Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine (CM) Zihua Wenfei Zhisou Granule (ZWZG) in postinfectious cough (PIC) patients with CM syndrome of wind-cold invading Fei (Lung, WCIF). METHODS: This is a multicenter, randomized, double-blind, parallel-group, placebo-controlled phase II clinical trial. PIC patients with WCIF syndrome were recruited from the Respiratory Departments in 6 hospitals across China between March 2019 and December 2020. Eligible patients were randomly assigned to group A (ZWZG-matched placebo 15 g), group B (active ZWZG 15 g), and group C (active ZWZG 10 g plus ZWZG-matched placebo 5 g) in a 1:1:1 ratio. All medications were taken orally 3 times daily for 14 consecutive days. The primary outcomes were cough relief rate and cough disappearance rate. The secondary outcomes included time to cough relief, time to cough disappearance, and changes in cough symptom score (CSS), cough Visual Analog Scale (VAS) value, Cough-Specific Quality of Life Questionnaire (CQLQ) score, and CM syndrome score from baseline (day 0) to post-treatment (day 14). Adverse events (AEs) in each group were recorded. RESULTS: A total of 198 patients were included in the full analysis set (FAS) and safety analysis set (SS), while 183 were enrolled in the per-protocol analysis set (PPS). In the FAS population, the cough relief rate was 47.76%, 90.77% and 84.85% in groups A, B, and C, respectively; while the cough disappearance rate was 31.34%, 72.31% and 68.18%, respectively. The cough relief rates and cough disappearance rates in groups B and C were significantly higher than group A (P<0.0001). Both the median time to cough relief and cough disappearance in groups B and C were shorter than group A (P<0.0001). Compared with group A, groups B and C showed significantly greater improvements from baseline to post-treatment in CSS during daytime and nighttime as well as VAS (P<0.05). There were no significant differences in changes from baseline to post-treatment in CQLQ and CM syndrome scores among 3 groups (P>0.05). Results in the PPS population were consistent with those in the FAS population. Groups B and C showed lower incidence in AEs than group A (P<0.05), while there was no significant difference between groups B and C (P>0.05). No drug-related severe AEs were reported. CONCLUSIONS ZWZG can increase cough disappearance rate and cough relief rate; and it is beneficial in shortening cough duration and reducing cough severity and frequency in patients suffering from PIC. It is safe and generally well tolerated. (Registration No. ChiCTR1900022078).
Humans ; Cough/drug therapy* ; Double-Blind Method ; Male ; Female ; Drugs, Chinese Herbal/adverse effects* ; Middle Aged ; Treatment Outcome ; Adult ; Aged ; Quality of Life

Peripheral nerve injury (PNI) encompasses damage to nerves located outside the central nervous system, adversely affecting both motor and sensory functions. Although peripheral nerves possess an intrinsic capacity for self-repair, severe injuries frequently result in significant tissue loss and erroneous axonal junctions, thereby impeding complete recovery and potentially causing neuropathic pain. Various therapeutic strategies, including surgical interventions, biomaterials, and pharmacological agents, have been developed to enhance nerve repair processes. While preclinical studies in animal models have demonstrated the efficacy of certain pharmacological agents in promoting nerve regeneration and mitigating inflammation, only a limited number of these agents have been translated into clinical practice to expedite nerve regeneration. Chinese herb medicine (CHM) possesses a longstanding history in the treatment of various ailments and demonstrates potential efficacy in addressing PNI through its distinctive, cost-effective, and multifaceted methodologies. This review critically examines the advancements in the application of CHM for PNI treatment and nerve regeneration. In particular, we have summarized the most commonly employed and rigorously investigated CHM prescriptions, individual herbs, and natural products, elucidating their respective functions and underlying mechanisms in the context of PNI treatment. Furthermore, we have deliberated on the prospective development of CHM in both clinical practice and fundamental research.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Peripheral Nerve Injuries/drug therapy* ; Animals ; Nerve Regeneration/drug effects* ; Medicine, Chinese Traditional

OBJECTIVE: To evaluate the protective effects of gentiopicroside (GPS) against reactive oxygen species (ROS)-induced NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in endothelial cells, aiming to reduce atherosclerosis. METHODS: Eight-week-old male ApoE-deficient mice were randomly divided into 2 groups (n=10 per group): the vehicle group and the GPS treatment group. Both groups were fed a high-fat diet for 16 weeks. GPS (40 mg/kg per day) was administered by oral gavage to the GPS group, while the vehicle group received an equivalent volume of the vehicle solution. At the end of the treatment, blood and aortic tissues were collected for assessments of atherosclerosis, lipid profiles, oxidative stress, and molecular expressions related to NLRP3 inflammasome activation, ROS production, and apoptosis. Additionally, in vitro experiments on human aortic endothelial cells treated with oxidized low-density lipoprotein (ox-LDL) were conducted to evaluate the effects of GPS on NLRP3 inflammasome activation, pyroptosis, apoptosis, and ROS production, specifically examining the role of the sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. SIRT1 and Nrf2 inhibitors were used to confirm the pathway's role. RESULTS: GPS treatment significantly reduced atherosclerotic lesions in the en face aorta (P<0.01), as well as in the thoracic and abdominal aortic regions, and markedly decreased sinus lesions within the aortic root (P<0.05 or P<0.01). Additionally, GPS reduced oxidative stress markers and proinflammatory cytokines, including interleukin (IL)-1 β and IL-18, in lesion areas (P<0.05, P<0.01). In vitro, GPS inhibited ox-LDL-induced NLRP3 activation, as evidenced by reduced NLRP3 (P<0.01), apoptosis-associated speck-like protein containing a CARD, cleaved-caspase-1, and cleaved-gasdermin D expressions (all P<0.01). GPS also decreased ROS production, apoptosis, and pyroptosis, with the beneficial effects being significantly reversed by SIRT1 or Nrf2 inhibitors. CONCLUSION GPS exerts an antiatherogenic effect by inhibiting ROS-dependent NLRP3 inflammasome activation via the SIRT1/Nrf2 pathway.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Reactive Oxygen Species/metabolism* ; Iridoid Glucosides/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Animals ; Atherosclerosis/metabolism* ; Inflammasomes/drug effects* ; Male ; Sirtuin 1/metabolism* ; Signal Transduction/drug effects* ; Humans ; Endothelial Cells/pathology* ; Mice ; Oxidative Stress/drug effects* ; Apoptosis/drug effects* ; Lipoproteins, LDL ; Mice, Inbred C57BL

OBJECTIVE: To investigate the Wnt signaling pathway and miRNAs mechanism of extracts of Plastrum Testudinis (PT) in the treatment of osteoporosis (OP). METHODS: Thirty female Sprague Dawley rats were randomly divided into 5 groups by random number table method, including sham group, ovariectomized group (OVX), ovariectomized groups treated with high-, medium-, and low-dose PT (160, 80, 40 mg/kg per day, respectively), with 6 rats in each group. Except for the sham group, the other rats underwent bilateral ovariectomy to simulate OP and received PT by oral gavage for 10 consecutive weeks. After treatment, bone mineral density was measured by dual-energy X-ray absorptiometry; bone microstructure was analyzed by micro-computed tomography and hematoxylin and eosin staining; and the expressions of osteogenic differentiation-related factors were detected by immunochemistry, Western blot, and quantitative polymerase chain reaction. In addition, Dickkopf-1 (Dkk-1) was used to inhibit the Wnt signaling pathway in bone marrow mesenchymal stem cells (BMSCs) and miRNA overexpression was used to evaluate the effect of miR-214 on the osteogenic differentiation of BMSCs. Subsequently, PT extract was used to rescue the effects of Dkk-1 and miR-214, and its impacts on the osteogenic differentiation-related factors of BMSCs were evaluated. RESULTS: PT-M and PT-L significantly reduced the weight gain in OVX rats (P<0.05). PT also regulated the bone mass and bone microarchitecture of the femur in OVX rats, and increased the expressions of bone formation-related factors including alkaline phosphatase, bone morphogenetic protein type 2, collagen type I alpha 1, and runt-related transcription factor 2 when compared with the OVX group (P<0.05 or P<0.01). Meanwhile, different doses of PT significantly rescued the inhibition of Wnt signaling pathway-related factors in OVX rats, and increased the mRNA or protein expressions of Wnt3a, β-catenin, glycogen synthase kinase-3β, and low-density lipoprotein receptor-related protein 5 (P<0.05 or P<0.01). PT stimulated the osteogenic differentiation of BMSCs inhibited by Dkk-1 and activated the Wnt signaling pathway. In addition, the expression of miR-214 was decreased in OVX rats (P<0.01), and it was negatively correlated with the osteogenic differentiation of BMSCs (P<0.01). MiR-214 mimic inhibited Wnt signaling pathway in BMSCs (P<0.05 or P<0.01). Conversely, PT effectively counteracted the effect of miR-214 mimic, thereby activating the Wnt signaling pathway and stimulating osteogenic differentiation in BMSCs (P<0.05 or P<0.01). CONCLUSION PT stimulates bone formation in OVX rats through β-catenin-mediated Wnt signaling pathway, which may be related to inhibiting miR-214 in BMSCs.
Animals ; MicroRNAs/genetics* ; Female ; Rats, Sprague-Dawley ; Wnt Signaling Pathway/genetics* ; Osteogenesis/genetics* ; Mesenchymal Stem Cells/cytology* ; Cell Differentiation/drug effects* ; Bone Density/drug effects* ; Ovariectomy ; Osteoporosis/drug therapy* ; beta Catenin/metabolism* ; Rats ; Intercellular Signaling Peptides and Proteins/metabolism* ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVE: To explore the early clinical efficacy of a three-stage external treatment with traditional Chinese medicine (TCM) in the treatment of talar bone contusion caused by acute ankle sprain. METHODS: A retrospective analysis was performed on 360 patients with primary lateral ankle sprain admitted from September 2021 to July 2024. Patients with talar bone contusion were selected based on MRI examination, and 73 cases were finally included. According to different treatment methods, they were divided into the observation group and the control group. The observation group consisted of 35 cases, including 16 males and 19 females, aged 24 to 37 years old with an average of (30.34±2.68) years old, and received the three-stage external TCM treatment combined with the "POLICE" protocol. The control group included 38 cases, including 18 males and 20 females, aged 24 to 35 years old with an average of (29.87±2.57) years old, and was treated with the "POLICE" protocol alone. The volume of bone marrow edema (BME) area shown by MRI before treatment and 6 weeks after treatment was measured using 3D Slicer software, and the BME improvement rate was calculated. The "Figure of 8" measurement method was used to assess ankle swelling before treatment and at 1 and 3 weeks after treatment. The visual analogue scale (VAS) was used to evaluate ankle pain before treatment and at 1 and 6 weeks after treatment. At 6 weeks after treatment, the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Karlsson ankle function score system were used to evaluate the improvement of ankle function. RESULTS: A total of 73 patients with talar bone contusion caused by ankle sprain completed the 6-week follow-up. At 6 weeks after treatment, the BME improvement rate in the observation group was (39.18±0.06)%, which was higher than (26.75±0.03)% in the control group, with a statistically significant difference (P<0.05). After 1 week of treatment, the VAS score in the observation group was (2.89±0.72) points, lower than (3.37±0.79) points in the control group, and the difference was statistically significant (P<0.05). The ankle swelling degree in the observation group was (50.20±3.19) cm, lower than (52.00±3.60) cm in the control group, with a statistically significant difference (P<0.05). After 3 weeks of treatment, there was no statistically significant difference in ankle swelling between the two groups. At 6 weeks after treatment, there was no statistically significant difference in VAS scores between the two groups. At 6 weeks after treatment, the AOFAS ankle-hindfoot score and Karlsson score in the observation group were (87.43±4.18) and (82.77±5.93) points, respectively, which were higher than (82.92±4.87) and (76.45±6.85) points in the control group, with statistically significant differences (P<0.05). According to the AOFAS ankle-hindfoot score, 8 cases were excellent and 27 cases were good in the observation group;2 cases were excellent, 33 cases were good, and 3 cases were fair in the control group. The difference between the two groups was statistically significant (χ²=7.089, P=0.029). CONCLUSION The three-stage external TCM treatment combined with the "POLICE" protocol has a significant early clinical efficacy. It can significantly reduce ankle pain and swelling in patients with bone contusion caused by acute lateral ankle sprain, promote the absorption of bone marrow edema, and accelerate the recovery of ankle function.
Ankle Injuries/drug therapy* ; Drugs, Chinese Herbal/administration & dosage* ; Talus/injuries* ; Retrospective Studies ; Administration, Cutaneous ; Magnetic Resonance Imaging ; Humans ; Male ; Female ; Young Adult ; Adult ; Contusions/etiology* ; Visual Analog Scale ; Musculoskeletal Pain/etiology* ; Recovery of Function/drug effects* ; Treatment Outcome ; Follow-Up Studies

OBJECTIVE: To analyze the distribution characteristics of glucose-6-phosphate-dehydrogenase (G6PD) mutations and their enzyme activity in newborns patients with G6PD deficiency in Guilin region. METHODS: From July 2022 to July 2024, umbilical cord blood samples from 4 554 newborns in Guilin were analyzed for G6PD mutations using fluorescence PCR melting curve analysis. Enzyme activity was detected in 4 467 cases using the rate assay. RESULTS: Among 4 467 newborns who underwent G6PD activity testing, 162 newborns (3.63%) were identified as G6PD-deficient, including 142 males (6.04%) and 20 females (0.94%), the prevalence of G6PD deficiency was significantly higher in males than in females (P < 0.001). Genetic analysis of 4 554 newborns detected G6PD mutations in 410 cases (9%), including 171 males (7.13%) and 239 females (11.09%), with a significantly higher mutation detection rate in females than in males (P < 0.001). A total of nine single mutations and four compound heterozygous mutations were identified. The most common mutations were c.1388G>A (33.66%), c.1376G>T (23.66%) and c.95A>G (16.34%). Among newborns who underwent both enzyme activity and genetic mutation testing, males with G6PD mutations had significantly lower enzyme activity than that of females with G6PD mutations(P < 0.001). Specifically, among newborns carrying the mutations c.1388G>A, c.1376G>T, c.95A>G, c.1024C>T or c.871G>A, males consistently exhibited lower enzymatic activity than females with the same mutations (P < 0.001). Furthermore, in male G6PD-deficient newborns, the enzyme activity levels in those carrying c.1388G>A, c.1376G>T, c.95A>G, c.1024C>T, or c.871G>A were lower than those in both the control group and the c.519C>T group (P < 0.05). CONCLUSION This study provides a comprehensive profile of G6PD deficiency incidence and mutation spectrum in the Guilin region. By analyzing enzyme activity and genetic mutation results, this study provides insights into potential intervention strategies and personalized management approaches for the prevention and treatment of neonatal G6PD deficiency in the region.
Humans ; Infant, Newborn ; Glucosephosphate Dehydrogenase Deficiency/epidemiology* ; Glucosephosphate Dehydrogenase/genetics* ; Female ; Male ; Mutation ; China/epidemiology*

BACKGROUND: Hyperthermia (HT), while a cancer treatment approach, isn't always effective alone. Therefore, identifying hyperthermia enhancers is crucial. We demonstrated that Mito-TEMPO ([2-[(1-Hydroxy-2,2,6,6-tetramethylpiperidin-4-yl) amino]-2-oxoethyl]-triphenylphosphanium, MT) acts as a potent thermosensitizer, promoting cell death in human cervical cancer (HeLa) cells. METHODS: Cells were pretreated with 0.4 mM MT for 5 minutes, followed by exposure to hyperthermia (42 °C for 60 minutes). The impacts of MT/HT on cell viability, proliferation, apoptosis, endoplasmic reticulum (ER) stress, apoptosis-related proteins and autophagy, autophagy-related proteins expression were measured. The relationships between autophagy and apoptosis were further investigated using the specific autophagy inhibitor chloroquine (CQ) and the autophagy inducer rapamycin (Rapa). RESULTS: The combined treatment reduced the mitochondrial membrane potential (MMP) and increased ROS production. It also upregulated the pro-apoptotic protein Bax and downregulated anti-apoptotic proteins such as Bcl-2 and MCL-1. As a result, Caspase-3 was activated. Additionally, the combined treatment upregulated the expression of p-PERK/PERK, ATF-4, CHOP proteins. Moreover, the combined treatment also increased the expression of LC3 II and p62, decreased expression of LAMP 1 and Cathepsin D and increased lysosomal pH, indicating coordinated changes in autophagy regulation. Notably, intensification of apoptosis induced by the combined treatment was observed with CQ, whereas attenuation was seen with Rapa. CONCLUSIONS MT effectively enhanced HT-induced apoptosis in HeLa cells. Elevated ER stress and interruption of autophagy flux are the possible underlying molecular mechanisms for this phenomenon. These findings suggested MT can act as a potential thermosensitizer, highlighting its versatility in cancer treatment strategies.
Humans ; Apoptosis/drug effects* ; Autophagy/drug effects* ; HeLa Cells ; Uterine Cervical Neoplasms/therapy* ; Female ; Hyperthermia, Induced ; Spin Labels ; Endoplasmic Reticulum Stress/drug effects* ; Cyclic N-Oxides/pharmacology* ; Cell Survival/drug effects*

OBJECTIVE: To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2). METHODS: The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology. RESULTS: Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors. CONCLUSION EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Animals ; Lipocalin-2/metabolism* ; Prefrontal Cortex/physiopathology* ; Male ; Mice ; Neurons/physiology* ; Disease Models, Animal ; Fear ; Behavior, Animal ; Mice, Inbred C57BL ; Neuroinflammatory Diseases/metabolism* ; Anxiety/therapy* ; Acupuncture Points