ObjectiveTo observe the intervention effect of Fufang Kangjiaolv capsules on anxiety-like behaviors in the rat model of chronic restraint stress （CRS） and explore the mechanism underlying the anti-anxiety effect via the microbiota-gut-brain axis. MethodsRats were assigned into blank， model， positive drug （diazepam， 1 mg·kg^-1）， and low-， medium-， and high-dose （0.75， 1.5， 3 g·kg^-1， respectively） Fufang Kangjiaolv capsules groups. After 14 days of administration， the elevated plus maze test， open field test， light and dark box test， and marble burying test were performed. Hematoxylin-eosin staining was employed to observe the pathological changes in the hippocampus and colon of rats， and Nissl staining was conducted to observe the damage of hippocampal neurons. The gut microbiota was analyzed by 16S rRNA gene sequencing. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of zonula occludens-1 （ZO-1） and occludin in the colon of rats. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in the colon， serum， and hippocampus were determined by enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of ZO-1， occludin， nuclear factor-κB p65 （NF-κB p65） in the colon tissue and NF-κB p65 and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. ResultsCompared with the blank group， the model group showed reductions in the time and frequency ratio of rats entering the elevated plus maze， the time and frequency of rats entering the central area of the open field， the time of entering the open box， the times of passing through the light and dark box， and the number of unburied beads （P<0.05， P<0.01）. Compared with the model group， Fufang Kangjiaolv capsules ameliorated the anxiety of the model rats to varying degrees， and the high-dose group had the best effect， with increases in the proportions of time and frequency of rats entering the open arm in the elevated plus maze （P<0.05）， the number of rats entering the central area in the open field （P<0.05）， the time of entering the open box， the times of passing through the light and dark boxes， and the number of unburied beads （P<0.01）. Moreover， the high-dose group showed alleviated pathological damage of hippocampal neurons and colon. The results of 16S rRNA gene sequencing showed that the model group had increased relative abundance of Firmicutes， Deferribacterota， Romboutsia， and Phascolarctobacterium， while it had decreased relative abundance of Bavcteroidota and Lactobacillus. The drug administration groups showed increased relative abundance of Bavcteroidota， Bacteroides， norank f norank o Clostridia UCG-014， and Blautia and decreased relative abundance of Firmicutes and Deferribacterota. Compared with the blank group， the model group showed down-regulated protein and mRNA levels of ZO-1 and occludin in the colon （P<0.01）， elevated levels of TNF-α， IL-6， and IL-β in the colon， serum， and hippocampus （P<0.01）， up-regulated protein level of NF-κB p65 in the colon and hippocampus （P<0.01）， and down-regulated protein level of BDNF in the hippocampus （P<0.05）. Compared with the model group， high-dose Fufang Kangjiaolv capsules up-regulated the mRNA levels of ZO-1 and occludin in the colon （P<0.01）， lowered the levels of TNF-α， IL-6， and IL-β in the colon， serum， and hippocampus （P<0.01）， up-regulated the protein levels of ZO-1 （P<0.01） and occludin （P<0.05） in the colon， down-regulated the protein level of NF-κB p65 in the colon and hippocampus （P<0.05）， and up-regulated the protein level of BDNF in the hippocampus. ConclusionFufang Kangjiaolv capsules can reduce the anxiety-like behaviors in the rat model of CRS by regulating the gut microbiota disturbance， up-regulating the expression of tight junction proteins in the colon， repairing intestinal mucosal mechanical barrier， and down-regulating NF-κB/BDNF signaling pathway， thereby reducing peripheral and central inflammation. This study proves the hypothesis that Fufang Kangjiaolv capsules play an anti-anxiety role via the microbiota-gut-brain axis， providing a new idea for further research.

Objective:To investigate immunological non-responders (INRs) and immunological responders (IRs) during long-term antiretroviral therapy (ART), and study the dynamics of HIV reservoir and α4β7 cells in INRs and IRs and their correlation.Methods:Twenty-six patients with chronic HIV infection who received ART for 5 years were included. They were divided into INRs (CD4 + T cell counts≤350 cells/μl, n=9) and IRs (CD4 + T cell counts≥500 cells/μl, n=17) based on immune reconstitution outcomes. The percentages and numbers of α4β7 cells in both groups at baseline, ART 1, 3, and 5 years were detected by flow cytometry, and the levels of HIV DNA and cell-associated HIV RNA were quantified by real-time fluorescent quantitative PCR during the same periods. HIV viral decay, α4β7 cells dynamics, and their correlations with T cells were compared at baseline, ART 1, 3 and 5 years between the two groups. Results:Over 5 years of ART, INRs exhibited higher HIV reservoir levels compared to IRs, but the decline trend was not slow. The counts of α4β7 cell were lower and the growth trend was slow in INRs ( P<0.05). α4β7 cell counts were strongly positively correlated with CD4 + T cell counts at all timepoints (Year 1: r=0.887; Year 3: r=0.878; Year 5: r=0.887; P all <0.001), while showing significantly negative correlations with activated CD38 + HLA-DR + CD4 + T cells (Year 1: r=-0.619, P=0.001), CD38 + HLA-DR + CD8 + T cells (Year 1: r=-0.517; Year 5: r=-0.532; P all <0.01), and PD-1 + CD4 + T cells (Year 1: r=-0.476, Year 5: r=-0.390, P all <0.05). Conclusions:During long-term ART, INRs maintained higher HIV reservoir and lower α4β7 cell counts compared with IRs, and decreased α4β7 cells may be associated with disease progression.

Forced normalization (FN) is a rare epileptic psychiatric disorder that usually characterized by the disappearance of seizures and acute psychosis in patients with paradoxical normalization of the electroencephalogram following a change in the dose of antiseizure medication (ASM) or the initiation of a new medication. This article reports a case of a young female patient with Lennox-Gastaut syndrome who developed FN twice after a change in the ASM regimen, which improved after ASM reduction and olanzapine treatment. Further literature review summarizing the clinical features of FN found that there were slightly more females than males in patients with FN, the onset was more common in young adults, and most patients had refractory epilepsy. The psychiatric and behavioral abnormalities included delusions, hallucinations, bizarre behavior, mania, depression, and dissociation. The changes in ASM were the main inducing factor. Most patients improved by adjusting ASM or adding antipsychotic drugs. By reviewing this case, this article aims to increase awareness of the clinical features, characteristics of mental behavioral abnormalities, treatment and prognosis of FN and to improve the clinical management of the disease.

Objective:To explore the therapeutic efficacy, adverse reactions, and factors influencing recurrence of botulinum toxin type A (BTX-A) in patients with trigeminal neuralgia (TN), and to provide clinical reference for the application of BTX-A in the treatment of TN.Methods:Clinical data and pre- and post-treatment Visual Analogue Scale (VAS) scores were collected from 198 patients with TN treated with BTX-A at the First Affiliated Hospital of Zhengzhou University from June 2020 to December 2022. Correlation analysis, univariate and multivariate Logistic regression were used to analyze factors influencing treatment efficacy, adverse reactions, and recurrence in patients. The predictive value of these factors for adverse reactions and recurrence was assessed using receiver operating characteristic curves.Results:Following BTX-A treatment, there were significant correlations between the frequency of TN attacks, time to peak efficacy, duration of efficacy, and VAS scores difference before and after treatment ( B=0.141, P=0.043; B=-0.134, P=0.023; B=-0.405, P0.001), as well as percentage difference in VAS score ( B=0.015, P=0.033; B=-0.011, P=0.034; B=-0.056, P0.001). Multiple branch involvement of the trigeminal nerve was an independent risk factor for the occurrence of TN adverse reactions ( OR=2.899, 95% CI 1.280-6.566, P=0.011). The area under the curve (AUC) for multiple branch involvement of the trigeminal nerve was 0.615 (95% CI 0.600-0.732). Multiple branch involvement of the trigeminal nerve ( OR=4.103, 95% CI 1.610-9.600, P=0.002) and peak onset time ( OR=0.950, 95% CI 0.922-0.978, P=0.001) were independent risk factors for TN recurrence and the combined AUC for these two factors was 0.713 (95% CI 0.600-0.827). Conclusions:The frequency of TN episodes, time to peak efficacy and maintenance duration of efficacy after BTX-A treatment were correlated with the difference in VAS scores and the percentage of difference. And the involvement of multiple branches of the trigeminal nerve was an independent risk factor affecting the occurrence of adverse reactions and TN recurrence.

Qingfeitang， specialized in resolving phlegm to stop cough and producing fluid to moisten dryness， is a classic prescription inherited and developed by physicians of successive generations and has been included in the Catalogue of Ancient Classic Prescriptions （First Batch） published by the National Administration of Traditional Chinese Medicine （TCM） in 2018. Relevant ancient books data and modern literature were collected by bibliometrics to analyze the historic origin， formula composition， herb origin， preparation methods， processing methods， clinical effect， and indications of Qingfeitang. The key information of Qingfeitang was summarized to provide reference for the clinical application of the decoction. In this study， a total of 43 pieces of effective data on relevant ancient literature， including 35 ancient TCM books， were collected based on a systematic collation of relevant historic and modern literature. Results showed that "Qingfeitang" was originated from the "Renshen Qingfeitang" recorded in the Taiping Holy Prescriptions for Universal Relief from the Qing dynasty. The name of "Qinfeitang" was first recorded in the Yeshi Luyanfang written by YE Dalian in the Song dynasty. We suggested the modern dosage and usage of Qingfeitang as follows： "Scutellariae Radix of 5.60 g， Platycodon grandiflora， Poria， Tangerine， Fritillaria， and Cortex Mori of 3.73 g respectively， Angelicae Sinensis Radix， Asparagi Radix， Gardeniae Fructus， Armeniacae Semen Amarum， and Ophiopogonis Radix of 2.61 g respectively， Schisandra of 1 g， and Glycyrrhizae Radix et Rhizoma of 1.12 g， and they were taken 3 times daily. The above formula is recommended to be decocted with 400 mL of water， with 3.37 g ginger and 6 g jujubae fructus， to 320 mL， and taken after a meal， three times per day". Qingfeitang has the effect of resolving phlegm to stop cough and producing fluid to moisten dryness， specialized in treating cough， asthma， rash， and other symptoms in ancient times. Modern applications are mainly focused on the respiratory system， used for treating diseases such as bronchopneumonia and cough. The above research results provide a reference basis for the later development and research of Qingfeitang.

Objective:To investigate immunological non-responders (INRs) and immunological responders (IRs) during long-term antiretroviral therapy (ART), and study the dynamics of HIV reservoir and α4β7 cells in INRs and IRs and their correlation.Methods:Twenty-six patients with chronic HIV infection who received ART for 5 years were included. They were divided into INRs (CD4 + T cell counts≤350 cells/μl, n=9) and IRs (CD4 + T cell counts≥500 cells/μl, n=17) based on immune reconstitution outcomes. The percentages and numbers of α4β7 cells in both groups at baseline, ART 1, 3, and 5 years were detected by flow cytometry, and the levels of HIV DNA and cell-associated HIV RNA were quantified by real-time fluorescent quantitative PCR during the same periods. HIV viral decay, α4β7 cells dynamics, and their correlations with T cells were compared at baseline, ART 1, 3 and 5 years between the two groups. Results:Over 5 years of ART, INRs exhibited higher HIV reservoir levels compared to IRs, but the decline trend was not slow. The counts of α4β7 cell were lower and the growth trend was slow in INRs ( P<0.05). α4β7 cell counts were strongly positively correlated with CD4 + T cell counts at all timepoints (Year 1: r=0.887; Year 3: r=0.878; Year 5: r=0.887; P all <0.001), while showing significantly negative correlations with activated CD38 + HLA-DR + CD4 + T cells (Year 1: r=-0.619, P=0.001), CD38 + HLA-DR + CD8 + T cells (Year 1: r=-0.517; Year 5: r=-0.532; P all <0.01), and PD-1 + CD4 + T cells (Year 1: r=-0.476, Year 5: r=-0.390, P all <0.05). Conclusions:During long-term ART, INRs maintained higher HIV reservoir and lower α4β7 cell counts compared with IRs, and decreased α4β7 cells may be associated with disease progression.

Forced normalization (FN) is a rare epileptic psychiatric disorder that usually characterized by the disappearance of seizures and acute psychosis in patients with paradoxical normalization of the electroencephalogram following a change in the dose of antiseizure medication (ASM) or the initiation of a new medication. This article reports a case of a young female patient with Lennox-Gastaut syndrome who developed FN twice after a change in the ASM regimen, which improved after ASM reduction and olanzapine treatment. Further literature review summarizing the clinical features of FN found that there were slightly more females than males in patients with FN, the onset was more common in young adults, and most patients had refractory epilepsy. The psychiatric and behavioral abnormalities included delusions, hallucinations, bizarre behavior, mania, depression, and dissociation. The changes in ASM were the main inducing factor. Most patients improved by adjusting ASM or adding antipsychotic drugs. By reviewing this case, this article aims to increase awareness of the clinical features, characteristics of mental behavioral abnormalities, treatment and prognosis of FN and to improve the clinical management of the disease.

Objective:To explore the therapeutic efficacy, adverse reactions, and factors influencing recurrence of botulinum toxin type A (BTX-A) in patients with trigeminal neuralgia (TN), and to provide clinical reference for the application of BTX-A in the treatment of TN.Methods:Clinical data and pre- and post-treatment Visual Analogue Scale (VAS) scores were collected from 198 patients with TN treated with BTX-A at the First Affiliated Hospital of Zhengzhou University from June 2020 to December 2022. Correlation analysis, univariate and multivariate Logistic regression were used to analyze factors influencing treatment efficacy, adverse reactions, and recurrence in patients. The predictive value of these factors for adverse reactions and recurrence was assessed using receiver operating characteristic curves.Results:Following BTX-A treatment, there were significant correlations between the frequency of TN attacks, time to peak efficacy, duration of efficacy, and VAS scores difference before and after treatment ( B=0.141, P=0.043; B=-0.134, P=0.023; B=-0.405, P0.001), as well as percentage difference in VAS score ( B=0.015, P=0.033; B=-0.011, P=0.034; B=-0.056, P0.001). Multiple branch involvement of the trigeminal nerve was an independent risk factor for the occurrence of TN adverse reactions ( OR=2.899, 95% CI 1.280-6.566, P=0.011). The area under the curve (AUC) for multiple branch involvement of the trigeminal nerve was 0.615 (95% CI 0.600-0.732). Multiple branch involvement of the trigeminal nerve ( OR=4.103, 95% CI 1.610-9.600, P=0.002) and peak onset time ( OR=0.950, 95% CI 0.922-0.978, P=0.001) were independent risk factors for TN recurrence and the combined AUC for these two factors was 0.713 (95% CI 0.600-0.827). Conclusions:The frequency of TN episodes, time to peak efficacy and maintenance duration of efficacy after BTX-A treatment were correlated with the difference in VAS scores and the percentage of difference. And the involvement of multiple branches of the trigeminal nerve was an independent risk factor affecting the occurrence of adverse reactions and TN recurrence.

Bispecific antibodies(BsAbs),as an important recent innovation in the field of tumor immunotherapy in recent years,can simultaneously or sequentially target different antigens or two different epitopes of the same antigen.Compared with traditional monoclonal antibodies,they can produce superior therapeutic effects.This article reviews the progress in clinical applications and safety research of BsAbs in cancer therapy,revealing that they(such as blinatumomab,glofitamab,teclistamab,amivantamab,etc.)exhibit significant therapeutic efficacy against hematological malignancies,lung cancer,cervical cancer,melanoma,and other cancers.For cytokine release syndrome(CRS)induced by BsAbs,prophylactic or pre-emptive medication is commonly administered in clinical practice;for neurotoxicity and infections triggered by BsAbs,clinical practice necessitates rigorous monitoring of patients'vital signs and the provision of essential treatments.In addition,different BsAbs exhibit variations in escalation dose,infusion rate,storage duration,and equipment requirements.Therefore,strict adherence to the instructions in the drug package inserts is essential during clinical operations to ensure safety and therapeutic efficacy.In the future,more multicenter trials need to be conducted to validate the efficacy and safety of BsAbs across different tumor types and patient populations,and long-term follow-up data should be accumulated to optimize treatment cycles and dosage regimens.

Objective:To compare the safety and efficacy of two different minimally invasive approaches to implant pedicle screw for the treatment of single-segment thoracolumbar spine fractures without nerve injury.Methods:This was a retrospective study. Eighty patients with mono-segmental thoracolumbar fractures treated with minimally invasive pedicle screw fixation at Beijing Friendship Hospital, Capital Medical University from January 2020 to June 2022 were included. There were 46 males and 36 females, the age was (45.93±7.91) years old, and ranged from 27 to 60 years old. They were divided into two groups according to different surgical techniques: percutaneous pedicle screw fixation group ( n=44) and Wiltse approach group ( n=36). The operative time, operative visible blood loss, hidden blood loss, total blood loss, fluoroscopy times, incision length, hospital time after surgery and ambulation time were compared. Visual analogue scale (VAS), Oswestry disability index (ODI), ratio of the vertebral anterior height, angle of injured vertebral endplate were recorded and compared between two groups before surgery and at 3 days, 6 months and 1 year after surgery. The accuracy of pedicle screw position and the facet joint violation rate were evaluated by using the postoperative CT scan. Perioperative related complications were investigated. Normally distributed numerical data were presented as mean ± standard deviation, and differences between the groups were compared using t-test. The counting data were expressed as percentages or rates and compared using χ2 test. Results:All patients were followed for a minimum of 12 months. There is no significant difference between the two groups in intraoperative visible blood loss, hospital time after surgery, ambulation time, postoperative VAS and ODI, ratio of vertebral anterior height and angle of injured vertebral endplate at 3 days after surgery, pedicle screw position accuracy and perioperative complications ( P>0.05). The operative time, hidden blood loss, total blood loss, intraoperative fluoroscopy times, facet joint violation rate in the percutaneous pedicle screw fixation group were remarkably higher than in the Wiltse approach group ( P<0.05). The ratio of vertebral anterior height in the percutaneous pedicle screw fixation group was dramatically lower than in the Wiltse approach group at 6 months and 1 year after surgery ( P<0.05). The postoperative injured vertebral endplate angle was higher in the percutaneous pedicle screw fixation group than that in the Wiltse approach group at 6 months and 1 year ( P<0.05). Conclusions:Both percutaneous pedicle screw fixation and Wiltse approach were safe and effective minimally invasive surgical procedures for the treatment of thoracolumbar fractures without neurological injury. The Wiltse approach can reduce fluoroscopy times and perioperative hidden blood loss, reduce the risk of facet joint violation, and maintain a better reduction than percutaneous pedicle screw fixation.