ObjectiveTo observe the effectiveness and safety of Jiuzihuichun decoction combined with spleen- strengthening moxibustion in patients with asthenospermia infertility with spleen-kidney deficiency pattern. MethodsA total of 82 patients with asthenospermia of spleen-kidney deficiency pattern in Shanghai Seventh People's Hospital were included. The patients were randomly divided into an observation group and a control group， with 41 patients in each group. The control group received oral administration of WuziYanzong pills combined with spleen-strengthening moxibustion. The dosage of Wuzi Yanzong pills was 1 bag each time， and it was taken twice a day. The spleen-strengthening moxibustion was carried out once a week. The observation group， on the other hand， took Jiuzi Huichun decoction orally combined with spleen-strengthening moxibustion. The Jiuzi Huichun Decoction was taken 200 mL each time， twice a day， with one dose in the morning and one in the evening. The spleen-strengthening moxibustion for the observation group was also performed once a week. The treatment course for both groups was 12 weeks， and they were followed up for an additional 12 weeks. During the treatment process，12 cases were either lost to follow-up or excluded. Eventually， 70 cases were available for evaluation，with 35 cases in the control group and 35 cases in the observation group. The pregnancy status of the patients' spouse within 6 months was recorded. The traditional Chinese medicine （TCM） syndrome scores of spleen-kidney deficiency pattern before and after treatment were evaluated. The semen volume，semen routine parameters，normal sperm morphology，sperm DNA fragmentation index，seminal plasma fructose，seminal plasma acid phosphatase， and seminal plasma α-glucosidase levels of the two groups were detected before and after treatment. In addition， the safety indicators related to liver and kidney functions of the two groups were detected before and after treatment. ResultsDuring the 6-month observation period， when compared with the situation before treatment in their respective groups，the semen volume of the observation group and the control group increased. In contrast， the sperm concentration，sperm motility，proportion of a+b-grade sperm，normal sperm morphology，seminal plasma fructose，seminal plasma acid phosphatase，seminal plasma α-Glucosidase，the proportion of a-grade sperm，linear sperm motility，linear sperm concentration， and linear sperm count all increased significantly（P<0.05）. At the same time， the sperm DNA fragmentation index and the TCM syndrome scores of the spleen-kidney deficiency pattern decreased significantly（P<0.05）. When the observation group was compared with the control group after treatment， the clinical efficacy of the observation group was better（Z=-2.276，P<0.05）. The pregnancy rate of the observation group's spouses was 14.3%，which was higher than the 2.9% of the control group. The sperm motility， the proportion of a+b-grade sperm，seminal plasma fructose，the proportion of a-grade sperm，normal sperm morphology，α-glucosidase， and linear sperm motility in the observation group were higher than those in the control group （P<0.05）. Moreover， the sperm DNA fragmentation index and the TCM syndrome scores of spleen-kidney deficiency pattern in the observation group were lower than those in the control group （P<0.01）. No serious adverse reactions occurred in the two groups，and no abnormalities were found in the safety indicators after treatment. ConclusionJiuzi Huichun decoction combined with spleen-strengthening moxibustion can enhance sperm viability and sperm concentration. It can also improve the TCM-related symptoms of asthenospermia of spleen-kidney deficiency pattern and sperm morphology. Additionally， it can reduce the sperm DNA fragmentation index and regulate the level of seminal plasma bioenzyme in patients with male asthenospermia infertility of spleen-kidney deficiency pattern. Therefore， it is worthy of further promotion and application in clinical practice.

Atrial fibrillation is the most common type of chronic cardiac arrhythmia. Catheter ablation and left atrial appendage occlusion are effective treatment methods for atrial fibrillation， but these procedures require anesthesia support. However， anesthetic drugs often cause side effects such as nausea， vomiting， involuntary movements， and respiratory depression. This paper presents a case of a successful one-stop procedure for cryoballoon ablation and left atrial appendage occlusion of atrial fibrillation performed entirely under acupuncture anesthesia. Thirty minutes before the procedure， acupuncture needles were inserted perpendicularly at bilateral Neiguan （PC 6）， Lieque （LU 7）， Ximen （PC 4） and （LU 6）. After obtaining the deqi （得气） sensation， an electroacupuncture device was connected， and electroacupuncture anesthesia was used for pain control throughout the procedure. The patient exhibited good tolerance and cooperation， with electroacupuncture anesthesia completely replacing intravenous anesthetics， ensuring the smooth completion of the surgery. Postoperative follow-up showed favorable outcomes.

Objective:To investigate the clinical features and prognosis of neuro-Beh?et′s syndrome (NBS) in children.Method:The clinical, brain magnetic resonance imaging and laboratory data of 5 children with NBS diagnosed in the Department of Pediatrics, General Hospital of Ningxia Medical University and Department of Rheumatology and Immunology, Children′s Hospital Affiliated to Capital Institute of Pediatrics from April 2014 to April 2024 were analyzed retrospectively. The follow-up method was retrospective outpatient or inpatient visit to evaluate the treatment effect of NBS.Result:Among the 5 NBS cases, 2 were male and 3 were female. The age of admission ranged from 8 to 17 years, the time from onset to diagnosis was 2 days to 4 years. Two patients had dizziness, headache and convulsions during the treatment of NBS, 1 patient had disturbance of consciousness, 1 patient gradually developed aphasia, limb movement disorder, dysphagia and muscle weakness after 4 years of Behcet's syndrome, and 1 patient had no clinical symptoms. C-reactive protein and erythrocyte sedimentation rate were increased in 4 cases, and cerebrospinal fluid white blood cells and immunoglobulin G were increased in 1 case. Brain magnetic resonance imaging of 4 children showed multiple lesions, including bilateral frontal lobe, occipital lobe, parietal lobe, periventricular and corpus callosum lesions. Brain magnetic resonance imaging showed multiple demyelinating diseases in 1 case, and cervical and thoracic magnetic resonance imaging showed slender cervical and thoracic spinal cord. All patients were treated with corticosteroids combined with immunosuppressants or biological agents. The children were followed up for 6 months to 4 years, and 4 cases had good treatment results, and 1 case finally gave up treatment.Conclusions:The clinical manifestations of NBS are not specific, and brain magnetic resonance imaging shows that the lesion location and morphology are not specific. NBS children treated with corticosteroids combined with immunosuppressive agents or biological agents have a good prognosis.

Objective To explore the association between oral microbiota and esophageal carcinogenesis. Methods A case-control study design was employed. A total of 309 subjects were recruited, consisting of 159 healthy controls, 32 cases of esophageal basal cell hyperplasia, 32 cases of low-grade intraepithelial neoplasia, 14 cases of high-grade intraepithelial neoplasia, and 72 cases of esophageal squamous cell carcinoma. Tongue swab samples were collected for 16S rRNA sequencing. The α-diversity and β-diversity of the microbiota were analyzed, and the characteristics of the microbial communities at different stages of esophageal carcinogenesis were compared. The strength of the association was expressed by odds ratio (OR) and 95% confidence interval (CI). Results α-diversity analysis indicated significant differences in the observed species number (Sobs) index across various stages of esophageal cancer progression (P<0.001). After adjusting for confounding factors such as age, gender, smoking, and alcohol consumption, the Simpson index was positively correlated with carcinogenesis (P=0.006). β-diversity analysis revealed differences in microbiota structure among the groups. After ordered multinomial logistic regression analysis and adjustment for multiple confounding factors, the relative abundance of Peptostreptococcus (OR: 2.06, 95%CI: 1.22–3.60), Patescibacteria (OR: 1.31, 95%CI: 1.04–1.67), Capnocytophaga (OR: 1.24, 95%CI: 1.05–1.54), and Bacteroidota (OR: 1.02, 95%CI: 1.00–1.05) was positively correlated with carcinogenesis. The relative abundance of Stomatobaculum (OR: 0.57, 95%CI: 0.30–1.00) and Actinobacteriota (OR: 0.95, 95%CI: 0.92–0.98) was negatively correlated with carcinogenesis. Conclusion Specific oral microbiotas are significantly associated with esophageal carcinogenesis, and synergistic or antagonistic interactions may be observed among the microbiota.

BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

OBJECTIVE: To investigate the safety and effectiveness of using the Taylor spatial frame (TSF) based on the Ilizarov tension-stress principle for treatment of post-burn foot and ankle deformities in adults. METHODS: A clinical data of 6 patients with post-burn foot and ankle deformities treated between April 2019 and November 2023 was retrospectively analyzed. There was 1 male and 5 females with an average age of 28.7 years (range, 20-49 years). There were 3 cases of simple ankle equinus, 2 cases of ankle equinus, midfoot rocker-bottom foot, and forefoot pronation, and 1 case of calcaneus foot and forefoot pronation. Preoperative American Orthopedic Foot and Ankle Society (AOFAS) score was 45.3±18.2, 12-Item Short-Form Health Survey (SF-12)-Physical Component Summary (PCS) score was 34.3±7.3 and Mental Component Summary (MCS) score was 50.4±8.8. Imaging examination showed tibial-calcaneal angle of (79.8±31.5)°, calcaneus-first metatarsal angle of (154.5±45.3)°, talus-first metatarsal angle of (-19.3±35.0)°. Except for 1 case with severe deformity that could not be measured, the remaining 5 cases had talus-second metatarsal angle of (40.6±16.4)°. The deformities were fixed with TSF after soft tissue release and osteotomy. Then, the residual deformities were gradually corrected according to software-calculated prescriptions. TSF was removed after maximum deformity correction and osteotomy healing. External fixation time, brace wearing time after removing the TSF, and pin tract infection occurrence were recorded. Infection severity was evaluated based on Checketts-Otterburns grading. Joint function was evaluated using AOFAS score and SF-12 PCS and MCS scores. Patient satisfaction was assessed using Likert score. Imaging follow-up measured relevant indicators to evaluate the degree of deformity correction. Deformity recurrence was observed during follow-up. RESULTS: The external fixation time was 103-268 days (mean, 193.5 days). The mild pin tract infections occurred during external fixation in all patients, which healed after pin tract care and oral antibiotics. No serious complication such as osteomyelitis, fractures, neurovascular injury, or skin necrosis occurred. After external fixation removal, 3 cases did not wear braces, while the remaining 3 cases wore braces continuously for 6 weeks, 8 weeks, and 3 years, respectively. All patients were followed up 13.9-70.0 months, with an average of 41.7 months. During follow-up, none of the 6 patients had recurrence of foot deformity. At 1 year after operation, the AOFAS score was 70.0±18.1, SF-12-PCS and MCS scores were 48.9±4.5 and 58.8±6.4, respectively, all showing significant improvement compared to preoperative values ( P<0.05). Imaging follow-up showed that all osteotomies healed, and all distraction cases achieved bony union at 6 months after stopping stretching. At 1 year after operation, tibial-calcaneal angle was (117.5±12.8)° and talus-first metatarsal angle was (-3.3±19.3)°, both showing significant improvement compared to preoperative values ( P<0.05). Calcaneus-first metatarsal angle was (132.0±14.4)°, which also improved compared to preoperative values but without significant difference ( P>0.05). Except for 1 case with severe deformity that could not be measured, the remaining 5 cases had talus-second metatarsal angle of (18.0±6.4)°. And there was no significant difference ( P>0.05) between pre-and post-operative data of 4 patients with complete data. At 1 year after operation, 1 patient was satisfied with effectiveness and 5 patients were very satisfied. CONCLUSION The TSF, by applying the Ilizarov tension-stress principle for gradual distraction and multi-planar adjustment, combined with soft tissue release and osteotomy, can effectively correct foot and ankle deformities after burns, especially equinus deformity with contracture of the posterior soft tissues of the lower leg. There are still limitations in treating cases with tight, adherent scars on the dorsum of the foot that require long-distance distraction. If necessary, a multidisciplinary approach combined with microsurgical techniques can be utilized.
Humans ; Adult ; Male ; Female ; Middle Aged ; Retrospective Studies ; External Fixators ; Young Adult ; Burns/complications* ; Foot Deformities, Acquired/etiology* ; Treatment Outcome ; Ilizarov Technique/instrumentation*

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

Radiation-induced thrombocytopenia (RIT) faces a perplexing challenge in the clinical treatment of cancer patients, and current therapeutic approaches are inadequate in the clinical settings. In this research, oxymatrine, a new molecule capable of healing RIT was screened out, and the underlying regulatory mechanism associated with magakaryocyte (MK) differentiation and thrombopoiesis was demonstrated. The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro. The ability to induce thrombopoiesis was subsequently demonstrated in Tg (cd41:enhanced green fluorescent protein (eGFP)) zebrafish and RIT model mice. In addition, we carried out network pharmacological prediction, drug affinity responsive target stability assay (DARTS) and cellular thermal shift assay (CETSA) analyses to explore the potential targets of oxymatrine. Moreover, the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, Western blot (WB), and immunofluorescence. Oxymatrine markedly promoted MK differentiation and maturation in vitro. Moreover, oxymatrine induced thrombopoiesis in Tg (cd41:eGFP) zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice. Mechanistically, oxymatrine directly binds to toll-like receptor 2 (TLR2) and further regulates the downstream pathway stimulator of interferon genes (STING)/nuclear factor-kappaB (NF-κB), which can be blocked by C29 and C-176, which are specific inhibitors of TLR2 and STING, respectively. Taken together, we demonstrated that oxymatrine, a novel TLR2 agonist, plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis, suggesting that oxymatrine is a promising candidate for RIT therapy.

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse group of plant metabolites renowned for their pharmacological properties. However, sustainable sources for these compounds remain limited. Consequently, researchers are focusing on elucidating BIA biosynthetic pathways and genes to explore alternative sources using synthetic biology approaches. CYP80B, a family of cytochrome P450 (CYP450) enzymes, plays a crucial role in BIA biosynthesis. Previously reported CYP80Bs are known to catalyze the 3'-hydroxylation of (S)-N-methylcoclaurine, with the N-methyl group essential for catalytic activity. In this study, we successfully cloned a full-length CYP80B gene (StCYP80B) from Stephania tetrandra (S. tetrandra) and identified its function using a yeast heterologous expression system. Both in vivo yeast feeding and in vitro enzyme analysis demonstrated that StCYP80B could catalyze N-methylcoclaurine and coclaurine into their respective 3'-hydroxylated products. Notably, StCYP80B exhibited an expanded substrate selectivity compared to previously reported wild-type CYP80Bs, as it did not require an N-methyl group for hydroxylase activity. Furthermore, StCYP80B displayed a clear preference for the (S)-configuration. Co-expression of StCYP80B with the CYP450 reductases (CPRs, StCPR1, and StCPR2), also cloned from S. tetrandra, significantly enhanced the catalytic activity towards (S)-coclaurine. Site-directed mutagenesis of StCYP80B revealed that the residue H205 is crucial for coclaurine catalysis. Additionally, StCYP80B exhibited tissue-specific expression in plants. This study provides new genetic resources for the biosynthesis of BIAs and further elucidates their synthetic pathway in natural plant systems.
Cytochrome P-450 Enzyme System/chemistry* ; Benzylisoquinolines/chemistry* ; Hydroxylation ; Plant Proteins/chemistry* ; Alkaloids/metabolism* ; Stephania tetrandra/genetics*