This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

OBJECTIVE: To explore the safety and efficacy of high-dose etoposide (VP-16) combined with recombinant human granulocyte colony-stimulating factor (rhG-CSF) as salvage mobilization for peripheral blood stem cells (PBSC) in newly diagnosed multiple myeloma (NDMM) patients. METHODS: From April 2021 to May 2023, eight NDMM patients who had failed to yield sufficient PBSC during initial mobilization with high-dose cyclophosphamide (CTX) combined with rhG-CSF underwent salvage mobilization with 1.2 g/m2 etoposide combined with rhG-CSF 10 μg/(kg·d). The effects and adverse reactions of initial mobilization and salvage mobilization were analyzed. RESULTS: For salvage mobilization and initial mobilization, the numbers of PBSC collections were 16 and 18, respectively. The mean value of total collected CD34⁺ cells were (11.90±5.75)×10⁶/kg and (1.67±0.75)×10⁶/kg (P =0.0010) in salvage mobilization group and initial mobilization group, respectively. The proportion of patients with a total collection of CD34⁺ cell count≥2×10⁶/kg were 100% and 37.5% (P =0.0625), and the proportion of patients with a total collection of CD34⁺ cell count≥5×10⁶/kg were 87.5% and 0% (P =0.0156) in salvage mobilization group and initial mobilization group, respectively. For five patients who underwent high-dose CTX initial mobilization but had a total CD34⁺ cell count < 2×10⁶/kg, successful collection was achieved through salvage mobilization with high-dose VP-16. Salvage mobilization with high-dose VP-16 was scheduled 2-3 weeks after failure of CTX mobilization. Adverse reactions of high-dose VP-16 mobilization did not increase compared to the initial mobilization with high-dose CTX. CONCLUSION As a salvage mobilization regimen, VP-16 1.2 g/m² combined with rhG-CSF is safe and highly effective in NDMM patients who failed to initial mobilization with high-dose CTX combined with rhG-CSF.
Humans ; Multiple Myeloma/therapy* ; Etoposide/therapeutic use* ; Hematopoietic Stem Cell Mobilization/methods* ; Cyclophosphamide/therapeutic use* ; Granulocyte Colony-Stimulating Factor ; Salvage Therapy ; Peripheral Blood Stem Cells ; Male ; Middle Aged ; Female ; Peripheral Blood Stem Cell Transplantation

Wuhutang is the 51st Chinese medicine prescription of Han ethnic group on in the catalogue of ancient classical prescriptions （the second batch） ，which originated from Renzhai' Straight Diections Prescriptions （《仁斋直指方》） by YANG Shiying in the Song dynasty，it is composed of 5 medicines， including Ephedrae Herba，Armeniacae Semen Amarum， Glycyrrhizae Radix et Rhizoma， tea and Gypsum Fibrosum. It treats shortness of breath and phlegm. Following the principle of textual research on the key information of ancient classical famous prescriptions， the author collected and recorded the ancient books of traditional Chinese medicine of Wuhutang with the method of Bibliometrics， and screened out 53 valid data， involving 41 ancient books. Based on the historical evolution， drug composition， main treatment of disease and syndrome， drug dosage， method of preparation and usage， drug origin and processing， the author conducted a dig and a systematic study of Wuhutang. The results show that：in the later generations， besides inheriting the original prescription， the composition of medicine was added or subtracted， and the frequency of addition of Mori Cortex was the most；in the treatment of disease and syndrome， most of them inherited the original prescription mainly treating asthma syndrome， also see in the treatment of asthma， cough and other lung disease， in the drug dosage and method of use ， it is suggested to inherit the original prescription， the dosage of each medicine is： Ephedrae Herba 2.89 g， Armeniacae Semen Amarum 4.13 g， Glycyrrhizae Radix et Rhizoma 1.65 g， tea 3.30 g， Gypsum Fibrosum 6.20 g， decoction， take warm clothes before eating；on the source of medcine，ephedra is made from the dried herbaceous stems of Ephedra sinica （Ephedraceae），bitter almond is made from the dried and mature seeds of Prunus armeniaca （Rosaceae），Licorice is made from the dried roots and rhizomes of Glycyrrhiza uralensis（Legumes）， tea is made from the buds leaves of Camellia sinensis（Camellia），plaster is made from Gypsum Fibrosum of sulfate mineral gypsum family. At the same time， we collected and sorted the modern clinical application literature of Wuhutang， and obtained 73 effective literatures， all of which are for the treatment of respiratory system diseases， especially for children's pneumonia and asthma， and mostly belong to"phlegm-heat obstructing the lung syndrome". Through the analysis and study of ancient books and modern applied literature， the historical evolution and prescription evolution of Wuhutang are clarified， and its key information is determined， in order to provide more accurate reference for the research and development of the classic Wuhutang and the rational addition and subtraction of the application.

ObjectiveTo analyze the clinical characteristics and the use of traditional Chinese medicine （TCM） therapy in cancer patients with COVID-19， and to provide reference for making TCM prevention and treatment strategies and determining diagnosis and treatment priorities for patients with malignant tumors in the COVID-19 epidemic. MethodsThe medical records of 225 malignant tumor cases with COVID-19 who were admitted to 7 national research centers from January 1st to 20th， 2023 were retrospectively collected， and the main symptoms and duration after infection， nucleic acid negative conversion time， use of TCM therapy， and changes in adverse reactions after resuming anti-tumor treatment were analyzed. ResultsA total of 222 malignant tumor patients with COVID-19 were included in the analysis， involving 205 mild cases and 17 moderate cases. The top four most frequently reported clinical symptoms were fever （165 cases）， expectoration or dry cough （99 cases）， decreased appetite （95 cases） and fatigue （85 cases）， of which 40 expectoration or dry cough cases ， 37 fatigue cases and 29 decreased appetite cases lasted for more than 14 days. One hundred and five patients with nucleic acid detection report had a median negative conversion time of 14 days. The nucleic acid negative conversion time was significantly longer in patients with lung cancer compared to those with digestive system malignant tumors， and in those with myelosuppression than those without （P＜0.01）. During the infection period， 47.30% （105/222） of the patients used Chinese patent medicine， and 21.17% （47/222） were treated with herbal decoctions. The use of TCM in patients during the prevention and rehabilitation period， was 1.80%（4/222） and 7.21%（16/222）， respectively. Fifty-five patients resumed anti-tumor treatment after nucleic acid negative conversion， and received TCM simultaneously. Observed adverse reactions， including gastrointestinal reactions， bone marrow suppression， and neurotoxicity， were all grade 1 to 2， and no new adverse events occurred during follow-up. ConclusionCertain malignant tumor patients with COVID-19 had prolonged symptoms and nucleic acid negative conversion time Rational use of TCM can help to promote the rehabilitation of the patients and ensure the smooth process of anti-tumor treatment after infection.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Diabetic nephropathy (DN) is one of the most common and serious microvascular complications in patients with diabetes mellitus. Diabetic renal fibrosis ( DRF) is a major pathological change in the development of DN. In recent years the incidence of renal fibrosis (RF) has remained high. For diabetic patients, RF may expose them to kidney transplantation or even death, which brings a great burden to themselves and their families. Therefore, learning the pathogenesis and the current treat ment status of DRF is crucial for the treatment of the disease and the development of new drugs. Here we review the general situa¬tion of DN, the general situation, molecular mechanism, and the treatment of DRF,looking forward to providing a reference for the research and treatment of DRF.

The study aimed to reveal for the first time the clinical characteristics, nutritional and metabolic status and support of hospitalized patients with common variant immunodeficiency disease (CVID), and provide reference to improve the long-term nutritional management for such patients. This is a retrospective cross-sectional study. Through searching the electronic medical record system of Peking Union Medical College Hospital, the study included 33 consecutive in-patients with CVID diagnosed in Jan 2016 to Jun 2021, with the male to female ratio of 16∶17. All their medical data, nutritional assessment and intervention retrospectively summarized and analyzed. Data with normal distribution were described using (x¯±s), and analyzed with independent sample t-test. Data with non-normal distribution were compared with non-parametric test. The results showed that the median onset-age of the included patients was 22 (10.0,36.5) years old, and the median duration was 9.0 (2.0,16.0) years. All patients had recurrent infections involving various systems (33/33), with development of autoimmune diseases (8/33) and lymphoproliferative disease or malignancy (9/33) in some cases among them. The nutritional risk screening 2002 (NRS 2002) scores revealed that 85.19% of adults had an NRS 2002≥3 points, and 33.33% of children had a BMI-for-age z score<-2. Weight loss occurred in 66.67% of patients (22/33), while 87.88% (29/33), 69.70% (23/33) and 81.82% (27/33) of patients respectively had anemia, hypoalbuminemia and decreased prealbumin. Among 22 patients with micronutrients status evaluated, 77.27% (17/22), 22.73% (5/22) and 31.82% (7/22) of patients respectively had lowered serum iron, folate deficiency and vitamin B12 insufficiency. Six patients underwent 25-OH-VD₃ measurement, and were all testified to have vitamin D deficiency. Among all patients with nutritional risk, 56.00% of them underwent nutritional support: oral nutritional supplements (14 cases), enteral feeding (4 cases) and parenteral nutrition (5 cases). In conclusion, the condition of malnutrition was prevalent in patients with CVID, but was under-recognized and undertreated to some degree.
Adult ; Child ; Humans ; Female ; Male ; Common Variable Immunodeficiency ; Nutritional Status ; Retrospective Studies ; Cross-Sectional Studies ; Malnutrition

The study aimed to reveal for the first time the clinical characteristics, nutritional and metabolic status and support of hospitalized patients with common variant immunodeficiency disease (CVID), and provide reference to improve the long-term nutritional management for such patients. This is a retrospective cross-sectional study. Through searching the electronic medical record system of Peking Union Medical College Hospital, the study included 33 consecutive in-patients with CVID diagnosed in Jan 2016 to Jun 2021, with the male to female ratio of 16∶17. All their medical data, nutritional assessment and intervention retrospectively summarized and analyzed. Data with normal distribution were described using (x¯±s), and analyzed with independent sample t-test. Data with non-normal distribution were compared with non-parametric test. The results showed that the median onset-age of the included patients was 22 (10.0,36.5) years old, and the median duration was 9.0 (2.0,16.0) years. All patients had recurrent infections involving various systems (33/33), with development of autoimmune diseases (8/33) and lymphoproliferative disease or malignancy (9/33) in some cases among them. The nutritional risk screening 2002 (NRS 2002) scores revealed that 85.19% of adults had an NRS 2002≥3 points, and 33.33% of children had a BMI-for-age z score<-2. Weight loss occurred in 66.67% of patients (22/33), while 87.88% (29/33), 69.70% (23/33) and 81.82% (27/33) of patients respectively had anemia, hypoalbuminemia and decreased prealbumin. Among 22 patients with micronutrients status evaluated, 77.27% (17/22), 22.73% (5/22) and 31.82% (7/22) of patients respectively had lowered serum iron, folate deficiency and vitamin B12 insufficiency. Six patients underwent 25-OH-VD₃ measurement, and were all testified to have vitamin D deficiency. Among all patients with nutritional risk, 56.00% of them underwent nutritional support: oral nutritional supplements (14 cases), enteral feeding (4 cases) and parenteral nutrition (5 cases). In conclusion, the condition of malnutrition was prevalent in patients with CVID, but was under-recognized and undertreated to some degree.
Adult ; Child ; Humans ; Female ; Male ; Common Variable Immunodeficiency ; Nutritional Status ; Retrospective Studies ; Cross-Sectional Studies ; Malnutrition

We aim to evaluate prostate health index as an additional risk-stratification tool in patients with Prostate Imaging Reporting and Data System score 3 lesions on multiparametric magnetic resonance imaging. Men with biochemical or clinical suspicion of having prostate cancer who underwent multiparametric magnetic resonance imaging in two tertiary centers (Queen Mary Hospital and Princess Margaret Hospital, Hong Kong, China) between January 2017 and June 2022 were included. Ultrasound-magnetic resonance imaging fusion biopsies were performed after prostate health index testing. Those who only had Prostate Imaging Reporting and Data System score 3 lesions were further stratified into four prostate health index risk groups and the cancer detection rates were analyzed. Out of the 747 patients, 47.3% had Prostate Imaging Reporting and Data System score 3 lesions only. The detection rate of clinically significant prostate cancer in this group was 15.0%. The cancer detection rates of clinically significant prostate cancer had statistically significant differences: 5.3% in prostate health index <25.0, 7.4% in prostate health index 25.0-34.9, 17.9% in prostate health index 35.0-54.9, and 52.6% in prostate health index ≥55.0 (P < 0.01). Among the patients, 26.9% could have avoided a biopsy with a prostate health index <25.0, at the expense of a 5.3% risk of missing clinically significant prostate cancer. Prostate health index could be used as an additional risk stratification tool for patients with Prostate Imaging Reporting and Data System score 3 lesions. Biopsies could be avoided in patients with low prostate health index, with a small risk of missing clinically significant prostate cancer.

Objective: Accumulating evidence has shown that aberrant alternative splicing events are closely associated with the onset and development of cancer. However, whether genetic variants-associated alternative splicing is linked to risk of endometrial cancer remains largely uncertain. Methods: We identified single nucleotide polymorphisms (SNPs) locates in the splicing number trait locus (sQTL) of endometrial cancer using the CancerSplicing QTL database. In parallel with bioinformatics analysis, we conducted a case-control study comprising 2,000 cases and 2,013 controls to assess the association between identified SNP which possesses mRNA splicing function and endometrial cancer susceptibility. Furthermore, we used the Kaplan-Meier Plotter, The Human Protein Atlas, SPNR, and Spliceman2 databases for sQTL and differential gene expression analyses to identify the genetic variant which most potentially influence the risk of endometrial cancer through alternative splicing to reveal the potential mechanism by which candidate SNPs regulate the risk of endometrial cancer. Results: The results indicated that SNP rs7128029 AConclusion These findings suggest that SNP rs7128029-mediated alternative splicing events in PSMD13 are associated with endometrial cancer risk and may be a potential early screening biomarker for endometrial cancer-susceptible populations.