Abstract In April 2021, type Ⅰ vaccine-derived poliovirus (VDPV) was detected from two fecal samples of a male infant with acute flaccid paralysis (AFP) in Zhejiang Province when he was admitted to the Children's Hospital Affiliated to Fudan University in Shanghai, with 12 and 14 nucleotide mutations in the VP1 region, respectively. The case had a history of immunization with three doses of poliovirus vaccines, and grade Ⅲ proximal muscle strength and grade Ⅱ distal muscle strength of the right lower limb. After symptomatic treatment, the activity of the right lower limb and the muscle strength was significantly restored, thus he was discharged. VDPV was not detected from subsequent (the 8th to 12th) fecal samples of the case and fecal samples of close contacts. No similar cases were found in medical institutions in the county, surrounding areas, neighboring villages or towns. Since the case did not exhibit clinical symptoms of poliomyelitis caused by VDPV, poliomyelitis was excluded, and the case was diagnosed with hemophilia type A based on the epidemiological investigation, laboratory tests, and the history of poliomyelitis vaccination. This event involved cross-provincial (municipal) cooperation and was responsed promptly, preventing further spread of the virus. It suggested that the sensitivity of the AFP case surveillance system should be maintained, environmental monitoring methods should be increased, and the poliomyelitis vaccination should be promoted to prevent the spread of the virus.

Isoliquiritigenin (ISL) is a chalcone compound isolated from licorice, known for its anti-diabetic, anti-cancer, and antioxidant properties. Our previous study has demonstrated that ISL effectively lowers blood glucose levels in type 2 diabetes mellitus (T2DM) mice and improves disturbances in glucolipid and energy metabolism induced by T2DM. This study aims to further investigate the effects of ISL on alleviating abnormal endoplasmic reticulum stress (ERS) caused by T2DM and to elucidate its molecular mechanisms. In vivo experiments were conducted using 8-week-old SPF male C57BL/6J mice. The T2DM animal model was established by high-fat and high-sugar diet combined with intraperitoneal injections of streptozotocin (STZ), in compliance with the ethical guidelines set by the Animal Welfare Committee of Beijing University of Chinese Medicine (approval number: BUCM-2022021503-1134). In vitro experiments employed human liver cancer HepG2 cells, which were induced with tunicamycin (TM) to establish the ERS cell model. Transcriptomic sequencing was used to analyze changes in gene expression in the liver samples of T2DM mice following ISL treatment. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to assess the regulatory effects of ISL on key ERS genes. Enzyme-linked immunosorbent assay (ELISA), Western blot (WB), and immunofluorescence techniques were used to evaluate ISL's effects on ERS-related proteins. Results indicate that ISL significantly downregulates the expression of ERS-related genes, reduces the level of glucose-regulated protein 78 (GRP78), and inhibits the phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK), thereby alleviating abnormal ERS induced by T2DM. Additionally, ISL increases the protein levels of insulin receptor substrate (IRS) 1 and IRS2 and enhances the phosphorylation of protein kinase B (Akt), thereby improving insulin sensitivity. In conclusion, ISL is able to alleviate T2DM associated symptoms by improving abnormal ERS and enhancing insulin sensitivity.

Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.

ObjectiveTo analyze the clinical treatment plan and traditional Chinese medicine （TCM） medication rule of children with primary nephrotic syndrome （PNS） in the First Affiliated Hospital of Henan University of Chinese Medicine. MethodsThe gender and age of children firstly diagnosed with nephrotic syndrome in the pediatric nephrology department of the First Affiliated Hospital of Henan University of Chinese Medicine from November 2019 to December 2022 were collected， and the use of immunosuppressive agents and related frequencies were counted. According to the inclusion and exclusion criteria， an independent TCM prescription database for children with nephrotic syndrome was established. Excel was used to analyze the relevant information of the literature. The frequency counting， association rule analysis， and cluster analysis were carried out on TCM in the prescription， and the high-frequent drugs were analyzed. Results（1） General information： A total of 711 children were included， consisting of 522 males （73.42%） and 189 females （26.58%）. The ratio of male to female was about 2.76∶1. The disease mainly occurred in infants and preschool age， and the average age of onset was （4.74 ± 3.48） years old. （2） Clinical treatment plan and use of immunosuppressive agents： Of the 711 children with PNS， 237 were treated with hormone alone （32.33%）， and 474 （66.67%） received immunosuppressive agents combined with hormones. In the initial treatment， hormone combined with Tacrolimus （TAC） was the preferred treatment （32.91%）. For children with refractory PNS who exhibited poor clinical efficacy， Rituximab （RTX） was mostly used for treatment， with a ratio of up to 23.63%. （3） TCM syndrome and medication rule： In PNS syndrome differentiation， Qi and Yin deficiency was identified as the main syndrome. This involved a total of 477 cases， accounting for 67.09%. Yang deficiency of spleen and kidney was observed in 118 cases， accounting for 16.60%. A total of 711 children were included， of which 706 children were treated with TCM. This involved a total of 706 prescriptions， 226 TCM， and 9 793 frequencies. There were 30 herbs used more than 95 times. The top five TCM were Radix et Rhizoma Glycyrrhizae （81.16%）， Radix Astragali （71.81%）， Poria （68.84%）， Rhizoma Atractylodis Macrocephalae （63.60%）， and Fructus Corni （57.37%）. The drug association rules and network diagram showed that the combination of ''Radix Astragali-Rhizoma Atractylodis Macrocephalae-Poria'' was the closest， and five types of combinations were obtained by cluster analysis. ConclusionIn the diagnosis and treatment of PNS in children， TAC combined with hormones shows good clinical efficacy and high safety. For children with refractory PNS， RTX combined with hormones can be used. TCM medication for PNS should follow the basic principles of strengthening the body and vital Qi and make good use of drugs such as Radix Astragali， Poria， Rhizoma Atractylodis Macrocephalae， and cornus to regulate the Yin and Yang balance and achieve better clinical efficacy.

ObjectiveTo analyze the clinical treatment plan and traditional Chinese medicine （TCM） medication rule of children with primary nephrotic syndrome （PNS） in the First Affiliated Hospital of Henan University of Chinese Medicine. MethodsThe gender and age of children firstly diagnosed with nephrotic syndrome in the pediatric nephrology department of the First Affiliated Hospital of Henan University of Chinese Medicine from November 2019 to December 2022 were collected， and the use of immunosuppressive agents and related frequencies were counted. According to the inclusion and exclusion criteria， an independent TCM prescription database for children with nephrotic syndrome was established. Excel was used to analyze the relevant information of the literature. The frequency counting， association rule analysis， and cluster analysis were carried out on TCM in the prescription， and the high-frequent drugs were analyzed. Results（1） General information： A total of 711 children were included， consisting of 522 males （73.42%） and 189 females （26.58%）. The ratio of male to female was about 2.76∶1. The disease mainly occurred in infants and preschool age， and the average age of onset was （4.74 ± 3.48） years old. （2） Clinical treatment plan and use of immunosuppressive agents： Of the 711 children with PNS， 237 were treated with hormone alone （32.33%）， and 474 （66.67%） received immunosuppressive agents combined with hormones. In the initial treatment， hormone combined with Tacrolimus （TAC） was the preferred treatment （32.91%）. For children with refractory PNS who exhibited poor clinical efficacy， Rituximab （RTX） was mostly used for treatment， with a ratio of up to 23.63%. （3） TCM syndrome and medication rule： In PNS syndrome differentiation， Qi and Yin deficiency was identified as the main syndrome. This involved a total of 477 cases， accounting for 67.09%. Yang deficiency of spleen and kidney was observed in 118 cases， accounting for 16.60%. A total of 711 children were included， of which 706 children were treated with TCM. This involved a total of 706 prescriptions， 226 TCM， and 9 793 frequencies. There were 30 herbs used more than 95 times. The top five TCM were Radix et Rhizoma Glycyrrhizae （81.16%）， Radix Astragali （71.81%）， Poria （68.84%）， Rhizoma Atractylodis Macrocephalae （63.60%）， and Fructus Corni （57.37%）. The drug association rules and network diagram showed that the combination of ''Radix Astragali-Rhizoma Atractylodis Macrocephalae-Poria'' was the closest， and five types of combinations were obtained by cluster analysis. ConclusionIn the diagnosis and treatment of PNS in children， TAC combined with hormones shows good clinical efficacy and high safety. For children with refractory PNS， RTX combined with hormones can be used. TCM medication for PNS should follow the basic principles of strengthening the body and vital Qi and make good use of drugs such as Radix Astragali， Poria， Rhizoma Atractylodis Macrocephalae， and cornus to regulate the Yin and Yang balance and achieve better clinical efficacy.

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.

OBJECTIVE To explore the potential mechanism of ketamine-induced cognitive impairment in mice based on metabolomics. METHODS Male C57BL/6 mice were randomly divided into control group and ketamine group （25 mg/kg）， with 12 mice in each group. Each group of mice was intraperitoneally injected with normal saline or corresponding drugs， 4 times a day， for 10 consecutive days. On the last 2 days of drug administration， the cognitive behavior was evaluated by Y maze and novel object recognition test， and the histopathological changes in the prefrontal cortex （PFC） were observed. Ultra-high performance liquid chromatography-tandem mass spectrometry technology was used to analyze the changes of metabolites in PFC， screen for differential metabolites， and perform pathway enrichment analysis. RESULTS Compared with the control group， the morphology of PFC neurons in the ketamine group of mice was inconsistent. There were cavities around the nucleus， and the number of deeply stained cells increased. The mean optical density value of the Nissl staining positive area was significantly reduced， and the alternation rate and discrimination index were significantly reduced （P＜0.05 or P＜0.01）. In the PFC tissue samples of mice of the two groups， there were a total of 114 differential metabolites， including 73 up-regulated and 41 down-regulated metabolites， including glutamine， succinic acid， ketoglutarate， and choline， etc. The differential metabolites mentioned above were mainly enriched in metabolism of alanine， aspartate and glutamate， metabolism of arginine and proline， γ aminobutyric acid synapses， pyrimidine metabolism， cholinergic synapses pathways， etc. CONCLUSIONS Ketamine can induce cognitive impairment in mice. Its neurotoxicity is related to abnormal synaptic transmission and energy metabolism， and neuroimmune regulation disorders.

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）.