Based on the pathogenesis of erectile dysfunction (ED) from the meridian-zangfu relationship and the "brain-heart-kidney-essence chamber" axis, it proposes that dysfunction of the "brain-heart-kidney-essence chamber" axis is closely related to the occurrence of ED. Among these, brain-heart disharmony is the key pathogenic factor, kidney deficiency and essence depletion constitute an important basis, and essence chamber stasis is a critical mechanism. The treatment approach emphasizes harmonizing the brain and heart, regulating the mind, tonifying the kidney and replenishing qi, unblocking qi and blood to harmonize the essence chamber. The primary acupoints include Baihui (GV20)-Neiguan (PC6)-Shenmen (HT7), Taixi (KI3)-Guanyuan (CV4)-Sanyinjiao (SP6), and Zhongji (CV3)-Dahe (KI12)-Gongsun (SP4), with additional acupoints selected based on syndrome differentiation. This approach aims to restore the clarity of the brain and heart, replenish kidney qi, and unblock the essence chamber, thereby facilitating the restoration of normal functions of the brain, heart, kidney, and essence chamber, and alleviating ED symptoms and improving overall clinical efficacy.
Humans ; Male ; Meridians ; Erectile Dysfunction/physiopathology* ; Kidney/physiopathology* ; Brain/physiopathology* ; Acupuncture Therapy ; Acupuncture Points ; Heart/physiopathology*

Objective To investigate the role and mechanism of SR8278,a synthetic antagonist of nuclear receptor subfamily 1 group D member 1(NR1D1),in alleviating the structural and functional impairment of the extraorbital lacrimal glands induced by jet lag in mice.Methods Totally 36 healthy wild C57BL/6J mice aged 8-10 weeks were randomly divid-ed into 3 groups(normal group,jet-lag group,and jet-lag+SR8278 group)after adapting to a circadian rhythm chamber under the 12 h light/12 h dark(12 h/12 h LD)cycle for 2 weeks,with 12 mice in each group.Mice in the normal group were fed in a circadian rhythm chamber in a 12 h LD cycle,mice in the jet-lag group were fed in a 12 h/12 h LD cycle with an 8-hour advanced LD schedule,and mice in the jet lag+SR8278 group were fed in a 12 h/12 h LD cycle with an 8-hour advanced LD schedule and received 25 mg·kg-1 SR8278.At the end of 5 days of intervention,locomotor activity,core body temperature and tear secretion of mice in each group were collected,and the weight of lacrimal gland tissues and size of lacrimal gland cells were measured.Immunohistochemical methods were used for histological evaluation of the extraor-bital lacrimal glands in mice.Lacrimal ribonucleic acid(RNA)was extracted for high-throughput RNA-sequencing analysis containing NR1D1,and the obtained transcriptomic data were used for KEGG and GO functional enrichment analysis.Re-sults Compared with the normal group,the jet-lag group had higher daytime activity,lower nighttime activity,higher daytime core body temperature,and lower nighttime core body temperature,with statistically significant differences(all P＜0.05).Compared with the jet-lag group,the jet-lag+SR8278 group had lower daytime activity,higher nighttime activi-ty,lower daytime core body temperature,and higher nighttime core body temperature,with statistically significant differ-ences(all P＜0.05).Compared with the normal group,the jet-lag group showed a decrease in lacrimal gland weight and tear secretion and an increase in size of lacrimal gland cells,with statistical significance(all P＜0.05);compared with the jet-lag group,the jet-lag+SR8278 group had an increase in lacrimal gland weight and tear secretion and a decrease in size of lacrimal gland cells,with statistical significance(all P＜0.05).Compared with the normal group,the jet-lag group showed a higher expression of NR1D1 in the lacrimal gland at night;compared with the jet-lag group,the jet-lag+SR8278 group showed a lower expression of NR1 D1 in the lacrimal gland at night(both P＜0.05).Bioinformatics analysis showed 947 significantly different genes in the jet-lag group and the jet-lag+SR8278 group,of which 43 are significantly upregulated genes,and 904 are significantly downregulated genes.The Notch signaling pathway has the most significant difference.Conclusion SR8278 effectively enhances the tear secretion function of jet-lagged mice by targeting NR1D1 inhibition.This process may be completed through the Notch signaling pathway.

Objective To investigate the modulatory effect of Yulian Pills(composed of Coptidis Rhizoma and Euodiae Fructus)on splenic memory follicular T helper cell(mTfh)in mice with dextran sodium sulfate(DSS)-induced ulcerative colitis.Methods Forty BALB/c mice were randomly divided into normal group,model group,Yulian Pills group(0.5 g·kg-1)and Mesalazine group(0.3 g·kg-1),10 mice in each group.The mouse model of ulcerative colitis was induced by ad libitum drinking 3%DSS solution for 7 days.During the experiment,the mental state,faecal characteristics,blood in stool and body mass of the mice were recorded daily,and the length and mass of the colon were measured and the colon mass index was calculated;HE staining was used to observe the pathological and morphological changes of the colon tissue;ELISA was used to determine the expression levels of interleukin(IL)-6 and IL-15 in the colon tissues;flow cytometry was used to determine the mTfh cell subpopulation in the spleen tissue expression;Western Blot was used to determine the protein expression levels of Roquin-1,AMPK-α,p-AMPK-α in colon tissues.Results Compared with the normal group,the mice in the model group showed a significant decrease in body mass(P＜0.01),a significant shortening of colon length(P＜0.01),significant increase in colon mass(P＜0.05)and colon mass index(P＜0.01),and severe pathological damage to colon tissues;the expression levels of the pro-inflammatory cytokines IL-6 and IL-15 in the colon tissues were significantly increased(P＜0.01);cell expression levels of CD4+CCR7-CXCR5+CD62L+,CD4+CCR7+CXCR5+ GL7+,CD4+CCR7-CXCR5+GL7+ were significantly increased in spleen tissues(P＜0.01),whereas the expression level of CD4+CCR7+CXCR5+CD62L+ cell was significantly decreased(P＜0.01);and protein expression levels of Roquin-1,AMPK-α,p-AMPK-α were significantly reduced in the colonic tissues(P＜0.05).Compared with the model group,mice in the Yulian Pills group and Mesalazine group showed a significant increase in body mass(P＜0.05),a significant extension of colon length(P＜0.01),a significant reduction in colon mass(P＜0.05),a significant decrease in the colon mass index(P＜0.01),and a more obvious improvement in pathological damage of the colon tissues;a significant decrease in the expression levels of IL-6 and IL-15 in the colon tissues(P＜0.01);cell expression levels of CD4+CCR7-CXCR5+CD62L+,CD4+CCR7+CXCR5+GL7+,CD4+CCR7-CXCR5+GL7+ in splenic tissues was significantly reduced(P＜0.01),whereas the expression level of CD4+CCR7+CXCR5+CD62L+ cell was significantly increased(P＜0.01);the protein expression levels of Roquin-1,AMPK-α,and p-AMPK-α were significantly increased in colon tissues(P＜0.05,P＜0.01).Conclusion The therapeutic effect of Yulian Pills on DSS-induced ulcerative colitis mice can ameliorate the histopathological damage of colon,which may be related to the activation of the Roquin-1/MPK-α signalling pathway,the down-regulation of the expressions of inflammatory cytokines IL-6 and IL-15,and the modulation of the homeostasis of the mTfh cell subpopulation.

ObjectiveTo investigate the application value of Qingre Huashi Sanjie enema prescription in the treatment of the patients with sequelae of pelvic inflammatory disease （syndrome of combined dampness，heat，and stasis） and the effects of this prescription on inflammatory mediators and T lymphocyte subsets. MethodThe patients with sequelae of pelvic inflammatory disease （syndrome of combined dampness，heat，and stasis） treated from May 2022 to August 2023 were included in this study and randomized into two groups （79 cases）. The control group was treated with conventional Western medicine，and the observation group was treated with Qingre Huashi Sanjie enema prescription on the basis of the therapy in the control group. Both groups were treated for 12 weeks. The serum levels of monocyte chemoattractant protein-1 （MCP-1），transforming growth factor-β₁ （TGF-β₁），and interleukin-6 （IL-6） were measured by enzyme linked immunoserbent assay （ELISA） before and after treatment in both groups. The erythrocyte sedimentation rate （ESR） and fibrinogen （FIB） were measured by an automatic blood rheology analyzer before and after treatment in both groups. The serum levels of CD4⁺，CD4⁺/CD8⁺ before and after treatment in both groups were measured by flow cytometry. The traditional Chinese medicine （TCM） symptom score and the 36-item short form survey （SF-36） score were assessed before and after treatment. The uterine artery resistance index （RI），uterine artery pulsatility index （PI），and uterine artery peak systolic velocity （PSV） were measured by Doppler before and after treatment. The clinical efficacy and the occurrence of adverse reactions were compared between the two groups. ResultAfter treatment，the levels of MCP-1，TGF-β₁，IL-6，ESR，and FIB decreased in both groups （P<0.01），and the decreases were larger in the observation group than in the control group （P<0.05，P<0.01）. After treatment，the serum levels of CD4⁺ and CD4⁺/CD8⁺ elevated in both groups （P<0.01） and the observation group had higher levels of CD4⁺ and CD4⁺/CD8⁺ than the control group （P<0.05，P<0.01）. The treatment in both groups decreased the TCM symptom score and TCM sign score and increased the SF-36 score （P<0.01），and the changes were more significant in the observation group than in the control group （P<0.05，P<0.01）. In addition，the treatment lowered RI and PI and elevated PSV （P<0.01），and the changes in these indicators were more significant in the observation group than in the control group （P<0.01）. The total response rate in the observation group was 93.67% （74/79），which was higher than that （79.75%，63/79） in the control group （χ²=6.645，P<0.05）. There was no significant difference in the occurrence of adverse reactions between the two groups. ConclusionFor the patients with sequelae of pelvic inflammatory disease （syndrome of combined dampness，heat，and stasis），Qingre Huashi Sanjie enema prescription can reduce inflammation，attenuate hypercoagulability，improve hemodynamics，and regulate the immune function，demonstrating a definite therapeutic effect.

Objective:To investigate the feasibility, safety and effectiveness of colonic interposition with vascular anastomosis in reconstructing the entire esophagus and hypopharynx after resection of hypopharyngeal cancer with esophageal cancer.Methods:We conducted a retrospective analysis of 4 male patients with simultaneous multiple primary cancers of the hypopharynx and esophagus, aged 47 to 58, treated in the Department of Head and Neck Surgery at the Hunan Cancer Hospital from February to August 2019. All cases underwent total hypopharyngectomy and total esophagectomy, of whom, three cases presented with total laryngectomy and one case with larynx preservation. Colonic interposition was performed using the left colic artery as a pedicle, with an average colonic length of 48.5 cm. The colon was elevated through the esophageal bed to the neck, and the branch of the colonic mesenteric artery was anastomosed to one of the neck arteries, including the inferior thyroid artery in one case, the transverse cervical artery in two cases, and the superior thyroid artery in one case, and all venous anastomoses were performed with the internal jugular veins.Results:The postoperative neck and abdominal wounds healed well without anastomotic leakage, and all patients were able to resume a regular oral diet within 21-30 days postoperatively. During the follow-up of 48-52 months, two cases died due to tumor recurrence, while the remaining two cases were disease-free survivals.Conclusion:Colonic interposition with vascular anastomosis is a safe and reliable reconstruction method suitable for repairing long-segment upper digestive tract defects after resection of hypopharyngeal cancer with esophageal cancer.

Background/Aims: The occurrence and development of circular RNAs in gastric cancer (GC) has attracted increasing attention. This study focused on investigating the biological role and molecular mechanism of circ_0043947 in GC. Methods: The expression levels of circ_0043947, miR-384 and CAMP response element binding protein (CREB1) were determined by quantitative real-time polymerase chain reaction or Western blotting. Cell proliferation, migration, and invasion, the cell cycle and apoptosis were determined using a cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, colony formation assay, wound healing assay, transwell assay, and flow cytometry assay. The interaction between miR-384 and circ_0043947 or CREB1 was verified by dual-luciferase reporter assay and RNA pull-down assay. The in vivo assay was conducted using a xenograft mouse model. Results: Circ_0043947 and CREB1 expression levels were significantly upregulated, whereas miR-384 expression levels were downregulated in GC tissues and cells. Functionally, knockdown of circ_0043947 inhibited cell proliferation, migration and invasion and induced G0/G1 phase arrest and apoptosis in vitro. Circ_0043947 could upregulate CREB1 expression by directly sponging miR-384. Rescue experiments showed that a miR-384 inhibitor significantly reversed the inhibitory effect of si-circ_0043947 on GC progression, and CREB1 overexpression significantly reversed the inhibitory effect of miR-384 mimics on the progression of GC cells. Furthermore, silencing of circ_0043947 inhibited tumor growth in vivo. Conclusions Circ_0043947 acted as an oncogenic factor in GC to mediate GC cell proliferation, migration, and invasion, the cell cycle and apoptosis by regulating the miR-384/CREB1 axis.Circ_0043947 may be a potential target for GC diagnosis and therapy.

Background/Aims: The occurrence and development of circular RNAs in gastric cancer (GC) has attracted increasing attention. This study focused on investigating the biological role and molecular mechanism of circ_0043947 in GC. Methods: The expression levels of circ_0043947, miR-384 and CAMP response element binding protein (CREB1) were determined by quantitative real-time polymerase chain reaction or Western blotting. Cell proliferation, migration, and invasion, the cell cycle and apoptosis were determined using a cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, colony formation assay, wound healing assay, transwell assay, and flow cytometry assay. The interaction between miR-384 and circ_0043947 or CREB1 was verified by dual-luciferase reporter assay and RNA pull-down assay. The in vivo assay was conducted using a xenograft mouse model. Results: Circ_0043947 and CREB1 expression levels were significantly upregulated, whereas miR-384 expression levels were downregulated in GC tissues and cells. Functionally, knockdown of circ_0043947 inhibited cell proliferation, migration and invasion and induced G0/G1 phase arrest and apoptosis in vitro. Circ_0043947 could upregulate CREB1 expression by directly sponging miR-384. Rescue experiments showed that a miR-384 inhibitor significantly reversed the inhibitory effect of si-circ_0043947 on GC progression, and CREB1 overexpression significantly reversed the inhibitory effect of miR-384 mimics on the progression of GC cells. Furthermore, silencing of circ_0043947 inhibited tumor growth in vivo. Conclusions Circ_0043947 acted as an oncogenic factor in GC to mediate GC cell proliferation, migration, and invasion, the cell cycle and apoptosis by regulating the miR-384/CREB1 axis.Circ_0043947 may be a potential target for GC diagnosis and therapy.

Background/Aims: The occurrence and development of circular RNAs in gastric cancer (GC) has attracted increasing attention. This study focused on investigating the biological role and molecular mechanism of circ_0043947 in GC. Methods: The expression levels of circ_0043947, miR-384 and CAMP response element binding protein (CREB1) were determined by quantitative real-time polymerase chain reaction or Western blotting. Cell proliferation, migration, and invasion, the cell cycle and apoptosis were determined using a cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, colony formation assay, wound healing assay, transwell assay, and flow cytometry assay. The interaction between miR-384 and circ_0043947 or CREB1 was verified by dual-luciferase reporter assay and RNA pull-down assay. The in vivo assay was conducted using a xenograft mouse model. Results: Circ_0043947 and CREB1 expression levels were significantly upregulated, whereas miR-384 expression levels were downregulated in GC tissues and cells. Functionally, knockdown of circ_0043947 inhibited cell proliferation, migration and invasion and induced G0/G1 phase arrest and apoptosis in vitro. Circ_0043947 could upregulate CREB1 expression by directly sponging miR-384. Rescue experiments showed that a miR-384 inhibitor significantly reversed the inhibitory effect of si-circ_0043947 on GC progression, and CREB1 overexpression significantly reversed the inhibitory effect of miR-384 mimics on the progression of GC cells. Furthermore, silencing of circ_0043947 inhibited tumor growth in vivo. Conclusions Circ_0043947 acted as an oncogenic factor in GC to mediate GC cell proliferation, migration, and invasion, the cell cycle and apoptosis by regulating the miR-384/CREB1 axis.Circ_0043947 may be a potential target for GC diagnosis and therapy.

Background/Aims: The occurrence and development of circular RNAs in gastric cancer (GC) has attracted increasing attention. This study focused on investigating the biological role and molecular mechanism of circ_0043947 in GC. Methods: The expression levels of circ_0043947, miR-384 and CAMP response element binding protein (CREB1) were determined by quantitative real-time polymerase chain reaction or Western blotting. Cell proliferation, migration, and invasion, the cell cycle and apoptosis were determined using a cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, colony formation assay, wound healing assay, transwell assay, and flow cytometry assay. The interaction between miR-384 and circ_0043947 or CREB1 was verified by dual-luciferase reporter assay and RNA pull-down assay. The in vivo assay was conducted using a xenograft mouse model. Results: Circ_0043947 and CREB1 expression levels were significantly upregulated, whereas miR-384 expression levels were downregulated in GC tissues and cells. Functionally, knockdown of circ_0043947 inhibited cell proliferation, migration and invasion and induced G0/G1 phase arrest and apoptosis in vitro. Circ_0043947 could upregulate CREB1 expression by directly sponging miR-384. Rescue experiments showed that a miR-384 inhibitor significantly reversed the inhibitory effect of si-circ_0043947 on GC progression, and CREB1 overexpression significantly reversed the inhibitory effect of miR-384 mimics on the progression of GC cells. Furthermore, silencing of circ_0043947 inhibited tumor growth in vivo. Conclusions Circ_0043947 acted as an oncogenic factor in GC to mediate GC cell proliferation, migration, and invasion, the cell cycle and apoptosis by regulating the miR-384/CREB1 axis.Circ_0043947 may be a potential target for GC diagnosis and therapy.

Lung cancer remains the leading cause of cancer deaths worldwide and is the most common cancer in males. Immune-checkpoint inhibitors (ICIs) that target programmed cell death protein-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) have achieved impressive efficacy in the treatment of non-small-cell lung cancer (NSCLC) (Pardoll, 2012; Champiat et al., 2016; Gao et al., 2022). Although ICIs are usually well tolerated, they are often accompanied by immune-related adverse events (irAEs) (Doroshow et al., 2019). Non-specific activation of the immune system produces off-target immune and inflammatory responses that can affect virtually any organ or system (O'Kane et al., 2017; Puzanov et al., 2017). Compared with adverse events caused by chemotherapy, irAEs are often characterized by delayed onset and prolonged duration and can occur in any organ at any stage of treatment, including after cessation of treatment (Puzanov et al., 2017; von Itzstein et al., 2020). They range from rash, pneumonitis, hypothyroidism, enterocolitis, and autoimmune hepatitis to cardiovascular, hematological, renal, neurological, and ophthalmic irAEs (Nishino et al., 2016; Kumar et al., 2017; Song et al., 2020). Hence, we conducted a retrospective study to identify validated factors that could predict the magnitude of the risk of irAEs in patients receiving PD-1/PD-L1 inhibitors; our approach was to analyze the correlation between the clinical characteristics of patients at the start of treatment and relevant indicators such as hematological indices and the risk of developing irAEs. Then, we developed an economical, practical, rapid, and simple model to assess the risk of irAEs in patients receiving ICI treatment, as early as possible.
Male ; Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; Immune Checkpoint Inhibitors/adverse effects* ; Programmed Cell Death 1 Receptor ; Retrospective Studies ; Apoptosis