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.

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.

This case report introduces Professor ZOU Wei 's experience of treating a patient with Wernicke encephalopathy using the "regulating spirit and promoting yang acupuncture method". The patient was diagnosed as spleen and stomach deficiency with internal liver wind. The treatment principle focused on regulating spirit and awakening the brain, strengthening the spleen, calming wind, and relaxing the tendons. Three groups of acupoints were selected: ①acupoints for awakening the brain by regulating spirit and unblocking meridians (Baihui [GV20], Qianshencong [EX-HN1] and bilateral Taiyang [EX-HN5], Fengchi [GB20]), etc.; ②acupoints for harmonizing the spleen, stomach, qi, and blood (bilateral Tianshu [ST25], Daheng [SP15], Taixi [KI3], etc.); ③acupoints for relaxing and softening the tendons (bilateral Waiguan [TE5], Hegu [LI4], Yanglingquan [GB34], Xuanzhong [GB39]).The needles were retained for 50 min per session, once daily, 7 days a week. After 16-week treatment, the patient was able to walk a few steps slowly with assistance, and other symptoms returned to normal. A two-month follow-up showed the patient's condition remained stable, walking distance further increased, and overall health significantly improved.
Humans ; Acupuncture Points ; Acupuncture Therapy ; Wernicke Encephalopathy/physiopathology*

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 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.

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.

Age-related macular degeneration(AMD)is a serious threat to the visual health of the elderly,and the dysfunction of retinal pigment epithelial cells(RPE)is a significant etiology risk.Aging process leads to RPE repli-cation senescence,and some environment factors like light exposure and cigarette exposure may lead to RPE stress premature aging,and the decreased lysosomal digestion ability of senescent RPE cells may lead to the accumulation of lipofuscin,triggering the occurrence of early AMD.A series of homeostatic imbalances in aging retina,such as cell senescence-renewal imbalance,oxidative stress-antioxidant imbalance,chronic inflammatory-anti-inflammatory imbalance,intestinal barrier and intestinal microbiota imbalance and pro-angiogenesis-antiangiogenic imbalance all contribute to the development of AMD.

Objective To evaluate the safety and efficacy of transcatheter arterial chemoembolization(TACE)combined with lenvatinib and camrelizumab in the treatment of advanced hepatocellular carcinoma(HCC).Methods The clinical data of a total of 63 patients with advanced HCC,who received TACE combined with lenvatinib and camrelizumab(triple therapy)or TACE combined with lenvatinib(dual therapy)at the Jingmen Municipal People's Hospital of China between April 2020 and December 2021,were retrospectively analyzed.Triple therapy group had 30 patients,and dual therapy group had 33 patients.The post-treatment tumor response,disease progression-free survival(PFS),overall survival(OS),and the incidence of adverse drug reactions were recorded.Results The median follow-up period of the two groups was 14 months(range of 4-26 months).Compared with the dual therapy group,in the triple therapy group the objective response rate(ORR)was remarkably higher(83.3%vs.57.6%,P=0.026),the disease control rate(DCR)was obviously higher(93.3%vs.69.7%,P=0.039),the median PFS was significantly longer(8.0 months vs.5.0 months,P＜0.01),and the median OS was strikingly longer(24.0 months vs.12.0 months,P=0.004).No statistically significant difference in the incidence of adverse drug reactions existed between the two groups(P＞0.05).Conclusion For the treatment of advanced HCC,TACE combined with lenvatinib and camrelizumab is clinically safe and effective.(J Intervent Radiol,2024,32:57-62)

Objective:To report a case of Kufor-Rakeb syndrome caused by novel ATP13A2 mutation, collect the cases related to ATP13A2 gene mutation published in recent years, summarize the clinical manifestations of the disease, and broaden the clinical diagnostic thinking. Methods:The clinical manifestations of a newly diagnosed patient with Kufor-Rakeb syndrome caused by ATP13A2 gene mutation admitted to Zhongda Hospital, Southeast University on November 26, 2021, were summarized. The related cases of ATP13A2 mutation published from January 2000 to December 2021 were searched through the PubMed and CNKI databases using the keywords "ATP13A2" and "Parkinson′s disease". The onset age, clinical symptoms, family history, genetic testing, and levodopa responsiveness results of the patients were collected. Results:The patient is a 52-year-old female with the main clinical symptoms of static tremor and bradykinesia. Physical examination showed a gear like increase in muscle tension in the right upper limb, involuntary shaking of the right hand and slow movement. She had good responsiveness to levodopa, and the magnetic resonance imaging and susceptibility weighted imaging of the head showed a lack of clear observation of bilateral black matter swallowtail sign. Whole exome sequencing showed that mutations c.3010A>G (p.S1004G) and c.1195+5G>A (splice) were found in the ATP13A2 gene, both of which were not reported. The c.3010A>G (p.S1004G) mutation originated from the mother, and the c.1195+5G>A (splice) mutation originated from the father. In the retrospective literature review, a total of 10 cases were collected, with onset ages ranging from 18 months to 24 years. Among them, 4/10 patients′ parents married close relatives, and the clinical manifestations were mainly motor symptoms of Parkinson′s disease. In addition, 5/10 patients had cognitive dysfunction, and 3/10 patients had mental symptoms. And demonstrations of most patients′ magnetic resonance imaging were normal in the early stage of the disease, and as the disease progressed, some patients′ imaging results showed specific changes, such as whole brain atrophy and changes in the corpus callosum. Meanwhile, 8/10 patients showed good responsiveness to levodopa. Conclusions:Kufor-Rakeb syndrome is a special type of adolescent levodopa responsive Parkinson′s disease caused by ATP13A2 mutation, which is an autosomal recessive disorder. In addition to motor symptoms such as static tremor and bradykinesia, its clinical manifestations may also be accompanied by non motor symptoms such as cognitive and psychiatric disorders. The disease responds well to treatment with levodopa.