This study investigates the reproductive protective effect and potential mechanism of Cistanches Herba extract(CHE) on a rat model of kidney-Yang deficiency induced by adenine. Rats were randomly divided into five groups: normal, model, low-dose CHE(0.6 g·kg~(-1)·d~(-1)), high-dose CHE(1.2 g·kg~(-1)·d~(-1)), and L-carnitine(100 mg·kg~(-1)·d~(-1)). The rats were administered adenine(200 mg·kg~(-1)·d~(-1)) by gavage for the first 14 days to induce kidney-Yang deficiency, while simultaneously receiving drug treatment. After 14 days, the modeling was discontinued, but drug treatment continued to 49 days. The content of components in CHE was analyzed by high-performance liquid chromatography. The adenine-induced kidney-Yang deficiency model was assessed through symptom characterization and measurement of testosterone(T) levels using an enzyme-linked immunosorbent assay kit. Pathological damage to the testis and epididymis was evaluated based on the wet weight and performing hematoxylin-eosin staining. Sperm density and motility were measured using computer-aided sperm analysis, and sperm viability was assessed using live/dead sperm staining kits, and sperm morphology was evaluated using eosin staining, thereby determining rat sperm quality. Metabolomics was used to analyze changes in serum metabolites, enrich related metabolic pathways, and explore the mechanism of CHE in improving reproductive function damage in rats with kidney-Yang deficiency syndrome. Compared to the normal group, the model group exhibited significant kidney-Yang deficiency symptoms, reduced T levels, decreased testicular and epididymal wet weights, and significant pathological damage to the testis and epididymis. The sperm density, motility, and viability decreased, with an increased rate of sperm abnormalities. In contrast, rats treated with CHE showed marked improvements in kidney-Yang deficiency symptoms, restored T levels, alleviated pathological damage to the testis and epididymis, and improved various sperm parameters. Metabolomics results revealed 286 differential metabolites between the normal and model groups(191 upregulated and 95 downregulated). Seventy-five differential metabolites were identified between the model and low-dose CHE groups(21 upregulated and 54 downregulated). A total of 24 common differential metabolites were identified across the three groups, with 22 of these metabolites exhibiting opposite regulation trends between the two comparison groups. These metabolites were primarily involved in linoleic acid metabolism, ether lipid metabolism, and pantothenic acid and coenzyme A biosynthesis, as well as metabolites including 13-hydroperoxylinoleic acid, lysophosphatidylcholine, and pantethine. CHE can improve kidney-Yang deficiency symptoms in rats, alleviate reproductive organ damage, and enhance sperm quality. The regulation of lipid metabolism may be a potential mechanism through which CHE improves reproductive function in rats with kidney-Yang deficiency. The potential bioactive compounds of CHE include echinacoside, verbascoside, salidroside, betaine, and cistanoside A.
Animals ; Male ; Rats ; Yang Deficiency/physiopathology* ; Metabolomics ; Kidney/physiopathology* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Cistanche/chemistry* ; Kidney Diseases/metabolism* ; Testis/metabolism* ; Humans ; Reproduction/drug effects* ; Testosterone/blood*

Process analytical technology(PAT) is a key means for digital transformation and upgrading of the traditional Chinese medicine(TCM) manufacturing process, serving as an important guarantee for consistent and controllable TCM product quality. Near-infrared(NIR) spectroscopy has become the core technology for measuring the TCM manufacturing process. By incorporating NIR spectroscopy into PAT and starting from the construction of a smart platform for the TCM manufacturing process, this paper systematically described the development history and innovative application of the combination of NIR spectroscopy with chemometrics in measuring the TCM manufacturing process by the research team over the past two decades. Additionally, it explored the application of a validation method based on accuracy profile(AP) in the practice of NIR spectroscopy. Furthermore, the software development progress driven by NIR spectroscopy supported by modeling technology was analyzed, and the prospect of integrating NIR spectroscopy in smart factory control platforms was exemplified with the construction practices of related platforms. By integrating with the smart platform, NIR spectroscopy could improve production efficiency and guarantee product quality. Finally, the prospect of the smart platform application in measuring the TCM manufacturing process was projected. It is believed that the software development for NIR spectroscopy and the smart manufacturing platform will provide strong technical support for TCM digitalization and industrialization.
Spectroscopy, Near-Infrared/methods* ; Drugs, Chinese Herbal/analysis* ; Software ; Medicine, Chinese Traditional ; Quality Control

This study aims to explore whether Albiziae Cortex-Tribuli Fructus can exert an anti-hepatic fibrosis effect by regulating the nuclear factor E2-related factor 2(Nrf2)/NOD-like receptor protein 3(NLRP3)/cysteine protease-1(caspase-1) pathway and analyze its potential mechanism. In the in vivo experiment, a mouse model of hepatic fibrosis was established by subcutaneous injection of carbon tetrachloride. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), collagen type Ⅳ(ColⅣ), laminin(LN), procollagen type Ⅲ(PCⅢ), and hyaluronic acid(HA) in the serum of mice were measured using a fully automated biochemical analyzer and ELISA. Hematoxylin and eosin(HE) and Masson staining were used to observe inflammation and collagen fiber deposition in the liver tissue. Western blot and RT-qPCR were employed to detect the protein and mRNA expression of collagen type Ⅰ(collagen Ⅰ), α-smooth muscle actin(α-SMA), Nrf2, NLRP3, gasdermin D(GSDMD), and caspase-1 in the hepatic tissue. In the in vitro experiment, human hepatic stellate cells(HSC-LX2) were pretreated with Nrf2 agonist or inhibitor, followed by the addition of blank serum, AngⅡ + blank serum, and AngⅡ + Albiziae Cortex-Tribuli Fructus-containing serum for intervention. Western blot was used to detect the protein expression of Nrf2, NLRP3, GSDMD, caspase-1, α-SMA, GSDMD-N, and apoptosis-associated speck-like protein(ASC) in cells. DCFH-DA fluorescence probe was used to detect the cellular ROS levels. The results from the in vivo experiment showed that, compared with the model group, Albiziae Cortex-Tribuli Fructus significantly reduced the serum levels of AST, ALT, ColⅣ, LN, PCⅢ, and HA, reduced the infiltration of inflammatory cells and collagen fiber deposition in the liver tissue, significantly upregulated the protein and mRNA expression of Nrf2 in the liver tissue, and significantly downregulated the protein and mRNA expression of collagen I, α-SMA, NLRP3, GSDMD, and caspase-1 in the liver tissue. The results from the in vitro experiment showed that Nrf2 activation decreased the protein expression of NLRP3, GSDMD, caspase-1, α-SMA, GSDMD-N, ASC, and ROS levels in HSC-LX2, while Nrf2 inhibition showed the opposite trend. Furthermore, Albiziae Cortex-Tribuli Fructus-containing serum directly decreased the expression of the above proteins and ROS levels. In conclusion, Albiziae Cortex-Tribuli Fructus can effectively improve hepatic fibrosis, and its mechanism of action may involve inhibiting pyroptosis through the regulation of the Nrf2/NLRP3/caspase-1 pathway.
Animals ; NF-E2-Related Factor 2/genetics* ; Liver Cirrhosis/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Caspase 1/genetics* ; Male ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Signal Transduction/drug effects* ; Humans ; Liver/metabolism* ; Mice, Inbred C57BL ; Plant Extracts ; Tribulus

This study primarily aimed to investigate the prevalence of human papillomavirus (HPV) and other common pathogens of sexually transmitted infections (STIs) in spermatozoa of infertile men and their effects on semen parameters. These pathogens included Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae, Pseudomonas aeruginosa , and Staphylococcus aureus . A total of 1951 men of infertile couples were recruited between 23 March 2023, and 17 May 2023, at the Department of Reproductive Medicine of The First People's Hospital of Yunnan Province (Kunming, China). Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping. Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs. The overall prevalence of HPV infection was 12.4%. The top five prevalent HPV subtypes were types 56, 52, 43, 16, and 53 among those tested positive for HPV. Other common infections with high prevalence rates were Ureaplasma urealyticum (28.3%), Ureaplasma parvum (20.4%), and Enterococcus faecalis (9.5%). The prevalence rates of HPV coinfection with Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae , and Staphylococcus aureus were 24.8%, 25.4%, 10.6%, 6.4%, 2.4%, 7.9%, 5.9%, 0.9%, and 1.3%, respectively. The semen volume and total sperm count were greatly decreased by HPV infection alone. Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability. Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters, emphasizing the necessity of semen screening for STIs.
Humans ; Male ; Infertility, Male/epidemiology* ; Coinfection/microbiology* ; Papillomavirus Infections/virology* ; Adult ; Sexually Transmitted Diseases/complications* ; China/epidemiology* ; Staphylococcus aureus/isolation & purification* ; Chlamydia trachomatis/isolation & purification* ; Prevalence ; Mycoplasma genitalium/isolation & purification* ; Ureaplasma urealyticum/isolation & purification* ; Neisseria gonorrhoeae/isolation & purification* ; Enterococcus faecalis/isolation & purification* ; Streptococcus agalactiae/isolation & purification* ; Herpesvirus 2, Human/genetics* ; Pseudomonas aeruginosa/isolation & purification* ; Semen/virology* ; Sperm Motility ; Spermatozoa/microbiology* ; Human Papillomavirus Viruses

OBJECTIVE: To investigate the short-term efficacy and safety of low-dose venetoclax combined with CHG (cytarabine+homoharringtonine+G-CSF) priming regimen in patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy. METHODS: The data of 14 patients with AML or high-risk MDS admitted to the department of hematology/oncology of the First Hospital of Tsinghua University and 2 cooperative institutions from July 2022 to August 2023 were retrospectively analyzed. All the patients were treated with low-dose venetoclax combined with CHG priming regimen and the early induction (one course) efficacy and adverse reactions were observed. RESULTS: Among the 14 patients, 10 were males and 4 were females, with a median age of 69.5 (46-83) years. After 1 cycle of induction chemotherapy, the complete remission (CR) rate was 64.3% (9/14) and overall response rate (ORR) was 78.6% (11/14). Among the 10 patients with adverse prognosis according to cytogenetics and molecular genetics, the CR rate was 50.0% (5/10), and ORR was 70.0% (7/10). In 7 patients with TP53 mutation, the CR rate was 42.9% (3/7) and ORR was 71.4% (5/7). In the 6 patients with complex karyotype, CR rate was 33.3% (2/6) and ORR was 66.7% (4/6). While the CR rate and ORR of 8 non-complex karyotype patients were both 87.5% (7/8), and the difference in CR rate between patients with complex karyotype and non-complex karyotype was statistically significant ( P < 0.05). The adverse reactions of chemotherapy were tolerable, without early treatment-related deaths. CONCLUSION Low-dose venetoclax combined with CHG priming regimen can be used as an effective treatment for AML and high-risk MDS patients who are ineligible for intensive chemotherapy, and it is safe and worthy of clinical application.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Aged ; Male ; Female ; Sulfonamides/therapeutic use* ; Middle Aged ; Myelodysplastic Syndromes/drug therapy* ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Aged, 80 and over ; Retrospective Studies ; Cytarabine/administration & dosage* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Homoharringtonine/therapeutic use*

OBJECTIVE: To investigate the significance of serum β₂-microglobulin (β₂-MG) for survival and relapse of patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era. METHODS: Clinical data of 92 patients with DLBCL admitted from December 2003 to July 2015 were retrospectively analyzed. The optimal cutoff value of β₂-MG levels for predicting prognosis of the DLBCL patients was determined using receiver operating characteristic (ROC) curve. KaplanMeier analysis was used to estimate progression-free survival (PFS) and overall survival (OS). Cox logistic regression analysis was used to explore potential prognostic factors associated with survival. Binary logistic regression analysis was used to analyze the relationship between various factors and relapse. RESULTS: The most discriminative cutoff value for β₂-MG level was determined to be 2.25 mg/L by the ROC curve. Subgroup analysis showed that patients in the elevated β₂-MG (＞2.25 mg/L) group had significantly worse PFS(P =0.006) and a trend toward worse OS compared with those in the low β₂-MG (≤2.25 mg/L) group(P =0.053). Univariate analysis showed that elevated β₂-MG, age>60 years, Ann Arbor stage III-IV, as well as IPI score ≥3 were associated with worse PFS. Binary logistic regression analysis showed that age＞60 years and β₂-MG＞2.25 mg/L were potential influencing factors for relapse of DLBCL patients. CONCLUSION Serum β ₂-MG might be an important predictor for the survival and relapse of DLBCL patients in the rituximab era.
Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; beta 2-Microglobulin/blood* ; Rituximab ; Retrospective Studies ; Prognosis ; Female ; Male ; Middle Aged ; Recurrence ; ROC Curve

OBJECTIVE: To evaluate the clinical effect and safety of acupuncture manipulation on treatment of intractable facial paralysis (IFP), and verify the practicality and precision of the Anzhong Facial Paralysis Precision Scale (Eyelid Closure Grading Scale, AFPPS-ECGS). METHODS: A multicentre, single-blind, randomized controlled trial was conducted from October 2022 to June 2024. Eighty-nine IFP participants were randomly assigned to an ordinary acupuncture group (OAG, 45 cases) and a characteristic acupuncture group (CAG, 44 cases) using a random number table method. The main acupoints selected included Yangbai (GB 14), Quanliao (SI 18), Yingxiang (LI 20), Shuigou (GV 26), Dicang (ST 4), Chengjiang (CV 24), Taiyang (EX-HN 5), Jiache (ST 6), Fengchi (GB 20), and Hegu (LI 4). The OAG patients received ordinary acupuncture manipulation, while the CAG received characteristic acupuncture manipulation. Both groups received acupuncture treatment 3 times a week, with 10 times per course, lasting for 10 weeks. Facial recovery was assessed at baseline and after the 1st, 2nd and 3rd treatment course by AFPPS-ECGS and the House-Brackmann (H-B) Grading Scale. Infrared thermography technology was used to observe the temperature difference between healthy and affected sides in various facial regions. Adverse events and laboratory test abnormalities were recorded. The correlation between the scores of the two scales was analyzed using Pearson correlation coefficient. RESULTS: After the 2nd treatment course, the two groups showed statistically significant differences in AFPPS-ECGS scores (P<0.05), with even greater significance after the 3rd course (P<0.01). Similarly, H-B Grading Scale scores demonstrated significant differences between groups following the 3rd treatment course (P<0.05). Regarding temperature measurements, significant differences in temperatures of frontal and ocular areas were observed after the 2nd course (P<0.05), becoming more pronounced after the 3rd course (P<0.01). Additionally, mouth corner temperature differences reached statistical significance by the 3rd course (P<0.05). No safety-related incidents were observed during the study. Correlation analysis revealed that the AFPPS-ECGS and the H-B Grading Scale were strongly correlated (r=0.86, 0.91, 0.93, and 0.91 at baseline, and after 1st, 2nd, and 3rd treatment course, respectively, all P<0.01). CONCLUSIONS Acupuncture is an effective treatment for IFP, and the characteristic acupuncture manipulation enhances the therapeutic effect. The use of the AFPPS-ECGS can more accurately reflect the recovery status of patients with IFP. (Trial registration No. ChiCTR2200065442).
Humans ; Acupuncture Therapy/methods* ; Facial Paralysis/therapy* ; Female ; Male ; Middle Aged ; Adult ; Treatment Outcome ; Acupuncture Points ; Aged

The liver performs multiple life-sustaining functions. Hepatic diseases, including hepatitis, cirrhosis, and hepatoma, pose significant health and economic burdens globally. Along with the advances in nanotechnology, mesoporous silica nanoparticles (MSNs) exhibiting diversiform size and shape, distinct morphological properties, and favorable physico-chemical features have become an ideal choice for drug delivery systems and inspire alternative thinking for the management of hepatic diseases. Initially, we introduce the physiological structure of the liver and highlight its intrinsic cell types and correlative functions. Next, we detail the synthesis methods and physicochemical properties of MSNs and their capacity for controlled drug loading and release. Particularly, we discuss the interactions between liver and MSNs with respect to the passive targeting mechanisms of MSNs within the liver by adjusting their particle size, pore diameter, surface charge, hydrophobicity/hydrophilicity, and surface functionalization. Subsequently, we emphasize the role of MSNs in regulating liver pathophysiology, exploring their value in addressing liver pathological states, such as tumors and inflammation, combined with multi-functional designs and intelligent modes to enhance drug targeting and minimize side effects. Lastly, we put forward the problems, challenges, opportunities, as well as clinical translational issues faced by MSNs in the management of liver diseases.

Objective To study the pharmacokinetic characteristics of etoricoxib tablets in healthy Chinese subjects and to evaluate the bioequivalence and safety of the test and reference formulations.Methods In a randomised,single-dose,two-period,two-sequence crossover trial,28 healthy subjects were enrolled under the fasting and fed conditions,respectively,who received a single oral dose of 60 mg of etoricoxib tablets in the test or reference formulation.The concentration of etoricoxib in plasma was detected by LC-MS/MS,and the main pharmacokinetic parameters were calculated to evaluate bioequivalence and using WinNonlin 8.2 software.Results The main pharmacokinetic parameters of the test and reference preparations were as follows:The fasting condition Cmax of etoricoxib were(1 176.96±287.95)and(1 164.93±189.65)ng·mL-1;AUC0-t were(18 651.95±6 100.27)and(19 241.39±6 107.48)ng·h·mL-1;and AUC0-∞ were(19 939.15±7 553.27)and(20 536.31±7 223.40)ng·h·mL-1.The fed condition Cmax of etoricoxib were(913.50±184.72)and(878.59±164.35)ng·mL-1;and AUC0-t were(19 085.22±5 155.01)and(18 669.54±4 508.21)ng·h·mL-1;AUC0-∞ were(20 103.77±5 567.02)and(19 528.05±4 989.74)ng·h·mL-1.The 90％confidence intervals for the geometric mean ratios of the main pharmacokinetic parameters in the fasting and fed conditions fell between 80.00％and 125.00％.The incidence of adverse events in the fasting and fed conditions were 28.57％and 21.43％,respectively.Conclusion Two kinds of etoricoxib tablets are bioequivalent,and have similar safety in healthy Chinese subjects.