This paper summarizes Professor WANG Xiuxia's clinical experience in treating hyperprolactinemia using the liver soothing therapy. Professor WANG identifies liver qi stagnation and rebellious chong qi （冲气） as the core pathomechanisms of hyperprolactinemia. Furthermore， liver qi stagnation may transform into fire or lead to pathological changes such as spleen deficiency with phlegm obstruction or kidney deficiency with essence depletion. The treatment strategy centers on soothing the liver， with a modified version of Qinggan Jieyu Decoction （清肝解郁汤） as the base formula. Depending on different syndrome patterns such as liver stagnation transforming into fire， liver stagnation with spleen deficiency， or liver stagnation with kidney deficiency， heat clearing， spleen strengthening， or kidney tonifying herbs are added accordingly. In addition， three paired herb combinations are commonly used for symptom specific treatment， Danggui （Angelica sinensis） with Chuanxiong （Ligusticum chuanxiong）， Zelan （Lycopus lucidus） with Yimucao （Leonurus japonicus） ， and Jiegeng （Platycodon grandiflorus） with Zisu （Perilla frutescens）.

ObjectiveTo investigate the expression of serum Aldo-keto reductase family 1 member B10 （AKR1B10） in patients with hepatocellular carcinoma （HCC） in northern China， and to provide a new and valuable biomarker for the clinical diagnosis of HCC. MethodsThis study was conducted among 102 patients with HCC， 119 patients with benign liver disease， and 132 patients with other malignant tumors who attended The Affiliated Hospital of Chengde Medical University and 148 healthy individuals who underwent physical examination from May 2020 to May 2024. ELISA and chemiluminescence were used to measure the serum levels of AKR1B10 and alpha-fetoprotein （AFP）. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between three groups and further comparison between two groups； the chi-square test was used for comparison of categorical data between groups. The area under the ROC curve （AUC） was used to assess diagnostic efficiency. ResultsThe expression level of AKR1B10 was 3 053.79 （1 475.67‍ ‍—‍ ‍4 605.86） pg/mL in the HCC group， 1 324.42 （659.68‍ ‍—‍ ‍2 023.88） pg/mL in the benign liver disease group， 660.68 （377.56‍ ‍—‍ ‍2 087.77） pg/mL in the other malignant tumor group， and 318.30 （82.73‍ ‍—‍ ‍478.82） pg/mL in the healthy group， with a significant difference between the four groups （H=240.86， P<0.001）， and further comparison between two groups showed that the HCC group had a significantly higher level than the other three groups （all P<0.001）. The ROC curve analysis of the HCC group and the other three groups showed that serum AKR1B10 had an optimal cut-off value of 1 584.97 pg/mL in the diagnosis of HCC， with an AUC of 0.86 （95% confidence interval ［CI］： 0.82‍ ‍—‍ ‍0.90）， a sensitivity of 74.3%， and a specificity of 85.2%. Compared with each indicator alone， a combination of AKR1B10 and AFP could improve the sensitivity （81.8%） and specificity （91.4%） of HCC diagnosis. AKR1B10 had an AUC of 0.84 （95%CI： 0.78‍ ‍—‍ ‍0.90） in the diagnosis of patients with early- or middle-stage HCC， with a sensitivity of 76.2% and a specificity of 81.2%. AKR1B10 had an AUC of 0.85 （95%CI： 0.77‍ ‍—‍ ‍0.92） in the diagnosis of patients with AFP-negative HCC， with a sensitivity of 81.6% and a specificity of 79.9%. ConclusionAKR1B10 is a promising serological marker for the diagnosis of HCC， and a combination of AKR1B10 and AFP can improve the detection rate of HCC patients in northern China， especially those with early- or middle-stage HCC and AFP-negative HCC.

Objective To investigate the status quo,driving factors and clinical intervention measures of intrinsic capacity(IC)in elderly patients with cerebrovascular disease.Methods Clinical data of 206 elderly patients with cerebrovascular disease admitted to our hospital from January to December 2024 were retrospectively collected.According to the IC score,they were divided into a low IC group(123 cases,IC score＜4)and a good IC group(83 cases,IC score≥4).The IC scores were compared between the two groups,and the driving factors affecting the IC were analyzed.Results The low IC group exhibited significantly lower IC score than the good IC group(1.94±0.49 vs 4.52±0.15,P＜0.01).The age ≥80 years,dysfunctions,three or more chronic diseases,frailty,albumin ≤ 35 g/L,pre-albumin ≤280 mg/L,rehabilitation guidance and regular exercises were the influencing factors of IC in elderly patients with cerebrovascular disease(P＜0.05,P＜0.01).Conclusion The IC of elderly patients with cerebrovascular disease is associated with many factors,and corresponding clinical intervention measures should be implemented to promote the improvement of patient's IC.

Objective:To investigate the clinical effect of free anterolateral thigh myocutaneous flap combined with oral repair membrane in the reconstruction of nasal mucosa defect after maxillary malignant tumor surgery. Methods:A total of 12 patients with maxillary gingival squamous cell carcinoma and maxillary sinus cancer who had been treated in Department of Oral and Maxillofacial Surgery, Beijing Anzhen Nanchong Hospital, Capital Medical University & Nanchong Central Hospital, were selected from November 2020 to November 2023. Free anterolateral thigh musculocutaneous flap transplantation combined with oral repair membrane were used in all patients. Meanwhile, maxillary soft and hard tissue defects and nasal mucosa defects left after tumor operation were repaired and reconstructed. The clinical effect was evaluated after 6-12 months follow-up. Results:Subtotal maxillary resection was performed in 1 case, total maxillary resection in 9 cases and extended maxillary resection in 2 cases. The musculocutaneous flaps of all patients survived, the facial appearance was basically symmetrical, no obvious depression deformity, the swallowing and speech function recovered well, the mouth and nasal cavity were closed completely, the food could be eaten through the mouth, and the lower nasal passage was not blocked. Conclusion:The free anterolateral thigh musculoflap combined with oral repair membrane can be used to repair and reconstruct maxillary malignant tumor complicated with extensive maxillary tissue and nasal mucosa defect after operation, and the appearance and function can be recovered well after operation, which is a choice for maxillary malignant tumor complicated with nasal mucosa defect.
Humans ; Myocutaneous Flap ; Plastic Surgery Procedures/methods* ; Maxillary Neoplasms/surgery* ; Carcinoma, Squamous Cell/surgery* ; Male ; Middle Aged ; Female ; Nasal Mucosa/surgery* ; Maxilla/surgery* ; Thigh/surgery* ; Maxillary Sinus Neoplasms/surgery*

Objective:To describe the clinical manifestations, genetic mutation site, diagnosis, and treatment of a patient with multisystem proteinopathy type 1 (MSP1) caused by valosin-containing protein ( VCP) gene mutation, and to improve clinicians′ understanding of this disease. Methods:A retrospective analysis was performed on clinical and genetic data from a confirmed VCP gene missense mutation-associated MSP1 case diagnosed at the Department of Neurology, Affiliated Zhongda Hospital, School of Medicine, Southeast University in January 2024. A 12-month follow-up and systematic literature review were performed for comprehensive analysis. Results:The 53-year-old male patient presented with progressive limb weakness over 7 months. Neurological examination demonstrated tongue fasciculations, asymmetric proximal muscle weakness in all four limbs, left patellar hyperreflexia, positive right Chaddock sign, and bilateral Hoffmann signs. Electrophysiological studies demonstrated extensive neurogenic damage. Lower-limb muscle magnetic resonance imaging (MRI) showed selective fatty infiltration in specific muscle groups. Biceps brachii biopsy pathology revealed rimmed vacuoles and grouped atrophy of typeⅡfibers. Immunofluorescence confirmed aberrant aggregation of VCP within atrophic myofibers, showing co-localization with p62 and transactive response DNA binding protein 43 (TDP-43). Whole-genome sequencing identified a heterozygous c.463C>T (p.Arg155Cys) missense mutation in exon 5 of the VCP gene, classified as a likely pathogenic mutation according to the guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. The patient was diagnosed with MSP1 with amyotrophic lateral sclerosis and inclusion body myopathy as the main clinical manifestation based on clinical manifestations, electrophysiology, imaging, histopathology, and genetic findings. After 12 months of riluzole therapy, disease progression remained relatively slow. Literature review identified 67 relevant articles, revealing 87 VCP mutation genotypes and 19 clinical phenotypes. Conclusions:MSP1 is a genetically and phenotypically heterogeneous spectrum of multisystem degenerative disorders. This case represents the first reported VCP-related MSP1 in China, characterized by amyotrophic lateral sclerosis combined with inclusion body myopathy. Riluzole treatment demonstrates slowed disease progression over 1 year.

Objective To examine the diagnosis and treatment of disseminated infection caused by Enterocytozoon bieneusi in a child with leukemia and improve the awareness of the pathogen in clinical and laboratory practice.Methods A case of disseminated infection caused by Enterocytozoon bieneusi in a child with leukemia in Shanghai Children's Hospital was retrospectively analyzed,including diagnosis and treatment details.Similar cases were identified from PubMed,Wanfang Data,VIP,and CNKI databases since database establishment until June 30,2024,using search terms"Enterocytozoon bieneusi".The relevant literature was reviewed.Results This child had acute lymphoblastic leukemia as the underlying disease and was admitted to hospital for antimicrobial treatment due to fever and abdominal discomfort.The case was considered bacterial infection complicated with Enterocytozoon bieneusi infection,confirmed by detection of Klebsiella pneumoniae in blood and detection of Enterocytozoon bieneusi in blood and ascites by metagenomic next-generation sequencing(mNGS).The treatment was switched to tigecycline plus trimethoprim-sulfamethoxazole at a sufficient dose,which resulted in resolution of symptoms.Six months later,the patient suffered from acute lymphoblastic leukemia and bone marrow depression,Enterocytozoon bieneusi disseminated infection,septic shock.Her family gave up treatment and the child died.Literature review indicated that most patients infected with Enterocytozoon bieneusi had underlying conditions such as organ transplantation,AIDS,and leukemia associated with poor immunity.The onset symptoms are diarrhea,abdominal discomfort,and fever.Enterocytozoon bieneusi was detected by using methods such as modified Masson's trichrome stain,fluorescent calcofluor white staining,molecular detection techniques,and immunofluorescence.The patients were treated with drugs such as albendazole,nitazoxanide,fumagillin,and trimethoprim-sulfamethoxazole.Conclusions Enterocytozoon bieneusi is an opportunistic pathogenic fungus that infects immunocompromised patients and can cause abdominal discomfort,diarrhea,fever,and even disseminated infection and death.Conventional laboratory methods cannot culture Enterocytozoon bieneusi.Molecular detection techniques can be used to identify the pathogen early.

Background and aims:Primary sclerosing cholangitis(PSC)is an autoimmune liver disease characterized by complex pathogenesis and limited available therapeutic options.The mechanisms underlying the development and progression of PSCs remain unclear.Liver X receptor beta(LXR-β)is recognized to modulate lipid metabolism and immune response,but its specific involvement in the PSC has not been elucidated.Here,we explored the role and mechanism of LXR-β in PSC induced by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine(DDC).Methods:CRISPR-Cas9 technology was applied to generate Abcb4(coding MDR2,next named as Mdr2),Nr1h2(coding LXR-β,next named as Lxrβ),and Rag2(coding RAG2)knockout mice.DDC was used to induce PSC.Hematoxylin and eosin and Sirius red staining were used to assess the extent of hepatic injury and fibrosis.Flow cytometry was used to observe immune cell subsets.Results:We observed a declining trend in hepatic Lxrβ in the PSC model.Unexpectedly,Lxrβ knockout failed to modulate DDC-induced PSC pathogenesis.Concomitantly,assessment of the influence of Rag2 deficiency on PSC progression revealed the absence of aggravated or alleviated hepatic injury or fibrosis in the Rag2-/-DDC mice.However,Lxrβ depletion intensified DDC-induced PSC in the Rag2-/-mice,with more abundant infiltrative inflammatory cells and more severe liver fibrosis.Compared with Rag2-/-DDC mice,Lxrβ-/-Rag2-/-DDC mice had higher serum ALT and AST levels and mRNA expression of proinflammatory and profibrotic genes.Flow cytometry showed that LXR-β deficiency resulted in a diminished population of hepatic innate immune cells.Conclusion:This study indicated innate immune cell LXR-β deficiency can exacerbate hepatic injury and fibrosis in murine models of PSC suggesting that LXR-β may regulate the function of innate immunity in the fibrotic advancement of PSC.

Objective To elucidate the mechanism through which Gypenoside L inhibits the growth of colon cancer by modulating carnitine palmitoyltransferase 1B (CPT1B),a pivotal enzyme in the fatty acid metabolism pathway. Methods Through in vitro experiments,various concentrations of Gypenoside LI LI were applied to inter-vene in colon cancer RKO and SW620 cells. The effects of Gypenoside LI on these cells were comprehensively evalu-ated using the CCK-8 assay,wound healing assay,colony formation assay,and live-dead cell staining,focusing on its impact on cell proliferation,migration,and apoptosis. Additionally,a human colon cancer tissue microarray (TMA) was utilized in conjunction with multiplex fluorescence immunohistochemistry to analyze the expression of CPT1B in colon cancer and adjacent tissues. SW620 cells were transfected with siRNA,and the mRNA and protein expression levels of CPT1B post-transfection were assessed using quantitative real-time PCR (qPCR) and Western blotting. Furthermore,an in vivo nude mouse colon cancer model was established to investigate the inhibitory effect of Gypenoside LI LI on colon cancer growth. Results In vitro experiments demonstrated that Gypenoside LI LI effectively inhibited the proliferation and migration of RKO and SW620 cells in a concentration-and time-dependent manner. Additionally,multiple fluorescence immunohistochemistry analyses revealed that the expression level of CPT1B in colon cancer tissues was significantly higher than that in adjacent non-tumor tissues. Gypenoside LI LI promoted ROS accumulation by inhibiting CPT1B expression. In vivo experiments further confirmed that Gypenoside LI LI could inhibit tumor formation in nude mice and reduce CPT1B expression. Conclusions This study elucidates the mechanism by which Gypenoside LI inhibits the growth of colon cancer cells. Specifically,it downregulates CPT1B,leading to increased accumulation of reactive oxygen species (ROS),disruption of fatty acid oxidation metabolism,and ultimately inducing apoptosis in colon cancer cells. These findings offer valuable insights into colon cancer treatment,suggesting new therapeutic strategies and potential drug targets.

Objective To explore the model of decreased ovarian reserve(DOR)induced by experimental autoimmune thyroiditis(EAT)in mice and investigate the protective mechanism of Jiexu Zichong Granules(ZCWS).Methods Ninety-six Kunming female mice were randomly divided into the J control group,BIW control group,J model group,and BIW model group.The mice were immunized with antigen(0.1 mg,once or twice per week)combined with high iodine water(0.64 g/L)for 7-19 weeks to validate the model.Subsequently,30 mice were randomly divided into the ZCWS group,model group,and control group.The DOR model was established by immunization with the antigen(0.2 mg per week)combined with high iodine water feeding for 13 weeks.The ZCWS group received oral administration of traditional Chinese medicine suspension(0.64 g/mL),while the remaining groups received an equivalent volume of physiological saline for 7 weeks.Thyroid and ovarian tissue morphology and related indicators were detected using HE staining,ELISA,IHC,and Western blot.Results Antigen immunization for 13 weeks(0.1-0.2 mg per week)combined with high iodine water feeding stably constructed the EAT DOR model.ZCWS reduced thyroid lymphocyte infiltration,follicular structure destruction,and serum TPOAb and TGAb levels(P<0.01).It inhibited MDA activity(P<0.01),increased GSH-Px and SOD activities(P<0.05),increased primordial,primary,and secondary follicles(P<0.05),and reduced atretic follicles(P<0.01).ZCWS upregulated AMH and downregulated FSH(P<0.01),regulated the expression of Bcl-2,Bax,and Caspase-3 proteins in ovarian tissue,downregulated Keap1 protein(P<0.01),and upregulated Nrf2(P<0.01),HO-1,and LONP1 proteins(P<0.05).It upregulated Bcl-2 protein(P<0.05),downregulated Bax(P<0.01),and Caspase-3(P<0.05)proteins,downregulated Keap1 protein(P<0.01),and upregulated Nrf2(P<0.01),HO-1,and LONP1 proteins(P<0.05)in ovarian tissue.Conclusion ZCWS improves ovarian reserve function in EAT mice by activating the Nrf2 pathway,inhibiting oxidative stress,and reducing follicular atresia.

A case of Sifrim-Hitz-Weiss syndrome(Sifrim-Hitz-Weiss syndrome,SIHIWES)is presented.The patient was a 35-year-old male with cryptorchidism,growth retardation,skeletal malformations,muscular atrophy,a wide forehead,special facial features like square face,small low-set and cup-shaped ears since birth.Whole-exon sequencing identified a heterozygous mutation(NM_001273:c.3047A>G(chr12-6701125)(p.K1016R))in CHD4 gene.The clinical significance of this mutation is currently unknown,and has not been previously reported.In light of the patient's symptoms,the case was diagnosed as Sifrim-Hitz-Weiss syndrome.This case represents the first instance of Sifrim-Hitz-Weiss syndrome in an adult patient in China.