Objective:To explore the clinical phenotype and genetic characteristics of a child with hereditary Spastic paraplegia type 52 (SPG52) due to variant of AP4S1 gene. Methods:A child diagnosed with SPG52 at the Department of Pediatrics of the First Affiliated Hospital of Anhui Medical University in May 2010 was selected as the study subject. Whole-exome sequencing (WES) was carried out for the child and his parents. Candidate variants were confirmed by Sanger sequencing. Pathogenicity of the candidate variant was interpreted according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). The study protocol was approved by the Ethics Committee of the Hospital (Ethics No.: PJ2024-04-56).Results:The child had presented with global developmental delay from infancy, and featured progressive lower limb spasticity, contractures, talipes equinovarus, and muscle weakness, but with no significant facial dysmorphism. His first febrile seizure occurred before one year of age, followed by several afebrile seizures. The seizures had remitted after 3 to 4 years of antiepileptic therapy, and electroencephalography was normal. However, he had severe intellectual disability, and MRI revealed reduced white matter. WES identified a homozygous AP4S1 c. 289C>T (p.Arg97*) variant in the child, for which both of his parents were heterozygous carriers. The variant was rated as pathogenic based on the ACMG guidelines. Literature review has identified 8 publications on SPG52, involving 18 patients from 12 pedigrees. Combined with our case, 14 had carried homozygous variants of the AP4S1 gene, 3 had compound heterozygous variants, and 2 had heterozygous variants, involving 12 distinct variant sites. The cohort included 7 males and 12 females. All patients exhibited progressive lower limb spasticity and weakness as the primary feature, with certain loss of independent ambulation. Most patients had intellectual disability, some had distinctive facial features, though febrile seizures or epilepsy were common. Electroencephalography often showed increased slow-wave activity. Brain MRI frequently demonstrated ventriculomegaly, a thin corpus callosum, and reduced white matter. Conclusion:The homozygous c. 289C>T (p.Arg97*) variant of the AP4S1 gene probably underlay the pathogenesis of SPG52 in this child. Above discovery has expanded the mutational spectrum of AP4S1 and provided valuable insights for the genetic diagnosis, counseling, and clinical management of SPG52.

AIM To explore the clinical effects of Jinfukang Oral Liquid combined with thymosin α1 on patients with non-small cell lung cancer due to Dual Deficiency of Qi and Yin.METHODS Seventy-five patients were randomly assigned into thymosin α1 group(15 cases)for 4-week administration,Jinfukang Oral Liquid group(30 cases)for 4-week administration,and combination group(30 cases)for 4-week administration.The changes in TCM clinical syndrome effects,immunity indices(CD3+T,Th,CTL,total NK,CD56dim CD16+NK,NKT,Treg,MDSC),lethality/inhibition ratios(CTL/Treg,total NK/Treg,NKT/Treg,CTL/MDSC,total NK/MDSC,NKT/MDSC)and FACT-L scores were detected.RESULTS The Jinfukang Oral Liquid group and combination group demonstrated higher total effective rates than the thymosin α1 group(P＜0.05).After the treatment,the Jinfukang Oral Liquid group and combination group displayed increased NKT(P＜0.05)and decreased MDSC(P＜0.05),which were more obvious than those in the thymosin α1 group(P＜0.05),and higher NKT was observable in the Jinfukang Oral Liquid group(P＜0.05);the Jinfukang Oral Liquid group and combination group displayed increased lethality/inhibition ratios(P＜0.05),among which NKT/Treg,CTL/MDSC,total NK/MDSC,NKT/MDSC were higher than those in the thymosin α1 group(P＜0.05),and higher CTL/MDSC,NKT/MDSC were observable in the Jinfukang Oral Liquid group(P＜0.05);the Jinfukang Oral Liquid group(except for physiological status,society and family status)and combination group(except for society and family status)displayed increased FACT-L scores(P＜0.05).CONCLUSION For the patients with non-small cell lung cancer due to Dual Deficiency of Qi and Yin,Jinfukang Oral Liquid single use or combined with thymosin α1 can enhance peripheral blood immune surveillance,inhibit immune escape,restore the balanced state of tumor immune responses,and improve TCM syndromes and life quality.

Objective:To explore the clinical phenotype and genetic characteristics of a child with hereditary Spastic paraplegia type 52 (SPG52) due to variant of AP4S1 gene. Methods:A child diagnosed with SPG52 at the Department of Pediatrics of the First Affiliated Hospital of Anhui Medical University in May 2010 was selected as the study subject. Whole-exome sequencing (WES) was carried out for the child and his parents. Candidate variants were confirmed by Sanger sequencing. Pathogenicity of the candidate variant was interpreted according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). The study protocol was approved by the Ethics Committee of the Hospital (Ethics No.: PJ2024-04-56).Results:The child had presented with global developmental delay from infancy, and featured progressive lower limb spasticity, contractures, talipes equinovarus, and muscle weakness, but with no significant facial dysmorphism. His first febrile seizure occurred before one year of age, followed by several afebrile seizures. The seizures had remitted after 3 to 4 years of antiepileptic therapy, and electroencephalography was normal. However, he had severe intellectual disability, and MRI revealed reduced white matter. WES identified a homozygous AP4S1 c. 289C>T (p.Arg97*) variant in the child, for which both of his parents were heterozygous carriers. The variant was rated as pathogenic based on the ACMG guidelines. Literature review has identified 8 publications on SPG52, involving 18 patients from 12 pedigrees. Combined with our case, 14 had carried homozygous variants of the AP4S1 gene, 3 had compound heterozygous variants, and 2 had heterozygous variants, involving 12 distinct variant sites. The cohort included 7 males and 12 females. All patients exhibited progressive lower limb spasticity and weakness as the primary feature, with certain loss of independent ambulation. Most patients had intellectual disability, some had distinctive facial features, though febrile seizures or epilepsy were common. Electroencephalography often showed increased slow-wave activity. Brain MRI frequently demonstrated ventriculomegaly, a thin corpus callosum, and reduced white matter. Conclusion:The homozygous c. 289C>T (p.Arg97*) variant of the AP4S1 gene probably underlay the pathogenesis of SPG52 in this child. Above discovery has expanded the mutational spectrum of AP4S1 and provided valuable insights for the genetic diagnosis, counseling, and clinical management of SPG52.

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.

In 1929, George Soulié de Morant and Paul Ferreyrolles co-authored their first acupuncture-moxibustion paper titled "L' Acuponcture en Chine vingt siècles avant J.-C. et la réflexothérapie moderne", greatly advancing the development of acupuncture-moxibustion in Europe. Their paper systematically explains the holistic view and the concept of yin-yang balance in traditional Chinese medicine, describes the techniques of acupuncture and moxibustion, innovatively classifies acupuncture-moxibustion as "reflexotherapy", organizes the effects of certain acupuncture points illustrated on human acupoint atlas; and for the first time, it summarizes the correspondence between acupuncture points and Weihe trigger points. In the historical background of the neo-Hippocratic movement, they used the existing theories at that time to explain acupuncture, and adopted the analogical medicine to explore the mechanisms of acupuncture-moxibustion, which gradually initiated the modern era of acupuncture-moxibustion in France. Such research method is conducive to reducing the unfamiliarity of acupuncture-moxibustion among westerners, deepening their understanding of its theories and therapeutic effect, and also integrating it with other medical research. It breaks through the limitations of traditional theories and obtains the self-improvement and progress.
Humans ; Moxibustion/history* ; Acupuncture Therapy/history* ; China ; History, Ancient ; History, 20th Century ; Acupuncture/history* ; Reflexotherapy/history* ; Acupuncture Points ; History, 19th Century ; Medicine, Chinese Traditional/history*

AIM To explore the clinical effects of Jinfukang Oral Liquid combined with thymosin α1 on patients with non-small cell lung cancer due to Dual Deficiency of Qi and Yin.METHODS Seventy-five patients were randomly assigned into thymosin α1 group(15 cases)for 4-week administration,Jinfukang Oral Liquid group(30 cases)for 4-week administration,and combination group(30 cases)for 4-week administration.The changes in TCM clinical syndrome effects,immunity indices(CD3+T,Th,CTL,total NK,CD56dim CD16+NK,NKT,Treg,MDSC),lethality/inhibition ratios(CTL/Treg,total NK/Treg,NKT/Treg,CTL/MDSC,total NK/MDSC,NKT/MDSC)and FACT-L scores were detected.RESULTS The Jinfukang Oral Liquid group and combination group demonstrated higher total effective rates than the thymosin α1 group(P＜0.05).After the treatment,the Jinfukang Oral Liquid group and combination group displayed increased NKT(P＜0.05)and decreased MDSC(P＜0.05),which were more obvious than those in the thymosin α1 group(P＜0.05),and higher NKT was observable in the Jinfukang Oral Liquid group(P＜0.05);the Jinfukang Oral Liquid group and combination group displayed increased lethality/inhibition ratios(P＜0.05),among which NKT/Treg,CTL/MDSC,total NK/MDSC,NKT/MDSC were higher than those in the thymosin α1 group(P＜0.05),and higher CTL/MDSC,NKT/MDSC were observable in the Jinfukang Oral Liquid group(P＜0.05);the Jinfukang Oral Liquid group(except for physiological status,society and family status)and combination group(except for society and family status)displayed increased FACT-L scores(P＜0.05).CONCLUSION For the patients with non-small cell lung cancer due to Dual Deficiency of Qi and Yin,Jinfukang Oral Liquid single use or combined with thymosin α1 can enhance peripheral blood immune surveillance,inhibit immune escape,restore the balanced state of tumor immune responses,and improve TCM syndromes and life quality.

This study aims to explore the synergistic effects of the main components in salvianolic acids for Injection(SAFI) on key pathological events in cerebral ischemia, elucidating the pharmacological characteristics of SAFI in neuroprotection. Two major pathological gene modules related to endothelial injury and neuroinflammation in cerebral ischemia were mined from single-cell data. According to the topological distance calculated in network medicine, potential synergistic component combinations of SAFI were screened out. The results showed that the combination of caffeic acid and salvianolic acid B scored the highest in addressing both endothelial injury and neuroinflammation, demonstrating potential synergistic effects. The cell experiments confirmed that the combination of these two components at a ratio of 1∶1 significantly protected brain microvascular endothelial cells(bEnd.3) from oxygen-glucose deprivation/reoxygenation(OGD/R)-induced reperfusion injury and effectively suppressed lipopolysaccharide(LPS)-induced neuroinflammatory responses in microglial cells(BV-2). This study provides a new method for uncovering synergistic effects among active components in traditional Chinese medicine(TCM) and offers novel insights into the multi-component, multi-target acting mechanisms of TCM.
Brain Ischemia/metabolism* ; Neuroprotective Agents/pharmacology* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Benzofurans/pharmacology* ; Mice ; Drug Synergism ; Caffeic Acids/pharmacology* ; Polyphenols/pharmacology* ; Humans ; Alkenes/pharmacology* ; Endothelial Cells/drug effects* ; Depsides

By employing the analytic hierarchy process(AHP), the CRITIC method(a weight determination method based on indicator correlations), and the AHP-CRITIC hybrid weighting method, the weight coefficients of evaluation indicators were determined, followed by a comprehensive score comparison. The grey correlation analysis was then performed to analyze the results calculated using the hybrid weighting method. Subsequently, a backpropagation-artificial neural network(BP-ANN) model was constructed to predict the extraction process parameters and optimize the extraction process for Shenxiong Huanglian Jiedu Granules(SHJG). In the extraction process, an L_9(3~4) orthogonal experiment was designed to optimize three factors at three levels, including extraction frequency, water addition amount, and extraction time. The evaluation indicators included geniposide, berberine, ginsenoside Rg_1 + Re, ginsenoside Rb_1, ferulic acid, and extract yield. Finally, the optimal extraction results obtained by the orthogonal experiment, grey correlation analysis, and BP-ANN method were compared, and validation experiments were conducted. The results showed that the optimal extraction process involved two rounds of aqueous extraction, each lasting one hour; the first extraction used ten times the amount of added water, while the second extraction used eight times the amount. In the validation experiments, the average content of each indicator component was higher than the average content obtained in the orthogonal experiment, with a higher comprehensive score. The optimized extraction process parameters were reliable and stable, making them suitable for subsequent preparation process research.
Drugs, Chinese Herbal/analysis* ; Neural Networks, Computer

This paper investigated the inhibitory effect of carbonized Scutellariae Radix(Cb-SR) on pyroptosis in endometrial epithelial cells of mice with endometritis and its correlation with the IKBKE/NLRP3 signaling axis. Mice model of endometritis was established by using an intrauterine injection of 10 μL polysaccharides(LPS, 5 mg·mL~(-1)), and the mice were randomly divided into model group(LPS), low-dose group of Cb-SR(L-Cb-SR, 0.55 g·kg~(-1)), medium-dose group of Cb-SR(M-Cb-SR, 1.10 g·kg~(-1)), high-dose group of Cb-SR(H-Cb-SR, 2.20 g·kg~(-1)), crude Scutellariae Radix group(Cr-SR, 1.63 g·kg~(-1)), and Fuke Qianjin Capsule group(FQC, 0.30 g·kg~(-1)), with 10 mice in each group. Ten healthy female mice were selected and injected with PBS of equal volume into the bilateral uterus, and they were set as the sham group. The mice in the drug treatment groups were given the corresponding doses of Cb-SR, Cr-SR, FQC, or physiological saline of equal volume by gavage twice a day for seven days. Thirty minutes after the last administration, each mouse was euthanized by cervical dislocation. Hematoxylin-eosin(HE) staining and transmission electron microscopy were applied to observe the histopathological morphology of the uterine tissue. Immunohistochemistry was used to detect the expression of CD38 and CD138. Myeloperoxidase(MPO) values in neutrophils were measured by the kit; Enzyme-linked immunosorbent assay(ELISA) was used to measure the secretion of interleukin-18(IL-18), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α). Immunofluorescence and Western blot were used to analyze the expression of the proteins related to the IKBKE/NLRP3 signaling axis. Mouse endometrial epithelial cells(MEECs) were separated and purified from the uterine tissue of pregnant female mice through in vitro experiments and injured by LPS for 24 h, and then they were cultured with Cb-SR-containing serum. The anti-endometritis effect of Cb-SR was investigated by CCK-8 assay, scanning electron microscopy, and Western blot. The results showed that Cb-SR significantly reduced MPO values, attenuated uterine tissue damage, inhibited the expression of CD38 and CD138, decreased the levels of IL-1β, IL-18, and TNF-α, and inhibited the expression of proteins associated with IKBKE/NLRP3 signaling axis in mice with endometritis. In addition, Cb-SR-containing serum reduced swelling of MEECs organelles induced by LPS, decreased the expression of inflammatory factors, and suppressed the expression of IKBKE/NLRP3 signaling axis-related proteins. These results suggest that Cb-SR can inhibit endometrial epithelial cell pyroptosis in endometritis by suppressing the IKBKE/NLRP3 signaling axis.
Animals ; Female ; Mice ; Pyroptosis/drug effects* ; Signal Transduction/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Drugs, Chinese Herbal/chemistry* ; Endometritis/chemically induced* ; Lipopolysaccharides/adverse effects* ; Scutellaria baicalensis/chemistry* ; Humans ; Epithelial Cells/drug effects*