Neuropathic pain （NP） is a chronic pain syndrome resulting from injury， inflammation， or dysfunction of the somatosensory nervous system. Its pathogenesis is complex and intimately associated with peripheral sensitization and maladaptive neuroplasticity within the central nervous system. The core clinical manifestations， including spontaneous pain， allodynia， and paresthesia， severely compromise patients’ quality of life and pose substantial challenges to clinical management. Endoplasmic reticulum stress （ERS）， a critical cellular defense mechanism against disrupted intracellular homeostasis， is primarily initiated and modulated through three canonical branches of the unfolded protein response （UPR）： the protein kinase RNA-like endoplasmic reticulum kinase （PERK） pathway， the inositol-requiring transmembrane kinase/endonuclease 1α （IRE1α） pathway， and the activating transcription factor 6 （ATF6） pathway. These signaling cascades play a pivotal role in the pathological progression of NP. Traditional Chinese medicine （TCM） exhibits unique advantages in the treatment of NP. Leveraging its hallmark characteristics of multi-target， multi-pathway， and holistic regulation， TCM can systematically modulate the ERS signaling network to inhibit neuronal apoptosis， attenuate neuroinflammatory infiltration， and rectify autophagic dysfunction， ultimately promoting the repair and regeneration of damaged neural tissue. This review systematically summarizes the core role of ERS in the occurrence and development of NP. It focuses on the latest research progress regarding ERS pathway modulation in NP amelioration by representative TCM interventions， including potential core bioactive components （e.g.， tanshinoneⅡ_A， catalpol， and formononetin）， classic and empirical compound formulas （e.g.， Huangqi Guizhi Wuwu decoction， Compound Qiying granules， and Tangluoning）， and TCM external therapies （e.g.， electroacupuncture， moxibustion with seed-sized moxa cone， and acupotomy）. Through an in-depth analysis of the functional characteristics and mechanisms of these TCM interventions， particularly their bidirectional regulation and multi-target synergy， this review aims to provide a solid theoretical foundation for further optimizing TCM-based strategies for NP prevention and treatment and to delineate future directions for clinical translation of related research achievements and targeted drug development.

Objective To explore the effect of nuclear respiratory factor 1(NRF1)activation of ATP binding cas-sette transporter C1(ABCC1)transcription on cisplatin resistance in lung adenocarcinoma cells and its potential mechanisms.Methods The expression levels of ABCC1 in lung adenocarcinoma tumor tissues were analyzed by on-cogenomic datasets.Cells were grouped into:sh-NC,sh-ABCC1,sh-NC+oe-NC,sh-NRF1+oe-NC and sh-NRF1+oe-ABCC1.Real-time polymerase chain reaction(RT-qPCR)was used to detect the expression of ABCC1 in lung adenocarcinoma cells.Cisplatin-resistant lung adenocarcinoma cell strains were constructed to detect the expression level of ABCC1.Cell proliferation,migration and invasion were assessed by colony formation and Transwell assay.The IC50 values of drug-resistant lung adenocarcinoma cells treated with different doses(0,0.001,0.002,0.004,0.008,0.016 and 0.032 mg/mL)of cisplatin were detected by CCK-8 assay.Western blot was used to detect the protein expression of epithelial-mesenchymal transition markers(E-cadherin,N-cadherin).Dual luciferase and ChIP assays were performed to verify the binding relationship between NRF1 and ABCC1.Results ABCC1 was highly expressed in lung adenocarcinoma tumor tissues and cells.Compared with cisplatin-sensitive lung adenocarci-noma cells,ABCC1 was highly expressed in cisplatin-resistant lung adenocarcinoma cells,and knockdown of ABCC1 significantly inhibited cell proliferation,migration and invasion,and increased the expression of E-cadherin(P<0.05)and decreased the expression of N-cadherin(P<0.05).Knockdown of ABCC1 significantly increased the sensitivity of lung adenocarcinoma cells to cisplatin(P<0.05).In addition,dual luciferase and ChIP experi-ments confirmed the binding relationship between NRF1 and ABCC1 promoter de-binding,and NRF1 could activate the transcription of ABCC1.Knockdown of NRF1 attenuated the inhibitory effect of over-expressed ABCC1 on the proliferation,migration,invasion and cisplatin-resistance of lung adenocarcinoma cells(P<0.05).Conclusions This study revealed the effect of the NRF1/ABCC1 axis enhancement is a potential strategy to overcome the barrier of cisplatin-resistance in chemotherapy of lung adenocarcinoma.

ObjectiveTo investigate the safety and efficacy of endoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips in the treatment of cirrhotic patients with gastric varices and gastric-renal shunt （GRS）. MethodsThe patients who attended Beijing Ditan Hospital， Capital Medical University， due to liver cirrhosis and gastric varices from February to June 2023 were enrolled， and all patients were confirmed to have GRS and received endoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips. The primary evaluation index was alleviation or disappearance of varicose veins after surgery， and the secondary evaluation indices were surgical completion and complications. ResultsA total of 11 patients were enrolled in this study， among whom there were 7 male patients and 4 female patients， with a median age of 55 years. Of all patients， 1 had Child class A liver function， 7 had Child class B liver function， and 3 had Child class C liver function. The maximum （median） diameter of the shunt was 8 mm， and the minimum （median） diameter of the shunt was 4 mm. The median blood flow velocity of the target vessel was 11 cm/s before treatment and 5 cm/s after occlusion with metal clips. The median amount of tissue adhesive injected was 2 mL， and the amount of lauromacrogol used was 1 mL. Disappearance of blood flow signals was observed in all patients after surgery （100%）， and the success rate of surgery was 100%. No patient experienced rebleeding after follow-up for 6 weeks. Gastroscopy at 1 month after surgery showed that gastric varices were eradicated or almost disappeared in 9 patients and were alleviated in 2 patients. ConclusionEndoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips is a feasible， safe， and effective treatment method for cirrhotic patients with gastric varices and GRS.

The ravages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide have sped up the development of relevant vaccines, which is accompanied by public concerns over possible adverse effects. We report a rare case of a 39-year-old woman who suffered from severe hyperglycemia and ketoacidosis with normal hemoglobin A1c four days after SARS-CoV-2 protein subunit vaccine, which is consistent with the diagnosis of fulminant type 1 diabetes (FT1D). She received insulin therapy and recovered after 24 days from onset of the symptoms. This is the first case of new-onset FT1D after SARS-CoV-2 protein subunit vaccination and one of only six that developed after any form of SARS-CoV-2 vaccination.We hope to raise awareness of this potential adverse consequence and recommend careful monitoring after vaccination in patients even without a medical history of diabetes.

In recent years, a number of policies have been implemented to strengthen the cultivation of general practitioners in China. However, the development of community-level health professionals is still lagging behind, the development is uneven among regions, the overall number of general practitioners is insufficient, and the quality of medical services needs to be improved. Based on the Shanhai (Mountain and Sea) promotion project, with the close cooperation between the Second Affiliated Hospital and the medical consortium unit Suichang County People′s Hospital, a " Joint Cultivation by Dual-Teachers " model has been applied in training general practitioners for Suichang county community since March 2021. In this article we discuss the optimization and integration of medical and health resources through the outreaching assistance of high-quality personnel, management and system of medical service, to comprehensively upgrade the primary care and the quality of grass-roots general practitioners in remote mountainous areas.

RBM46 is a germ cell-specific RNA-binding protein required for gametogenesis, but the targets and molecular functions of RBM46 remain unknown. Here, we demonstrate that RBM46 binds at specific motifs in the 3'UTRs of mRNAs encoding multiple meiotic cohesin subunits and show that RBM46 is required for normal synaptonemal complex formation during meiosis initiation. Using a recently reported, high-resolution technique known as LACE-seq and working with low-input cells, we profiled the targets of RBM46 at single-nucleotide resolution in leptotene and zygotene stage gametes. We found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions. In Rbm46 knockout mice, the RBM46-target cohesin subunits displayed unaltered mRNA levels but had reduced translation, resulting in the failed assembly of axial elements, synapsis disruption, and meiotic arrest. Our study thus provides mechanistic insights into the molecular functions of RBM46 in gametogenesis and illustrates the power of LACE-seq for investigations of RNA-binding protein functions when working with low-abundance input materials.
Animals ; Mice ; 3' Untranslated Regions/genetics* ; Cell Cycle Proteins/metabolism* ; Gametogenesis/genetics* ; Meiosis/genetics* ; Nuclear Proteins/genetics* ; RNA-Binding Proteins/genetics*

Objective:To evaluate and summarize the best evidence for exercise intervention in patients with hypertension, and to provide the basis for clinical medical workers to manage hypertension.Methods:We searched UpToDate, BMJ Best Practice, the Cochrane Library, the International Guideline Collaborative Network to collect guidelines, systematic evaluation, and evidence summary. The retrieval time was from database establishment to June 1st 2022. Two researchers independently conducted literature quality evaluation and extracted evidence from the included literature.Results:A total of 13 articles were included, including 10 guidelines, 1 expert consensus and 2 Meta analysis. A total of 23 pieces of best evidence were collected, mainly involving 8 aspects, including exercise principles, exercise assessment, exercise environment, pre-exercise preparation, exercise program, post-exercise collation, tracking and review, exercise compliance.Conclusions:Exercise has a positive effect on improving blood pressure in patients with hypertension. The suggestions summarized in this study can be tried to guide clinical practice.

Biliary atresia is a rare infant disease that predisposes patients to liver transplantation and death if not treated in time. However, early diagnosis is challenging because the clinical manifestations and laboratory tests of biliary atresia overlap with other cholestatic diseases. Therefore, it is very important to develop a simple, safe and reliable method for the early diagnosis of biliary atresia. Herein, a novel NIR-II fluorescence probe, HZL2, with high quantum yield, excellent biocompatibility, low cytotoxicity and rapid excretion through the liver and gallbladder was developed based on the oil/water partition coefficient and permeability. A simple fecal sample after injection of HZL2 can be used to efficiently identify the success of the mouse model of biliary atresia for the first time, allowing for an early diagnosis of the disease. This study not only developed a simple and safe method for the early diagnosis of biliary atresia with great potential in clinical translation but also provides a research tool for the development of pathogenesis and therapeutic medicines for biliary atresia.

Humans ; Female ; Prevalence ; Breast Neoplasms ; Cancer Survivors ; Non-alcoholic Fatty Liver Disease ; Liver

Objective:To analyze the molecular epidemiological characteristics of the Corona virus disease 2019 (COVID-19) cases in Shijiazhuang, which can reveal the origin of the outbreak and provide a scientific basis for COVID-19 prevention and control.Methods:From January 2 to January 8, 2021, a total of 404 samples from 170 COVID-19 cases were collected from the Shijiazhuang Fifth Hospital. The consensus sequence of 2019 novel Coronavirus(2019-nCoV) was obtained through multiplex polymerase chain reaction-based sequencing. The sequences of 170 COVID-19 cases were analyzed by the PANGOLIN, and the data were statistically analyzed by T-test.Results:Among the 404 COVID-19 samples, a total of 356 samples obtained high quality genome sequences (>95%,100×sequencing depth). The whole genome sequences of 170 COVID-19 cases were obtained by eliminating repeated samples. All 170 sequences were recognized as lineage B1.1 using PANGOLIN. The number of single nucleotide polymorphism arrange from 18-22 and most of the single nucleotide polymorphism were synonymous variants. All of 170 genomes could be classified into 48 sub-groups and most of the genomes were classified into 2 sub-groups (66 and 31, respectively).Conclusions:All cases in this study are likely originated from one imported case. The viruses have spread in the community for a long time and have mutated during the community transmission.