Mechanism of Qizhenziyin mixture in the treatment of hypogonadism based on network pharmacology analysis and molecular docking / 药学实践杂志

Objective To investigate the mechanism of Qizhenziyin mixture in the treatment of hypogonadism by using the network pharmacology approach. Methods The active components of Qizhenziyin mixture were obtained by searching TCMSP ，TCMID and HIT databases.The related targets of candidate compounds were obtained by searching STITCH databases. The potential targets of Qizhenziyin mixture in the treatment of hypogonadism were obtained by mapping the disease genes of hypogonadism with Genecards and DisGeNet databases. The protein interaction platform database (STRING) was used to construct the interaction relationship between action targets. The target protein interaction （PPI） network was constructed by introducing Cytoscape software. The mechanism of Qizhenziyin mixture in the treatment of hypogonadism was explained through the enrichment analysis of GO, KEGG and molecular docking technology. Results A total of 148 drug-disease chemical compounds, 96 drug-disease intersection targets, 1085 disease targets were obtained；the components for treating diseases are: quercetin，kaempferol, luteolin, etc; enrichment analysis of GO revealed 1792 biological processes （BP）, 31 cellular components (CC) and 79 molecular functions (MF)；the results of KEGG pathway enrichment analysis indicated such as FOXO signaling pathway, prostate cancer, AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, etc.The results of molecular docking showed that kaempferol and LEP had the best and stable binding energy. Conclusion The active components of Qizhenziyin mixture may play a role of the treatment of hypogonadism by improving insulin resistance and the expression of testosterone synthetase of Leydig cells.

Study on preparation technology of long-acting sustained-release oral ulcer membrane based on analytic hierarchy process and orthogonal design / 药学实践杂志

Objective To prepare a sustained-release membrane with longer adhesion time and dissolution time, and compare it with the commercially available oral ulcer membrane. Method Adhesion strength, adhesion time, swelling coefficient, dissolution time, etc. were used as the inspection indicators, and a combination of single factor inspection and analytic hierarchy process were used to screen the membrane -forming materials. The dispersion method of clotrimazole, ornidazole and borneol were investigated to prevent the drug from seed out. The method of combining orthogonal experiment and analytic hierarchy process were used to optimize the dosage of CMC-Na, PVA-1788 and glycerin; and the commercial products were compared. Results Through single-factor investigation and orthogonal experiment, the optimal ratio of excipients was selected as CMC-Na∶PVA-1788∶glycerol (3∶1∶0.08). The water-insoluble component clotrimazole, ornidazole and borneol were treated by precipitation in liquid with good effect. The best method was used to prepare the membrane. The adhesion strength was 102 g. The adhesion time was 55 min. The swelling coefficient was 1 939.52. The average dissolution time was 110 min. The appearance was white and the surface was free of bubbles, soft and elastic. The membrane forming time at 60 ℃ was 300 min and the demolding effect was better which could be completely peeled off with moderate thickness. Conclusion The oral ulcer membrane developed in this method has good appearance, comfortable use, strong adhesion, long adhesion time and dissolution time, and could stay on the ulcer surface for a long time to form physical isolation, and slowly release the drug during the dissolution process, which could play the role of long-term pain relief, antibacterial, anti-inflammatory and promote healing effects on oral ulcers.

Changes of serum CTX-1 and P1NP in patients with skeletal fluorosis in tea-drinking-borne endemic fluorosis area in Qinghai Province / 中华地方病学杂志

Objective:To observe the changes of serum C-terminal peptide of type Ⅰ collagen (CTX-1) and N-terminal lengthening peptide of type Ⅰ collagen (P1NP) in adult patients with skeletal fluorosis in the tea-drinking-borne endemic fluorosis area in Qinghai Province, and to find sensitive indicators for diagnosis of skeletal fluorosis.Methods:From April to August 2019, a case-control study was carried out in tea-drinking-borne endemic fluorosis area in Zhiduo County, Yushu Tibetan Autonomous Prefecture, and Gangcha County, Haibei Tibetan Autonomous Prefecture of Qinghai Province. According to the Diagnostic Standard for Endemic Skeletal Fluorosis (WS/T 192-2008), the clinical diagnosis and X-ray examination of skeletal fluorosis were carried out for permanent residents ≥25 years old and living for more than 10 years in the area, combined with face-to-face inquiry and investigation of past disease history, lifestyle and clinical manifestations. The patients with skeletal fluorosis and healthy people were selected as skeletal fluorosis group and control group, respectively. Randomized urine samples and fasting venous blood from the two groups were collected. The content of fluoride in urine was determined by ion selective electrode method, and the contents of CTX-1 and P1NP in serum were determined by enzyme-linked immunosorbent assay (ELISA).Results:A total of 127 people in the disease area were investigated, including 63 cases in skeletal fluorosis group and 64 cases in control group. There was no statistically significant difference in age and sex ratio between the two groups ( t = 0.42, χ 2 = 0.07, P > 0.05). The X-ray examination results showed that the patients with skeletal fluorosis were mainly mild, accounting for 71.43% (45/63); X-ray changes were mainly ossification of interosseous membrane and tendon. The urinary fluoride in control group and skeletal fluorosis group was 1.62 (1.12, 1.95) and 3.22 (2.38, 4.89) mg/L, respectively, with statistically significant difference between the two groups ( Z = 7.07, P < 0.001). The difference of serum CTX-1 and P1NP contents between the two groups was statistically significant ( Z = 2.00, 4.89, P < 0.05). Conclusions:The levels of serum CTX-1 and P1NP in patients with skeletal fluorosis are higher than those in healthy people. Serum CTX-1 and P1NP may be used as sensitive indicators for diagnosis of skeletal fluorosis.

Analysis of external quality control assessment results of fluorine and arsenic in Qinghai Province in 2021 / 中华地方病学杂志

Objective:To learn about the detection quality and external quality control assessment of fluoride and arsenic in laboratories at all levels in Qinghai Province.Methods:The Z-score method was used to analyze and evaluate the evaluation results of 1 provincial, 8 municipal and 43 county level laboratories of disease prevention and control institutions participating in the external quality control assessment of water fluoride and brick tea fluoride in Qinghai Province in 2021, as well as 1 provincial, 1 municipal and 2 county level laboratories of disease prevention and control institutions participating in the external quality control assessment of water arsenic and urine arsenic. The feedback rate and qualification rate of external quality control of each assessment laboratory were calculated.Results:In 2021, the feedback rate of external quality control of water fluoride, brick tea fluoride, water arsenic and urine arsenic in provincial and municipal level laboratories of Qinghai Province were 100.00%; except that the qualified rate of water fluoride was 7/9, the qualified rate of external quality control of other projects was 100.00%. The feedback rate of external quality control of water fluoride, brick tea fluoride, water arsenic and urine arsenic in county level laboratories was 100.00%; except that the qualified rate of water fluoride was 86.05% (37/43), the qualified rate of external quality control of other projects was 100.00%. In the specific assessment results of the laboratory, the assessment results of water fluoride sample FS20210101 from 1 provincial, 1 municipal and 2 county level laboratories, and FS20210102 from 1 county level laboratory were suspicious; the assessment results of water fluoride sample FS20210101 from 3 county level laboratories were not satisfactory; the assessment results of fluoride and arsenic sample in other laboratories were satisfactory.Conclusions:The qualified rate of external quality control of fluoride and arsenic in laboratories at all levels in Qinghai Province is relatively high, but some county level laboratories are still dissatisfied with the assessment results of water fluoride. Therefore, it is necessary to strengthen the detection level of water fluoride in laboratories.

Research advances in signaling pathways associated with potential anti-liver fibrosis drugs and targets / 临床肝胆病杂志

Liver fibrosis is a key step in the progression of chronic liver diseases to liver cirrhosis and even liver cancer. In recent years， a large number of studies have shown the necessity of intervening in the process of liver fibrosis， and various anti-liver fibrosis drugs and active ingredients have been discovered. Non-coding RNAs also play an important role in the process of liver fibrosis， and searching for upstream non-coding RNAs that can regulate signaling pathways can provide new insights for anti-liver fibrosis treatment. This article introduces the process of liver fibrosis mediated by the TGF-β， Wnt/β-catenin， PI3K/Akt/mTOR， NF-κβ， Hippo， and MAPK signaling pathways， lists the latest anti-liver fibrosis drugs or active components in each signaling pathway， and summarizes the research advances in anti-liver fibrosis targets and drugs mediated by related non-coding RNAs， so as to provide new research ideas and treatment methods for anti-liver fibrosis treatment.

Effect and Mechanism of Yiyi Fuzi Baijiangsan on Apoptosis of Human Colon Cancer HCT116 Cells / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of Yiyi Fuzi Baijiangsan （YYFZBJ） on the apoptosis of colon cancer cell line HCT116. MethodYYFZBJ at different concentrations （0.5， 1， 2， 4， 6， 8， 10， 12， 14， 16 g·L-1） was used to intervene in HCT116 cells for 24， 48， 72 h. The cell counting kit-8 （CCK-8） method was used to determine the effect of YYFZBJ on cell proliferation in vitro. The cells were divided into a blank group， a capecitabine group（1.8 g·L-1）， and low-， medium-， and high-dose YYFZBJ groups （6， 10， and 14 g·L-1） and treated for 48 hours. Flow cytometry was used to detect the apoptosis. Hoechst 33342 staining was used to observe the apoptotic morphology of cells. Mitochondrial membrane potential （MMP） was analyzed by a mitochondrial-targeted deep-red fluorescent probe （Mito-Tracker Red CMXRos）. The expression of proteins related to the mitochondrial apoptosis pathway， such as B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cytochrome C （Cyt C）， cysteinyl aspartate-specific protease （Caspase）-9， Caspase-3， cleaved Caspase-9， and cleaved Caspase-3 was detected by Western blot. The mRNA levels of Bcl-2， Bax， Cyt C， Caspase-9， and Caspase-3 were determined by real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， YYFZBJ （8， 10， 12， 14， 16 g·L-1） significantly inhibited the proliferation of HCT116 cells in vitro （P<0.05） in a dose-dependent manner. Compared with the blank group， the medium- and high-dose YYFZBJ groups and the capecitabine group showed increased apoptosis rates of colon cancer cells （P<0.05）. The YYFZBJ groups and the capecitabine group showed reduced number of colon cancer cells with significantly changed cellular morphology and cell apoptosis manifestations， such as strong dark blue fluorescence， nucleus concentration， shrinkage， and fragmentation. With the increase in the mass concentration of YYFZBJ， the blue fluorescence intensity was significantly enhanced. Compared with the blank group， the YYFZBJ groups and the capecitabine group showed reduced MMP in a dose-dependent manner， decreased protein and mRNA levels of Bcl-2， and increased protein expression of Bax， Cyt C， Caspase-9， Caspase-3， cleaved Caspase-9， and cleaved Caspase-3 and mRNA expression of Bax， Cyt C， Caspase-9， and Caspase-3 （P<0.05）. ConclusionYYFZBJ can induce the apoptosis of colon cancer HCT116 cells through the mitochondrial apoptosis pathway.

Chimeric flap pedicled with superficial branch of superficial iliac circumflex artery in repair of soft tissue defects of dorsal hand and metacarpal bone / 中华显微外科杂志

Objective:To investigate the effect of chimeric flap pedicled with superficial branch of superficial iliac circumflex artery in repair of soft tissue defect of dorsal hand combined with metacarpal bone defect.Methods:From May 2015 to January 2022, 34 patients(28 males and 6 females) of soft tissue defects of dorsal hand with metacarpal bone defects were treated in the Department of Orthopedics of Yibin Third People's Hospital. The age of patients ranged from 22 to 51 years old, with an average age of 37 years old. The areas of soft tissue defects after debridement were 2.5 cm×5.0 cm-4.5 cm×9.0 cm, and the defects were all in dorsal hand and dorsal wrist. The lengths of metacarpal bone defect were 1.8-4.1 cm. All the patients had only single metacarpal bone defect, among which: 14 patients had defects in first metacarpal bone, 7 in second metacarpal bone, 4 in third metacarpal bone, 8 in fourth metacarpal bone and 1 in fifth metacarpal bone. All the patients were repaired by chimeric flap pedicled with superficial branch of superficial iliac circumflex artery. The size of flaps were 3.6 cm×5.4 cm-5.2 cm×9.5 cm. Anticoagulation, thermal preservation and plaster fixation were applied for 4-6 weeks after surgery. Postoperative follow-ups included regularly outpatient clinic visit, telephone or Wechat reviews. Follow-up items covered: the feeling and appearance of flaps in recipient sites, healing of the donor sites and recovery of hand functions.Results:All the 34 chimeric flaps survived. Regular follow-up lasted for 3 to 15(average, 10) months. All incisions in the donor sites of hip healed in stage I. TPD of the flaps was 5.1-7.3(mean, 6.4) mm. Appearance of flaps in the receiving area were satisfactory without swelling. Movement of wrists and metacarpophalangeal joints met the basic requirement of movement. The healing time of metacarpal defect was 2-3 months with an average of 2.8 months. Hand functions were evaluated at excellent in 6 patients and good in 28, according to the Evaluation Standard of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association.Conclusion:The chimeric flap pedicled with superficial branch of superficial iliac circumflex artery is an ideal flap to repair the soft tissue defect in dorsal hand combined with metacarpal bone defect. It has advantages of less donor site damage, good blood supply of flap, simple surgical procedure, and one-stage repair of a combined soft tissue and metacarpal bone defects.

Coryoint flap of lower abdominal wall for covering extremely large soft tissue circular defects on limbs / 中华显微外科杂志

Objective:To investigate the results of coryoint flap harvested from lower abdominal wall for covering extremely soft tissue circular defects on limbs.Methods:From March 2018 to June 2020, 15 patients who suffered from severe degloved injury were admitted into the Department of Hand Surgery, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University. The injuries were characterised as extreme circular defects on limbs. The dimension of defects ranged from 25.0 cm×9.0 cm to 30.0 cm×18.0 cm. All wounds were taken through emergency debridement and managed by VSD. Using lower abdomen as a donor site, a conjoined flap was dissected when the wound surface became granulating. The perforator vessels of the flaps included vessels of deep inferior epigastric artery(DIEA), superficial inferior epigastric artery(SIEA) and superficial circumflex iliac artery(SCIA). The donor sites were primary closed. Postoperative follow-ups were conducted by the surgeons in the same surgical team at outpatient clinic.Results:Fourteen flaps survived completely without significant complications. Distal necrosis occurred in 1 flap, which healed with a skin graft in the second stage surgery. All flaps were reviewed during the postoperative follow-up that lasted for 18-24(mean 20) months. The aesthetic outcomes were achieved on the recipient site without hairy nor hyper-pigmentation. A concealed linea scare left at the donor sites without hernia and limited function. At the last follow-up, 5 patients were in excellent and 2 in good evaluated by following the Disabilities of the arm, shoulder and hand(DASH). With the Lower extremity functional scale(LEFS), 5 patients were in excellent and 3 in good.Conclusion:The simultaneous reconstruction of extremely large soft tissue circular defects on limbs with best possible salvage surgery can be achieved by a conjoined flap. A conjoined flap offers a concealed donor site, easy to design, flexible perforators design and larger size of soft tissue.

Determination of camphor residue and borneol content in Qingchang suppository by GC / 药学实践杂志

Objective To establish a gas chromatography for simultaneous determination of camphor residue and borneolum content in Qingchang Suppository. Methods Gas chromatograph method was used. The chromatographic column was Agilent capillary column(30 m×0.25 mm×0.25 µm). The column temperature was 140 ℃. The sample injection temperature was 250 ℃. The FID detector temperature was 250 ℃. Results Camphor，borneol and isoborneol content showed good linear in the extent of 0.0299~1.497(r=1.000), 0.0205~1.025(r=1.000), 0.0097~0.4830 µg (r=1.000). RSDs of precision，stability and repeatability test results were less than 2%. The recovery was 99.7%, 101.0%, 102.5%. Conclusion This method is simple and quick with accurate result, which could be used for the content determination of Borneol in Qingchang Suppository.

Analysis of clinicopathological and molecular abnormalities of angioimmunoblastic T-cell lymphoma / 北京大学学报(医学版)

OBJECTIVE@#To analyze the clinicopathological features, molecular changes and prognostic factors in angioimmunoblastic T-cell lymphoma (AITL).@*METHODS@#Sixty-one cases AITL diagnosed by Department of Pathology of Peking University Cancer Hospital were collected with their clinical data. Morphologically, they were classified as typeⅠ[lymphoid tissue reactive hyperplasia (LRH) like]; typeⅡ[marginal zone lymphoma(MZL)like] and type Ⅲ [peripheral T-cell lymphoma, not specified (PTCL-NOS) like]. Immunohistochemical staining was used to evaluate the presence of follicular helper T-cell (TFH) phenotype, proliferation of extra germinal center (GC) follicular dendritic cells (FDCs), presence of Hodgkin and Reed-Sternberg (HRS)-like cells and large B transformation. The density of Epstein-Barr virus (EBV) + cells was counted with slides stained by Epstein-Barr virus encoded RNA (EBER) in situ hybridization on high power field (HPF). T-cell receptor / immunoglobulin gene (TCR/IG) clonality and targeted exome sequencing (TES) test were performed when necessary. SPSS 22.0 software was used for statistical analysis.@*RESULTS@#Morphological subtype (%): 11.4% (7/61) cases were classified as type Ⅰ; 50.8% (31/61) as type Ⅱ; 37.8% (23/61) as type Ⅲ. 83.6% (51/61) cases showed classical TFH immunophenotype. With variable extra-GC FDC meshwork proliferation (median 20.0%); 23.0% (14/61) had HRS-like cells; 11.5% (7/61) with large B transformation. 42.6% (26/61) of cases with high counts of EBV. 57.9% (11/19) TCR+/IG-, 26.3% (5/19) TCR+/IG+, 10.5% (2/19) were TCR－/IG－, and 5.3% (1/19) TCR－/IG+. Mutation frequencies by TES were 66.7% (20/30) for RHOA, 23.3% (7/30) for IDH2 mutation, 80.0% (24/30) for TET2 mutation, and 33.3% (10/30) DNMT3A mutation. Integrated analysis divided into four groups: (1) IDH2 and RHOA co-mutation group (7 cases): 6 cases were type Ⅱ, 1 case was type Ⅲ; all with typical TFH phenotype; HRS-like cells and large B transformation were not found; (2) RHOA single mutation group (13 cases): 1 case was type Ⅰ, 6 cases were type Ⅱ, 6 cases were type Ⅲ; 5 cases without typical TFH phenotype; 6 cases had HRS-like cells, and 2 cases with large B transformation. Atypically, 1 case showed TCR－/IG－, 1 case with TCR－/IG+, and 1 case with TCR+/IG+; (3) TET2 and/or DNMT3A mutation alone group (7 cases): 3 cases were type Ⅱ, 4 cases were type Ⅲ, all cases were found with typical TFH phenotype; 2 cases had HRS-like cells, 2 cases with large B transformation, and atypically; (4) non-mutation group (3 cases), all were type Ⅱ, with typical TFH phenotype, with significant extra-GC FDC proliferation, without HRS-like cells and large B transformation. Atypically, 1 case was TCR－/IG－. Univariate analysis confirmed that higher density of EBV positive cell was independent adverse prognostic factors for both overall survival (OS) and progression free survival(PFS), (P=0.017 and P=0.046).@*CONCLUSION@#Pathological diagnoses of ALTL cases with HRS-like cells, large B transformation or type Ⅰ are difficult. Although TCR/IG gene rearrangement test is helpful but still with limitation. TES involving RHOA, IDH2, TET2, DNMT3A can robustly assist in the differential diagnosis of those difficult cases. Higher density of EBV positive cells counts in tumor tissue might be an indicator for poor survival.

Clinicopathological features and prognosis of anorectal melanoma: A report of 68 cases / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinicopathological characteristics of anorectal mucosal melanoma (ARMM), and to evaluate the prognostic factors.@*METHODS@#A total of 68 primary ARMM surgical specimens from 2010 to 2018 were retrospectively studied. Slides were reviewed to evaluate pathological features. Slingluff staging method was used for staging.@*RESULTS@#(1) Clinical features: The median age at diagnosis in this group was 61.5 years, with a male-to-female ratio 1 ∶1.62. The most common complaint was blooding (49 cases). For anatomic site, anorectum was the prevalent (66.2%), followed by rectum (20.6%). At the time of diagnosis, 28 cases were stage Ⅰ (localized stage, 41.2%), 25 cases were stage Ⅱ (regional lymph node metastasis, 36.8%), and 15 cases were stage Ⅲ (distant metastasis, 22.1%). Five patients underwent wide local excision, the rest abdominoperineal resection, and 48 patients received adjuvant therapy after surgery. (2) Pathological features: Grossly 88.2% of the tumors were exophytic polypoid masses, with the median tumor size 3.5 cm and the median tumor thickness 1.25 cm. Depth of invasion below lamina muscularis mucosae ranged from 0-5.00 cm (median 1.00 cm). The deepest site of tumor invasion reached muscular layer in 27 cases, and perirectal tissue in 16 cases. Melanin pigmentation was absent or not obvious in 67.6% of the cases. The predominant cytology was epithelioid (45 cases, 66.2%). The rate for ulceration, necrosis, lymphovascular invasion, and perineural invasion was 89.7%, 35.3%, 55.9%, and 30.9%, respectively. The median mitotic count was 18/mm2. The positive rate of S100, HMB-45 and Melan-A were 92.0%, 92.6% and 98.0%, respectively. The median of Ki-67 was 50%. The incidences of mutations within CKIT, BRAF and NRAS genes were 17.0% (9 cases), 3.8% (2 cases) and 9.4% (5 cases), respectively. (3) Prognosis: Survival data were available in 66 patients, with a median follow-up of 17 months and a median survival time of 17.4 months. The 1-year, 2-year and 5-year overall survival rate was 76.8%, 36.8% and 17.2%, respectively. The rate of lymphatic metastasis at diagnosis was 56.3%. Forty-nine patients (84.5%) suffered from distant metastasis, and the most frequent metastatic site was liver. Univariate analysis revealed that tumor size (>3.5 cm), depth of invasion below lamina muscularis mucosae (>1.0 cm), necrosis, lymphovascular invasion, BRAF gene mutation, lack of adjuvant therapy after surgery, deep site of tumor invasion, and high stage at diagnosis were all poor prognostic factors for overall survival. Multivariate model showed that lymphovascular invasion and BRAF gene mutation were independent risk factors for lower overall survival, and high stage at diagnosis showed borderline negative correlation with overall survival.@*CONCLUSION@#The overall prognosis of ARMM is poor, and lymphovascular invasion and BRAF gene mutation are independent factors of poor prognosis. Slingluff staging suggests prognosis effectively, and detailed assessment of pathological features, clear staging and genetic testing should be carried out when possible. Depth of invasion below lamina muscularis mucosae of the tumor might be a better prognostic indicator than tumor thickness.

Investigation on health status of workers exposed to glyphosate / 中华劳动卫生职业病杂志

Objective: To analyze the concentrations of glyphosate and its metabolites in occupational exposed workers and their possible effects on human health, so as to provide a reference for improving the safe use of glyphosate and toxicity research. Methods: From April to December 2020, 247 workers directly exposed to glyphosate in 5 enterprises were selected as the contact group, and 237 workers who were not exposed to glyphosate and other pesticides in the same enterprise were selected as the control group. Questionnaire survey and occupational health examination were conducted on objects, and the concentrations of glyphosate and its metabolites in the air of workplaces and biological samples were detected. The correlation between the concentrations and the difference of health examination between the two groups were analyzed. Results: The urine glyphosate concentration (0.022-47.668 mg/L), the rate of exceeding the standard (60.32%, 149/247) and the urine aminomethyl phosphonic acid concentration (<0.010-1.624 mg/L) in the contact group were higher than those in the control group [urine glyphosate concentration (<0.020-4.482 mg/L), the rate of exceeding the standard (2.53%, 6/237) and the urine aminomethyl phosphonic acid concentration (<0.010-0.524 mg/L) ], respectively (P<0.001). The exceeding standard rate of glyphosate concentration in the workplace was 33.67% (33/98). The concentration of glyphosate in the workplace was positively correlated with the concentrations of glyphosate and aminomethylphosphonic acid in urine (r(s)=0.804, 0.238, P<0.001), and the concentration of glyphosate in urine was positively correlated with the concentration of aminomethylphosphonic acid in urine (r(s)=0.549, P<0.001). The alanine aminotransferase (ALT), white cell ratio, creatinine, uric acid, the abnormal rates of ALT and total protein (TP) in the contact group were higher than those in the control group, and TP was lower than that in the control group, the differences were statistically different (P<0.05). The abnormal rates of overall liver function, overall renal function, blood routine test, urine routine test, electrocardiogram, liver B ultrasound and blood lipid in the contact group were significantly higher than those in the control group (P<0.05) . Conclusion: The concentration of glyphosate in the workplace is related to the concentrations of glyphosate and aminomethyl phosphonic acid in the urine of workers, and exposure to glyphosate may have some harmful effects on human health.

The eye irritation test and pharmacokinetic study of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits / 药学实践杂志

Objective To study the eye irritation and the pharmacokinetics of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits. Methods The eye irritation of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits was observed by histological cross-sections of external ocular tissues stained with HE. The aqueous humor of rabbit eyes was extracted by corneal puncture and analyzed by HPLC-MS for pharmacokinetic study. Results Tacrolimus-loaded cationic nanoemulsion-based in-situ gel had no significant irritation on rabbit eyes. The pharmacokinetic parameter showed that the AUC of tacrolimus-loaded cationic nanoemulsion-based in-situ gel was (128.34±13.09) ng·h/ml, which was 1.13 times of tacrolimus-loaded cationic nanoemulsion (113.61±12.36) ng·h/ml and 1.88 times of Talymus® (68.25±10.82) ng·h /ml. Conclusion Tacrolimus-loaded cationic nanoemulsion-based in-situ gel had the advantages of low irritation, long retention time and high bioavailability in rabbit eyes. It has a good potential for clinical application.

Literature analysis of compatible stability of commonly used intravenous drugs in ICU / 中国药房

OBJECTIVE To analyze the compatible stability of commonly used intravenous drugs in the intensive care units （ICU）， and to provide a reference for improving medication safety in clinic. METHODS The commonly used intravenous drugs in the ICU of Hebei General Hospital were investigated and confirmed in April 1-30， 2022， and used as keywords to retrieve the relevant literature about compatible stability from PubMed， CNKI， Wanfang Data and other databases， and manually filtered with Micromedex database at the same time. Then， the compatible stability results of the included literature were analyzed descriptively. RESULTS Totally 32 commonly used intravenous drugs and 39 mixed infusion combinations were collected from ICU of this hospital. A total of 40 studies were included， only 2 studies followed all quality requirements； 18 studies validated their methods to guarantee correct reproducibility； 33 studies evaluated physical stability， including precipitate formation and pH changes； 32 studies evaluated chemical compatibility， mainly content/concentration changes. A total of 666 possible two-drug combinations were obtained from the included literature， of which 254 combinations of stability data were available， including 176 were stable， 68 were unstable， and 10 were contradictory. Totally 412 combinations had no stability results. Among two-drug combinations in ICU of this hospital， 42 combinations were stable， 14 combinations were unstable， and 2 combinations were contradictory. CONCLUSIONS The pH， solvent， excipients and preparation concentration are the factors that affect the stability. There are drug combinations with unstable compatibility of commonly used intravenous drugs in ICU of this hospital. The stability study methods are limited， and the stability data cannot meet the actual clinical needs.

Mechanism of Qiwei Guibao Granules in treatment of premature ovarian failure based on proteomics / 中国中药杂志

In this study, the underlying mechanism of Qiwei Guibao Granules(QWGB) in the treatment of premature ovarian fai-lure(POF) was explored by the proteomics technique. Firstly, the POF model was induced in mice by intragastric administration of Tripterygium wilfordii glycosides solution at 50 mg·kg~(-1) for 14 days. Ten days prior to the end of the modeling, the estrous cycle of mice was observed every day to evaluate the success of modeling. From the 1st day after modeling, the POF model mice were treated with QWGB by gavage every day and the treatment lasted four weeks. On the 2nd day after the end of the experiment, blood was collected from the eyeballs and the serum was separated by centrifugation. The ovaries and uterus were collected and the adipose tissues were carefully stripped. The organ indexes of the ovaries and uterus of each group were calculated. The serum estrogen(E_2) level of mice in each group was detected by ELISA. Protein samples were extracted from ovarian tissues of mice, and the differential proteins before and after QWGB intervention and before and after modeling were analyzed by quantitative proteomics using tandem mass tags(TMT). As revealed by the analysis of differential proteins, QWGB could regulate 26 differentially expressed proteins related to the POF model induced by T. wilfordii glycosides, including S100A4, STAR, adrenodoxin oxidoreductase, XAF1, and PBXIP1. GO enrichment results showed that the 26 differential proteins were mainly enriched in biological processes and cellular components. The results of KEGG enrichment showed that those differential proteins were involved in signaling pathways such as completion and coalescence cascades, focal adhesion, arginine biosynthesis, and terpenoid backbone biosynthesis. The complement and coalescence cascades signaling pathway was presumably the target pathway of QWGB in the treatment of POF. In this study, the proteomics technique was used to screen the differential proteins of QWGB in the treatment of POF in mice induced by T. wilfordii glycosides, and they were mainly involved in immune regulation, apoptosis regulation, complement and coagulation cascade reactions, cholesterol metabolism, and steroid hormone production, which may be the main mechanisms of QWGB in the treatment of POF.

Effects of different extraction methods on chemical compositions and biological activities of polysaccharides from Lycium barbarum / 中国中药杂志

In this study, five polysaccharides from Lycium barbarum(LBPs)(LBP-1-LBP-5) were selectively extracted by different extraction methods, and the chemical composition, structural characteristics, and biological activities of LBPs were explored. The results of chemical composition analysis showed that alkaloids were not detected in the five LBPs. The total polysaccharide content was(81.95%±1.6%)-(92.96%±0.76%), the uronic acid content was(8.26%±0.46%)-(24.81%±0.46%), and the protein content was(0.06%±0.03%)-(1.35%±0.13%). The monosaccharide compositions of the five LBPs were basically same, mainly including glucose, xylose, and galactose. However, there was significant difference in the content ratio of different monosaccharide. The results of infrared spectra analysis indicated that the five LBPs had typical infrared spectral characteristics of polysaccharides. The results of nuclear magnetic resonance characteristic spectrum analysis revealed that the five LBPs had two configurations of α and β. Meanwhile, there were triple helix structures in LBP-2, LBP-3, and LBP-4, which enhanced the activities of polysaccharides. The results of activities screening suggested that the biological activities of the five LBPs were significantly different. LBP-3 showed the highest lipid oxidation clearance rate, and its antioxidant activity was equivalent to that of the positive control group. The inhibitory rate of LBP-4 on α-amylase and its activation rate of alcohol dehydrogenase were better than those of other fractions, and the inhibitory rate of LBP-4 on α-amylase was slightly higher than that of the positive control group when the mass concentration was 10 g·L~(-1). LBP-2 showed stronger inhibitory activity against α-glucosidase and hyaluronidase. This study provides references for the precise development and utilization of LBPs.

Quality evaluation of Commelina communis from different origins based on multicomponent content determination combined with chemometrics / 中国中药杂志

This research established a high-performance liquid chromatography(HPLC) method for simultaneous determination of isoorientin, orientin, vitexin, and isovitexin in Commelina communis to conduct content difference analysis and quality evaluation of 62 batches of C. communis from different origins. The HPLC content determination was performed on a Dikma Platisil ODS chromatographic column(4.6 mm×250 mm, 5 μm), with acetonitrile-0.1% formic acid(14∶86) as the mobile phase. The detection wavelength was set at 348 nm, the flow rate was 1.0 mL·min~(-1), and the column temperature was 35 ℃. The differences in origins and quality of 62 batches of C. communis were studied by chemometrics. The results showed that the determination of four components mani-fested a good linear relationship in the range of mass concentration(r>0.999 9), and the average recovery rate was 96.17%-103.0%. The relative standard deviations(RSDs) of precision, stability, and repeatability were all less than 2.0%. The content of four components from high to low was isoorientin>isovitexin>orientin>vitexin. Forty-seven batches of C. communis with clear origins were classified into six categories by chemometrics. C. communis from different origins had different qualities. Generally, C. communis from Western China, Central China, and South of China had superior qualities. The HPLC method established in this study is specific, simple, and efficient, which provides references for the comprehensive evaluation of the quality of C. communis. The chemometrics shows that the qualities of C. communis from different origins are largely different. Isoorientin can be used as an index to determine the content of C. communis, and its content limit should be set no less than 0.023%.

Association between blood pressure during 12-28 weeks gestation and pre-eclampsia: predictive value of blood pressure trajectories constructed by latent class growth modeling / 中华心血管病杂志

Objective: To explore the associations between blood pressure trajectories during pregnancy and risk of future pre-eclampsia in a large cohort enrolling pregnant women at gestational age of ~12 weeks from community hospitals in Tianjin. Latent class growth modeling (LCGM) was used to model the blood pressure trajectories. Methods: This was a large prospective cohort study. The study enrolled pregnant women of ~12 weeks of gestation in 19 community hospitals in Tianjin from November 1, 2016 to May 30, 2018. We obtained related information during 5 antepartum examinations before gestational week 28, i.e., week 12, week 16, week 20, week 24 and week 28. LCGM was used to model longitudinal systolic (SBP) and diastolic blood pressure (DBP) trajectories. For the association study, the predictors were set as SBP and DBP trajectory membership (built separately), the outcome was defined as the occurrence of preeclampsia after 28 weeks of gestation. Results: A total of 5 809 cases with known pregnant outcomes were documented. After excluding 249 cases per exclusion criteria, 5 560 cases with singleton pregnancy were included for final analysis. There were 128 cases preeclampsia and 106 cases gestational hypertension in this cohort. Univariate logistic regression and multivariate logistic regression showed the higher baseline SBP level and DBP level were related with increased risk of preeclampsia. Four distinctive SBP trajectories and DBP trajectories from 12 weeks to 28 weeks of gestation were identified by LCGM. After controlling for potential confounders (baseline BMI, being primipara or not, white blood cell counts, hemoglobin level, platelet counts and alanine aminotransferase level), the OR for SBP latent classification trajectory_ 4 was 4.023 (95%CI: 2.368 to 6.835, P<0.001), and the OR for SBP latent classification trajectory_3 was 1.854 (95%CI: 1.223 to 2.811, P=0.004). Logistic regression showed that: using the DBP latent classification trajectory_1 as the reference group, the OR for DBP latent classification trajectory_4 was 4.100 (95%CI: 2.571 to 6.538, P<0.001), and 2.632 (95%CI: 1.570 to 4.414, P<0.001) for DBP latent classification trajectory_2. After controlling for potential confounders (baseline BMI, being primipara or not, white blood cell counts, hemoglobin level, platelet counts and alanine aminotransferase level), the OR for DBP_traj_4 was 2.527 (95%CI: 1.534 to 4.162, P<0.001), and the OR for DBP_traj_3 was 1.297 (95%CI: 0.790 to 2.128, P=0.303), and 2.238 (95%CI: 1.328 to 3.772, P=0.002) for DBP_traj_2. Therefore, BP trajectories from 12 weeks to 28 weeks identified by LCGM served as novel risk factors that independently associated with the occurrence of preeclampsia. Receiver operating characteristic (ROC) curve analysis showed incremental diagnostic performance by combing baseline blood pressure levels with blood pressure trajectories. Conclusion: By applying LCGM, we for the first time identified distinctive BP trajectories from gestational week 12 to 28, which can independently predict the development of preeclampsia after 28 weeks of gestation.

Lipidomic investigation of the protective effects of Polygonum perfoliatum against chemical liver injury in mice / 中西医结合学报

OBJECTIVE@#Recent investigations have demonstrated that Polygonum perfoliatum L. can protect against chemical liver injury, but the mechanism behind its efficacy is still unclear. Therefore, we studied the pharmacological mechanism at work in P. perfoliatum protection against chemical liver injury.@*METHODS@#To evaluate the activity of P. perfoliatum against chemical liver injury, levels of alanine transaminase, lactic dehydrogenase, aspartate transaminase, superoxide dismutase, glutathione peroxidase and malondialdehyde were measured, alongside histological assessments of the liver, heart and kidney tissue. A nontargeted lipidomics strategy based on ultra-performance liquid chromatography quadrupole-orbitrap high-resolution mass spectrometry method was used to obtain the lipid profiles of mice with chemical liver injury and following treatment with P. perfoliatum; these profiles were used to understand the possible mechanisms behind P. perfoliatum's protective activity.@*RESULTS@#Lipidomic studies indicated that P. perfoliatum protected against chemical liver injury, and the results were consistent between histological and physiological analyses. By comparing the profiles of liver lipids in model and control mice, we found that the levels of 89 lipids were significantly changed. In animals receiving P. perfoliatum treatment, the levels of 8 lipids were significantly improved, relative to the model animals. The results showed that P. perfoliatum extract could effectively reverse the chemical liver injury and significantly improve the abnormal liver lipid metabolism of mice with chemical liver injury, especially glycerophospholipid metabolism.@*CONCLUSION@#Regulation of enzyme activity related to the glycerophospholipid metabolism pathway may be involved in the mechanism of P. perfoliatum's protection against liver injury. Please cite this article as: Peng L, Chen HG, Zhou X. Lipidomic investigation of the protective effects of Polygonum perfoliatum against chemical liver injury in mice. J Integr Med. 2023; 21(3): 289-301.

Spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium

Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.