Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Anxiety disorder is a highly prevalent psychological illness, and research has shown that obesity is a significant risk factor for its development. This study explored the ameliorative effects and mechanisms of saponins from Panax japonicus(SPJ) on anxiety disorder in mice fed a high-fat diet(HFD). Fifty C57BL/6J mice were randomly divided into normal control diet(NCD) group, HFD group, and low-and high-dose SPJ groups. At week 12, six mice from the HFD group were further divided into a control group(treated with DMSO) and an exogenous fibroblast growth factor 21(FGF21) group(administered rFGF21). The anxiety-like behavior of the mice was assessed using the open field test and elevated plus maze test. Hematoxylin-eosin(HE) staining and oil red O staining were performed to observe pathological changes in the liver and adipose tissue. Glucose metabolism was evaluated through the glucose tolerance test(GTT) and insulin tolerance test(ITT). Western blot analysis was performed to detect the expression of FGF21 and its downstream-related proteins in the liver and cortex, along with the expression of brain-derived neurotrophic factor(BDNF), disks large homolog 4(DLG4), and synaptophysin(SYP) in the cortex. Real-time quantitative fluorescent PCR(qPCR) was used to detect the expression of FGF21 and its receptor genes in the liver and cortex. Immunofluorescence staining was employed to examine the expression of neuronal activator c-Fos, FGF21, and the FGF21 co-receptor β-klotho in the cerebral cortex. The results showed that SPJ significantly improved the frequency of activity in the open arms of the elevated plus maze and the central area of the open field in HFD mice, up-regulated the expression of BDNF, DLG4, and SYP, and effectively alleviated anxiety-like behaviors in HFD mice. Compared with the NCD group, HFD mice exhibited up-regulated expression of FGF21 in the liver and cerebral cortex, while the expression of fibroblast growth factor receptor 1(FGFR1) and β-klotho was significantly down-regulated, suggesting that HFD mice exhibited FGF21 resistance. SPJ markedly up-regulated the β-klotho levels in HFD mice, reversing FGF21 resistance. Further comparison with exogenously administered FGF21 revealed that SPJ activates brain cortical regions in a consistent manner, and additionally, SPJ promotes the number and colocalization of c-Fos and β-klotho positive cells in the brain cortex. In summary, SPJ effectively alleviates anxiety-like behaviors in HFD mice. Its mechanism is associated with up-regulation of β-klotho expression in the brain, reversal of FGF21 resistance, and subsequent activation of neurons in the cerebral cortex and amygdala.
Animals ; Diet, High-Fat/adverse effects* ; Fibroblast Growth Factors/genetics* ; Mice ; Male ; Panax/chemistry* ; Mice, Inbred C57BL ; Anxiety/etiology* ; Saponins/administration & dosage* ; Brain-Derived Neurotrophic Factor/genetics* ; Humans ; Liver/metabolism* ; Drugs, Chinese Herbal/administration & dosage*

OBJECTIVE: To analyze the significance of total vitamin D (tVD), total procollagen type I amino-terminal propeptide (tPINP) and β-CrossLaps (β-CTx) in the staging and prognosis of patients with multiple myeloma (MM). METHODS: A total of 54 patients with newly diagnosed MM admitted to the Second Affiliated Hospital of Fujian Medical University from 2020 to 2022 were selected as the observation group (MM group), and 50 healthy persons who underwent physical examinations in our hospital were selected as the control group. The expression levels of tVD, tPINP and β-CTx in the two groups were detected by chemiluminescence method. The differences in the expression levels of tVD, tPINP and β-CTx among MM patients at different ISS stages were analyzed. The expression levels of tVD, tPINP and β-CTx in MM patients with different levels of hemoglobin (Hb), serum calcium (Ca), creatinine (Crea), albumin (ALB), β₂-microglobulin (β₂-MG) and lactate dehydrogenase (LDH) were compared. The correlations between the expression levels of tVD, tPINP, β-CTx and the aforementioned clinical parameters were analyzed, respectively. The relationship between the expression levels of tVD, tPINP, β-CTx and the progression-free survival (PFS) of MM patients was analyzed. RESULTS: The expression level of tVD in the MM group was significantly lower than that in the control group (21.73±14.45 ng/ml vs 30.78±9.94 ng/ml, P =0.022). The expression level of β-CTx in the MM group was significantly higher than that in the control group (1.43±0.99 ng/ml vs 0.53±0.29 ng/ml, P =0.013). The tVD level in MM patients with ISS stage I-II was significantly higher than that of MM patients with ISS stage III (29.50±14.59 ng/ml vs 12.62±7.73 ng/ml, P =0.028), indicating that the higher the ISS stage, the lower the tVD level. The tPINP and β-CTx levels in MM patients with high Ca levels (>2.65 mmol/L) were significantly higher than those in patients with low Ca levels (≤2.65 mmol/L) (P =0.016, P =0.021). The tVD level of MM patients was positively correlated with the ALB level (r =0.570), tPINP was positively correlated with Ca and β₂-MG levels (r =0.791,r =0.673), and β-CTx was positively correlated with tPINP level (r =0.616). The PFS of the low tVD expression group was significantly lower than that of the high tVD expression group (P =0.041). CONCLUSION The expression level of tVD is decreased in MM patients, which can be used as an indicator to evaluate the disease stage and prognosis of the patients. The β-CTx expression level is increased in MM patients. tPINP and β-CTx may be correlated with clinical symptoms such as osteolytic lesions and renal function changes in MM patients.
Humans ; Multiple Myeloma/pathology* ; Procollagen/blood* ; Vitamin D/blood* ; Prognosis ; Peptide Fragments/blood* ; Collagen Type I/blood* ; Female ; Male ; Middle Aged ; Aged ; Neoplasm Staging

OBJECTIVE: To illustrate the role of dehydrocorydaline (DHC) in chronic constriction injury (CCI)-induced neuropathic pain and the underlying mechanism. METHODS: C57BL/6J mice were randomly divided into 3 groups by using a random number table, including sham group (sham operation), CCI group [intrathecal injection of 10% dimethyl sulfoxide (DMSO)], and CCI+DHC group (intrathecal injection of DHC), 8 mice in each group. A CCI mouse model was conducted to induce neuropathic pain through ligating the right common sciatic nerve. On day 14 after CCI modeling or sham operation, mice were intrathecal injected with 5 µL of 10% DMSO or 10 mg/kg DHC (5 µL) into the 5th to 6th lumbar intervertebral space (L5-L6). Pregnant ICR mice were sacrificed for isolating primary spinal neurons on day 14 of embryo development for in vitro experiment. Pain behaviors were evaluated by measuring the paw withdrawal mechanical threshold (PWMT) of mice. Immunofluorescence was used to observe the activation of astrocytes and microglia in mouse spinal cord. Protein expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), phosphorylation of N-methyl-D-aspartate receptor subunit 2B (p-NR2B), and NR2B in the spinal cord or primary spinal neurons were detected by Western blot. RESULTS: In CCI-induced neuropathic pain model, mice presented significantly decreased PWMT, activation of glial cells, overexpressions of iNOS, TNF-α, IL-6, and higher p-NR2B/NR2B ratio in the spinal cord (P<0.05 or P<0.01), which were all reversed by a single intrathecal injection of DHC (P<0.05 or P<0.01). The p-NR2B/NR2B ratio in primary spinal neurons were also inhibited after DHC treatment (P<0.05). CONCLUSION An intrathecal injection of DHC relieved CCI-induced neuropathic pain in mice by inhibiting the neuroinflammation and neuron hyperactivity.
Animals ; Neuralgia/etiology* ; Mice, Inbred C57BL ; Analgesics/pharmacology* ; Neuroinflammatory Diseases/pathology* ; Constriction ; Male ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Nitric Oxide Synthase Type II/metabolism* ; Mice, Inbred ICR ; Microglia/pathology* ; Spinal Cord/drug effects* ; Female ; Mice ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Constriction, Pathologic/complications* ; Interleukin-6/metabolism* ; Astrocytes/metabolism* ; Chronic Disease ; Neurons/metabolism*

Objective:To analyze the efficacy of endoscopic surgery for frontal sinus meningoencephalocele and cerebrospinal fluid (CSF) leaks, and to explore endoscopic surgical strategy.Methods:A total of 35 patients with frontal sinus meningoencephalocele and CSF leaks who underwent endoscopic transnasal surgery at Beijing Tongren Hospital, Capital Medical University between May 2007 and December 2023 were enrolled in this retrospective case series, including 29 males and 6 females, with the age of (35.23±15.76) years. High-resolution sinus CT and magnetic resonance cisternography were undertaken before surgery. The primary outcome measure was the success rate of endoscopic surgical repair. Statistical analysis was conducted using SPSS 27 and GraphPad Prism 8 software.Results:Of the 35 cases, 21 (60.0%) were traumatic, and 14 (40.0%) were non-traumatic. The most common defect was in the posterior frontal sinus wall (24 cases, 68.6%), with a defect size of (10.4±4.8) mm 2. Twenty-six cases (74.3%) underwent endoscopic transnasal Draf Ⅱa-Ⅲ frontal sinusotomy, and 9 cases (25.7%) underwent endoscopic transnasal Darf Ⅱb-Ⅲ frontal sinusotomy combined with frontal trephination. The average follow-up time was (84.72±57.42) months. The success rate of one-time endoscopic repair was 97.1% (34/35). One patient required a second procedure, resulting in an overall success rate of 100%. Thirty-three patients had a widely patent frontal sinus ostium postoperatively, while two experienced stenosis. Conclusions:Endoscopic surgery is effective for treating frontal meningoencephalocele and CSF leaks while preserving frontal sinus drainage. Combined frontal trephination is recommended for defects that are difficult to repair using the conventional transnasal approach.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

This study explored the effects of propofol on the activity of glutamatergic neurons in the paraventricular thalamus (PVT) and the underlying mechanisms at the molecular level using whole-cell patch-clamp techniques. Acute brain slices containing the PVT were obtained from 8 weeks old C57BL/6J mice. The electrophysiological characteristics of PVT neurons were recorded in current-clamp mode, then single-cell sequencing was used to identify neuronal types. The firing frequencies before, during, and after propofol or intralipid application were recorded as F_B, F_D and F_W; and the membrane potentials were recorded as MP_B and MP_D. Picrotoxin (PTX) was used to block inhibitory gamma-aminobutyric acid type A (GABA_A) receptors during the application of propofol at 10 μmol·L^-1. Then, GABA_A receptor-mediated spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) were recorded, and the effects of 10 μmol·L^-1 propofol were investigated. The animal experiments were approved by the Medical Animal Administrative Committee of Shanghai Medical College Fudan University. The results showed that there were no significant differences in F_B, F_D and F_W during intralipid and 2 μmol·L^-1 propofol application. With propofol at 5, 10 and 20 μmol·L^-1, F_D decreased significantly when compared with F_B, and F_W increased significantly as compared with F_D (P < 0.01). The inhibition degree of the three concentration groups was significantly different (P < 0.01). In addition, with propofol at 20 μmol·L^-1, MP_D hyperpolarized significantly (P < 0.01). In the presence of PTX, 10 μmol·L^-1 propofol could not suppress the firing frequency of PVT glutamatergic neurons. Propofol at 10 μmol·L^-1 prolonged the decay time of sIPSCs (P < 0.01) and mIPSCs (P < 0.05), and increased the amplitude (P < 0.01) of mIPSCs of PVT glutamatergic neurons. Together, these results indicate that propofol can inhibit the activity of PVT glutamatergic neurons in a concentration-dependent and reversible manner, and the effect is likely to be mediated by postsynaptic GABA_A receptors.

Objective To analyze the effect of body mass index (BMI) on pulmonary function and quality of life in elderly patients with chronic obstructive pulmonary disease (COPD), and to provide theoretical basis for the diagnosis and treatment of COPD. Methods A total of 1 278 patients who visited the respiratory department of our hospital from January 2019 to June 2022 were selected as the research objects, including 368 COPD patients, 225 of whom were in stable stage and 143 of whom were in acute exacerbation stage. According to BMI, they were divided into low group (n=31, BMI<18.5kg/m²), normal group (n=198,18.5kg/m2≤BMI<24 kg/m²), overweight group (n=106, 24kg/m²≤BMI<28 kg/m²) and obese group (n=33,BMI≥28 kg/m²). Health-related quality of life (HRQOL) was used to evaluate the quality of life of patients. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC were measured by pulmonary function instrument to evaluate the pulmonary function grade of patients. Logistic regression was used to analyze the risk factors of pulmonary function and quality of life in COPD patients. Results There were significant differences in age, smoking, BMI and hyperlipidemia between stable COPD patients and acute exacerbation COPD patients with different BMI groups (P<0.05). There were significant differences in the proportion of pulmonary function Ⅲ/Ⅳ, FEV1/FVC, FEV1pred and HRQOL scores among different BMI groups (P<0.05) . The FEV1/FVC and FEV1pred in patients with acute exacerbation and stable COPD from high to low were obese group, overrecombination group, normal group and too low group, and the differences were statistically significant (P<0.05). The HRQOL scores of COPD patients in acute exacerbation and stable stage from high to low were obese group, overweight group, normal group and too low group, and the difference was statistically significant (P<0.05). Low body mass index was a risk factor for pulmonary function in COPD patients at stable stage (OR=2.52) and acute exacerbation stage (OR=2.83) (P<0.05). High body mass index was a risk factor for quality of life in patients with stable COPD (OR=2.43) and acute exacerbation (OR=2.65) (P<0.05). Conclusion BMI can affect pulmonary function and quality of life in COPD patients. Patients should maintain normal BMI, which can improve pulmonary function and quality of life.