Category: Statistics

Zhongguo Zhong Yao Za Zhi. 2024 Jun;49(11):3061-3069. doi: 10.19540/j.cnki.cjcmm.20240202.701.

ABSTRACT

In order to study the toxic effect and mechanism of triptolide(TP) on the reproductive system of female rats with Ⅱ type collagen induced arthritis(CIA), 50 SD rats were randomly divided into normal control group, CIA model group, and three groups receiving TP tablets at clinically equivalent doses of 0. 5, 1, and 2 times, respectively(with TP dosages of 3. 75, 7. 5, and 15 μg·kg~(-1)·d~(-1)), each comprising 10 rats. Intragastric administration was started on the day after the first immunization, once a day, for 42 days.The results were taken on the 21st and 42nd days to calculate the uterine and ovarian organ indexes; pathological and morphological changes in uterus and ovaries were observed under a light microscope; and the levels of estradiol(E_2) and cytochrome P450A1(aromatase,CYP19A1) in ovarian homogenate were detected by ELISA. Furthermore, immunohistochemistry was employed to detect the expression levels of transforming growth factor β3( TGFβ3) pathway-related proteins, mothers against decapentaplegic homolog 3(Smad3) and steroidogenic factor-1(SF-1) in ovarian tissues. In vitro, the mouse Chinese hamster ovary(CHO) cell line was established, and after 24 hours of TP administration(30, 60, 120 nmol·L~(-1)), cell proliferation was detected by the thiazolyl blue tetrazolium bromide(MTT) method, apoptosis by the flow cytometry, and TGFβ3, Smad3 and SF-1 protein expression in cells by the Western blot method, and the nuclear entry of SF-1 was detected by immunofluorescence. The results showed that compared with the CIA model group, all TP administration groups showed decreased number of uterine glands, total follicles, mature follicles, and corpus luteum on days 21 and 42 of administration, but there was no statistical difference, and only the administration of 2 times the clinically equivalent dose of TP could significantly increase the number of atretic follicles at 42 days of administration. TP at 3. 75 μg·kg-1·d-1significantly reduced the level of E_2 at 21 days of administration and the expression of TGFβ3 and Smad3 factors in ovarian tissues,but had no significant effect on the rate-limiting enzyme in estrogen synthesis CYP19A1. TP at 7. 5 and 15 μg·kg~(-1)·d~(-1) significantly reduced the expression of SF-1 regardless of administration for 21 days or 42 days. TP can significantly promote ovarian cell apoptosis in vitro, with apoptosis mainly concentrated in the late stage of apoptosis after 24 hours of administration. In addition, 60 nmol·L~(-1) TP significantly reduced the protein expression of TGFβ3, Smad3 and SF-1 in a dose-dependent manner. In summary, intragastric administration of TP at less than 2 times the clinically equivalent dose for 21 days and 42 days did not cause obvious reproductive damage to the uterus and ovarian tissues of CIA rats, and the number of atretic follicles changed significantly only when the 2 times the clinically equivalent dose was administered for 42 days. TP exerted reproductive toxicity in vivo on reproductive target organs and in vitro on ovarian cells by inhibiting the expression of TGFβ3/Smad3/SF-1 pathway.

PMID:39041166 | DOI:10.19540/j.cnki.cjcmm.20240202.701

Zhongguo Zhong Yao Za Zhi. 2024 Jun;49(11):2889-2896. doi: 10.19540/j.cnki.cjcmm.20240315.102.

ABSTRACT

To determine the optimal harvesting period and rational medicinal parts of Zanthoxylum nitidum, the main effective components of cultivated Z. nitidum samples, which originate from various growth years, harvesting months, and different parts were analyzed and compared with the wild samples. HPLC was performed on a Kinetex C18 column(4. 6 mm×100 mm, 2. 6 μm) with the gradient elution of 0. 3% phosphoric acid solution-acetonitrile(80 ∶ 20) containing 0. 2% triethylamine. The flow rate was 1. 0 m L·min-1, and the detection wavelength was 273 nm. The column temperature was 30 ℃. Nitidine chloride and chelerythrine, the main effective components, were determined as the markers. The results showed there was no significant difference in the contents of the main effective components among the roots of wild and cultivated Z. nitidum, as well as the roots and roots + stems of cultivated Z. nitidum. The statistical results of HCA and PCA indicated that the roots and stems could be clearly distinguished, but no distinction could be made between wild and cultivated products, which was consistent with the results of the significance analysis. The total contents of nitidine chloride and chelerythrine in roots and stems of Z. nitidum of 1-6 years old were 0. 114%-0. 256% and 0. 030%-0. 133%, respectively. These results suggested a positive correlation between the content of the main effective components and the growth years. No significant difference was observed between the contents of samples harvested in different seasons, indicating that the harvest season had no effect on the content of the main effective components of the Z. nitidum samples. The total contents of nitidine chloride and chelerythrine of the dried Z. nitidum samples(excluding branches) from three plantation bases were 0. 308%±0. 123% in Yunfu, 0. 192%±0. 025% in Maoming, and 0. 197%±0. 052% in Nanning, respectively, and they were all not less than 0. 15%, or in other words, the roots(including fibrous roots, taproots, and underground stems) and stems(aboveground stems) of Z. nitidum transplanted for more than 2. 5 years can meet the medical requirements. This study demonstrates that the cultivated Z. nitidum could be used as a valid substitute for the wild Z. nitidum, which provides a guarantee for the sustainable development and the application of Z. nitidum resources. The stems and roots could be considered medicinal parts of Z. nitidum. It is recommended to revise the medicinal parts of Z. nitidum to dried roots and stems in the next edition of Chinese Pharmacopoeia, and the medicinal parts can be harvested all year round. In order to ensure the content of effective components and clinical effectiveness, the root and stem should be harvested for medical use after the seedlings of Z. nitidum have been transplanted for more than three years.

PMID:39041148 | DOI:10.19540/j.cnki.cjcmm.20240315.102

Zhongguo Zhong Yao Za Zhi. 2024 Jul;49(13):3462-3472. doi: 10.19540/j.cnki.cjcmm.20240414.104.

ABSTRACT

To comprehensively reveal and utilize the plant resources of Lycium in China, this study determined and compared the content of monosaccharides, polysaccharides, proteins, carotenoids, organic acids, and phenols in the dried fruits of 8 different Lycium species. Furthermore, the traits including the hundred-fruit weight, shape index, and the ratio of seed to fruit were measured, and the correlations between the content of chemical compounds and fruit traits were assessed. The results showed that L. truncatum, L. barbarum var. auranticarpum, and L. dasystemum var. rubricaulium were the species with high content of monosaccharides. L. barbarum and L. barbarum var. auranticarpum were the species with high content of total polysaccharides, and L. barbarum was the species with high content of carotenoids. L. yunnanense and L. chinense var. potaninii had high content of soluble proteins. L. truncatum, L. dasystemum, and L. barbarum showed high content of organic acids and phenols. L. barbarum and L. barbarum var. auranticarpum demonstrated high fruit weight, while L. yunnanense and L. chinense had high ratios of seed to fruit. The multivariate statistical analysis indicated that polysaccharides, carotenoids, hundred-fruit weight, ratio of seed to fruit, scopolamine, fructose, 5-O-feruloylquinic acid, kaempferol-3-O-rutinoside, scopoletin, cryptochlorogenic acid, and caffeic acid were the main differential compounds in the fruits among different species of Lycium. Moreover, the results of correlation ananysis showed strong correlations between fruit traits and compound content. Specifically, the hundred-fruit weight had positive correlations with the content of total polysaccharides and scopola-mine. The ratio of seed to fruit was negatively correlated with the content of rutin, kaempferol-3-O-rutinoside, fructose, and glucose and positively correlated with the content of succinic acid, soluble proteins, and zeaxanthin. The results implied that chemical compounds presented different distribution patterns in the fruits of 8 Lycium species. This study provides a basis for the comprehensive development and utilization, targeted breeding, and value-added application of Lycium plants.

PMID:39041118 | DOI:10.19540/j.cnki.cjcmm.20240414.104

Zhongguo Zhong Yao Za Zhi. 2024 Jul;49(13):3409-3413. doi: 10.19540/j.cnki.cjcmm.20240516.101.

ABSTRACT

This article outlined the composition and species characteristics of Chinese materia medica(CMM) resources identified in the fourth national survey of CMM resources. The survey was conducted based on field investigations and office collation, adhering to the "four principles", which emphasized the existence of survey records, voucher specimens, actual photographs, and evidence of medicinal use, so as to summarize the species of CMM resources and ensure the scientific integrity and accuracy of the results. According to the results, China had a total of 18 817 CMM resources, including 15 321 medicinal plants, 826 medicinal fungi, 2 517 medicinal animals, and 153 medicinal minerals. Additionally, the fourth national survey of CMM resources also conducted specialized investigations on 3 151 species of unique medicinal plants, 464 species of rare and endangered medicinal plants, and 196 new species in China. These latest statistics on these CMM resources will provide the most up-to-date foundational data for the protection, management, development, and utilization of these resources over an extended period, offering scientific guidance for the development of the traditional Chinese medicine(TCM) industry.

PMID:39041112 | DOI:10.19540/j.cnki.cjcmm.20240516.101

Zhongguo Zhong Yao Za Zhi. 2024 Jun;49(12):3396-3403. doi: 10.19540/j.cnki.cjcmm.20240306.501.

ABSTRACT

This study utilized a prospective, large-sample, multi-center, and registered key specialty approach of hospitals to monitor the application of Reduning Injection. A total of 100 249 adolescent patients aged 14 years and below who received Reduning Injection were monitored, resulting in 83 cases of adverse events, with 76 of them being classified as adverse drug reaction(ADR). The calculated incidence rate of ADR for Reduning Injection was 0.076%, indicating a very rare ADR. The main symptoms of ADR were pruritus, diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsion, and chills. All ADR cases were reported for the first time, including three new ADR cases and 73 known ADR cases. The categories of ADR was general ADR. All ADR was mild in severity. There were more males than females in ADR patients. One patient had a history of ADR, and the drug causing ADR was buprofen. The largest number of ADR cases occurred when the dosage of Reduning injection was 5-10 mL. The dropping speed was 30 drops or less per min, and the solvent type was 5% glucose injection. The most common manifestation of ADR patients was pruritus, followed by diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsions, and chills. 72 patients(94.74% of ADR patients) discontinued the drug, and three patients(3.95% of ADR patients) were given oxygen inhalation. 47 cases(61.84% of ADR patients) were treated with medication, of which dexamethasone was the most used(24 cases, 46.15% of ADR patients). 76 ADR patients were cured or improved. ADRs are more likely to occur when diagnosed with acute bronchitis by western medicine and cough by traditional Chinese medicine(TCM), TCM syndrome type is wind heat syndrome, and the combination medicine is ambroxol hydrochloride and bromhexine hydrochloride injection, ascorbic acid/vitamin C injection. This result provides an evidence-based safety basis for active pharmacovigilance of Reduning Injection in adolescents aged 14 years and below.

PMID:39041103 | DOI:10.19540/j.cnki.cjcmm.20240306.501

Zhongguo Zhong Yao Za Zhi. 2024 Jun;49(12):3385-3395. doi: 10.19540/j.cnki.cjcmm.20240219.501.

ABSTRACT

The efficacy and safety of Shenshao Capsules in combination with conventional western medicine for the treatment of angina pectoris in coronary heart disease were systematically evaluated. Computer search of seven databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library, was conducted to identify randomized controlled trial(RCT) on Shenshao Capsules for the treatment of angina pectoris in coronary heart disease up to December 2023. According to inclusion and exclusion criteria, articles were screened, and data was extracted. Cochrane bias risk assessment tool 2.0(RoB 2.0) was used to evaluate the quality of the included articles. Meta-analysis was performed by RevMan 5.4 and Stata/SE 15.1 software, and evidence quality was rated by the GRADE system. TSA 0.9.5.10 beta software was used for the trial sequential analysis(TSA). Twelve RCTs, with a total of 1 128 participants(567 in the experimental group and 561 in the control group), were included. Meta-analysis showed that Shenshao Capsules + conventional western medicine significantly improved clinical efficacy(RR=1.20, 95%CI[1.15, 1.26], P<0.000 01) and electrocardiogram efficacy(RR=1.16, 95%CI[1.04, 1.30], P=0.01), reduced the frequency of weekly angina pectoris attacks(MD=-2.85, 95%CI[-5.27,-0.43], P=0.02), daily angina pectoris attacks(MD=-0.30, 95%CI[-0.57,-0.03], P=0.03) and the duration of angina pectoris attacks(RR=-2.28, 95%CI[-3.44,-1.12], P=0.000 1). There was no statistically significant difference in adverse reactions between the two groups(RR=1.33, 95%CI[0.71, 2.51], P=0.37). TSA indicated that the cumulative evidence for clinical efficacy exceeded the traditional boundary but did not exceed the TSA boundary, suggesting a potential false positive result. According to GRADE assessment, except for clinical efficacy, which was rated as low-quality evidence, the remaining outcomes were rated as very low-quality evidence. The results indicate that Shenshao Capsules + conventional western medicine may have certain advantages in improving clinical efficacy and electrocardiographic efficacy, reducing the frequency and duration of angina pectoris attacks. However, due to the limitations of this study, more rigorous and high-quality RCT is needed to validate its efficacy and safety.

PMID:39041102 | DOI:10.19540/j.cnki.cjcmm.20240219.501

Zhongguo Zhong Yao Za Zhi. 2024 Jun;49(12):3312-3319. doi: 10.19540/j.cnki.cjcmm.20231220.401.

ABSTRACT

Urine metabolomics based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS) was utilized to investigate the metabolic regulation mechanism of Tingli Dazao Xiefei Decoction(TLDZ) in rats with allergic asthma. SD male rats were divided into a normal group, a model group, a dexamethasone group, and a TLDZ group. The allergic asthma model was established by intraperitoneal injection of ovalbumin(OVA) to induce allergy, combined with atomization excitation. Urine metabolites from all rats were collected by UHPLC-Q-TOF-MS. The metabolic profiles of rats in each group were built by principal component analysis(PCA). Besides, the differential metabolites between the model group and the TLDZ group were selected by orthogonal partial least squares discriminant analysis(OPLS-DA), t-test(P<0.05), and variable importance in the projection(VIP) values of more than 3. The differential metabolites were identified through HMDB, METLIN, and other online databa-ses. Heat maps and clustering analysis for relative quantitative information of biomarkers in each group were drawn by MeV 4.8.0 software. Finally, MetaboAnalyst, MBRole, and KEGG databases were used to enrich related metabolic pathways and construct metabolic networks. The result demonstrated that TLDZ could effectively regulate the disordered urine metabolic profiles of asthmatic rats. Combined with multivariate statistical analysis and online databases, a total of 45 differential metabolites with significant changes(P<0.05) between the model group and the TLDZ group were screened out. Metabolic pathways including histidine metabolism, tryptophan metabolism, and arginine and proline metabolism were enriched. TLDZ could improve asthma by regulating related metabolic pathways and interfering with pathological processes such as immune homeostasis airway inflammation. The study investigates the molecular mechanism of anti-asthma of TLDZ from the perspective of urine metabolomics, and combined with previous pharmacological studies, it provides a scientific basis for the clinical development and application of TLDZ in the treatment of asthma.

PMID:39041094 | DOI:10.19540/j.cnki.cjcmm.20231220.401

Clin Mol Hepatol. 2024 Jul 23. doi: 10.3350/cmh.2024.0333. Online ahead of print.

ABSTRACT

INTRODUCTION: Combination immunotherapy, exemplified by atezolizumab plus bevacizumab, has become the standard of care for inoperable hepatocellular carcinoma (HCC). However, the lack of predictive biomarkers and limited understanding of response mechanisms remain a challenge.

METHODS: Using data from the IMbrave150plus cohort, we applied an immune signature score (ISS) predictor to stratify HCC patients treated with atezolizumab plus bevacizumab or with sorafenib alone into potential high and low response groups. By applying multiple statistical approaches including a Bayesian covariate prediction algorithm, we refined the signature to 10 key genes (ISS10) for clinical use while maintaining similar predictive power to the full model. We further validated ISS10 in an independent HCC cohort treated with nivolumab plus ipilimumab.

RESULTS: The study identified a significant association between the ISS and treatment response. Among patients classified as high responders, those treated with the atezolizumab plus bevacizumab combination exhibited improved overall and progression-free survival as well as better objective response rate compared to those treated with sorafenib. We also observed a significant correlation between ISS10 and response to nivolumab plus ipilimumab treatment. Analysis of immune cell subpopulations revealed distinct characteristics associated with ISS subtypes. In particular, the ISS10 high subtype displayed a more favorable immune environment with higher proportions of anti-tumor macrophages and activated T-cells, potentially explaining its better response.

CONCLUSIONS: Our study suggests that ISS and ISS10 are promising predictive biomarkers for enhanced therapeutic outcomes in HCC patients undergoing combination immunotherapy. These markers are crucial for refining patient stratification and personalized treatment approaches to advance the effectiveness of standard-of-care regimens.

PMID:39038962 | DOI:10.3350/cmh.2024.0333

AJNR Am J Neuroradiol. 2024 Jul 22:ajnr.A8424. doi: 10.3174/ajnr.A8424. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Accelerated and blood-suppressed post-contrast 3D intracranial vessel wall MRI (IVW) enables high-resolution rapid scanning but is associated with low SNR. We hypothesized that a deep-learning (DL) denoising algorithm applied to accelerated, blood-suppressed post-contrast IVW can yield high-quality images with reduced artifacts and higher SNR in shorter scan times.

MATERIALS AND METHODS: Sixty-four consecutive patients underwent IVW, including conventional post-contrast 3D T1-sampling perfection with application-optimized contrasts by using different flip angle evolution (SPACE) and delay-alternating with nutation for tailored excitation (DANTE) blood-suppressed and CAIPIRINHIA-accelerated (CAIPI) 3D T1-weighted TSE post-contrast sequences (DANTE-CAIPI-SPACE). DANTE-CAIPI-SPACE acquisitions were then denoised using an unrolled deep convolutional network (DANTECAIPI-SPACE+DL). SPACE, DANTE-CAIPI-SPACE, and DANTE-CAIPI-SPACE+DL images were compared for overall image quality, SNR, severity of artifacts, arterial and venous suppression, and lesion assessment using 4-point or 5-point Likert scales. Quantitative evaluation of SNR and contrast-to-noise ratio (CNR) was performed.

RESULTS: DANTE-CAIPI-SPACE+DL showed significantly reduced arterial (1 [1-1.75] vs. 3 [3-4], p<0.001) and venous flow artifacts (1 [1-2] vs. 3 [3-4], p<0.001) compared to SPACE. There was no significant difference between DANTE-CAIPI-SPACE+DL and SPACE in terms of image quality, SNR, artifact ratings and lesion assessment. For SNR ratings, DANTE-CAIPI-SPACE+DL was significantly better compared to DANTE-CAIPI-SPACE (2 [1-2], vs. 3 [2-3], p<0.001). No statistically significant differences were found between DANTECAIPI-SPACE and DANTE-CAIPI-SPACE+DL for image quality, artifact, arterial blood and venous blood flow artifacts, and lesion assessment. Quantitative vessel wall SNR and CNR median values were significantly higher for DANTE-CAIPI-SPACE+DL (SNR: 9.71, CNR: 4.24) compared to DANTE-CAIPI-SPACE (SNR: 5.50, CNR: 2.64), (p<0.001 for each), but there was no significant difference between SPACE (SNR: 10.82, CNR: 5.21) and DANTE-CAIPI-SPACE+DL.

CONCLUSIONS: Deep-learning denoised post-contrast T1-weighted DANTE-CAIPI-SPACE accelerated and blood-suppressed IVW showed improved flow suppression with a shorter scan time and equivalent qualitative and quantitative SNR measures relative to conventional post-contrast IVW. It also improved SNR metrics relative to post-contrast DANTE-CAIPI-SPACE IVW. Implementing deep-learning denoised DANTE-CAIPI-SPACE IVW has the potential to shorten protocol time while maintaining or improving the image quality of IVW.

ABBREVIATIONS: DL=deep learning; IVW=Intracranial vessel wall MRI; SPACE=sampling perfection with application-optimized contrasts by using different flip angle evolution; DANTE=delay-alternating with nutation for tailored excitation; CAIPI=controlled aliasing in parallel imaging; CNR=contrast-to-noise ratio.

PMID:39038956 | DOI:10.3174/ajnr.A8424

Inj Prev. 2024 Jul 22:ip-2024-045257. doi: 10.1136/ip-2024-045257. Online ahead of print.

ABSTRACT

OBJECTIVES: There has been extensive debate in the USA as to how laws regulating the carrying of concealed firearms affect crime and public safety. This study examines whether US state laws making it easier for civilians to obtain permits to carry concealed handguns in public increase defensive gun uses against violent threats and attacks in public.

METHODS: We used National Crime Victimization Survey data from 39 metropolitan statistical areas (MSAs) in the USA over a 19-year period (1986-2004) to examine whether laws making it easier for civilians to obtain concealed carry permits are linked to higher levels of defensive gun use against violence in public spaces of metropolitan areas. Bivariate χ² tests and multivariate logistic regression models (controlling for actor and situational characteristics) were used with 7196 public incidents to examine whether the likelihood of the victim using a gun against an attacker(s) varied based on the type of concealed carry law in the MSA at the time of the incident.

RESULTS: The prevalence of self-defensive gun use in this sample was not clearly related to the passage of permissive gun carrying laws. Although defensive gun use was more common in MSAs with permissive gun carrying laws, this difference was not consistently related in magnitude or statistical significance to the passage of those laws or the length of time they had been in effect.

CONCLUSIONS: Permissive concealed carry permit laws do not produce evident increases in self-defensive gun uses against crime in public locations.

PMID:39038941 | DOI:10.1136/ip-2024-045257