and tremor marks， and the contrast between nucleus and cytoplasm was appropriate， with good transparency， uniform staining， and no tissue loss. The excellent rate and score of HE staining in the environmental fast group were higher than those in the traditional group， but the difference was not statistically significant （χ² = 3.125，P₁ = 0.070；t = 0.965，P₂ = 0.334）. ②After IHC staining of the two groups of sections， the positive location of the cells was accurate， the staining was specific and uniform， the staining intensity was moderate， the staining sensitivity was good， and there was no tissue loss. The excellent rate of IHC staining and the positive rate of IHC staining in the environmental fast group were lower than those in the traditional group， but the difference was not statistically significant （χ₁² = 2.769，P₁ = 0.092；χ₂² = 0.800，P₂ = 0.375）. ③The background and outline of the two groups of WDL tissue sections were clear， the staining was uniform， the cells were clear and visible， the nuclear boundary was clear， the hybridization signal was clear and bright under the background fluorescence， and there was no miscellaneous signal. The two groups of sections were hybridized successfully， and MDM2 showed positive amplification. The number of cells successfully hybridized in the environment-friendly fast group was lower than that in the traditional group， but the difference was not statistically significant （t = 1.414，P = 0.230）. ConclusionsThe tissue treatment method of using environment-friendly sample release agent combined with ultrasound can ensure the detection effect of HE staining， IHC staining and MDM2 gene detection of pathological tissue sections， and is more efficient and environment-friendly， suitable for promotion and use in hospitals at all levels.

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.
Humans ; Male ; Female ; Adult ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Middle Aged ; Retrospective Studies ; Hematologic Neoplasms/therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Leukemia, Myeloid, Acute/therapy* ; Recurrence ; Graft vs Host Disease/etiology* ; Chronic Disease

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ²=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ²=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.
Humans ; Cytomegalovirus ; Retrospective Studies ; Cohort Studies ; Prospective Studies ; Cytomegalovirus Infections/prevention & control* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Graft vs Host Disease/prevention & control* ; Recurrence ; Antiviral Agents/therapeutic use*

ObjectiveTo observe the protective effect and mechanism of Tianhuang formula (THF) against renal injury in hyperuricemia nephropathy (HN) mice through network pharmacology. MethodAll mice were randomly divided into a normal group, a model group, a febuxostat group (5 mg·kg^-1), a low-dose THF group (L-THF, 60 mg·kg^-1), and a high-dose THF group (H-THF, 120 mg·kg^-1). The mice in the normal group were treated with 0.5% sodium carboxymethylcellulose (CMC-Na) by gavage daily. The HN model was induced by oral administration of 500 mg·kg^-1 hypoxanthine and intraperitoneal injection of 200 mg·kg^-1 oteracil potassium in mice except for those in the blank group. The mice in the groups with drug intervention were treated with corresponding drugs by gavage for three weeks. The levels of serum uric acid, creatinine, urea nitrogen, and 24-h albuminuria were measured. The renal injury was observed by hematoxylin-eosin (HE) staining and PAS staining, and renal fibrosis was observed by Sirius red staining. The effects and molecular mechanism of THF in HN mice were analyzed by Western blot, network pharmacology, and molecular docking. ResultBiochemical results indicated that compared with model group, BUN and 24 h urinary protein levels were significantly decreased in L-THF group (P<0.05), SUA and SCr levels were significantly decreased (P<0.01), and SUA, BUN, SCr and 24 h urinary protein levels in H-THF group were significantly decreased (P<0.01). The results of pathological staining showed that the kidney injury and interstitial fibrosis were improved in different doses of THF groups (P<0.05). Western blot results showed that the Nod-like receptor heat protein domain associated protein 3 (NLRP3) inflammatorome, interleukin-1β (IL-1β), fibronectin (FN), uric acid transporter 1 (URAT1), phosphorylated p65 (p-p65) and phosphorylated nuclear transcription factor (NF) -κB were inhibited in the H-THF group The expression of protein-producing α (p-IκBα) was reduced to the normal level (P<0.01), but the expression of IL-1β, URAT1 and p-IκBα in HN mice was not affected in the L-THF group. ConclusionTHF ameliorates renal inflammation and fibrosis by inhibiting the activation of NF-κB and NLRP3 inflammasomes to alleviate HN

ObjectiveTo evaluate the curative effect of Jiedu Huayu granules （JDHY） in the treatment of chronic liver failure （CLF） with the syndrome of toxic heat and stasis and investigate the influence on the inflammatory state. MethodA total of 136 patients were randomly divided into a control group and an observation group with 68 cases in each group. In addition to the comprehensive western medicine treatment， patients in the control group received Yinchen Haotang granules orally at 1 dose/day and those in the observation group received JDHY at 10 g/time，3 times/day. The treatment lasted for eight weeks. The endotoxin （ET），diamine oxidase （DAO），aromatic amino acids （AAA），branched chain amino acids （BCAA），blood ammonia，calcitonin （PCT），tumor necrosis factor-α （TNF-α），interleukin （IL）-1，IL-6，IL-17，regulatory T cells （Treg cells），helper T cells 17 （Th17），Th17/Treg ratio，total bilirubin （TBil），albumin （Alb），alanine aminotransferase （ALT），aspartate aminotransferase （AST），prothrombin activity （PTA）， and D-dimer （D-D） levels before and after treatment were detected. The Child-Pugh grading scores of liver function， toxic heat and stasis syndrome scores， and the model scores of end-stage liver disease（MELD） before and after treatment were recorded. The fatality rate and survival were recorded at the follow-up for 48 weeks. ResultCompared with the control group after treatment， the observation group showed decreased ET，DAO， and blood ammonia， increased BCAA/AAA ratio （P<0.01）， reduced PCT，TNF-α，IL-1，IL-6， and IL-17 （P<0.01）， elevated Treg cells， dwindled Th17 and Th17/Treg ratio （P<0.01）， diminished TBil，ALT，AST， and D-D levels， and up-regulated Alb and PTA（P<0.01）. The Child-Pugh grading score，MELD score， and toxic-heat and stasis syndrome score of the observation group were lower than those of the control group （P<0.01）. The total response rate in the observation group was 93.65% （59/63），which was higher than 79.03% （49/62） in the control group （χ²=5.683，P<0.05）. The fatality rate of the observation group eight weeks after treatment was 6.35% （4/63），which was lower than 19.35% （12/62） of the control group （χ²=4.757，P<0.05）. There was no significant difference in mortality between the two groups 16，24， and 48 weeks after treatment. As revealed by the Log-rank test，the difference in survival curves between the two groups was not statistically significant. ConclusionJDHY can remove toxins from the body，regulate immune function，relieve inflammation，improve liver function， and reduce the severity of the disease in CLF patients with the syndrome of toxic heat and stasis. It is significant in clinical efficacy and worthy of clinical application.

OBJECTIVE: To explore the relationship between drug treatment and outcomes in patients with late-onset severe pneumonia (LOSP) after allogeneic stem cell transplantation (allo-SCT). METHODS: We retrospectively analyzed the effects of the initiation time of treatment drugs, especially antiviral drugs and glucocorticoids on the clinical outcomes in 82 patients between January 2016 and August 2021 who developed LOSP after allo-SCT in Peking University People's Hospital. Univariate analysis was performed by Mann-Whitney U test and χ² test, and multivariate analysis was performed by Logistic regression. When multiple groups (n>2) were involved in the χ² test, Bonferroni correction was used for the level of significance test. RESULTS: Of all 82 patients in this study, the median onset time of LOSP was 220 d (93-813 d) after transplantation, and the 60-day survival rate was 58.5% (48/82). The median improvement time of the survival patients was 18 d (7-44 d), while the median death time of the died patients was 22 d (2-53 d). Multivariate analysis showed that the initiation time of antiviral drugs from the onset of LOSP (< 10 d vs. ≥10 d, P=0.012), and the initiation time of glucocorticoids from antiviral drugs (< 10 d vs. ≥10 d, P=0.027) were the factors affecting the final outcome of the patients with LOSP at the end of 60 d. According to the above results, LOSP patients were divided into four subgroups: group A (antiviral drugs < 10 d, glucocorticoids ≥10 d), group B (antiviral drugs < 10 d, glucocorticoids < 10 d), group C (antiviral drugs ≥10 d, glucocorticoids ≥10 d) and group D (antiviral drugs ≥10 d, glucocorticoids < 10 d), the 60-day survival rates were 91.7%, 56.8%, 50.0% and 21.4%, respectively. CONCLUSION Our study demonstrated that in patients who developed LOSP after allo-SCT, the initiation time of antiviral drugs and glucocorticoids were associated with the prognosis of LOSP, and the survival rate was highest in patients who received antiviral drugs early and glucocorticoids later. It suggested that for patients with LOSP of unknown etiology should be highly suspicious of the possibility of a secondary hyperimmune response to viral infection.
Antiviral Agents/therapeutic use* ; Glucocorticoids/therapeutic use* ; Hematopoietic Stem Cell Transplantation/methods* ; Humans ; Pneumonia/etiology* ; Prognosis ; Retrospective Studies ; Transplantation, Homologous/adverse effects*

Objective: To investigate whether haplotype hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of pre transplant minimal residual disease (Pre-MRD) positive acute B lymphoblastic leukemia (B-ALL) compared with HLA- matched sibling donor transplantation (MSDT) . Methods: A total of 998 patients with B-ALL in complete remission pre-HSCT who either received haplo-HSCT (n=788) or underwent MSDT (n=210) were retrospectively analyzed. The pre-transplantation leukemia burden was evaluated according to Pre-MRD determinedusing multiparameter flow cytometry (MFC) . Results: Of these patients, 997 (99.9% ) achieved sustained, full donor chimerism. The 100-day cumulative incidences of neutrophil engraftment, platelet engraftment, and grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) were 99.9% (997/998) , 95.3% (951/998) , and 26.6% (95% CI 23.8% -29.4% ) , respectively. The 3-year cumulative incidence of total chronic GVHD was 49.1% (95% CI 45.7% -52.4% ) . The 3-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) of the 998 cases were 17.3% (95% CI 15.0% -19.7% ) and 13.8% (95% CI 11.6% -16.0% ) , respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 69.1% (95% CI 66.1% -72.1% ) and 73.0% (95% CI 70.2% -75.8% ) , respectively. In the total patient group, cases with positive Pre-MRD (n=282) experienced significantly higher CIR than that of subjects with negative Pre-MRD [n=716, 31.6% (95% CI 25.8% -37.5% ) vs 14.3% (95% CI 11.4% -17.2% ) , P<0.001]. For patients in the positive Pre-MRD subgroup, cases treated with haplo-HSCT (n=219) had a lower 3-year CIR than that of cases who underwent MSDT [n=63, 27.2% (95% CI 21.0% -33.4% ) vs 47.0% (95% CI 33.8% -60.2% ) , P=0.002]. The total 998 cases were classified as five subgroups, including cases with negative Pre-MRD group (n=716) , cases with Pre-MRD<0.01% group (n=46) , cases with Pre-MRD 0.01% -<0.1% group (n=117) , cases with Pre-MRD 0.1% -<1% group (n=87) , and cases with Pre-MRD≥1% group (n=32) . For subjects in the Pre-MRD<0.01% group, haplo-HSCT (n=40) had a lower CIR than that of MSDT [n=6, 10.0% (95% CI 0.4% -19.6% ) vs 32.3% (95% CI 0% -69.9% ) , P=0.017]. For patients in the Pre-MRD 0.01% -<0.1% group, haplo-HSCT (n=81) also had a lower 3-year CIR than that of MSDT [n=36, 20.4% (95% CI 10.4% -30.4% ) vs 47.0% (95% CI 29.2% -64.8% ) , P=0.004]. In the other three subgroups, the 3-year CIR was comparable between patients who underwent haplo-HSCT and those received MSDT. A subgroup analysis of patients with Pre-MRD<0.1% (n=163) was performed, the results showed that cases received haplo-HSCT (n=121) experienced lower 3-year CIR [16.0% (95% CI 9.4% -22.7% ) vs 40.5% (95% CI 25.2% -55.8% ) , P<0.001], better 3-year LFS [78.2% (95% CI 70.6% -85.8% ) vs 47.6% (95% CI 32.2% -63.0% ) , P<0.001] and OS [80.5% (95% CI 73.1% -87.9% ) vs 54.6% (95% CI 39.2% -70.0% ) , P<0.001] than those of MSDT (n=42) , but comparable in 3-year NRM [5.8% (95% CI 1.6% -10.0% ) vs 11.9% (95% CI 2.0% -21.8% ) , P=0.188]. Multivariate analysis showed that haplo-HSCT was associated with lower CIR (HR=0.248, 95% CI 0.131-0.472, P<0.001) , and superior LFS (HR=0.275, 95% CI 0.157-0.483, P<0.001) and OS (HR=0.286, 95% CI 0.159-0.513, P<0.001) . Conclusion: Haplo HSCT has a survival advantage over MSDT in the treatment of B-ALL patients with pre MRD<0.1% .
B-Lymphocytes ; Graft vs Host Disease ; HLA Antigens/genetics* ; Haplotypes ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Leukemia, B-Cell/complications* ; Leukemia, Lymphocytic, Chronic, B-Cell/complications* ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Recurrence ; Retrospective Studies ; Siblings