Ulcerative colitis is a chronic relapsing inflammatory bowel disease. Modern research indicates that immune dysregulation resulting from disruptions in circadian rhythm is closely associated with its pathogenesis. Both Western chronomedicine and traditional Chinese medicine（TCM）" treatment based on temporal factors" emphasize the temporal relationship between natural rhythms and human physiology and pathology. The " midnight-noon and ebb-flow " theory represents the concrete application and deepening of TCM " treatment based on temporal factors" within the realm of chronomedicine. This article correlates the onset time of ulcerative colitis with specific periods in the " midnight-noon and ebb-flow"theory：the Mao period（05：00-07：00），when the yangming large intestine meridian of hand is dominant； the Si period（09：00-11：00），when the taiyin spleen meridian of foot is dominant； and the You period（17：00-19：00），when the shaoyin kidney meridian of foot is dominant. According to this perspective，if the disease manifests during the Mao period，the pathogenesis is attributed to dampnessheat accumulation and disorder of qi and blood. Treatment should focus on clearing heat，resolving dampness，and harmonizing qi and blood，using modified formulas such as Shaoyao Decoction or Baitouweng Decoction. If it occurs during the Si period，the pathogenesis involves spleen deficiency with dampness obstruction and disharmony of qi and blood. Treatment should focus on strengthening the spleen，eliminating dampness，and restoring qi and blood，using modified formulas such as Huangya Decoction or Shenling Baizhu Powder. If it presents during the You period，the pathogenesis is characterized by fire failing to warm earth，and consumption resulting in qi and blood leakage. Treatment should focus on warming the kidney and spleen，and securing qi and blood，using modified formulas such as Sishen Pill or Tianhun Decoction. In addition to oral administration of Chinese herbal medicine，comprehensive therapies including acupuncture，herbal enemas，and acupoint application can provide novel insights for the clinical diagnosis and treatment of ulcerative colitis.

Background Studies have shown that benzo(a)pyrene (BaP) exhibits neurotoxicity and can induce cognitive dysfunction. Olfactory dysfunction is an early marker of mild cognitive impairment; however, the mechanism by which BaP exposure causes this impairment is still unclear. Objective To investigate the effects of BaP exposure on olfactory function in mice. Methods Thirty 5-month-old male C57BL/6 mice were randomly assigned to five groups (n=6 per group): blank control, solvent control (olive oil), and low, medium and high doses (0.72, 1.44, and 2.89 mg·kg⁻¹, respectively). Following one week of acclimatization, BaP was administered intranasally every other day. Behavioral changes were assessed using the buried food test and Morris water maze (MWM). Olfactory bulb tissues were subsequently harvested for analysis. Hematoxylin-eosin (HE) staining was used to evaluate pathological changes, while immunofluorescence and quantitative polymerase chain reaction (qPCR) were employed to examine the expression and distribution of protein and mRNA expressions and distributions of olfactory marker protein (OMP), membrane-spanning 4-pass A1 (MS4A1), trace amine-associated receptor1 (TAAR1). Results The buried food test revealed that BaP exposure significantly prolonged the time taken to find food in a dose-dependent manner (F=56.753, P< 0.01). MWM results showed significant main effects for both time (F=128.5, P<0.01) and dose (F=3.889, P<0.05), with a significant interaction effect between them (F=2.128, P<0.05). HE staining showed that in the 2.89 mg·kg⁻¹ group, although granule remained abundant, mitral cell layer neurons exhibited structural atrophy and deep staining. Immunofluorescence demonstrated a decreased distribution of OMP, MS4A1, and TAAR1 in the olfactory nerve layer and glomerular layers in the 2.89 mg·kg⁻¹ group compared with the blank control group (F=11.590, P<0.01; F=12.807, P<0.01; F=7.436, P<0.01). Furthermore, mRNA expression levels of OMP, MS4A1, and TAAR1 in the 2.89 mg·kg⁻¹ group were also significantly downregulated compared to the control group (F=6.720, P<0.01; F=16.931, P<0.01; F=48.060, P<0.01). Conclusion BaP exposure leads to olfactory dysfunction in mice by inducing pathological damage to mitral cells and reducing the expression of key olfactory receptors and markers in the olfactory bulb.

Background Studies have shown that benzo(a)pyrene (BaP) exhibits neurotoxicity and can induce cognitive dysfunction. Olfactory dysfunction is an early marker of mild cognitive impairment; however, the mechanism by which BaP exposure causes this impairment is still unclear. Objective To investigate the effects of BaP exposure on olfactory function in mice. Methods Thirty 5-month-old male C57BL/6 mice were randomly assigned to five groups (n=6 per group): blank control, solvent control (olive oil), and low, medium and high doses (0.72, 1.44, and 2.89 mg·kg⁻¹, respectively). Following one week of acclimatization, BaP was administered intranasally every other day. Behavioral changes were assessed using the buried food test and Morris water maze (MWM). Olfactory bulb tissues were subsequently harvested for analysis. Hematoxylin-eosin (HE) staining was used to evaluate pathological changes, while immunofluorescence and quantitative polymerase chain reaction (qPCR) were employed to examine the expression and distribution of protein and mRNA expressions and distributions of olfactory marker protein (OMP), membrane-spanning 4-pass A1 (MS4A1), trace amine-associated receptor1 (TAAR1). Results The buried food test revealed that BaP exposure significantly prolonged the time taken to find food in a dose-dependent manner (F=56.753, P< 0.01). MWM results showed significant main effects for both time (F=128.5, P<0.01) and dose (F=3.889, P<0.05), with a significant interaction effect between them (F=2.128, P<0.05). HE staining showed that in the 2.89 mg·kg⁻¹ group, although granule remained abundant, mitral cell layer neurons exhibited structural atrophy and deep staining. Immunofluorescence demonstrated a decreased distribution of OMP, MS4A1, and TAAR1 in the olfactory nerve layer and glomerular layers in the 2.89 mg·kg⁻¹ group compared with the blank control group (F=11.590, P<0.01; F=12.807, P<0.01; F=7.436, P<0.01). Furthermore, mRNA expression levels of OMP, MS4A1, and TAAR1 in the 2.89 mg·kg⁻¹ group were also significantly downregulated compared to the control group (F=6.720, P<0.01; F=16.931, P<0.01; F=48.060, P<0.01). Conclusion BaP exposure leads to olfactory dysfunction in mice by inducing pathological damage to mitral cells and reducing the expression of key olfactory receptors and markers in the olfactory bulb.

Proteolysis-targeting chimeras (PROTACs) have shown considerable therapeutic potential across diverse fields such as cancer, inflammation, and neurodegenerative diseases, with numerous candidates already progressing into clinical trials. More recently, their application in antiviral therapy has been rapidly gaining momentum. This review systematically outlines the mechanistic foundations and design principles of PROTACs, highlights recent advances targeting coronaviruses (including SARS-CoV-2), hepatitis C virus, human immunodeficiency virus, and influenza viruses, and critically assesses key challenges—particularly the limited diversity of E3 ligase ligands, suboptimal oral bioavailability, and the lack of integrated platforms for druggability evaluation. Looking ahead, innovations in ligand discovery, pathway modulation, delivery technologies, and conditionally activated PROTAC designs are anticipated to overcome these barriers, ushering in a new era of precise and effective antiviral therapeutics.

OBJECTIVE: To explore the clinical phenotypes and genetic characteristics of a child with Acid-labile subunit deficiency (ALS). METHODS: A male child diagnosed with ALS at Dongguan Maternal and Child Health Care Hospital in March 2021 was selected as the study subject. Clinical data of his family was collected. Peripheral blood samples were collected from the child and his parents. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out, and Sanger sequencing was used for family verification of candidate variants. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of the candidate variant was classified. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2020-6). RESULTS: The patient, a 5-year-and-7-month-old boy, presented with short stature and delayed bone age. Endocrine examinations showed decreased serum concentrations of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP3). WES revealed that he has harbored compound heterozygous variants of the IGFALS gene, namely c.741_742del, p.Y248Pfs83 and c.272del, p.P91Rfs31. Sanger sequencing verified that the variants were inherited from his father and mother, respectively. According to the ACMG guidelines, c.741_742del, p.Y248Pfs83 and c.272del, p.P91Rfs31 variants were classified as likely pathogenic (PVS1+PM2_supporting). Based on the pre-set literature search strategy, 11 research literature on ALS were retrieved, which involved a total of 33 families and 62 patients. Combined with the patient in this study, 31 IGFALS gene variants were identified among the 63 patients, which mainly consisted of missense variants (20 types), with variant sites concentrated in exon 2. The main clinical features were short stature in conjunct with delayed puberty, with a significant genotype-phenotype correlation. CONCLUSION The IGFALS gene variants NM_004970.2: c.741_742del, p.Y248Pfs83 and c.272del, p.P91Rfs31 may be the genetic etiology in this family. This study has expanded the variant spectrum of the IGFALS gene and provided valuable information for the diagnosis, genetic counseling and clinical treatment of the disease.
Humans ; Male ; Phenotype ; Child, Preschool ; Carrier Proteins/genetics* ; Glycoproteins/deficiency* ; Exome Sequencing ; Female ; Mutation ; Insulin-Like Growth Factor I/metabolism* ; Growth Disorders/genetics*

AIM:This study aims to investigate the effects of Jiedu-Shengji ointment(JDSJG)on wound healing in diabetic rats by modulating the protein kinase R-like endoplasmic reticulum kinase(PERK)/inositol-requiring enzyme 1(IRE1)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)pathway in the context of endoplasmic reticulum stress(ERS).METHODS:Male Sprague-Dawley rats were randomly assigned to four groups:control group,model group,detoxification muscle ointment group,and sulfadiazine silver cream group.All groups,except the control,were administered an intraperitoneal injection of 45 mg/kg streptozotocin to induce diabetes.The control and model groups received daily applications of normal saline,while the detoxification myogen ointment and sulfadiazine silver cream groups received their respective treatments daily.After dressing changes,wounds were bandaged with sterile gauze.Following 14 d of continuous treatment,wound healing was assessed and healing rates calculated.Histopathologi-cal changes in wound tissues were analyzed using HE staining.Transmission electron microscopy was utilized to observe the number,morphology,and swelling of endoplasmic reticulum in the wound tissues.The expression and distribution of PERK,IRE1 and thioredoxin interacting protein(TXNIP)was assessed by immunohistochemistry,while Western blot was used to measure the levels of apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),TXNIP and NLRP3.ELISA was conducted to quantify the inflammatory cytokines interleukin-18(IL-18)and IL-1β.RE-SULTS:After 14 d of intervention,significant differences were observed in wound tissue parameters across the groups.The model group exhibited a significantly lower wound healing rate compared to the control group(P<0.01),with in-creased wound exudation,poor granulation tissue growth,and elevated the protein levels of PERK,IRE1,TXNIP,CHOP,NLRP3 and ASC(P<0.01),as well as significantly higher levels of IL-1β and IL-18(P<0.01).In contrast,the detoxification muscle ointment group showed a marked improvement in wound healing rate(P<0.01),reduced inflamma-tory exudation,improved granulation tissue growth,and significant decreases in TXNIP expression(P<0.01),along with lower levels of PERK,IRE1,CHOP,ASC and NLRP3(P<0.01).Additionally,the IL-1β and IL-18 were significantly reduced(P<0.01).CONCLUSION:Jiedu Shengji ointment alleviates excessive ERS and mitigates chronic inflammato-ry responses,thereby promoting the healing of diabetic wounds.These effects may be attributed to the inhibition of exces-sive activation of the PERK/IRE1/NLRP3 pathway.

AIM:This study aims to investigate the effects of Jiedu-Shengji ointment(JDSJG)on wound healing in diabetic rats by modulating the protein kinase R-like endoplasmic reticulum kinase(PERK)/inositol-requiring enzyme 1(IRE1)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)pathway in the context of endoplasmic reticulum stress(ERS).METHODS:Male Sprague-Dawley rats were randomly assigned to four groups:control group,model group,detoxification muscle ointment group,and sulfadiazine silver cream group.All groups,except the control,were administered an intraperitoneal injection of 45 mg/kg streptozotocin to induce diabetes.The control and model groups received daily applications of normal saline,while the detoxification myogen ointment and sulfadiazine silver cream groups received their respective treatments daily.After dressing changes,wounds were bandaged with sterile gauze.Following 14 d of continuous treatment,wound healing was assessed and healing rates calculated.Histopathologi-cal changes in wound tissues were analyzed using HE staining.Transmission electron microscopy was utilized to observe the number,morphology,and swelling of endoplasmic reticulum in the wound tissues.The expression and distribution of PERK,IRE1 and thioredoxin interacting protein(TXNIP)was assessed by immunohistochemistry,while Western blot was used to measure the levels of apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),TXNIP and NLRP3.ELISA was conducted to quantify the inflammatory cytokines interleukin-18(IL-18)and IL-1β.RE-SULTS:After 14 d of intervention,significant differences were observed in wound tissue parameters across the groups.The model group exhibited a significantly lower wound healing rate compared to the control group(P<0.01),with in-creased wound exudation,poor granulation tissue growth,and elevated the protein levels of PERK,IRE1,TXNIP,CHOP,NLRP3 and ASC(P<0.01),as well as significantly higher levels of IL-1β and IL-18(P<0.01).In contrast,the detoxification muscle ointment group showed a marked improvement in wound healing rate(P<0.01),reduced inflamma-tory exudation,improved granulation tissue growth,and significant decreases in TXNIP expression(P<0.01),along with lower levels of PERK,IRE1,CHOP,ASC and NLRP3(P<0.01).Additionally,the IL-1β and IL-18 were significantly reduced(P<0.01).CONCLUSION:Jiedu Shengji ointment alleviates excessive ERS and mitigates chronic inflammato-ry responses,thereby promoting the healing of diabetic wounds.These effects may be attributed to the inhibition of exces-sive activation of the PERK/IRE1/NLRP3 pathway.

Background and Aims:In the era of minimally invasive surgery,the role of pancreatic tumor enucleation(PTE)in treating benign or low-grade malignant tumors is gaining attention.The Da Vinci robot offers advantages such as enhanced visualization and flexible instrument manipulation,which can ensure the safe implementation of PTE.However,whether robotic pancreatic tumor excision(RPTE)is superior to laparoscopic pancreatic tumor enucleation(LPTE)remains undetermined.Therefore,this study was performed to explore this aspect. Methods:The clinical data of 38 patients who underwent surgical treatment for benign or low-grade malignant tumors in the Third Xiangya Hospital of Central South University from April 2020 to May 2024 were collected.Among them,18 cases underwent RPTE(RPTE group),and 20 cases underwent LPTE(LPTE group).Relevant clinical variables were compared between the two groups,and subgroup comparisons were further conducted for patients with tumors in the head and neck/body/tail of the pancreas. Results:The average operative time for the entire group was 125 min,with an average intraoperative blood loss of 67.89 mL,and no C-grade pancreatic fistula occurred.The incidence rates of B-grade pancreatic fistula,postoperative bleeding,and readmission were 39.5％,21.1％,and 18.4％,respectively,with an average postoperative hospital stay of 11.44 d.Overall,the RPTE group had shorter operative time and less intraoperative blood loss than the LPTE group(both P＜0.05).There were no statistically significant differences between the two groups regarding the incidence of B-grade pancreatic fistula,intraoperative bleeding,readmission rate,and postoperative hospital stay(all P＞0.05).Subgroup analysis showed that for patients with head tumors,the RPTE group had shorter operative time,less intraoperative blood loss,and a lower incidence of postoperative bleeding than the LPTE group(all P＜0.05).However,the differences in the incidence of B-grade pancreatic fistula,readmission rate,and postoperative hospital stay were not statistically significant(all P＞0.05).In patients with neck/body/tail tumors,the RPTE group also had shorter operative time and less intraoperative blood loss(both P＜0.05),but the differences in incidence of B-grade pancreatic fistula,incidence of postoperative bleeding,readmission rate,and postoperative hospital stay were not statistically significant(all P＞0.05). Conclusion:Minimally invasive PTE for the treatment of benign or low-grade malignant pancreatic tumors is safe.Compared to LPTE,RPTE can significantly reduce operative time and intraoperative blood loss and shows certain advantages in reducing postoperative complications,particularly for patients with head tumors.However,the conclusion of this study needs to be confirmed by larger prospective studies.

In recent years, the incidence rate of tubal infertility has been rising. In China, most patients with tubal infertility prioritize conservative management or tubal reconstruction surgery in order to preserve fallopian tubes as far as possible. In order to meet the reproductive needs of tubal infertile patients, clinicians in the reproductive field need to evaluate various infertility risk factors comprehensively, weigh the pros and cons, and explore individualized reproductive programs which are more in line with the interests of patients. Correspondingly, higher requirements for the imaging evaluation efficiency of the fallopian tubes have been put forward. Hysterosalpingo-contrast sonography (HyCoSy), as a first-line imaging technique for evaluating tubal patency, still faces many controversies and dilemmas despite its value being widely recognized in clinical practice. This paper aims to provide viewpoints for the advancement of HyCoSy by reviewing literature and summarizing experiences.

Objective:The transjugular or transfemoral approach is used as a common method for hepatic venous pressure gradient (HVPG) measurement in current practice. This study aims to confirm the safety and effectiveness of measuring HVPG via the forearm venous approach.Methods:Prospective recruitment was conducted for patients with cirrhosis who underwent HVPG measurement via the forearm venous approach at six hospitals in China and Japan from September 2020 to December 2020. Patients' clinical baseline information and HVPG measurement data were collected. The right median cubital vein or basilic vein approach for all enrolled patients was selected. The HVPG standard process was used to measure pressure. Research data were analyzed using SPSS 22.0 statistical software. Quantitative data were used to represent medians (interquartile ranges), while qualitative data were used to represent frequency and rates. The correlation between two sets of data was analyzed using Pearson correlation analysis.Results:A total of 43 cases were enrolled in this study. Of these, 41 (95.3%) successfully underwent HVPG measurement via the forearm venous approach. None of the patients had any serious complications. The median operation time for HVPG detection via forearm vein was 18.0 minutes (12.3~38.8 minutes). This study confirmed that HVPG was positively closely related to Child-Pugh score ( r = 0.47, P = 0.002), albumin-bilirubin score ( r = 0.37, P = 0.001), Lok index ( r = 0.36, P = 0.02), liver stiffness ( r = 0.58, P = 0.01), and spleen stiffness ( r = 0.77, P = 0.01), while negatively correlated with albumin ( r = -0.42, P = 0.006). Conclusion:The results of this multi-centre retrospective study suggest that HVPG measurement via the forearm venous approach is safe and feasible.