ObjectiveTo explore the clinical efficacy and mechanism of Bupi Qingfei prescription （BPQF） in treating stable bronchiectasis in the patients with syndromes of lung-spleen Qi deficiency and phlegm-heat accumulation in the lungs. MethodsA randomized， double-blind， placebo-controlled trial was conducted. Patients were randomized into BPQF and placebo control （PC） groups. On the basis of conventional Western medicine treatment， the BPQF granules and placebo were respectively administered at 10 g each time， twice a day， for a course of 24 weeks. The TCM symptom scores， Quality of Life Questionnaire for Bronchiectasis （QOL-B） scores， lung function indicators， T lymphocyte subsets， level of inflammatory factors in the sputum， level of neutrophil elastase （NE） in the sputum， and occurrence of adverse reactions were observed before and after treatment in the two groups. ResultsA total of 64 patients completed the study， encompassing 32 in the BPQF group and 32 in the PC group. After treatment， the BPQF group showed decreased TCM symptom scores （P<0.01）， increased QOL-B scores （P<0.01）， and declined levels of tumor necrosis factor （TNF）-α and NE （P<0.05， P<0.01）. The PC group showed decreased TCM symptom （except spleen deficiency） scores （P<0.01）， increased the QOL-B health cognition and respiratory symptom domain scores （P<0.05， P<0.01）， and a declined TNF-α level （P<0.01）. Moreover， the BPQF group had lower TCM symptom （except chest tightness） scores （P<0.05， P<0.01）， higher QOL-B （except treatment burden） scores （P<0.05， P<0.01）， and lower levels of interleukin-6 and TNF-α （P<0.05） than the PC group. Neither group showed serious adverse reactions during the treatment process. ConclusionBPQF can ameliorate the clinical symptoms of stable bronchiectasis patients who have lung-spleen Qi deficiency or phlegm-heat accumulation in the lungs by regulating the immune balance and inhibiting airway inflammatory responses.

Objective: To investigate the epidemiological characteristics and spatial-temporal clustering of severe fever with thrombocytopenia syndrome (SFTS) in Huai'an City, Jiangsu Province from 2011 to 2024, so as to provide a basis for optimizing local SFTS prevention and control strategies, and identifying high-risk areas and key populations. Methods: Data on SFTS incidence and deaths in Huai'an City from 2011 to 2024 were collected from the Infectious Disease Reporting Information System of the Chinese Disease Prevention and Control Information System. The reported incidence, mortality, and fatality rates were calculated. Descriptive analysis was performed on temporal, population, and regional distribution. The average annual percent change (AAPC) was used to analyze the trend in the reported incidence of SFTS. Global and local spatial autocorrelation analyses were employed to examine the spatial distribution patterns and spatial association patterns of SFTS incidence while spatio-temporal scanning analyses was used to assess the spatial-temporal clustering of SFTS. Results: A total of 337 SFTS cases were reported in Huai'an City from 2011 to 2024, with the reported incidence rising from 0.17/100 000 to 1.88/100 000. There were 20 deaths, with an average annual mortality of 0.03/100 000, and a fatality rate of 5.93%. The incidence showed obvious seasonality, with a peak in May and June (148 cases, accounting for 43.92%). Spring and summer accounted for 107 cases (31.75%) and 159 cases (47.18%), respectively. The reported SFTS cases were mainly male, farmers, and individuals aged ≥41 years, accounting for 56.38%, 79.23%, and 96.74%, respectively. The population distribution of death cases was basically consistent with that of incident cases. Xuyi County was a high-incidence area, with a total of 332 reported cases, accounting for 98.52%. All death cases were reported in this county. Spatial autocorrelation analyses revealed a positive spatial correlation in SFTS incidence from 2019 to 2024, with Moran's I values ranging from 0.214 to 0.336 (all P<0.05). Heqiao Town, Tianquanhu Town, and Guiwu Town in Xuyi County were identified as high-high clustering areas. Spatio-temporal scanning analyses showed that cluster 1 was consistent with the high-high clustering areas, with an aggregation time from the second quarter of 2019 to the second quarter of 2022. Conclusions From 2011 to 2024, the reported incidence of SFTS in Huai'an City showed an upward trend, with a high incidence in spring and summer. Males, farmers, and the middle-aged and elderly population were the key populations for prevention and control. Xuyi County was the key area for prevention and control.

ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

OBJECTIVE To investigate the effects of medicated serum of Siwutang on autophagy of ovarian granulosa cells （KGN cells） in polycystic ovarian syndrome （PCOS） and its underlying mechanism. METHODS Blank serum and different- concentration medicated serum of Siwutang were prepared by intragastric administration of normal saline and different doses of Siwutang [0.52， 1.04， 2.08 g/（kg·d）] in 3-month-old female SD rats. After screening the intervention concentration of Siwutang medicated serum， KGN cells were divided into control group （without any treatment）， dehydroepiandrosterone （DHEA） group （treated with 50 μmol/L DHEA for 48 h）， blank serum group （treated with 50 μmol/L DHEA for 48 h and with 10% blank serum for 72 h） and medium-concentration of Siwutang medicated serum group （treated with 50 μmol/L DHEA for 48 h and with 10% medium-concentration Siwutang medicated serum for 72 h）. The number of autophagosomes was observed in each group， and protein expressions of pathway-related proteins [fructose-1， 6-bisphosphatase 1 （FBP1），mammalian target of rapamycin （mTOR）， phosphorylated mTOR （p-mTOR）]， autophagy-related proteins [p62， microtubule-associated protein 1 light chain 3 （LC3）] and mRNA expression of FBP1 were also detected. The （transfected） cells were further divided into Siwutang group （treated with 10% medium dose of Siwutang medicated serum for 72 h after 48 h intervention with 50 μmol/L DHEA）， Siwutang+si-NC group [negative control small interfering RNA （siRNA） transfected cells treated with 50 μmol/L DHEA for 48 h， and then with 10% medium-concentration of Siwutang medicated serum for 72 h] and Siwutang+si-FBP1 group （FBP1 siRNA transfected cells treated with 50 μmol/L DHEA for 48 h， and then with 10% medium-concentration Siwutang medicated serum for 72 h）. The effects of knocking down FBP1 on the above-mentioned effects of Siwutang were detected. RESULTS Compared with control group， DHEA group exhibited an increase in the number of autophagosomes， an elevated LC3-Ⅱ/LC3-Ⅰ and p-mTOR/mTOR， as well as increases in protein and mRNA expressions of FBP1， and decreased protein expression of p62 （P＜0.05）. Compared to both DHEA group and blank serum group， the medium-concentration of Siwutang medicated serum group showed a decrease in the number of autophagosomes， a decrease in LC3-Ⅱ/LC3-Ⅰ， and increases in p-mTOR/mTOR， protein expression of p62， protein and mRNA expressions of FBP1 （P＜0.05）. After knocking down FBP1， compared with Siwutang+si-NC group， Siwutang+si-FBP1 group showed a significant decrease in cell viability， protein expression of p62 ， protein and mRNA expressions of FBP1 as well as p-mTOR/mTOR， and an increase in LC3-Ⅱ/LC3-Ⅰ （P＜0.05）. CONCLUSIONS Siwutang can promote the phosphorylation of mTOR protein by up- regulating the protein and mRNA expressions of FBP1 in KGN cells， thus inhibiting autophagy of KGN cells.

OBJECTIVE To investigate the effects of medicated serum of Siwutang on autophagy of ovarian granulosa cells （KGN cells） in polycystic ovarian syndrome （PCOS） and its underlying mechanism. METHODS Blank serum and different- concentration medicated serum of Siwutang were prepared by intragastric administration of normal saline and different doses of Siwutang [0.52， 1.04， 2.08 g/（kg·d）] in 3-month-old female SD rats. After screening the intervention concentration of Siwutang medicated serum， KGN cells were divided into control group （without any treatment）， dehydroepiandrosterone （DHEA） group （treated with 50 μmol/L DHEA for 48 h）， blank serum group （treated with 50 μmol/L DHEA for 48 h and with 10% blank serum for 72 h） and medium-concentration of Siwutang medicated serum group （treated with 50 μmol/L DHEA for 48 h and with 10% medium-concentration Siwutang medicated serum for 72 h）. The number of autophagosomes was observed in each group， and protein expressions of pathway-related proteins [fructose-1， 6-bisphosphatase 1 （FBP1），mammalian target of rapamycin （mTOR）， phosphorylated mTOR （p-mTOR）]， autophagy-related proteins [p62， microtubule-associated protein 1 light chain 3 （LC3）] and mRNA expression of FBP1 were also detected. The （transfected） cells were further divided into Siwutang group （treated with 10% medium dose of Siwutang medicated serum for 72 h after 48 h intervention with 50 μmol/L DHEA）， Siwutang+si-NC group [negative control small interfering RNA （siRNA） transfected cells treated with 50 μmol/L DHEA for 48 h， and then with 10% medium-concentration of Siwutang medicated serum for 72 h] and Siwutang+si-FBP1 group （FBP1 siRNA transfected cells treated with 50 μmol/L DHEA for 48 h， and then with 10% medium-concentration Siwutang medicated serum for 72 h）. The effects of knocking down FBP1 on the above-mentioned effects of Siwutang were detected. RESULTS Compared with control group， DHEA group exhibited an increase in the number of autophagosomes， an elevated LC3-Ⅱ/LC3-Ⅰ and p-mTOR/mTOR， as well as increases in protein and mRNA expressions of FBP1， and decreased protein expression of p62 （P＜0.05）. Compared to both DHEA group and blank serum group， the medium-concentration of Siwutang medicated serum group showed a decrease in the number of autophagosomes， a decrease in LC3-Ⅱ/LC3-Ⅰ， and increases in p-mTOR/mTOR， protein expression of p62， protein and mRNA expressions of FBP1 （P＜0.05）. After knocking down FBP1， compared with Siwutang+si-NC group， Siwutang+si-FBP1 group showed a significant decrease in cell viability， protein expression of p62 ， protein and mRNA expressions of FBP1 as well as p-mTOR/mTOR， and an increase in LC3-Ⅱ/LC3-Ⅰ （P＜0.05）. CONCLUSIONS Siwutang can promote the phosphorylation of mTOR protein by up- regulating the protein and mRNA expressions of FBP1 in KGN cells， thus inhibiting autophagy of KGN cells.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

This study elucidates the mechanism of Rhodiolae Crenulatae Radix et Rhizoma(RCRR) in protecting brain microvascular endothelial cells from oxygen-glucose deprivation(OGD) injury and reveals the modern pharmacological mechanism of RCRR's traditional use in nourishing Qi and promoting blood circulation to protect endothelial cells. The scratch assay was employed to assess the migratory capacity of endothelial cells. Immunofluorescence and Western blot techniques were employed to assess the protein expression of tight junction proteins zonula occludens-1(ZO-1), occludin, claudin-5, and proteins of the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/glycogen synthase kinase-3beta(GSK3β) pathway. The results demonstrated that 63 bioactive components and 125 potential core targets of RCRR were identified from the ETCM, TCMBank, and SwissTargetPrediction databases, as well as from the literature. A total of 1 708 brain microvascular endothelial cell-related targets were identified from the GeneCards and OMIM databases, and 52 targets were obtained by intersecting drug components with cell targets. The protein-protein interaction(PPI) network analysis revealed that AKT1, epidermal growth factor receptor(EGFR), matrix metalloproteinase 9(MMP9), estrogen receptor 1(ESR1), proto-oncogene tyrosine-protein kinase(SRC), peroxisome proliferator-activated receptor gamma(PPARG), GSK3β, and matrix metalloproteinase 2(MMP2) were considered hub genes. The KEGG enrichment analysis identified the PI3K/AKT pathway as the primary signaling pathway. Cell experiments demonstrated that RCRR-containing serum could enhance the migratory capacity of brain microvascular endothelial cells and the expression of tight junction proteins following OGD injury, which may be associated with the downregulation of the PI3K/AKT/GSK3β pathway. This study elucidates the pharmacological mechanism of RCRR in protecting brain microvascular endothelial cells through network pharmacology, characterized by multiple components and targets. These findings were validated through in vitro experiments and provide important ideas and references for further research into the molecular mechanisms of RCRR in protecting brain microvascular endothelial cells.
Endothelial Cells/cytology* ; Glycogen Synthase Kinase 3 beta/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Phosphatidylinositol 3-Kinases/genetics* ; Signal Transduction/drug effects* ; Brain/metabolism* ; Humans ; Animals ; Rhizome/chemistry* ; Microvessels/metabolism* ; Brain Ischemia/drug therapy*

The chemical components of Carthami Flos were investigated by using macroporous resin, silica gel column chromatography, reversed-phase octadecylsilane(ODS) column chromatography, Sephadex LH-20, and semi-preparative high-performance liquid chromatography(HPLC). The planar structures of the compounds were established based on their physicochemical properties and ultraviolet-visible(UV-Vis), infrared(IR), high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), and nuclear magnetic resonance(NMR) spectroscopic technology. The absolute configurations were determined by comparing the calculated and experimental electronic circular dichroism(ECD). Six flavonoid C-glycosides were isolated from the 30% ethanol elution fraction of macroporous resin obtained from the 95% ethanol extract of Carthami Flos, and identified as saffloquinoside F(1), 5-hydroxysaffloneoside(2), iso-5-hydroxysaffloneoside(3), isosafflomin C(4), safflomin C(5), and vicenin 2(6). Among these, the compounds 1 to 3 were new chalcone C-glycosides. The compounds 1, 2, 4, and 5 could significantly increase the viability of H9c2 cardiomyocytes damaged by oxygen-glucose deprivation/reoxygenation(OGD/R) at a concentration of 50 μmol·L~(-1), showing their good cardioprotective activity.
Glycosides/pharmacology* ; Flowers/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Carthamus tinctorius/chemistry* ; Chalcones/pharmacology* ; Animals