Sennoside A (SA), a typical prodrug, exerts its laxative effect only after its transformation into rheinanthrone catalyzed by gut microbial hydrolases and reductases. Hydrolases have been identified, but reductases remain unknown. By linking a photoreactive group to the SA scaffold, we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling (ABPP). From lysates of an active strain, Bifidobacterium pseudocatenulatum (B. pseudocatenulatum), 397 proteins were enriched and subsequently identified using mass spectrometry (MS). Among these proteins, chromate reductase/nicotinamide adenine dinucleotide (NADH) phosphate (NADPH)-dependent flavin mononucleotide (FMN) reductase/oxygen-insensitive NADPH nitroreductase (nfrA) was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource (UniProt) database screening. We also determined that recombinant nfrA could reduce SA. Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.

Objective:To investigate the relationship between symptoms of vertigo and vestibular functions and short-term hearing outcomes in patients with flat descending sudden sensorineural hearing loss （SSNHL）. Methods:A retrospective review was conducted of the vestibular symptoms observed in 48 patients with unilateral flat-down sudden sensorineural hearing loss treated at the Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. Symptoms of vertigo and the results of cervical vestibular-evoked myogenic potentials （cVEMP）, ocular VEMP （oVEMP）, caloric test and video head-impulse test （vHIT） were collected to determine whether these factors could predict therapeutic efficacy. Results:The symptoms of vertigo was not correlated with prognosis （P>0.05） or with abnormal vestibular functions （P>0.05）. Patients with abnormal cVEMP, oVEMP, caloric test or vHIT showed significantly lower effective rates （32.0%, 44.0%, 32.0%, and 24.0%, respectively）; the greater the number of abnormal tests, the poorer the outcome. Patients with all four tests abnormal gained only （3.13±15.97） dB HL in hearing recovery, whereas those with normal cVEMP, oVEMP, caloric test or vHIT showed better chances of hearing improvements by （29.22±20.31）, （31.18±21.59）, （26.17±21.31）, and （26.38±24.05） dB HL, respectively. Conclusion:Vestibular function effectively predicts prognosis in flat descending SSNHL. Patients with abnormal vestibular tests, regardless of symptoms of vertigo, responded poorly to treatment, whereas those with normal cVEMP, oVEMP, caloric test and vHIT results achieved better hearing recovery. Abnormal vestibular function implies more extensive and severe inner-ear lesions in patients with SSNHL.
Humans ; Male ; Female ; Retrospective Studies ; Prognosis ; Adult ; Middle Aged ; Vertigo/diagnosis* ; Hearing Loss, Sensorineural/diagnosis* ; Young Adult ; Hearing Loss, Sudden/diagnosis* ; Adolescent ; Aged ; Vestibular Evoked Myogenic Potentials

Metabolic dysfunction-associated steatotic liver disease (MASLD), the most prevalent chronic liver condition globally, lacks adequate and effective therapeutic remedies in clinical practice. Recent studies have increasingly highlighted the close connection between the ubiquitin-proteasome system (UPS) and the progression of MASLD. This relationship is crucial for understanding the disease's underlying mechanism. As a sophisticated process, the UPS govern protein stability and function, maintaining protein homeostasis, thus influencing a multitude of elements and biological events of eukaryotic cells. It comprises four enzyme families, namely, ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), ubiquitin-protein ligases (E3), and deubiquitinating enzymes (DUBs). This review aims to delve into the array of pathways and therapeutic targets implicated in the ubiquitination within the pathogenesis of MASLD. Therefore, this review unveils the role of ubiquitination in MASLD while spotlighting potential therapeutic targets within the context of this disease.

Objective:To explore the mediating effect of depression between self-efficacy and fear of progression in elderly patients with post-stroke epilepsy.Methods:From January 2023 to June 2024, 200 elderly patients with post-stroke epilepsy at Zhumadian Central Hospital were selected as study subjects using convenience sampling. The survey was conducted using the General Information Questionnaire, General Self-Efficacy Scale (SSEQ), Patient Health Questionnaire-9 (PHQ-9), and Fear of Progression Questionnaire-Short Form (FOP-Q-SF) .Results:A total of 200 questionnaires were distributed, and 198 valid questionnaires were collected, with a valid response rate of 99.00%. Among 198 elderly patients with post-stroke epilepsy, the SSEQ, PHQ-9, and FOP-Q-SF scores were (52.35±4.20), (13.46±1.57), and (35.70±2.10), respectively. Pearson correlation analysis revealed that SSEQ scores were negatively correlated with both PHQ-9 and FOP-Q-SF scores, while PHQ-9 scores were positively correlated with FOP-Q-SF scores ( P<0.01). Mediating analysis showed that depression partially mediated the relationship between self-efficacy and fear of progression in elderly patients with post-stroke epilepsy. The mediating effect was -0.046, with a total effect of -0.346, and the mediating effect accounted for 13.30% of the total effect. Conclusions:Depression partially mediates the relationship between self-efficacy and fear of progression in elderly patients with post-stroke epilepsy. Controlling depression not only helps enhance patients' self-efficacy but may also reduce their fear of progression.

Objective To explore the effect of hyperbaric oxygen combined with synchronous brain bionic electrical stimulation on patients with stroke-related sleep disorders.Methods From November,2023 to November,2024,a total of 68 stroke patients with stroke-related sleep disorders ad-mitted to Huashan Hospital,Fudan University were selected.They were randomly divided into control group(n=34)and experimental group(n=34).The control group received routine hyperbaric oxygen therapy,while the ex-perimental group received routine hyperbaric oxygen therapy combined with synchronous brain bionic electrical stimulation inside the chamber,for four weeks.Pittsburgh Sleep Quality Index(PSQI),sleep-monitoring wrist-bands,Self-rating Anxiety Scale(SAS)and Self-rating Depression Scale(SDS)were used to assess the outcomes before and after treatment..Results Four patients in the control group and one in the experimental group dropped out.After treatment,the scores of each factors of PSQI decreased in both groups(t>2.693,P<0.05),and were lower in the experimental group than in the control group(t>2.699,P<0.01),expect hypnotic drug use(P>0.05);the total sleep time,deep sleep time and rapid eye movement sleep time became longer in both groups(|t|>7.270,P<0.001),and they were longer in the experimental group than in the control group(|t|>5.712,P<0.001);the scores of SAS and SDS decreased in both groups(t>9.530,P<0.001),and they were less in the experimental group than in the control group(t>4.740,P<0.001).Conclusion Synchronous brain bionic electrical stimulation in hyperbaric oxygen chamber could effectively prolong the total sleep time,deep sleep time and rapid eye movement time of patients with stroke-related sleep disorders,re-lieve anxiety and depression after stroke,and improve sleep quality.

Objective To investigate the efficacy of extracorporeal shock wave therapy(ESWT)combined with ultrasound-guided corticosteroid injection(CSI)for the treatment of primary frozen shoulder(PFS).Methods Ninety-nine patients with PFS who visited the pain department of the Affiliated Hospital of Xuzhou Medical University between April 2024 and July 2024 were enrolled and randomly divided into three groups according to the randomized number table method:ESWT group(T group),CSI group(I group),and combined treatment group(TI group),with 33 patients in each group.Visual analogue scale(VAS)scores,shoulder range of motion(SROM),and Constant-Murley shoulder scores(CMS)were recorded before treatment and at 1,4,8,and 12 weeks post-treatment.Additionally,the patients'Ascens Insomnia Scale(AIS)scores were recorded before treatment and 1 month after treatment.The occurrence of adverse effects and the use of remedial medications during the treatment period were also documented.Results Compared with pre-treatment,VAS scores decreased,and SROM and CM scores improved at all time points after treatment in all three groups(P<0.05).AIS scores also decreased in all three groups at 1 month post-treatment(all P<0.05).Intergroup comparisons revealed that the TI group exhibited signifi-cantly lower VAS pain scores,greater SROM(forward flexion and backward extension),and higher CM scores at 4,8,and 12 weeks post-treatment compared to the T and I groups(Bonferroni-corrected P<0.05).No statistically significant differences were observed between the T and I groups for these measures(Bonferroni-corrected P>0.05).Additionally,there were no statistically significant differences in AIS scores or adverse effects occurrence among the three groups at 1 month post-treatment(P>0.05).Conclusion The combined treatment demonstrated greater efficacy compared to trigger point extracorporeal shock wave therapy alone and periapical steroid injection alone,resulting in significant improvement in the patient's clinical symptoms and quality of life.

Objective:To investigate the clinical and pathological significance of the DICER1 mutation in follicular thyroid carcinoma (FTC).Methods:Sixty-eight cases of primary FTC resected between 2009 and 2023 were retrieved from The Affiliated Hospital of Qingdao University, Qingdao, China. Sanger sequencing was performed to identify DICER1 and TERT promoter mutations in all cases. Cases with DICER1 or TERT promoter mutations were subject to additional examination of potential mutations in KRAS, HRAS, and NRAS. The clinical and pathological features of DICER1-mutant FTCs were then analyzed. The relationship between DICER1 mutations and TERT-promoter/RAS mutations was also assessed.Results:DICER1 mutations were detected in 16 of the 68 FTC cases (23.5%), with 11 near E1813 at exon 25, 6 near D1709 at exon 24, and 1 in the splice region of exon 25. Two cases harbored two (distinct) mutations. All patients with DICER1-mutant FTC were female. Compared with patients with DICER1-wild-type FTC, those with DICER1-mutant were much younger, and had a higher proportion of minimally invasive subtype. Nine FTCs with DICER1 mutations were subject to further sequencing on adjacent non-cancerous tissues or lymph node tissues, but no mutations were detected. TERT-promoter or RAS hotspot mutations were not identified in any of the DICER1-mutant cases. However, TERT-promoter mutation was found in 6 DICER1-wild-type cases (8.8%, 6/68), with 3 cases also having RAS hotspot mutations and exhibiting highly aggressive biological behaviors.Conclusion:DICER1 mutations may occur in FTCs and appear mutually exclusive with RAS and TERT-promoter mutations, warranting further study as RAS-like mutations.

Sennoside A(SA),a typical prodrug,exerts its laxative effect only after its transformation into rhei-nanthrone catalyzed by gut microbial hydrolases and reductases.Hydrolases have been identified,but reductases remain unknown.By linking a photoreactive group to the SA scaffold,we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling(ABPP).From lysates of an active strain,Bifidobacterium pseudocatenulatum(B.pseu-docatenulatum),397 proteins were enriched and subsequently identified using mass spectrometry(MS).Among these proteins,chromate reductase/nicotinamide adenine dinucleotide(NADH)phosphate(NADPH)-dependent flavin mononucleotide(FMN)reductase/oxygen-insensitive NADPH nitroreductase(nfrA)was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource(UniProt)database screening.We also determined that recombinant nfrA could reduce SA.Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.

This paper introduces Professor WANG Jihong's clinical experience in treating refractory lateral epicondylitis using the Wang's crescent technique of blade needle. Based on the classical theories of Huangdi Neijing (the Yellow Emperor's Inner Classic) such as the "twelve sinew meridians" "short needling" and "shu needling", Professor WANG applies a self-designed blade needle with crescent needling method. This approach forms a distinctive treatment philosophy characterized by "sinew meridians as the foundation, selecting points at the pain site; using chicken-claw needling technique deliverd at both internal and external; integration of heaven, earth, and man, using both short and shu needling; treating tendon injuries and inflammation with the crescent technique of blade needle". It embodies the therapeutic concept of "treating tendons and bones simultaneously, harmonizing yin and yang", and shows unique advantages in the treatment of this condition.
Acupuncture Therapy/methods* ; Humans ; Tennis Elbow/therapy* ; Male ; Middle Aged ; Adult ; Needles ; Female ; Acupuncture Points

This article introduces the clinical experience of Professor WANG Jihong in treatment of post-stroke hypermyotonia with Lai's tongyuan therapy (therapy for removing obstruction and consolidating vital essence). Regarding the pathogenesis of this disease, Professor WANG Jihong emphasizes a "trinity" approach, "the mind disturbed, qi and blood unbalanced, and yuan (vital essence) not consolidated". In treatment, "the unblocking, conducting and nourishing are taken as the fundamental" to "prevent from over-dredging, balancing yin and yang, and avoiding over-replenishing". In clinical practice, the combined measure is adopted with acupuncture, tuina and herbal medicine. In acupuncture, the acupoints are selected according to the front-back combination of the points of the conception vessel and the governor vessel (basic prescription: Yintang [GV24⁺], Baihui [GV20] and Niesanzhen; prescription for promoting the governor vessel: Dazhui (GV14), Jinsuo [GV8], Xinshu [BL15], Pishu [BL20] and etc.; and the prescription for consolidating the vital essence: Danzhong (CV17), Zhongwan [CV12], Tianshu [ST25], Qihai [CV6]) and etc., as well as those on the four limbs for "opening, closing and pivoting of yin and yang" (on the upper limbs of the affected side: Jiquan [HT1], Jianyu [LI15], Quchi [LI11], Quze [PC3] and etc.; on the lower limbs of the affected side: Huantiao [GB30], Liangqiu [ST34], Xuehai [SP10], Yanglingquan [GB34]) and etc. The above points co-act on regulating the conception vessel and the governor vessel, and balancing yin and yang. Tuina is delivered on the governor vessel, the bladder meridian of foot-taiyang and wind points on the area between the head and nape, so as to promote the governor vessel, benefit the orifices, strengthen the spine and relax tendons. Herbal medicine works on nourishing the liver to soften tendons, nourishing blood to remove wind, regulating qi to replenish the spleen, consolidating the root to cultivate the vital essence, activating blood circulation to unblock meridians, and removing stasis to resolve phlegm. Tongyuan therapy provides a certain instruction in treatment of post-stroke hypermyotonia.
Humans ; Acupuncture Therapy ; Acupuncture Points ; Stroke/complications* ; Male ; Female ; Middle Aged ; Aged ; Drugs, Chinese Herbal ; Adult