ObjectiveTo explore the pharmacological mechanism involved in the treatment of allergic cough （AC） by Xiaoer Huatan Zhike granules （XEHT） based on proteomics and network pharmacology. MethodsAfter sensitization by intraperitoneal injection of 1 mL suspension containing 2 mg ovalbumin （OVA） and 100 mg aluminum hydroxide， a guinea pig model of allergic cough was constructed by nebulization with 1% OVA. The modeled guinea pigs were randomized into the model， low-， medium- and high-dose （1， 5， 20 g·kg^-1， respectively） XEHT， and sodium montelukast （1 mg·kg^-1） groups （n=6）， and another 6 guinea pigs were selected as the blank group. The guinea pigs in drug administration groups were administrated with the corresponding drugs by gavage， and those in the blank and model groups received the same volume of normal saline by gavage， 1 time·d^-1. After 10 consecutive days of drug administration， the guinea pigs were stimulated by 1% OVA nebulization， and the coughs were observed. The pathological changes in the lung tissue were observed by hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was performed to measure the levels of C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the bronchoalveolar lavage fluid （BALF） and immunoglobulin G （IgG） and immunoglobulin A （IgA） in the serum. Immunohistochemistry （IHC） was employed to observe the expression of IL-6 and TNF-α in the lung tissue. Transmission electron microscopy was employed observe the alveolar type Ⅱ epithelial cell ultrastructure. Real-time PCR was employed to determine the mRNA levels of IL-6， interleukin-1β （IL-1β）， and TNF-α in the lung tissue. Label-free proteomics was used to detect the differential proteins among groups. Network pharmacology was used to predict the targets of XEHT in treating AC. The Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed to search for the same pathways from the results of proteomics and network pharmacology. ResultsCompared with the blank group， the model group showed increased coughs （P<0.01）， elevated levels of CRP， TNF-α， IL-6， and MDA and lowered level of SOD in the BALF （P<0.05， P<0.01）， elevated levels of IgA and IgG in the serum （P<0.05， P<0.01）， congestion of the lung tissue and infiltration of inflammatory cells， increased expression of IL-6 and TNF-α （P<0.01）， large areas of low electron density edema in type Ⅱ epithelial cells， obvious swelling and vacuolization of the organelles， karyopyknosis or sparse and dissolved chromatin， and up-regulated mRNA levels of IL-6， IL-1β， and TNF-α （P<0.01）. Compared with the model group， the drug administration groups showed reduced coughs （P<0.01）， lowered levels of CRP， TNF-α， IL-6， and MDA and elevated level of SOD in the BALF （P<0.05， P<0.01）， alleviated lung tissue congestion， inflammatory cell infiltration， and type Ⅱ epithelial cell injury， and decreased expression of IL-6 and TNF-α （P<0.01）. In addition， the medium-dose XEHT group and the montelukast sodium group showcased lowered serum levels of IgA and IgG （P<0.05， P<0.01）. The medium- and high-dose XEHT groups and the montelukast sodium showed down-regulated mRNA levels of IL-6， IL-1β， and TNF-α and the low-dose XEHT group showed down-regulated mRNA levels of IL-6 and TNF-α （P<0.05， P<0.01）. Phospholipase D， mammalian target of rapamycin （mTOR）， and epidermal growth factor receptor family of receptor tyrosine kinase （ErbB） signaling pathways were the common pathways predicted by both proteomics and network pharmacology. ConclusionProteomics combined with network pharmacology reveal that XEHT can ameliorate AC by regulating the phospholipase D， mTOR， and ErbB signaling pathways.

Objective: To establish a method for determining the content of bear bile powder in Longze Xiongdan capsules with taursodeoxycholic acid（TUDCA） and taurchenodeoxycholic acid（TCDCA） as indexes.
Methods: HPLC series evaporation photodetector was adopted on Chrom Core AQ C₁₈ column(4.6 mm×250 mm, 5 μm), with the mobile phase comprising of acetonitrile ( A ) and 5 mmol·L^-1 ammonium acetate solution (B) in a gradient elution (0-40 min, 25%A; 40-50 min, 25%A→29%A; 50-80 min, 29%A; 80-100 min, 29%A→40%A) at the flow rate of 1.0 mL·min^-1. The column temperature was 30 ℃. The ELSD was used, of which the drift tube temperature was 110 ℃ and the flow rate of carrier gas（N₂） was 2.5 L·min^-1.
Results: In the ranges of 1.069-9.57 μg and 0.740 46-7.404 64 μg, logarithms of the injected amount of TUDCA and TCDCA presented good linear relationships with logarithms of the peak area, respectively. The RSDs of precision, repeatability and stability tests were all lower than 2.0%. At three concentration levels the recoveries of TUDCA and TCDCA were 95.2%-97.7% and 91.9%-95.9%, respectively. Samples of 42 batches showed that the contents of TUDCA and TCDCA were 0.18-0.43 and 0.10-0.44 mg·granule^-1, respectively.
Conclusion: This method can be used for the quality control of bear bile powder in Longze Xiongdan capsules, thus provides a scientific basis for improving its quality standard.

OBJECTIVE To systematically evaluate the real-world effectiveness and safety of belimumab in the treatment of lupus nephritis （LN） in Chinese adult patients. METHODS Retrieved from PubMed， Embase， Web of Science， Cochrane Library， Wanfang data， CNKI， VIP and CBM， real-world studies on belimumab in the treatment of LN in Chinese adult patients were collected from the inception to July 7th， 2023. Two reviewers independently screened the literature， extracted data， and assessed the quality of the included studies. Meta-analysis was then performed using RevMan 5.3 software. RESULTS A total of 10 real- world studies were included， involving 253 Chinese adult patients with LN. The results of the meta-analysis demonstrated that the complete renal response rate， partial renal response rate， and the incidence of adverse reaction rate in Chinese adult patients with LN treated with belimumab were 61% （95%CI was 46%-76%， P＜0.000 01）， 23%（95%CI was 2%-44%， P＝0.03）， and 30% （95%CI was 16%-43%， P＜0.000 01）， respectively. Belimumab could reduce the 24-hour urinary protein （MD＝－1.71， 95%CI was －3.02-－0.40， P＝0.01）， urine protein-creatinine ratio （MD＝－1.76，95%CI was －2.06-－1.46，P＜0.000 01）， the systemic lupus erythematosus disease activity index （MD＝－8.63， 95%CI was －12.12-－5.13， P＜0.000 01）， and glucocorticoids dosage （MD＝－18.65， 95%CI was －31.82-－5.48， P＝0.006）. In addition， it could elevate the levels of complement C3 （MD＝0.19， 95%CI was 0.08-0.30， P＝0.000 6） and complement C4 （MD＝0.06， 95%CI was 0.02-0.09， P＝0.001）. However， belimumab could not improve the levels of serum creatinine and estimated glomerular filtration rate （P＞0.05）. CONCLUSIONS Belimumab has good efficacy and safety in Chinese adult patients with LN.

Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease. Anti-fibrosis treatment is a significant therapy for heart disease, but there is still no thorough understanding of fibrotic mechanisms. This study was carried out to ascertain the functions of cytokine receptor-like factor 1 (CRLF1) in cardiac fibrosis and clarify its regulatory mechanisms. We found that CRLF1 was expressed predominantly in cardiac fibroblasts. Its expression was up-regulated not only in a mouse heart fibrotic model induced by myocardial infarction, but also in mouse and human cardiac fibroblasts provoked by transforming growth factor-‍β1 (TGF‍-‍β1). Gain- and loss-of-function experiments of CRLF1 were carried out in neonatal mice cardiac fibroblasts (NMCFs) with or without TGF-‍β1 stimulation. CRLF1 overexpression increased cell viability, collagen production, cell proliferation capacity, and myofibroblast transformation of NMCFs with or without TGF‍-‍β1 stimulation, while silencing of CRLF1 had the opposite effects. An inhibitor of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and different inhibitors of TGF-‍β1 signaling cascades, comprising mothers against decapentaplegic homolog (SMAD)‍-dependent and SMAD-independent pathways, were applied to investigate the mechanisms involved. CRLF1 exerted its functions by activating the ERK1/2 signaling pathway. Furthermore, the SMAD-dependent pathway, not the SMAD-independent pathway, was responsible for CRLF1 up-regulation in NMCFs treated with TGF-‍β1. In summary, activation of the TGF-‍β1/SMAD signaling pathway in cardiac fibrosis increased CRLF1 expression. CRLF1 then aggravated cardiac fibrosis by activating the ERK1/2 signaling pathway. CRLF1 could become a novel potential target for intervention and remedy of cardiac fibrosis.
Animals ; Humans ; Mice ; Disease Models, Animal ; Fibroblasts/metabolism* ; Fibrosis ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinase 3/metabolism* ; Myocardial Infarction/metabolism* ; Receptors, Cytokine/metabolism* ; Signal Transduction ; Transforming Growth Factor beta1/pharmacology*

【Objective】 To investigate the effects of recombinant human coagulation factor Ⅶa combined with Bakri balloon compression on oxidative stress and coagulation in patients with refractory postpartum hemorrhage. 【Methods】 Prospectively, 80 patients with refractory postpartum hemorrhage in Chengdu Fifth People′s Hospital from June 2019 to June 2022 were selected and grouped according to the random number table method. The control group (n=40) was treated with Bakri balloon compression, and the observation group (n=40) was treated with recombinant human coagulation factor Ⅶa combined with Bakri balloon compression. The bleeding-related indexes and adverse effects were observed in both groups, and the prenatal and 24 h postpartum oxidative stress, coagulation function and inflammatory factors were compared between the two groups. 【Results】 The blood loss in the observation group and the control group was (683.96±146.52) vs(796.63±152.41)mL during operation, (812.46±161.53) vs(965.39±166.22)mL in 2 h after delivery, (899.53±178.74) vs(1 084.31±203.67)mL in 24 h after delivery, and the transfusion volume was (512.31±104.76) vs(683.25±113.52)mL, and the onset time of hemostasis was (14.63±3.18) vs (21.72±5.29) min (P<0.05); the difference in the incidence of adverse reactions between the two groups was not significant (P>0.05). At 24 h postpartum, NE, Cor, SOD and MDA were higher than those before delivery in both groups, but the observation group was lower than the control group (P<0.05); TT, APTT and PT were longer and Fib was lower in both groups than before delivery, but TT, APTT and PT were shorter and Fib was higher in the observation group than in the control group (P<0.05); CRP, IL-8 and TNF-α were higher in both groups than before delivery, but the observation group was lower than in the control group (P<0.05). 【Conclusion】 Hemostasis in patients with refractory postpartum hemorrhage treated with recombinant human coagulation factor Ⅶa combined with Bakri balloon compression was effective, which can improve coagulation, reduce transfusion, decrease oxidative stress injury and inflammatory response without increasing adverse effects.

Polymyxin B and polymyxin E (colistin) are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae. Yet resistance to this last-line drugs is a major public health threat and is rapidly increasing. Polymyxin S₂ (S₂) is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and colistin. To predict the possible resistant mechanism of S₂ for wide clinical application, we experimentally induced bacterial resistant mutants and studied the preliminary resistance mechanisms. Mut-S, a resistant mutant of K. pneumoniae ATCC BAA-2146 (Kpn2146) induced by S₂, was analyzed by whole genome sequencing, transcriptomics, mass spectrometry and complementation experiment. Surprisingly, large-scale genomic inversion (LSGI) of approximately 1.1 Mbp in the chromosome caused by IS26 mediated intramolecular transposition was found in Mut-S, which led to mgrB truncation, lipid A modification and hence S₂ resistance. The resistance can be complemented by plasmid carrying intact mgrB. The same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146 (Mut-B and Mut-E, respectively). This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in K. pneumoniae. The findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics.

Atherosclerosis (AS) is a chronic and progressive arterial disease. It is an important cause of the occurrence and development of cardiovascular and cerebrovascular diseases. With the development of Traditional Chinese Medicine (TCM), TCM has many advantages in the therapy of AS, with less adverse reactions. Studies have shown that TCM can resist AS, and the mechanism mainly belongs to regulating lipid metabolism, anti-lipid peroxidation, anti-inflammation, anticoagulation, and protecting the structure and function of vascular endothelial cells. The mechanism of TCM for AS is warranted to be studied systematically, and the chemical components need to be further clarified.

Objective:To discuss the displacement characteristics of Garden type III femoral neck fracture and investigate the reliability, validity and clinical value of the frontal Garden index in assessing the displacement degree of Garden type III femoral neck fracture.Methods:The pelvis X-ray films of 98 patients with Garden type III femoral neck fracture treated at Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital) from October 2010 to October 2018 were collected, including 47 males and 51 females; aged 19-89 years [(64.9±16.2) years]. Three-dimensional data of the hip with 64-slice CT were available in 21 patients. Each patient′s frontal Garden index was measured three times by three senior doctors, which was repeated twice in turn. The distribution characteristics of the frontal Garden index were statistically described. The reliability of the frontal Garden index was tested by Spearman correlation coefficient and Kappa coefficient, including test-retest reliability and intra-rater consistency. The contact area of fracture ends and upper-shift distance of the femoral neck were calculated based on three-dimensional CT data of the hip in 21 patients. Correlation analysis of the contact area of fracture ends and upper-shift distance of the femoral neck with the frontal Garden index was performed by multiple correlation analysis to assess the validity of the frontal Garden index.Results:The Frontal Garden index of 98 patients with Garden type III femoral neck fracture was (136±15) °, with the minimum value of 90 ° and maximum value of 159 °, and was found to be normally distributed ( P>0.05). Spearman correlation coefficient of the test-retest reliability was 0.93, 0.97 and 0.95, respectively (all P<0.01). Kappa coefficient of the intra-rater consistency was 0.87, 0.91 and 0.86, respectively (all P<0.01). The frontal Garden index was positively correlated with the contact area of fracture ends ( r=0.80, P<0.01), and was negatively with the upper-shift distance of the femoral neck ( r=-0.77, P<0.01). Conclusions:The displacement degree of Garden type III femoral neck fracture shows diversity and normal distribution. The frontal Garden index can credibly and effectively measure the displacement degree of Garden type III femoral neck fracture, which may help to choose the treatment plan.

Objective:To investigate the contents of soil metal elements in the plague high incidence area and resting area in the plague natural foci of Qingnan region in Qinghai Province, and to compare and analyze the differences of the contents of soil metal elements between the two areas.Methods:A total of 69 soil samples were collected from 11 sites in the plague high incidence area (Yushu Prefecture) and resting area (Guoluo Prefecture) in Qingnan region, including 39 samples from high incidence area and 30 samples from resting area. The contents of 12 soil metal elements, such as iron (Fe), magnesium (Mg), calcium (Ca), barium (Ba), cobalt (Co), copper (Cu), manganese (Mn), lead (Pb), rubidium (Rb), titanium (Ti), vanadium (V) and zinc (Zn), were measured by X-ray fluorescence spectrometry and SPSS 20.0 software was used for Spearman correlation and other statistical analysis.Results:The contents of Fe and Ca in the soil of the plague natural foci of Qingnan region were relatively high. The contents of 12 soil metal elements in the high incidence area were significantly higher than those in the resting area ( P < 0.01 or < 0.05). There were statistical significant differences in the contents of Mg, Ca, Ba, Mn, Pb and Zn in the soil among the sample plots of the plague high incidence area ( P < 0.01 or < 0.05). There were statistical significant differences in the contents of Fe, Mg, Ca, Rb and Ti in the soil among the sample plots of the plague resting area ( P < 0.05 or < 0.01). Except for Mg and Ca, Fe was positively correlated with other metal elements in the high incidence area and resting area ( P < 0.01 or < 0.05), and Fe was strongly positively correlated with Rb, Ti and V ( r = 0.780 - 0.838). Mg was only positively correlated with Ca in the high incidence area and resting area ( P < 0.01). Ca was negatively correlated with Mn, Pb, Rb, Ti, V and Zn in the high incidence area, and with Rb and Zn in the resting area ( P < 0.01 or < 0.05). The rest of the metal elements were mostly positively correlated in the high incidence area and resting area. Conclusions:The contents of Fe and Ca are rich in the plague natural foci of Qingnan region in Qinghai Province. There are correlations among most soil metal elements in the high incidence area and resting area. The correlation between the contents of soil metal elements in the plague natural foci and the epidemic of plague is worth further exploring.

Objective: The aim of the present study was to introduce a new technique for laparoscopic para-aortic lymphadenectomy (PAL): an invented retroperitoneum suspension needle combined with modified trocar placement. Methods: This prospective pilot study randomly categorized women with cervical cancer of stage I–II into 2 groups. The patients in the study group would have laparoscopic PAL with our new technique, while those in the control group with control method. Patients' characteristics and perioperative outcomes were compared between the 2 groups. Results: A total of 37 patients were included in our study, of which 20 cases in the study group and 17 cases in the control group. As a result, the mean number of para-aortic lymph nodes (PALNs) resected in the study group was significantly more than that in the control group (p<0.001). The time for resecting PALNs (p<0.001) and total operative time (p<0.001) in the study group decreased significantly than those in the control group. Conclusions For laparoscopic PAL, this new technique was effective and practical.