Traditional Chinese medicine(TCM), a treasure of the Chinese nation, contains abundant chemical components and demonstrates unique pharmacological activities, showing important values in clinical applications. With profound connotations and broad application prospects, TCM urgently needs us to further explore and conduct systematic research. Puerarin is a small-molecule natural isoflavonoid carbon glycoside extracted from plants of Pueraria. It is also the main active ingredient of Puerariae Lobata Radix, a Chinese herbal medicine with both medicinal and edible values. Puerarin has a variety of pharmacological effects such as blood pressure-lowering, anti-atherosclerosis, anti-ischemia-reperfusion injury, antithrombotic, anti-tumor, anti-inflammatory, liver-protecting, nerve cell-protecting, and intestinal microbiota-regulating effects. It is also an active ingredient that has been widely studied. This article comprehensively reviews the research progress in the pharmacological effects and molecular mechanisms of puerarin over the years, aiming to provide references and theoretical support for the in-depth research and development as well as clinical application of puerarin.
Isoflavones/chemistry* ; Humans ; Animals ; Drugs, Chinese Herbal/chemistry* ; Pueraria/chemistry*

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals ; Disease Models, Animal ; Mice ; Pneumonia/genetics* ; Medicine, Chinese Traditional ; Male ; Humans ; Cytokines/immunology* ; Female ; Lipopolysaccharides/adverse effects* ; Lung/drug effects* ; Drugs, Chinese Herbal ; Ovalbumin ; Mice, Inbred BALB C

background Current assessment of noise-induced hearing loss relies on the hearing threshold statistical distribution table of ISO 7029-2017 standard (ISO 7029), which is based on foreign population data and lacks a hearing threshold distribution table derived from pure-tone audiometry data of the Chinese population, hindering accurate evaluation of hearing loss in this group. Objective To establish a statistical distribution table of hearing threshold level (HTL) for otologically normal Chinese adults and to provide a scientific basis for revising the diagnostic criteria of occupational noise-induced deafness in China. Methods A total of 1271 otologically normal Chinese adults aged 18-60 years were divided into four groups with 10-year age intervals. Based on the pure tone audiometry data and power function operation formula, the relevant parameters of the median and percentile calculation formula of ISO 7029 were adjusted. Based on the adjusted parameters, a statistical distribution table of HTL of normal Chinese adults in otology was preliminarily constructed according to the calculation formula of ISO 7029. A nonparametric rank sum test was used to compare the difference between the adjusted median deviation value and the ISO 7029 calculation. Results Except for a few frequencies (2000, 3000, and 8000 Hz), the value of parameter α adjusted for the auditory threshold deviation of the Chinese population (α_CHN-md) increased with the increase of frequency, while the value of parameter β adjusted for the auditory threshold deviation of the Chinese population (β_CHN-md) decreased with the increase of frequency. The preliminary distribution table of otologically normal Chinese adults' median hearing threshold deviation (ΔH_CHN-md) showed that the hearing threshold deviation increased with age and frequency. At 8000 Hz, the increase in ΔH_CHN-md with age was the greatest for both men and women, from 0 dB to 23 dB and 21 dB respectively. The minimal threshold elevation was noted at 500, 1000, and 2000 Hz, which increased from 0 dB to 2 dB. In otologically normal Chinese adults, the maximum increase of ΔH_CHN-md with frequency was observed at age of 50 years, which increased from 2 dB at 500 Hz to 23 dB at 8000 Hz in men and from 2 dB at 500 Hz to 21 dB at 8000 Hz in women. The comparison results with the ISO 7029 calculation showed that the trend was consistent. The median hearing threshold deviation value of the adjusted Chinese population was lower than that of the ISO 7029 calculation (ΔH_md). However, they had no significant statistical difference (P>0.05). For otologically normal normal Chinese men and women, the maximum difference of ΔH_md between the 50-year-old group and the ISO calculation at 8000 Hz was 7 dB and 9 dB, respectively. Conclusion This preliminary analysis of hearing threshold deviations in otologically normal Chinese adults suggests that current standards may potentially underestimate hearing loss at frequencies below 8000 Hz while possibly overestimating it at 8000 Hz. These findings require further validation through expanded sample sizes to more accurately assess the characteristics of hearing thresholds in the Chinese population and their discrepancies with existing standards.

OBJECTIVE: To compare the effectiveness of using a composite loop plate to reconstruct the coracoclavicular ligament around the coracoid process and using a clavicular hook plate for fixation in treatment of Rockwood type Ⅲ acute acromioclavicular joint dislocation. METHODS: A retrospective analysis was conducted on the clinical data of 60 patients with Rockwood type Ⅲ acute acromioclavicular joint dislocation who were admitted between June 2022 and September 2023 and met the selection criteria. Among them, 30 patients were treated with the composite loop plate to reconstruct the coracoclavicular ligament around the coracoid process (loop plate group) and 30 with clavicular hook plate fixation (hook plate group). There was no significant difference in baseline data between the two groups ( P>0.05), including gender, age, injured side, cause of injury, disease duration, preoperative visual analogue scale (VAS) score for pain, and Constant-Murley score. The incision length, operation time, length of hospital stay, and the occurrence of complications during follow-up were recorded. The Constant-Murley score and VAS score were used to evaluate shoulder joint function and pain, and the differences (change values) of the indicators between before operation and at 6 months after operation were calculated for inter-group comparison. In the loop plate group, the coracoclavicular distance (CCD) on the anteroposterior X-ray films of the acromioclavicular joint was measured at 1 day and 6 months after operation to assess the loss of acromioclavicular joint reduction. RESULTS: The incision length of the loop plate group was significantly shorter than that of the hook plate group ( P<0.05). There was no significant difference in the operation time and the length of hospital stay between the two groups ( P>0.05). All incisions healed by first intention after operation. All patients were followed up 12-18 months (mean, 16.3 months). There was no significant difference in the follow-up time between groups ( P>0.05). The Constant-Murley scores and VAS scores of both groups significantly improved at 6 months after operation when compared with those before operation ( P<0.05); the differences in the change values of the two indicators between groups were significant ( P<0.05). The CCD of the loop plate group were (10.40±0.83) mm at 1 day and (10.70±0.68) mm at 6 months and no repositioning loss was observed. Three cases in the hook plate group had residual shoulder joint pain after operation. The difference in the accidence of complications between groups was not significant ( P>0.05). CONCLUSION For Rockwood type Ⅲ acute acromioclavicular joint dislocation, compared with the clavicular hook plate fixation, the composite loop plate for reconstructing the coracoclavicular ligament around the coracoid process has the advantages of simple operation, safety, minimally invasive, good functional recovery, and fewer complications. Moreover, it avoids the need for a second surgery to remove the internal fixation device, and the patient acceptance and satisfaction are higher.
Humans ; Acromioclavicular Joint/surgery* ; Bone Plates ; Male ; Retrospective Studies ; Female ; Adult ; Ligaments, Articular/injuries* ; Joint Dislocations/surgery* ; Coracoid Process/injuries* ; Treatment Outcome ; Middle Aged ; Plastic Surgery Procedures/instrumentation* ; Fracture Fixation, Internal/instrumentation* ; Young Adult ; Clavicle/surgery*

OBJECTIVE: To compare clinical effect of anterior tibial plateau fracture line and anterior tibial fenestration reduction in treating anterolateral tibial plateau column fracture combined with posterior lateral column collapse. METHODS: Fifty-two patients with Schatzker typeⅡ tibial plateau anterolateral column fracture combined with posterolateral column collapse admitted from January 2016 to December 2021 were retrospectively analyzed and divided into two groups according to fracture reduction methods. There were 27 patients in fracture line group, including 19 males and 8 females, aged from 26 to 62 years old with an average of (43.2±11.4) years old;the time from injury to operation ranged from 4 to 8 days with an average of (5.8±1.5) days;treated with reduction and internal fixation via fracture line of lateral platform front. There were 25 patients in fenestrate group, including 13 males and 12 females, aged from 22 to 69 years old with an average of (40.8±11.1) years old;the time from injury to operation ranged from 4 to 8 days with an average of (6.0±1.4) days;treated with tibial fenestration reduction and internal fixation. The amount of bone graft, operation time, fracture healing time and complications were compared between two groups. Posterior slope angle (PSA) and posterior slope angle of the lateral tibial plateau was compared before surgery, 2 days and 6 months after surgery. The knee function was evaluated by Hospital for Speical Surgery (HSS) at 2 days and 6 months after surgery, respectively. Fracture reduction was evaluated by Rasmussen anatomic score of knee joint. RESULTS: Both of group were followed up from 12 to 24 months (16.0±3.4) months. No redisplacement of fracture, internal and external inversion deformity of knee joint, or instability of knee joint were found between two groups during follow-up. In fracture line group, 1 patient occurred wound fat liquefaction and 2 patients occurred lower limb intermuscular venous thrombosis occurred. In fenestration group, 1 patient occurred joint stiffness, 1 patient occurred lower limb intermuscular venous thrombosis, and 1 patient occurred superficial wound infection;there were no significant difference in complications between two groups (P>0.05). Bone graft volume, operative time and fracture healing time in fracture line group were (3.6±2.3) cm³, (123.4±18.2) min and (13.8±1.8) weeks, while in feneplast group were (4.8±1.8) cm³, (135.5±22.5) min and (15.2±2.0) weeks, respectively;the difference between two groups was statistically significant (P<0.05). The collapse depth of lateral platform articular surface at 2 days and 6 months after surgery were (0.8±0.1) and (0.9±0.1) mm in fracture line group, which were lower than those in fenestration group (0.9±0.1) and (1.1±0.1) mm, respectively (P<0.05). After 2 days and 6 months, , PSA in fracture line group were (9.4±1.5) ° and (10.1±1.9) °, respectively, which were lower than those in fenestration group (10.5±1.5) ° and (11.3±1.9) ° (P<0.05). Rasmussen anatomical scores in fracture line group at 2 days and 6 months were 16(16, 18) and 16(14, 16) points, respectively, which were better than those in fenestrated group (16, 16) and 14(14, 16) points (P< 0.05). The collapse depth, PSA and Rasmussen anatomical score between two groups were better than those before surgery (P<0.05). There was no significant difference in HSS score between two groups at 2 days after surgery (P>0.05). At six months after surgery, HSS score in fracture line group (86.7±3.6) was higher than that in fenestration group (84.1±3.91) (P<0.05). HSS score at 6 months after surgery was better than that at 2 days after surgery (P<0.05). CONCLUSION Both anterior tibial plateau fracture line and anterior tibial fenestration could be used to treat anterolateral tibial plateau column fracture with posterior lateral column collapse. Compared with fenestration group, transfracture line group had advantages of less intraoperative bone grafting, shorter operative time, shorter fracture healing time, better articular surface reduction effect and better knee functional recovery.
Humans ; Male ; Female ; Middle Aged ; Tibial Fractures/physiopathology* ; Adult ; Fracture Fixation, Internal/methods* ; Aged ; Retrospective Studies ; Tibia/injuries* ; Tibial Plateau Fractures

The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic acid (5-ALA). Furthermore, this study aimed to explore the underlying mechanism of the protective effects of 5-ALA. First, we collected and stored mouse testicular fragments in different media, including Hank's balanced salt solution (HBSS; n = 5), Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 (DMEM/F12; n = 5), and alpha-minimum essential medium (αMEM; n = 5). Storage of testicular tissue in HBSS preserved the integrity of testicular morphology better than that in the DMEM/F12 group ( P < 0.05) and the αMEM group ( P < 0.01). Testicular fragments were subsequently placed in HBSS with various concentrations of 5-ALA (0 [control], 1 mmol l -1 , 2 mmol l -1 , and 5 mmol l -1 ) to determine the most effective concentration of 5-ALA. The 2 mmol l -1 5-ALA group ( n = 3) presented the highest positive rate of spermatogonial stem cells compared with those in the control, 1 mmol l -1 , and 5 mmol l -1 5-ALA groups. Finally, the tissue fragments were preserved in HBSS with control ( n = 3) and 2 mmol l -1 5-ALA ( n = 3) under low-temperature conditions. A comparative analysis was performed against fresh testes ( n = 3) to elucidate the underlying mechanism of 5-ALA. Gene set enrichment analysis (GSEA) for WikiPathways revealed that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was downregulated in the 2 mmol l -1 5-ALA group compared with that in the control group (normalized enrichment score [NES] = -1.57, false discovery rate [FDR] = 0.229, and P = 0.019). In conclusion, these data suggest that using 2 mmol l -1 5-ALA in HBSS effectively protected the viability of spermatogonial stem cells upon hypothermic transportation.
Male ; Animals ; Testis/cytology* ; Aminolevulinic Acid/pharmacology* ; Mice ; Organ Preservation/methods* ; Organ Preservation Solutions/pharmacology* ; Cryopreservation/methods*

Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella (MMAF). Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement. Mammalian sperm-associated antigen 17 ( SPAG17 ) encodes a conserved axonemal protein of cilia and flagella, forming part of the C1a projection of the central apparatus, with functions related to ciliary/flagellar motility, skeletal growth, and male fertility. This study investigated two novel homozygous SPAG17 mutations (M1: NM_206996.2, c.829+1G>T, p.Asp212_Glu276del; and M2: c.2120del, p.Leu707*) identified in four infertile patients from two consanguineous Pakistani families. These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa. Quantitative real-time polymerase chain reaction (PCR) of patients' spermatozoa also revealed a significant decrease in SPAG17 mRNA expression, and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella. However, no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients. Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls. Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17 (SPATA17), a component of the C1a projection, and sperm-associated antigen 6 (SPAG6), a marker of the spring layer, revealed disrupted expression of both proteins in the patients' spermatozoa. Altogether, these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme, expanding the phenotypic spectrum of SPAG17 mutations in humans.
Humans ; Male ; Infertility, Male/pathology* ; Sperm Tail/ultrastructure* ; Homozygote ; Microtubule-Associated Proteins/genetics* ; Axoneme/genetics* ; Spermatozoa/ultrastructure* ; Adult ; Mutation ; Sperm Motility/genetics* ; Pedigree ; Microtubules ; Microtubule Proteins/genetics*

OBJECTIVE: To investigate the inhibitory effect of Tanreqing Injection (TRQ) on the activation of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome in macrophages infected with influenza A virus and the underlying mechanism based on mitophagy pathway. METHODS: The inflammatory model of murine macrophage J774A.1 induced by influenza A virus [strain A/Puerto Rico/8/1934 (H1N1), PR8] was constructed and treated by TRQ, while the mitochondria-targeted antioxidant Mito-TEMPO and autophagy specific inhibitor 3-methyladenine (3-MA) were used as controls to intensively study the anti-inflammatory mechanism of TRQ based on mitophagy-mitochondrial reactive oxygen species (mtROS)-NLRP3 inflammasome pathway. The levels of NLRP3, Caspase-1 p20, microtubule-associated protein 1 light chain 3 II (LC3II) and P62 proteins were measured by Western blot. The release of interleukin-1β (IL-1β) was tested by enzyme linked immunosorbent assay, the mtROS level was detected by flow cytometry, and the immunofluorescence and co-localization of LC3 and mitochondria were observed under confocal laser scanning microscopy. RESULTS: Similar to the effect of Mito-TEMPO and contrary to the results of 3-MA treatment, TRQ could significantly reduce the expressions of NLRP3, Caspase-1 p20, and autophagy adaptor P62, promote the expression of autophagy marker LC3II, enhance the mitochondrial fluorescence intensity, and inhibit the release of mtROS and IL-1β (all P<0.01). Moreover, LC3 was co-localized with mitochondria, confirming the type of mitophagy. CONCLUSION TRQ could reduce the level of mtROS by promoting mitophagy in macrophages infected with influenza A virus, thus inhibiting the activation of NLRP3 inflammasome and the release of IL-1β, and attenuating the inflammatory response.
Mitophagy/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Animals ; Macrophages/virology* ; Inflammasomes/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Mitochondria/metabolism* ; Reactive Oxygen Species/metabolism* ; Influenza A virus/physiology* ; Interleukin-1beta/metabolism* ; Cell Line ; Injections

Objective:To assess the relationship between basophil levels and mortality in patients with intra-abdominal infection.Methods:Information on patients with intraperitoneal infection admitted to the intensive care unit were extracted from the MIMIC database.A time-dependent Cox regression model was used to adjust for confounders associated with 28-day mortality.Propensity score matching(PSM)was used to balance the baseline differences be-tween groups with different basophil levels,and a restricted cube chart(RCS)was used to show the relationship between basophil count and 28-day mortality in patients with intra-abdominal infection.Results:A total of 4403 patients with intra-abdominal infection were enrolled in the MIMIC database.Patients with high basophil levels have lower mortality than those with low basophil levels.There was an L-shaped curve between basophil level and 28-day mortality,with a cut-off value of 0.47×109/L.Cox regression analysis showed that basophil levels were an independent protective factor for mortal-ity in patients with intra-abdominal infection after adjusting for potential confounders(HR=0.586,95%CI:0.443-0.769).Protective factors for death at basophil levels remained after PSM adjusted for potential confounders(HR=0.628,95%CI:0.470-0.832).Conclusion:Basophil level is an independent protective factor for mortality in patients with intra-abdominal infection,and basophil levels should be dynamically monitored to better evaluate the prognosis of patients.