ObjectiveTo observe the clinical efficacy of Sanren Runchang formula in treating constipation-predominant irritable bowel syndrome （IBS-C） by regulating the brain-gut axis and the effects of the formula on serum levels of 5-hydroxytryptamine （5-HT）， vasoactive intestinal peptide （VIP）， and substance P （SP）. MethodsA randomized controlled design was adopted， and 72 IBS-C patients meeting Rome Ⅳ criteria were randomized into observation and control groups （36 cases）.The observation group received Sanren Runchang formula granules twice daily， and the control group received lactulose oral solution daily for 4 weeks. IBS Symptom Severity Scale （IBS-SSS）， IBS Quality of Life Scale （IBS-QOL）， and Bristol Stool Form Scale （BSFS） were used to assess clinical symptoms， and bowel movement frequency was recorded. The Self-Rating Anxiety Scale （SAS） and Self-Rating Depression Scale （SDS） were employed to evaluate psychological status. ELISA was employed to measure the serum levels of 5-HT， VIP， and SP. ResultsThe total response rate in the observation group was 91.67% （33/36）， which was higher than that （77.78%， 28/36） in the control group （χ²=4.50， P<0.05）. After treatment， both groups showed increased defecation frequency and BSFS scores， decreased IBS-SSS total score， abdominal pain and bloating scores， IBS-QOL health anxiety， anxiety， food avoidance， and behavioral disorders scores， SAS and SDS scores， serum 5-HT and VIP levels， and increased SP levels （P<0.05， P<0.01）. Moreover， the observation group showed more significant changes in the indicators above than the control group （P<0.05， P<0.01）. The SP level showed no significant difference between the two groups. During the 4-week follow-up， the recurrence rate was 5.88% in the observation group and 31.25% in the control group. No adverse events occurred in observation group， and 2 cases of mild diarrhea occurred in the control group. ConclusionSanren Runchang formula demonstrated definitive efficacy in alleviating gastrointestinal symptoms and improving the psychological status and quality of life in IBS-C patients， with a low recurrence rate. The formula can regulate serum levels of neurotransmitters such as 5-HT and VIP， suggesting its potential regulatory effect on the brain-gut axis through modulating neurotransmitters and neuropeptides. However， its complete mechanism of action requires further investigation through detection of additional brain-gut axis-related biomarkers.

Objective:To investigate the effects of Juglone on the apoptosis of osteosarcoma(OS)cells(U2OS and MG63 cells)through the cysteinyl aspartate specific proteinase-3(Caspase-3)/gasdermin E(GSDME)-mediated pyroptosis pathway.Methods:The U2OS and MG63 cells were cultured in vitro and divided into control group,different concentrations(5,10 and 20 μmol·L-1)of Juglone groups and Caspase-3 inhibitor Z-DEVD-FMK group(10 μmol·L-1 Juglone+30 μmol·L-1 Z-DEVD-FMK).The survival rates of cells in various groups were assessed by cell counting kit-8(CCK-8)assay,and the apoptotic rates were detected by flow cytometry.Lactate dehydrogenase(LDH)release assay was used to measure the release rates of LDH from the cells.Western blotting method was used to detect the expression levels of apoptosis-related proteins including B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),cleaved-Caspase-3 and poly(ADP-ribose)polymerase(PARP)and pyroptosis-related proteins including GSDME full form(GSDME-F)and GSDME N-terminal(GSDME-N).The levels of interleukin-1β(IL-1β)and interleukin-18(IL-18)in the cell supernataut in various groups were measured by enzyme-linked immunosorbent assay(ELISA)method.Results:Compared with control group,the survival rates of cells in 5,10,and 20 μmol·L-1Juglone groups were significantly decreased(P＜0.05 or P＜0.01),and the 50％inhibitory concentration(IC50)values of U2OS cells and MG63 cells were 8.4 and 10.2 μmol·L-1,respectively.Compared with control group,the apoptotic rates and LDH release rates of U2OS and MG63 cells in 5 and 10 μmol·L-1Juglone groups were significantly increased(P＜0.05 or P＜0.01).Compared with control group,the expression levels of Bax,cleaved-Caspase-3,and cleaved-PARP proteins in 5 and 10 μmol·L-1 Juglone groups were significantly increased(P＜0.01),while the expression levels of Bcl-2 protein were significantly decreased(P＜0.01).Compared with control group,the levels of IL-1β and IL-18 in cell supernatant in 5 and 10 μmol·L-1Juglone groups were increased(P＜0.01).Compared with control group,the expression levels of cleaved-Caspase-3 and GSDME-N proteins in 5 and 10 μmol·L-1 Juglone groups were significantly increased(P＜0.01),while there was no difference in the expression level of GSDME-F protein(P＞0.05).Compared with 10 μmol·L-1 Juglone group,the expression levels of cleaved-Caspase-3 and GSDME-N in Z-DEVD-FMK group were significantly decreased(P＜0.01),while there was no difference in the expression level of GSDME-F protein(P＞0.05).Conclusion:Juglone can induce the apoptosis of U2OS and MG63 cells and cause the Caspase-3/GSDME-mediated pyroptosis.

A case of Sifrim-Hitz-Weiss syndrome(Sifrim-Hitz-Weiss syndrome,SIHIWES)is presented.The patient was a 35-year-old male with cryptorchidism,growth retardation,skeletal malformations,muscular atrophy,a wide forehead,special facial features like square face,small low-set and cup-shaped ears since birth.Whole-exon sequencing identified a heterozygous mutation(NM_001273:c.3047A>G(chr12-6701125)(p.K1016R))in CHD4 gene.The clinical significance of this mutation is currently unknown,and has not been previously reported.In light of the patient's symptoms,the case was diagnosed as Sifrim-Hitz-Weiss syndrome.This case represents the first instance of Sifrim-Hitz-Weiss syndrome in an adult patient in China.

Objective To observe the therapeutic effect and mechanism of electroacupuncture at Yanglingquan(GB34)and Quchi(LI11)points for post-stroke spasticity(PSS)in rats.Methods The rats were randomly divided into sham-operated group,model group,electroacupuncture group and electroacupuncture+CA1[Janus kinase 2(JAK2)agonist]group.The PSS model was prepared by the modified middle cerebral artery occlusion combined with internal capsule injection of N-methyl-D-aspartate(NMDA)receptor method in all groups of rats except the sham-operated group.After the intervention,the neurological deficit scale scoring,Ashworth Spasticity Scale(Ashworth)scoring and electrophysiological determination were carried out;the levels of interleukin 6(IL-6),tumor necrosis factor α(TNF-α)and γ-aminobutyric acid(GABA)in the brain tissues were detected by enzyme-linked immunosorbent assay(ELISA);the content of glutamate(Glu)was observed by colorimetry;the pathological changes in brain tissues were observed by hematoxylin-eosin(HE)staining method;the protein expression levels of JAK2,phosphorylated JAK2(p-JAK2),signal transducer and activator of transcription 3(STAT3),and phosphorylated STAT3(p-STAT3)in brain tissues were detected by Western Blot method.Results The neurological deficit scale scores,Ashworth scores,contents of IL-6,TNF-α and Glu as well as p-JAK2/JAK2 and p-STAT3/STAT3 ratios in brain tissues in the model group were all significantly higher than those in the sham-operated group(P<0.05),and the muscular tension signal value and GABA content in brain tissues in the model group were significantly lower than those in the sham-operated group(P<0.05);compared with the model group,the neurological deficit scale scores,Ashworth scores,contents of IL-6,TNF-α and Glu as well as p-JAK2/JAK2 and p-STAT3/STAT3 ratios in brain tissues were significantly lower in the electroacupuncture group(P<0.05),and the muscular tension signal value and GABA content in brain tissues were significantly higher in the electroacupuncture group(P<0.05);compared with the electroacupuncture group,the neurological deficit scale scores,Ashworth scores,contents of IL-6,TNF-α and Glu as well as p-JAK2/JAK2 and p-STAT3/STAT3 ratios in brain tissues in the electroacupuncture+CA1 group were significantly higher(P<0.05),and the muscular tension signal value and GABA content in brain tissues in the electroacupuncture+CA1 group were significantly lower(P<0.05).Conclusion Electroacupuncture may inhibit inflammatory responses and regulate the neuronal excitation/inhibition balance by inhibiting the JAK2/STAT3 pathway,thus relieving PSS in rats.

Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Dysregulated RNA splicing is a well-recognized characteristic of colorectal cancer (CRC); however, its intricacies remain obscure, partly due to challenges in profiling full-length transcript variants at the single-cell level. Here, we employ high-depth long-read scRNA-seq to define the full-length transcriptome of colorectal epithelial cells in 12 CRC patients, revealing extensive isoform diversities and splicing alterations. Cancer cells exhibited increased transcript complexity, with widespread 3'-UTR shortening and reduced intron retention. Distinct splicing regulation patterns were observed between intrinsic-consensus molecular subtypes (iCMS), with iCMS3 displaying even higher splicing factor activities and more pronounced 3'-UTR shortening. Furthermore, we revealed substantial shifts in isoform usage that result in alterations of protein sequences from the same gene with distinct carcinogenic effects during tumorigenesis of CRC. Allele-specific expression analysis revealed dominant mutant allele expression in key oncogenes and tumor suppressors. Moreover, mutated PPIG was linked to widespread splicing dysregulation, and functional validation experiments confirmed its critical role in modulating RNA splicing and tumor-associated processes. Our findings highlight the transcriptomic plasticity in CRC and suggest novel candidate targets for splicing-based therapeutic strategies.
Humans ; Colorectal Neoplasms/metabolism* ; RNA Isoforms/metabolism* ; Single-Cell Analysis ; RNA Splicing ; Gene Expression Regulation, Neoplastic ; RNA, Neoplasm/metabolism* ; Transcriptome

Objective:To validate the validity of the auricular cartilage fish-shaped framework in comprehensive rhinoplasty for Chinese Han females.Methods:The clinical data of Chinese Han female patients with short nose and saddle nasal deformity undergoing primary rhinoplasty at the Department of Plastic Surgery, the First Affiliated Hospital of Nanchang University, from August 2021 to October 2023, were retrospectively analyzed. Patients underwent comprehensive rhinoplasty, involving the implantation of an auricular cartilage fish-shaped framework at the nasal tip and a dorsal nasal implant on the nasal bridge.Postoperative follow-up monitored for complications. At 6-month postoperatively, a satisfaction survey was conducted among the patients, their family, or friends using a scale where: very satisfied with improvement=4, moderately satisfied with improvement=3, Slightly satisfied with improvement=2, No improvement=1. Additionally, two plastic surgeons evaluated the postoperative outcomes using a scale where: excellent=5, very good=4, good=3, fair=2, poor=1.Preoperative and 6-month postoperative photographs were processed using Image J software to measure the following parameters: nasolabial angle, nasofacial angle, nasofrontal angle, columellar lobular angle, nasal height, and nasal length. Paired t-tests were used for statistical analysis, with P < 0.05 considered statistically significant. Results:A total of 18 patients were included, with a mean age of (26.4 ± 7.2) years (range: 18-45 years). The mean postoperative follow-up duration was (23.0 ± 9.3) months (range: 6 months to 3 years). All patients recovered well, with no severe complications occurring.The mean patient satisfaction score regarding the postoperative outcome was 3.50 ± 0.62. The mean satisfaction score from family or friends was 3.33 ± 0.69. The two evaluating plastic surgeons rated the outcomes as 4.17 ± 0.85 and 3.94 ± 0.93, respectively, both falling between the excellent and very good categories on the assessment scale.Statistically significant differences (all P < 0.01) were found between preoperative and 6-month postoperative measurements for all assessed nasal parameters. Nasolabial angle: 99.68° ± 2.95° vs. 95.37° ± 1.09°; nasofacial angle: 29.47° ± 2.99° vs. 32.82° ± 2.23°; nasofrontal angle: 140.72° ± 5.18° vs. 133.79° ± 4.43°; columellar lobular angle: 44.86° ± 3.43° vs. 39.23° ± 6.44°; nasal height: (57.52 ± 0.60) mm vs. (58.41 ± 0.39) mm; nasal length: (50.08 ± 0.54) mm vs. (50.64 ± 0.31) mm. Conclusion:The use of the auricular cartilage fish-shaped framework combined with a prosthesis in rhinoplasty, requiring only unilateral or bilateral auricular cartilage, effectively improved low nose and short nose deformities in the majority of Chinese Han females. This validates the favorable outcome of this framework in comprehensive rhinoplasty for this population.

Objective:The purpose of this study was to investigate the diagnostic value and clinical significance of cochlear microphonics (CM) combined with otoacoustic emission (OAE) in patients with auditory neuropathy (AN).Methods:The study included patients who were diagnosed with bilateral AN and had CM originating from both sides. The CM amplitude, latency, duration and intensity-amplitude (I/O) function curve were recorded by CM test. According to whether the distortion product otoacoustic emissions (DPOAE) passed through, the patients were divided into three groups: bilateral OAE passed group (OAE PP Group), bilateral OAE failed group (OAE RR Group), and unilateral OAE passed through one side failed group (OAE PR Group). OAE was elicited by four or more frequencies of 750-8 000 Hz. The characteristics of CM and its related influencing factors were analyzed, and data were processed and analyzed by SPSS 26.0 software. Results:(1) A total of 256 patients (512 ears) with AN were enrolled, including 161 patients (322 ears) in OAE PP group, 32 patients (64 ears) in OAE PR group and 63 patients (126 ears) in OAE RR group. OAE failed in 30.9% of patients with AN. (2) When the stimulation intensity was 100 dB nHL, the CM amplitude of OAE passing ear (OAE P+CM P group) in AN patients aged 3 years was 0.43±0.17μV, which was significantly higher than that of OAE not passing ear (OAE R+CM P group) (0.29±0.15) μV ( t=4.876， P<0.001). The CM duration of the OAE P+CM P group was (5.18±1.04) ms, which was longer than that of the OAE R+CM P group at 4.60±1.12 ms ( P=0.005). The I/O function curve of OAE P+CM P group showed a nonlinear trend, while, that of OAE R+CM P group showed a linear trend. (3) In the OAE P+CM P group of AN patients, the amplitude of CM was negatively correlated with the onset age, test age, disease course, PTA, and ASSR threshold ( P<0.001), with correlation coefficients of r=-0.475, r=-0.519, r=-0.367, r=-0.374, and r=-0.494, respectively. In the OAE R+CM P group of AN patients, the amplitude of CM was negatively correlated with the onset age, test age, and ASSR threshold ( P<0.05), with correlation coefficients of r=-0.271, r=-0.240, and r=-0.287, respectively. Conclusions:Excluding patients with high-frequency steeply sloping hearing loss, when ABR is absent or abnormal and OAE is absent, CM detection can reduce the rate of missed diagnosis of AN. The analysis of CM amplitude and I/O function curve is helpful to determine the lesion site of AN patients, which is convenient for early diagnosis and effective intervention.

Microplastics(particles<5 μm in diameter),generated through plastic processing or natural degradation,have emerged as novel environmental contaminants with increasing threats to ecosys-tems and human health.Recent studies have demonstrated the accumulation of microplastics in various environmental matrices,human tissues and even placentas,highlighting the urgent need to investigate their health effects.These particles enter the human system primarily through dietary intake and water consumption,yet critical knowledge gaps remain regarding their bioaccumulation potential,toxicological profiles,and synergistic interactions with co-existing environmental contaminants.The Drosophila mela-nogaster(fruit fly),a well-established model organism,offers distinct advantages for contaminant toxicity assessment,including a compact life cycle,small body size,rapid reproduction,ease of laboratory maintenance,and extensive availability of transgenic strains.In particular,its genome has a high degree of homology with the human genome,which further enhances its scientific relevance for toxicological studies.In this review,we summarize the advantages of Drosophila models in microplastic toxicity studies,with particular emphasis on recent advances in understanding intestinal toxicity,neuro toxicity,genotox-icity,reproductive toxicity,developmental toxicity,and transgenerational toxicity.We point to critical research gaps that require urgent investigation,including the bioaccumulation dynamics of microplas-tics,metabolic transformation and elimination pathways,multi-pollutant interaction effects,molecular mechanisms of toxicity,and comprehensive health risk assessment frameworks.The review aims to provide data for elucidating the mechanisms of microplastic toxicity and formulating evidence-based prevention strategies.

Background The Inner Mongolia Autonomous Region is a vast area with a wide array of ecological environments, resulting in considerable regional variations in air pollution characteristics. Current research is limited by a scarcity of systematic, region-wide studies and risk assessments. Objective To assess the health risks associated with inhalation exposure to nine heavy metal and metalloid elements in atmospheric fine particulate matter (PM_2.5) for the population of the Inner Mongolia Autonomous Region. Methods From the 10th to the 16th of each month throughout 2023, atmospheric PM_2.5 samples were collected at designated monitoring sites in 12 leagues (cities) across the Inner Mongolia Autonomous Region to analyze the characteristics and trends in concentration. The health risk assessment model developed by the United States Environmental Protection Agency was employed to evaluate both the non-carcinogenic and carcinogenic risks associated with the heavy metal elements beryllium (Be), cadmium (Cd), chromium (Cr), hydrargyrum (Hg), plumbum (Pb), manganese (Mn), and nickel (Ni) and the metalloid elements stibium (Sb) and arsenic (As). Results In 2023, a total of 1206 valid PM_2.5 samples were analyzed from the Inner Mongolia Autonomous Region. The annual average PM_2.5 concentrations in Inner Mongolia, as well as in the cities of Ordos, Wuhai, and the Alxa League, all exceeded the national limit of 35 μg·m⁻³. The PM_2.5 concentrations across the leagues (cities) exhibited a clear seasonal variation, peaking in winter, followed by spring, and reaching a minimum in summer and autumn. The median PM_2.5 concentration in Ordos throughout the year was higher than that in the other leagues (cities) of the region. Concerning health risks, the non-carcinogenic risks associated with the 9 elements detected in each league (city) were all below 1, indicating acceptable levels. However, the non-carcinogenic risk values for Mn, Cr, and As were relatively high; specifically, Ordos City displayed the highest non-carcinogenic risk values for Mn (7.74×10⁻¹) and Cr (2.97×10⁻²), while Chifeng City recorded the highest value for As (2.34×10⁻³). The carcinogenic risk values for As, Cd, Cr, and Ni fell within the range of 1×10⁻⁹ to 1×10⁻⁵, representing an acceptable level. The health risks varied with age, and the elderly residents faced the highest non-carcinogenic and carcinogenic health risks. Conclusion While the carcinogenic and non-carcinogenic risks from heavy metals and metalloids within atmospheric PM_2.5 in the Inner Mongolia Autonomous Region are generally within acceptable limits, the potential risks that Mn, As, and Cr pose to the health of elderly people warrants particular attention, and Ordos and Chifeng cities exhibit notably higher health risks among other areas. It is recommended that regular, long-term monitoring be conducted, taking into account the specific conditions at monitoring sites across each league (city), and that targeted air quality management strategies be implemented to protect public health.