Lingguizhugan Decoction (LGZG) demonstrates significant efficacy in treating various cardiovascular diseases clinically, yet its precise mechanism of action remains elusive. This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol (ISO) continuous stimulation-induced chronic heart failure (CHF) in mice, providing direct experimental evidence for further clinical applications. In vivo, continuous ISO infusion was administered to mice, and ventricular myocytes were utilized to explore LGZG?s potential mechanism of action on the ?1-adrenergic receptor (?1-AR)/Gs/G protein-coupled receptor kinases (GRKs)/?-arrestin signaling deflection system in the heart. The findings reveal that LGZG significantly reduced the messenger ribonucleic acid (mRNA) expression of hypertrophy-related biomarkers [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF. Furthermore, LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling and downregulated the downstream transcriptional activity of cAMP-response element binding protein (CREB) and the expression of the coactivator CBP/P300. Notably, LGZG downregulated the expression of ?-arrestin1 and GRK 2/3/5 while upregulating the expression of ?1-AR and ?-arrestin2. These results suggest that LGZG inhibits Gs/cAMP/PKA signaling and ?-arrestin/GRK-mediated desensitization and internalization of ?1-AR, potentially exerting cardioprotective effects through the synergistic regulation of the ?1-AR/Gs/GRKs/?-arrestin signaling deflection system via multiple pathways.
Animals ; Heart Failure/genetics* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Male ; G-Protein-Coupled Receptor Kinases/genetics* ; Mice, Inbred C57BL ; Humans ; Isoproterenol ; Arrestins/genetics* ; Chronic Disease

OBJECTIVE To analyze the metabolites of Zhideke granules and speculate its metabolic pathway in rats in vivo. METHODS Male SD rats were randomly divided into blank group and administration group （Zhideke granules， 9.45 g/kg）； they were given ultrapure water or relevant medicine， twice a day， every 6-8 h， for 3 consecutive days. Serum， urine and feces samples of rats were collected， and their metabolites were identified by UPLC-Q-Exactive-MS technique after intragastric administration of Zhideke granules； their metabolic pathways were speculated. RESULTS After intragastric administration of Zhideke granules， 16 prototype components （i.g. irisflorentin， baicalin， chlorogenic acid） and 11 metabolites （i.g. hydration products of kaempferol or luteolin， methylation products of chlorogenic acid， and hydroxylation products of baicalin） were identified in serum， urine and feces of rats. Among them， 8 prototype components and 4 metabolites were identified in serum samples； 10 prototype components and 7 metabolites were identified in urine samples； 8 prototype components and 5 metabolites were identified in the fecal samples. CONCLUSIONS The metabolites of Zhideke granules in rats mainly include baicalin， irisflorentin，chlorogenic acid， and the main metabolic pathways included methylation， hydroxylation， glucuronidation.

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
Female ; Humans ; Uterine Cervical Neoplasms/drug therapy* ; Prospective Studies ; Quality of Life ; Neoplasm Staging ; Chemoradiotherapy ; Chemotherapy, Adjuvant/adverse effects* ; Adjuvants, Immunologic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies

Objective To establish the HPLC method of assay for diphenhydramine hydrochloride in compound diphenhydramine cream. Method HPLC analysis was carried on ACE5C₁₈S/N-A66766 column (150 mm×4.6 mm, 5 µm) with the mobile phase of methanol-water-triethylamine (70:30:0.67, adjusting pH to 6.50 with phosphoric acid) at room temperature. The detection wavelength was set at 230 nm and the flow rate was 1.0 ml/min. The analyte was extracted from the cream and 20 μl of sample was injected. Results The calibration curve of diphenhydramine hydrochloride was linear in the range of 39.52-197.6 µg/ml (r=0.999 7). The average recovery of diphenhydramine hydrochloride was 100.5% (RSD=1.25%, n=9). The repeatability of the method was expressed using RSD with 0.78% (n=6). The results of assay were 101.3%, 99.83% and 99.62%. Conclusion The method is accurate, sensitive, selective and repeatable, which can be applied for improving the quality standard of compound diphenhydramine cream.

Objective To investigate the disease characteristics and key factors of pharmaceutical care in patients with diabetes and osteoporosis, and provide references for clinical rational and effective medication. Methods Clinical pharmacist participated in the drug analysis of a patient with type 2 diabetes and osteoporosis. The pharmaceutical recommendations were proposed to assist physicians in optimizing the treatment plan, combined with the patient’s disease characteristics and pathological characteristics. Results After the reorganization of the treatment plan and pharmaceutical care, the patient's treatment effect had been significantly improved. Conclusion The pathogenesis of diabetic osteoporosis is complex. The current treatment is based on hypoglycemic combined with anti-osteoporosis drugs. Through chronic disease drug management and pharmaceutical monitoring, rational drug use could be promoted.

Objective:To investigate the status quo of the knowledge, attitude and practice (KAP) of standardized insulin injection at home in Shanghai community diabetic patients and analyze its influencing factors.Methods:In this cross-sectional study, totally 1 947 diabetic patients who signed to be managed by 21 community health service centers in Fengxian District, Shanghai from May to October 2020 who used insulin pen injections at home were selected by continuous enrolment. They were investigated with a general information questionnaire and a questionnaire on KAP of standardized insulin injection. Univariate analysis and multiple linear regression were used to analyze the influencing factors of patients' KAP of standardized insulin injection at home. A total of 1 947 questionnaires were distributed, and 1 697 valid questionnaires were recovered, with an effective recovery rate of 87.2%.Results:The total KAP score of insulin standard injection in the 1 697 diabetic patients was (51.01±6.81) , which was at a moderate level. Among all the items in the questionnaire, the 3 items with the lowest compliance rate were: checking the injection site every time before insulin injection (14.4%) , agreeing to put the discarded insulin needles into the capped hard-shell container (16.1%) , agreeing to and implementing insulin pen needle replacement after each use (20.6%) . Multiple linear regression analysis showed that age, education, type of medical insurance, and whether they had received insulin injection guidance were the influencing factors to the KAP of standardized insulin injection at home ( P<0.01) , which accounted for 8.6% of the total variation. Conclusions:Community medical staff should pay attention to the health education of insulin injection at home for diabetic patients, improve the content and form of education based on the characteristics of the community population, thereby improving the compliance rate of injection site inspection, replacement of insulin pen needles and standardized disposal of discarded needles, further standardizing insulin injection behavior, and improving clinical outcomes such as glycemic control in patients.

Objective:To analyze the clinical features, diagnosis and treatment plan, clinical outcomes of pregnancy with cervical cancer.Methods:The clinical data of 10 pregnant women with cervical cancer from January 2008 to October 2018 in Dalian Obstetrics and Gynecology Hospital Affiliated to Dalian Medical University, the First Hospital of Dalian Medical University, Dalian Central Hospital, Dalian Women and Children′s Medical Center and Wafangdian Central Hospital of Liaoning Province were retrospectively analyzed.Results:The incidence of pregnancy with cervical cancer was 0.004% (10/238 128). Among the 10 cases of pregnancy with cervical cancer, the gestational weeks ≤ 20 weeks at the time of diagnosis was in 6 cases, and they all chose to terminate the pregnancy; the gestational weeks 20 +1 to 30 weeks at the time of diagnosis was in 1 case, and the patient chose to terminate the pregnancy; the gestational weeks >30 weeks at the time of diagnosis was in 2 cases, and they all chose to continue the pregnancy; 1 case was diagnosed after delivery. There were 3 newborns, including 1 premature infants, and they all survived. Conclusions:It is helpful to the diagnose of the disease to strengthen cervical cancer screening before pregnancy and improve the examination of patients with abnormal symptoms during pregnancy. The treatment plan should be individualized according to the pregnancy status, stage of the disease, and wishes of the patient and family.

OBJECTIVE: To assess the value of combined chromosomal karyotyping and chromosomal microarray analysis (CMA) for prenatal diagnosis. METHODS: G-banding karyotyping and CMA were simultaneously performed on 546 women who were subjected to amniocentesis during middle pregnancy. RESULTS: In total 82 cases were detected with chromosomal abnormalities. The two methods were consistent in 43 cases, which included 14 trisomy 21, 6 trisomy 18, 1 trisomy 13, 14 sex chromosomal aneuploidies, 4 chromosomal deletions, 3 chromosomal duplications and 1 sex chromosomal mosaicism. Fifteen fetuses with chromosomal abnormalities detected by CMA were missed by karyotyping analysis, which included 9 microdeletions and 6 microduplications. Sixteen fetuses with chromosomal abnormalities detected by karyotyping analysis were missed by CMA, which included 15 chromosomal translocations and 1 sex chromosomal mosaicism. In 7 cases, the results of karyotyping analysis and CMA were inconsistent. One supernumerary marker chromosome detected by karyotyping analysis was verified by CMA as 9p13.1p21.1 duplication. CONCLUSION Combined chromosomal karyotyping and CMA can significantly improve the detection rate for chromosomal abnormalities, which has a great value for prenatal diagnosis.
Chromosome Aberrations ; Chromosome Disorders ; diagnosis ; genetics ; Female ; Humans ; Karyotyping ; Microarray Analysis ; Pregnancy ; Prenatal Diagnosis

Objective To compare the differences and clinical value of prognostic evaluation between American Joint Committee on Cancer (AJCC) TNM staging system 7th edition and 8th edition for gastric cancer (GC).Methods The retrospective case-control study was conducted.The clinicopathological data of 1 383 GC patients who were admitted to the First People's Hospital of Changzhou between January 2008 and August 2012 were collected.Distal gastrectomy,proximal gastrectomy + pyloroplasty or total gastrectomy were performed according to preoperative evaluation and intraoperative exploration.Observation indicators:(1) surgical and postoperative situations;(2) follow-up and survival situations;(3) T staging comparison between AJCC TNM staging system 7th edition and 8th edition;(4) N staging comparison of AJCC TNM staging system 8th edition;(5) prognostic analysis in N staging of AJCC TNM staging system 8th edition;(6) TNM staging comparison between AJCC TNM staging system 7th edition and 8th edition;(7) prognostic analysis in different TNM staging between AJCC TNM staging system 7th edition and 8th edition.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to October 2017.Measurement data with normal distribution were represented as x ± s.Measurement data with skewed distribution were described as M (range).The survival curve and survival rate were respectively drawn and calculated by the Kaplan-Meier method,and the Log-rank test was used for survival analysis.Results (1) Surgical and postoperative situations:1 383 GC patients underwent successful radical gastrectomy,including 923 with distal gastrectomy,165 with proximal gastrectomy and 295 with total gastrectomy.Of 1 383 patients,115 with postoperative complications were improved by symptomatic treatment,including 87 with surgical complications and 28 with non-surgical complications.Postoperative pathological examinations:total number of intraoperative lymph node dissection and number of lymph node metastasis were 25± 12 and 7±4;577 didn't have lymph node metastasis and 806 had regional lymph node metastasis;308 were in early GC and 1 075 in advanced GC.(2) Follow-up and survival situations:1 383 patients were followed up for 1-117 months,with a median time of 34 months.The 1-,3-and 5-year survival rates of 1 383 patients were respectively 90.5％,71.9％ and 61.1％.(3) T staging comparison between AJCC TNM staging system 7th edition and 8th edition:T staging definition between AJCC TNM staging system 7th edition and 8th edition was identical.T staging of 1 383 patients:308,192,65,628 and 190 were respectively detected in T1,T2,T3,T4a and T4b stagings.(4) N staging comparison between AJCC TNM staging system 7th edition and 8th edition:N staging definition between AJCC TNM staging system 7th edition and 8th edition was identical.N staging of 1 383 patients:577,255,207,230 and 114 were respectively detected in N0,N1,N2,N3a and N3b stagings.N3a and N3b were classified as N3 staging of AJCC TNM staging system 7thedition,but they were classified as independent staging of AJCC TNM staging system 8th edition.(5) Prognostic analysis in N staging of AJCC TNM staging system 8th edition:5-year survival rate of patients in N0,N1,N2,N3a and N3b stagings was respectively 85.6％,76.5％,59.4％,45.2％ and 32.5％ based on AJCC TNM staging system 8th edition,with a statistically significant difference in survival (x2 =394.400,P＜0.05).There was a statistically significant difference between N0 and N 1 stagings (x2 =45.630,P＜0.05),between N 1 and N2 stagings (x2 =19.470,P＜0.05),between N2 and N3a stagings (x2 =7.602,P＜0.05) and between N3a and N3b stagings (x2=13.020,P＜0.05).(6) TNM staging comparison between AJCC TNM staging system 7th edition and 8th edition:TNM staging of 366 patients had changes,including 2 in T1N3b staging,2 in T2N3b staging,18 in T3N3b staging,120 in T4aN2 staging,149 in T4aN3a staging,34 in T4bN0 staging and 41 in T4bN2 staging;364 were detected in staging Ⅲ in 7th edition and 8th edition,and sub-staging of staging Ⅲ had a change;2 in T1N3b of ⅡB staging were redistricted into Ⅲ B staging based on AJCC TNM staging system 8th edition.(7) Prognostic analysis in different TNM staging between AJCC TNM staging system 7th edition and 8th edition:according to 7th edition,cases and 5-year survival rate were respectively 247,89.5％ in Ⅰ A staging and 147,83.7％ in Ⅰ B staging and 77,75.9％ in ⅡA staging and 207,70.5％ in ⅡB staging and 136,61.0％ in ⅢA staging and 236,37.5％ in Ⅲ B staging and 333,35.4％ in Ⅲ C staging,with a statistically significant difference in survival among sub-stagings (x2 =228.800,P＜0.05).There was a statistically significant difference in survival among Ⅰ,Ⅱ and Ⅲ stagings (x2=189.000,P＜0.05) and between ⅢA and ⅢB or ⅢC stagings (x2=22.710,18.010,P＜0.05).There was no statistically significant difference in survival between Ⅰ A and Ⅰ B stagings (x2=0.179,P＞0.05),between Ⅱ A and Ⅱ B stagings (x2 =0.265,P＞0.05),and between Ⅲ B and Ⅲ C stagings (x2 =1.550,P＞0.05).According to 8th edition,cases and 5-year survival rate were respectively 247,89.5％ in Ⅰ A staging and 147,83.7％ in Ⅰ B staging and 77,75.9％ in Ⅱ A staging and 205,70.7％ in Ⅱ B staging and 288,53.8％ in ⅢA staging and 258,37.3％ in ⅢB staging and 161,28.5％ in ⅢC staging,with a statistically significant difference in survival among sub-stagings (x2=234.900,P ＜ 0.05).There was no statistically significant difference in survival between Ⅰ A and Ⅰ B stagings (x2 =0.179,P＞0.05) and between Ⅱ A and ⅡB stagings (x2 =0.564,P＞0.05).There was statistically significant differences in survival between Ⅲ A and Ⅲ B or ⅢC stagings (x2 =29.790,43.060,P＜0.05) and between Ⅲ B and Ⅲ C stagings (x2 =7.494,P＜0.05).Further analysis showed that changes of TNM staging system between 7th edition and 8th edition were in T3N3b,T4aN2,T4aN3a,T4bN0 and T4bN2 stagings,5-year survival rate in above stagings was respectively 16.7％,35.8％,30.2％,47.1％ and 26.8％,with statistically significant differences in survival between T3N3b and T4aN2,T4aN3a,T4bN0 and T4bN2 stagings (x2 =19.590,8.039,12.070,3.853,P＜0.05),between T4aN2 and T4aN3a,T4bN2 stagings (x2 =6.529,3.859,P ＜ 0.05),between T4aN3a and T4bN0 stagings (x2 =10.400,P＜0.05) and between T4bN0 and T4bN2 stagings (x2=4.636,P＜0.05).There was no statistically significant difference in survival between T4aN2 and T4bN0 stagings (x2 =3.607,P＞0.05) and between T4aN3a and T4bN2 stagings (x2 =0.029,P＞0.05).Conclusions Compared with AJCC TNM staging system 7th edition,N3a and N3b stagings are classified as independent staging in AJCC TNM staging system 8th edition,and 8th edition is more accurate in prognostic evaluation of GC patients in stage Ⅲ.

Objective To investigate the factors affecting the efficacy of leflunomide combined with medium/low dose corticosteroids in the treatment of progressive IgA nephropathy (IgAN).Methods Clinical and pathological parameters were collected retrospectively in patients of primary IgAN with proteinuria＞ 1.0 g/24 h and chronic kidney disease (CKD) stage 1-3 treated with leflunomide combined with medium/low dose corticosteroids in Ren Ji Hospital,School of Medicine,Shanghai Jiao Tong University from Jan 2005 to Dec 2010.According to the treatment effects,patients were divided into complete remission group and non-complete remission group.The biochemical and pathological indexes of the two groups were compared.Results A total of 42 patients were included.The remission rates at 3,6,9 and 12 months were 62％,64％,67％ and 74％,respectively.Seventeen (40.5％) and fourteen (33.3％) patients achieved complete and partial remission after one-year treatment,and the remission rate remained stable within one year after withdrawal of drugs.The 24hour proteinuria was 1.50 (0.67,2.66) g,which was significantly reduced compared with the baseline 2.44 (1.36,3.74) g (P ＜ 0.01).The decrease rate was 31.3％.There was a slight decrease in proteinuriawithin one year after withdrawal of drugs.Estimated glomerular filtration rate (eGFR) remained stable during the treatment and a year of follow-up.No serious adverse event was observed during the followup period.Among 31 responder patients,6(19.4％) patients relapsed.Logistic multivariate regression analysis suggested that the degree of renal interstitial inflammatory infiltration was an independent predictor of complete remission with one-year treatment of leflunomide combined with medium / low dose corticosteroids (HR=0.067,95％ CI 0.008-0.535,P=0.011).Conclusions IgAN treated with leflunomide and medium/low dose corticosteroids can achieve remission in early stage,and the remission rate remains stable after withdrawal of drugs.It is a safe option for the treatment of IgAN.Renal interstitial inflammatory infiltration is an independent predictor of complete remission.