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*

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

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 effect and safety of Chinese medicine (CM) Fuzheng Huazhuo Decoction (FHD) in treating patients with coronavirus disease 2019 (COVID-19) who persistently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This retrospective cohort study was conducted at Shanghai New International Expo Center shelter hospital in China between April 1 and May 30, 2022. Patients diagnosed as COVID-19 with persistently positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results for ⩾8 days after diagnosis were enrolled. Patients in the control group received conventional Western medicine (WM) treatment, while those in the FHD group received conventional WM plus FHD for at least 3 days. The primary outcome was viral clearance time. Secondary outcomes included negative conversion rate within 14 days, length of hospital stay, cycle threshold (Ct) values of the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes, and incidence of new-onset symptoms during hospitalization. Adverse events (AEs) that occurred during the study period were recorded. RESULTS: A total of 1,765 eligible patients were enrolled in this study (546 in the FHD group and 1,219 in the control group). Compared with the control group, patients receiving FHD treatment showed shorter viral clearance time for nucleic acids [hazard ratio (HR): 1.500, 95% confidence interval (CI): 1.353-1.664, P<0.001] and hospital stays (HR: 1.371, 95% CI: 1.238-1.519, P<0.001), and a higher negative conversion rate within 14 days (96.2% vs. 82.6%, P<0.001). The incidence of new-onset symptoms was 59.5% in the FHD group, similar to 57.8% in the control group (P>0.05). The Ct values of ORF1ab and N genes increased more rapidly over time in the FHD group than those in the control group post-randomization (ORF1ab gene: β =0.436±0.053, P<0.001; N gene: β =0.415 ±0.053, P<0.001). The incidence of AEs in the FHD group was lower than that in the control group (24.2% vs. 35.4%, P<0.001). No serious AEs were observed. CONCLUSION FHD was effective and safe for patients with persistently positive SARS-CoV-2 PCR tests. (Registration No. ChiCTR2200063956).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/virology* ; Adult ; Aged ; Treatment Outcome

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

Phosgene is a highly reactive chemical substance and a prevalent chemical warfare agent,and it is vitally important for rapid and accurate detection of phosgene to counteract terrorist threats and industrial accidents.In this work,a phosgene probe,designated as SX-Pho,which incorporated benzimidazole and hydroxyl groups as recognition motifs,was prepared through Suzuki coupling and Debus-Radziszewski methodologies to incorporate an electron-donating carbazole moiety.This probe exhibited a large Stokes shift(Approximately 130 nm).Upon exposure to triphosgene/triethylamine conditions(in situ phosgene generation),the fluorescence emission of probe at 470 nm underwent significant quenching,with a 20-fold reduction in intensity,while the fluorescence lifetime decreased from 3.30 ns to 3.06 ns.Concentration titration experiments demonstrated that SX-Pho achieved a lower detection limit of 57.8 nmol/L with high specificity and interference resistance.Preton nuclear magnetic resonance spectroscopy(1H NMR),high-resolution mass spectrometry,and density functional theory(DFT)calculations confirmed the cyclization reaction between hydroxyl groups,imines,and phosgene.The extent of overlap between the highest occupied molecular orbital(HOMO)and the lowest unoccupied molecular orbital(LUMO)was notably decreased,leading to the suppression of radiative transitions.The energy gap underwent a reduction of 0.43 eV,while the non-radiative transition was augmented,resulting in fluorescence quenching and achieving rapid detection of phosgene.Based on this,probe-loaded test strips were prepared.The color change under 365 nm illumination allowed visual discrimination of phosgene at concentrations below 20 μL/L.Furthermore,using a smartphone's built-in RGB application to measure the intensity of the blue(B)channel after the test strips were exposed to phosgene enabled both qualitative and quantitative detection.The detection range was 1.82-50 μL/L,with a limit of detection(LOD)of 1.814 μL/L.

Objective To observe the morphology of the superficial,middle,and deep layers of the masseter muscle and related bony structures in the lateral facial region of adults through gross anatomy,and to probe into the effects of these muscle layers on the bony structures of the lateral facial region.Methods The bilateral masseter muscles of 12 adult cadavers were exposed,and the superficial,middle,and deep layers were separated and measured for muscle length,tendon length,and muscle belly length.After the masseter muscles were stripped,the total thickness was measured,and the mandible and zygomatic arch were exposed to measure the angle of the mandibular angle,thickness of the zygomatic arch,and width of the zygomatic arch.Observations were made of the masseter tuberosities,and statistical analysis was conducted on their interrelations.Results The zygomatic arch thickness was positively correlated with the length of superficial,middle and deep masseter muscles and the length of superficial and middle masseter belly(r superficial masseter length=0.624,r middle masseter length=0.787,r deep masseter length=0.423,r superficial masseter belly length=0.493,r middle masseter belly length=0.548).The width of the zygomatic arch was positively correlated with the lengths of the superficial and middle muscle layers and the middle muscle belly length(r superficial masseter length=0.527,r middle masseter length=0.521,r middle masseterbelly length=0.437).The angle of the mandibular angle was only negatively correlated with the middle muscle belly length(r=-0.422).The tuberosities of the superficial and middle masseter muscles were not affected by the corresponding muscle layers;However,the tuberosity of the deep masseter was negatively correlated with the length of the deep muscle and the length of the deep tendon(r deep masseter length=-0.543,r deep masseter tendon length=-0.443).Conclusion In the masseter muscle layers of Chinese individuals,the superficial and middle layers have the most significant impact on the bony structures structures of the lateral facial region.These findings are of guiding significance for the remodeling of structures in the lateral facial region.

A serious of rare earth luminescent micro/nano-materials with various properties were synthesized via chemical method for fluorescent development of latent fingerprints(LFPs).Three evaluation indexes namely contrast,sensitivity and selectivity were introduced to evaluate the effects of LFP development.Quantitative formulas for calculating the contrast,sensitivity and selectivity were further put forward,and a quality evaluation system based on Python was thus established.In addition,the objective evaluation value was finally confirmed to be consistent with the subjective visual judgment.The reproducibility of this evaluation method was finally confirmed.The effects of luminescence intensity and color of developing materials on the contrast,particle size of developing materials on the sensitivity,and micromorphology and surface property of developing materials on the selectivity were discussed in detail.Five effective ways were also proposed to promote the quality of LFP development,such as increasing the luminescence intensity,tuning the luminescence color,decreasing the particle size,adjusting the micromorphology,and modifying the surface property.This quality evaluation system based on Python could evaluate the effects of LFP development objectively,accurately and comprehensively,exhibiting easy operability,high efficiency,sensitive response,accurate and reliable results,and wide applicability,which would provide beneficial references for the reasonable selection of LFP development methods as well as objective evaluation of evidence value.