OBJECTIVE To study the safety of Shuangshu decoction in rats and its efficacy in improving functional dyspepsia （FD） in rats. METHODS In safety test， 40 rats were divided into blank control group， Shuangshu decoction low-dose， medium- dose and high-dose groups [108， 216， 324 g/（kg·d）， calculated by raw medicine， the same applies below]； they were given relevant medicine intragastrically， for continuous 14 days. The mortality and toxic reactions of rats were recorded， and the organ indexes of the liver， kidney， spleen， lung and heart of rats were calculated； the pathological morphological changes in the liver， kidney， spleen， lung， heart， stomach， duodenum， and colon were observed to evaluate the acute toxicity of Shuangshu decoction. Another 40 rats were grouped and administered in the same way for 30 consecutive days. The mortality and toxic reactions of the rats were recorded， and the corresponding organ indexes were calculated. The pathological morphological changes in the corresponding organs were observed， and blood routine and serum biochemical indicators were measured， in order to assess the subacute toxicity of Shuangshu decoction. In pharmacodynamic experiments: 50 rats were divided into blank control group， model group， and Shuangshu decoction low-， medium-， and high-dose groups （9.45， 18.9， 37.8 g/kg）， with 10 rats in each group. Except for blank control group， rats in all other groups were used to establish the FD rat model by subcutaneous injection of loperamide （3.5 mg/kg）. Rats in each group were administered the corresponding drug solution/normal saline intragastrically， once a day， for 14 consecutive days. After the last medication， fecal moisture content， intestinal propulsion rate， gastric emptying rate and serum level of motilin were all detected， and interstitial cell of Cajal （ICC） ultrastructure of rats was observed in colon tissue. RESULTS The safety experiments showed that no death occurred in each dose group， and no significant difference was found in organ coefficient， routine blood and serum biological index， compared to blank control group （P＞0.05）； no abnormality was found in organ appearance and pathological sections. The results of the pharmacodynamic experiments showed that， compared with the blank control group， the fecal moisture content， gastric emptying rate， intestinal propulsion rate， and serum motilin levels in the model group were significantly decreased （P＜0.05）； in the colonic tissue， the mitochondria in the ICC exhibited severe swelling with the disappearance of cristae， and the endoplasmic reticulum was dilated. Compared with model group， the rats in Shuangshu decoction high-dose group showed significant increases in the above quantitative indicators （P＜ 0.05）； additionally， there was a large number of mitochondria in the ICC of the colonic tissue， with clear cristae and regular arrangement. CONCLUSIONS Shuangshu decoction is safe and has a beneficial improving effect on FD rats； its mechanism of action may be related to the regulation of gastrointestinal hormone expression to promote gastric emptying and intestinal propulsion， as well as the repair of mitochondrial structure in ICCs to restore gastrointestinal function.

Acute liver failure (ALF) is a life-threatening condition associated with macrophage-mediated inflammatory responses. Effective therapies and drugs are still lacking to date. Here, we reveal that a derivative of xanthohumol, CAM12203, alleviates lipopolysaccharide (LPS) + d-galactosamine (D-GalN)-induced ALF through limiting macrophage-mediated inflammation, with the most significant impact on interleukin-1β (IL-1β) transcription. Through biotin labeling-mediated pull-down and LC-MS/MS analysis, diacylglycerol kinase ζ (DGKζ), a lipid-metabolizing kinase, is identified as the direct target of CAM12203. Mechanistically, DGKζ is induced in macrophages upon inflammatory stimuli and is upregulated observed on clinical liver failure samples. Its product phosphatidic acid (PA) boosts phospholipase C (PLC)-inositol 1,4,5-trisphosphate (IP₃)-Ca²⁺ signaling and subsequent janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) cascade, ultimately promoting IL-1β production and liver failure. DGKζ knockdown/ablation or inhibition significantly impairs the DGKζ-STAT3-IL-1β pathway along with ALF progression. Finally, CAM12203 is confirmed to be a new DGKζ inhibitor and acts against inflammation in a DGKζ-reliant manner. Taken together, CAM12203 inhibits IL-1β transcription in macrophages by binding to DGKζ and blocking the DGKζ-STAT3 axis, thereby exerting an ameliorative effect on ALF. These results not only highlight CAM12203 as a promising lead compound for ALF treatment, but also define DGKζ as a novel therapeutic target.

Anxiety disorder is a major symptom of autism spectrum disorder (ASD) with a comorbidity rate of ~40%. However, the neural mechanisms of the emergence of anxiety in ASD remain unclear. In our study, we found that hyperactivity of basolateral amygdala (BLA) pyramidal neurons (PNs) in Shank3 InsG3680 knock-in (InsG3680^+/+) mice is involved in the development of anxiety. Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs. Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680^+/+ mice. Further study found that the diminished control of the BLA by medial prefrontal cortex (mPFC) and optogenetic activation of the mPFC-BLA pathway also had a rescue effect, which increased the feedforward inhibition of the BLA. Taken together, our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680^+/+ mice.
Animals ; Prefrontal Cortex/metabolism* ; Basolateral Nuclear Complex/metabolism* ; Mice ; Anxiety/metabolism* ; Nerve Tissue Proteins/genetics* ; Male ; Gene Knock-In Techniques ; Pyramidal Cells/physiology* ; Mice, Transgenic ; Neural Pathways/physiopathology* ; Mice, Inbred C57BL ; Microfilament Proteins

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Objective　To study the clinical and epidemiological characteristics of the monkeypox epidemic in Longgang District, Shenzhen, and conduct a comprehensive analysis and discussion to provide a reference for monkeypox epidemic prevention and control. Methods An epidemiological investigation was conducted on 16 monkeypox cases found in the medical institutions of Longgang District on June 2023. The distribution of cases, high-risk exposure characteristics (contact objects, methods, locations, etc.), incidence characteristics, and medical treatment situation were analyzed. Relevant discussions on epidemic prevention and control were further conducted in light of the actual situation and the problems encountered. Results The cases were all unmarried young men and men who have sex with men (MSM) population. The disease was transmitted from person to person through same-sex contact, with non-fixed sexual partners as the source of infection and exposure locations being relatively concealed, and the average incubation period was 8.42 days. Most cases were discovered through active seeking medical attention, accounting for 68.78% (11/16). Fever was the primary initial symptom accounting for 56.25% (9/16), with the main symptoms being a rash and fever, at 100% and 68.75% (11/16), respectively. Time from fever to rash onset was mainly 0-3 days, accounting for 90.91% (10/11). The eruption site involveed multiple different parts of the body, and there was no special order of eruption. The time interval from onset to seeking medical attention and from onset to discovery was similar, with 5.91 days and 5.94 days respectively. The majority of cases were HIV infected, accounting for 68.75% (11/16)。Conclusions The monkeypox epidemic is prevalent in MSM populations and is transmitted through male to male contact through human transmission. However, due to unstable sexual partners and concealed exposure locations, tracing the source is difficult, with an average incubation period of 8.42 days. The symptoms are mainly fever and rash, with a long time from onset to medical treatment. The initial manifestations are mild, leading to missed diagnoses on the first visit, resulting in difficulty in timely discovery and prevention of further cases. At the same time, investigating and handling the epidemic are challenging, making the prevention and control of the outbreak a difficult task.

Objective RNA sequencing(RNA-seq)and bioinformatic analysis were combined and used to explore the anti-inflammatory effects and mechanisms of naringenin(Nar)in lipopolysaccharide(LPS)-stimulated human peri-odontal ligament stem cells(hPDLSCs).Methods Cell counting kit-8,quantitative real-time reverse transcription poly-merase chain reaction(qRT-PCR),and enzyme-linked immunosorbent assay(ELISA)were adopted to detect the effects of Nar on the proliferation and expression of inflammatory factors in LPS-stimulated hPDLSCs,screening for the opti-mal anti-inflammatory concentration of Nar.Differentially expressed genes(DEGs)were screened using|log2FC|≥1 and P≤0.05 as criteria.Volcano plot analysis,Kyoto En-cyclopedia of Genes and Genomes(KEGG)pathway en-richment analysis,the String database,and the MCODE module of Cytoscape were utilized to select core genes and enriched pathways.The effects on the nuclear factor κB(NF-κB)signaling pathway were verified using ELISA,qRT-PCR,and Western blot.Results Appropriate concentrations of Nar could alleviate the expression of inflammatory fac-tors and promote the proliferation of hPDLSCs stimulated by LPS.The best anti-inflammatory effect was achieved with 20 μmol/L Nar.RNA-seq showed significant enrichment of inflammation-related signaling pathways.The anti-inflamma-tory effect of Nar was mediated by inhibiting the NF-κB signaling pathway,similar to the effect of the NF-κB inhibitor BAY 11-7802.Conclusion Nar could exert its anti-inflammatory effects by inhibiting the NF-κB signaling pathway,making it a potential therapeutic option for the adjuvant treatment of periodontitis.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective·To assess the accuracy and time of the two-in-one registration technique by comparing it with the U-shaped tube registration in dynamic navigation implantation.Methods·Thirty standardized 3D-printed models with mandibular posterior sites missing a single tooth were randomly divided into three groups:two-in-one registration group,U-shaped tube registration group and free-hand implantation group,and the implant surgical plan was designed by the"YIZHIMEI"DCARER oral implant surgery navigation system.Cone beam CT before and after operation was taken.The implant platform deviation,implant apex deviation and angular deviation of the actual implant positions and the designed implant positions were measured.The operating time for using two-in-one registration technique and the U-shaped tube registration technique was recorded to evaluate the complexity of the two registration techniques.The one-way ANOVA and SNK(Student-Newman-Keuls)test were used to analyze the implant platform deviation,implant apex deviation and angular deviation of each group.Results·There were no statistically significant differences in implant platform deviation,implant apex deviation and angular deviation between the two-in-one registration group and the U-shaped tube registration group(P>0.05).However,the implant platform deviation,implant apex deviation and angular deviation of the two-in-one registration group and the U-shaped tube group were lower than those in the free-hand implantation group,and the differences were statistically significant(P<0.001).The operating time required for the two-in-one registration was shorter than that for the U-shaped tube registration process,and the difference was statistically significant(P<0.001).Conclusion·The accuracy of the two-in-one dynamic navigation registration technique used in implanting on a model of mandibular posterior sites missing a single tooth is similar to that of the U-shaped tube dynamic navigation registration technique.But the two-in-one registration takes less time for registration procedure than the U-shaped tube registration,and is easier to operate.

Objective: To explore the association between processed food consumption and anxiety symptoms among college students in Yunnan Province, so as to provide a reference for the prevention and treatment of anxiety symptoms in this population. Methods: A cluster random sample of 2 515 first year students from two universities in Yunnan Province was selected to carry out a longitudinal investigation which included a baseline survey (November 2021, T1) and three follow up visits (June 2022, T2; November 2022, T3; June 2023, T4). The food frequency questionnaire was administered to assess processed food consumption, and the Depression Anxiety Stress Scale-21 (DASS-21, Chinese version) was used to evaluate anxiety symptoms. A generalized estimation equation model was used to analyze the relationship between processed food consumption and anxiety symptoms. Results: The detection rates of T1-T4 anxiety symptoms among college students in Yunnan Province were 29.70%, 36.70%, 37.69% and 38.73 %, respectively, and the corresponding anxiety symptom scores were 4(0,8), 4(0,10), 4(0,12), 2(0,14). After controlling for demographic variables and confounding factors in the generalized estimation equation model, a statistically significant association was found between consumption of carbonated beverages ( β=0.06, 95%CI =0.03-0.08), and other processed snacks ( β= 0.04 , 95%CI =0.01-0.07) ( P <0.05). The stratified analysis by gender showed that the consumption of carbonated beverages ( β=0.08, 95%CI =0.05-0.12) and fast food ( β=0.03, 95%CI =0.00-0.06) was significantly associated with anxiety symptoms in female college students ( P <0.05). There was no significant association between processed food consumption and anxiety symptoms in male college students ( P >0.05). Conclusions Processed food consumption by college students in Yunnan Province may increase the risk of anxiety symptoms, particularly among female students. There is a need to strengthen guidance in respect to processed food consumption, so as to prevent and treat anxiety symptoms.

PiT2 is an inorganic phosphate (Pi) transporter whose mutations are linked to primary familial brain calcification (PFBC). PiT2 mainly consists of two ProDom (PD) domains and a large intracellular loop region (loop7). The PD domains are crucial for the Pi transport, but the role of PiT2-loop7 remains unclear. In PFBC patients, mutations in PiT2-loop7 are mainly nonsense or frameshift mutations that probably cause PFBC due to C-PD1131 deletion. To date, six missense mutations have been identified in PiT2-loop7; however, the mechanisms by which these mutations cause PFBC are poorly understood. Here, we found that the p.T390A and p.S434W mutations in PiT2-loop7 decreased the Pi transport activity and cell surface levels of PiT2. Furthermore, we showed that these two mutations attenuated its membrane localization by affecting adenosine monophosphate-activated protein kinase (AMPK)- or protein kinase B (AKT)-mediated PiT2 phosphorylation. In contrast, the p.S121C and p.S601W mutations in the PD domains did not affect PiT2 phosphorylation but rather impaired its substrate-binding abilities. These results suggested that missense mutations in PiT2-loop7 can cause Pi dyshomeostasis by affecting the phosphorylation-regulated cell-surface localization of PiT2. This study helps understand the pathogenesis of PFBC caused by PiT2-loop7 missense mutations and indicates that increasing the phosphorylation levels of PiT2-loop7 could be a promising strategy for developing PFBC therapies.
Humans ; Cell Membrane ; Mutation, Missense ; Phosphates/metabolism* ; Sodium-Phosphate Cotransporter Proteins, Type III/genetics*