Locomotion, a fundamental motor function encompassing various forms such as swimming, walking, running, and flying, is essential for animal survival and adaptation. The mesencephalic locomotor region (MLR), located at the midbrain-hindbrain junction, is a conserved brain area critical for controlling locomotion. This review highlights recent advances in understanding the MLR’s structure and function across species, from lampreys to mammals and birds, with a particular focus on insights gained from optogenetic studies in mammals. The goal is to uncover universal strategies for MLR-mediated locomotor control. Electrical stimulation of the MLR in species such as lampreys, salamanders, cats, and mice initiates locomotion and modulates speed and patterns. For example, in lampreys, MLR stimulation induces swimming, with increased intensity or frequency enhancing propulsive force. Similarly, in salamanders, graded stimulation transitions locomotor outputs from walking to swimming. Histochemical studies reveal that effective MLR stimulation sites colocalize with cholinergic neurons, suggesting a conserved neurochemical basis for locomotion control. In mammals, the MLR comprises two key nuclei: the cuneiform nucleus (CnF) and the pedunculopontine nucleus (PPN). Both nuclei contain glutamatergic and GABAergic neurons, with the PPN additionally housing cholinergic neurons. Optogenetic studies in mice by selectively activating glutamatergic neurons have demonstrated that the CnF and PPN play distinct roles in motor control: the CnF drives rapid escape behaviors, while the PPN regulates slower, exploratory movements. This functional specialization within the MLR allows animals to adapt their locomotion patterns and speed in response to environmental demands and behavioral objectives. Similar to findings in lampreys, the CnF and PPN in mice transmit motor commands to spinal effector circuits by modulating the activity of brainstem reticular formation neurons. However, they achieve this through distinct reticulospinal pathways, enabling the generation of specific behaviors. Further insights from monosynaptic rabies viral tracing reveal that the CnF and PPN integrate inputs from diverse brain regions to produce context-appropriate behaviors. For instance, glutamatergic neurons in the PPN receive signals from other midbrain structures, the basal ganglia, and medullary nuclei, whereas glutamatergic neurons in the CnF rarely receive inputs from the basal ganglia but instead are strongly influenced by the periaqueductal grey and inferior colliculus within the midbrain. These differential connectivity patterns underscore the specialized roles of the CnF and PPN in motor control, highlighting their unique contributions to coordinating locomotion. Birds exhibit exceptional flight capabilities, yet the avian MLR remains poorly understood. Comparative studies suggest that the pedunculopontine tegmental nucleus (PPTg) in birds is homologous to the mammalian PPN, which contains cholinergic neurons, while the intercollicular nucleus (ICo) or nucleus isthmi pars magnocellularis (ImC) may correspond to the CnF. These findings provide important clues for identifying the avian MLR and elucidating its role in flight control. However, functional validation through targeted experiments is urgently needed to confirm these hypotheses. Optogenetics and other advanced techniques in mice have greatly advanced MLR research, enabling precise manipulation of specific neuronal populations. Future studies should extend these methods to other species, particularly birds, to explore unique locomotor adaptations. Comparative analyses of MLR structure and function across species will deepen our understanding of the conserved and evolved features of motor control, revealing fundamental principles of locomotion regulation throughout evolution. By integrating findings from diverse species, we can uncover how the MLR has been adapted to meet the locomotor demands of different environments, from aquatic to aerial habitats.

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Objective:To explore therapeutic effect of cardiac rehabilitation based on traditional exercise on heart failure(HF).Methods:We searched databases including CNKI,Wanfang,VIP,Pubmed and Cochrane library for literature about application of cardiac rehabilitation exercise based on traditional exercises in HF patients before Mar 2023.Literature were screened according to inclusion and exclusion criteria,while article quality assessment and da-ta extraction were performed,and RevMan 5.3 software was used to perform Meta analysis.Results:Meta analysis indicated that compared with control group,there were significant increase in LVEF[MD=4.51,95％CI(1.70,7.33),P=0.002]and 6 min walking distance[6MWD,MD=51.90,95％CI(39.24,64.57),P=0.001],and sig-nificant reductions in left ventricular end-systolic diameter[MD=-1.64,95％CI(-3.18,-0.11),P=0.040],left ventricular end-diastolic diameter[MD=-2.49,95％C1(-3.28,-1.69),P=0.001],score of Minnesota living with heart failure questionnaire[MD=-6.89,95％CI(-8.64,-5.33),P=0.001]and level of N-ter-minal pro-brain natriuretic peptide[MD=-151.46,95％CI(-208.21,-94.70),P=0.001]in observation group.Conclusion:Cardiac rehabilitation based on traditional exercise can significantly improve heart function,in-crease 6 min walking distance and improve quality of life in patients with heart failure.

Objective : To analyze the difference of urinary iodine level in Hashimoto thyroiditis ( HT) patients， and to explore the possible relationship between urinary iodine level and HT under different iodine nutritional sta- tus，so as to provide some references for reasonable iodine intake in HT patients． Methods : A total of 101 hospi- talized HT patients were selected as HT group and divided into 3 groups according to thyroid function : HT group with hyperthyroidism (41 cases) ．There were 25 cases in HT group with normal thyroid function．There were 35 cases in HT combined with hypothyroidism group．In addition，30 healthy subjects were selected as control group. Serum levels of thyroid stimulating hormone(TSH) ，triiodothyronine(T3 ) ，thyroxine (T4 ) ，thyroid peroxidase an- tibody (TPOAb) and thyroglobulin antibody (ATG) were detected by chemiluminescence assay．The size and mor- phological structure of thyroid organs were examined by ultrasonography．Urinary iodine was determined by catalytic spectrophotometry with arsenic and cerium．The nutritional status of iodine was classified into iodine deficiency ( < 100 μg/ L) ，iodine adequacy( 100 －199 μg/ L) ，iodine adequacy (200 －299 μg/ L) and iodine excess ( ≥ 300 μg/ L) ．Non-parametric test was used to compare urinary iodine level between HT group and control group，one- way ANOVA and t test were used to compare urinary iodine level between HT group and control group ，and Spearman correlation analysis was used to compare the correlation between urinary iodine level and T3 ，T4 ，TSH， ATG and TPOAb under different iodine nutrition status. Results : Compared with control group，ATG and TPOAb levels in HT group increased (P＜0. 001) ，and urinary iodine levels increased (P＜0. 05) ，with statistical signifi- cance．Compared with the control group in different thyroid function states，only the HT group with hypothyroidism increased the urinary iodine level (P＜0. 01) ，and the difference was statistically significant．Spearman correlation analysis showed that urine iodine level was positively correlated with ATG and TPOAb levels in iodine excess condi- tion (P＜0. 05) ，and urine iodine level was positively correlated with TSH level in iodine sufficient condition and iodine excess condition in HT patients (P＜0. 05) ． Conclusion The urinary iodine level of HT patients was high- er than that of normal people．When the urinary iodine level of residents is ≥ 300 μg/ L，iodine intake is prone to HT．When the urinary iodine level of HT patients is ≥ 200 μg/ L，iodine consumption is prone to hypothyroidism， and iodine intake should be limited.

Objective To explore the effect of emodin on inflammatory response in preeclampsia(PE)rats by regulating the AMP activated protein kinase(AMPK)/thioredoxin-interacting protein(TXNIP)/NOD-like receptor pyrin domain-containing protein 3(NLRP3)signaling pathway.Methods PE rat model was established by subcutaneous injection of L-arginine methyl ester(100 mg·kg-1).Sixty female rats were randomly divided into control group,model group,emodin group(40 mg·kg-1 emodin),Compound B10 group(100 mg·kg-1 Compound B10),emodin+Compound B10 group(40 mg·kg-1 emodin+100 mg·kg-1 Compound B10),with 12 rats in each group.The control group and the model group were intraperitoneally injected with the same amount of 0.9％NaCl.The 24 h urine was collected,and the total urinary protein content was determined by Coomassie brilliant blue method.The protein levels of AMPK/TXNIP/NLRP3 signaling pathway were detected by Western blot.Results The total urinary protein levels of control group,model group,emodin group,Compound B10 group and emodin+Compound B10 group were(54.34±6.26),(136.37±15.43),(76.38±8.61),(215.39±25.14)and(110.93±13.92)g·L-1,respectively;urine volume were(10.59±0.92),(15.38±1.49),(11.51±1.13),(21.49±2.50)and(14.71±1.49)mL,respectively;AMPK protein levels were 0.63±0.06,1.57±0.18,0.81±0.09,2.34±0.23 and 1.38±0.15,respectively;TXNIP protein levels were 0.33±0.04,0.79±0.08,0.49±0.10,1.13±0.12 and 0.82±0.09,respectively;NLRP3 protein levels were 0.46±0.05,0.83±0.09,0.56±0.07,1.25±0.14 and 0.78±0.08,respectively.The above indexes:Model group was compared with control group,emodin group and Compound B10 group,emodin+Compound B10 group was compared with emodin group,the differences were statistically significant(all P＜0.05).Conclusion Emodin may alleviate inflammatory reaction in PE rats by inhibiting AMPK/TXNIP/NLRP3 signal axis,thereby improving placental injury.

Objective To evaluate the pharmacokinetics and safety of dapoxetine hydrochloride tablets in healthy Chinese subjects,and to assess the impact of food on dapoxetine pharmacokinetics.Methods A single-center,open-lable,two-period,randomized parallel study was conducted.A total of 22 healthy adult male subjects were enrolled and administered a single 30 mg oral dose of dapoxetine hydrochloride tablets,both under fasting and fed condition.Venous blood samples were collected at different time points,and dapoxetine concentrations in human plasma were measured using liquid chromatography tandem mass spectrometry(LC-MS/MS).Pharmacokinetic parameters were calculated using Phoenix WinNonlin 6.3 software,and statistical analysis was conducted with SPSS 19.0 software.Results The main pharmacokinetic parameters after oral administration of dapoxetine hydrochloride tablets in fasting and fed were as follows:Cmax were(230.71±88.91)and(216.27±58.32)ng·mL-1;AUC0-t were(1 054.99±442.11)and(1 292.56±534.49)ng·h·mL-1;AUC0-∞ were(1 175.03±510.58)and(1 447.42±656.25)ng·h·mL-1;tmax were(1.23±0.59)and(2.40±0.90)h;t1/2 were(15.95±6.13)and(16.21±6.34)h.Comparisons between the fasting and fed states,showed statistically significant differences in AUC0-t,AUC0-∞ and tmax(all P＜0.05),but not in Cmax and t1/2(all P＞0.05).The incidence of adverse events was 31.82％in the fasting state and 22.73％in the fed state,with no significant difference(P＞0.05).Conclusion Dapoxetine hydrochloride tablets were rapidly absorbed and eliminated in both fasting and fed states,with good safety;food slowed the absorption rate of dapoxetine and increaseed its overall exposure.

Hepatocellular carcinoma （HCC） is a common tumor in the digestive tract， the formation mechanism of which remains to be fully elucidated. Although surgery， radiation， chemotherapy， targeted therapy， and immunotherapy have achieved significant results in the treatment of HCC， these methods are accompanied by a considerable number of adverse reactions and complications. In recent years， Chinese medicine has shown remarkable efficacy in the treatment of HCC， and both basic experiments and clinical studies have confirmed the effectiveness of Chinese medicine， which exerts therapeutic effects via multiple components and multiple targets. However， the pathogenesis of HCC is exceptionally complex and not fully understood， which means that studies remain to be carried out regarding the specific mechanism of Chinese medicine in preventing and treating HCC. Network pharmacology and molecular biology can be employed to decipher the mechanism of Chinese medicine in the treatment of diseases. Studies have shown that Chinese medicine can regulate various pathways such as the mitogen-activated protein kinase （MAPK）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Hedgehog， Wnt/β-catenin， nuclear factor-κB （NF-κB）， Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3）， and transforming growth factor-β （TGF-β）/Smad signaling pathways. Chinese medicine can exhibit its anti-HCC effects by inducing cell apoptosis， inhibiting cell proliferation and migration， and blocking the cell cycle via the above pathways. However， the specific mechanisms remain to be systematically studied. This study comprehensively reviews the regulatory effects of Chinese medicine on HCC-related signaling pathways to reveal the molecular mechanisms of Chinese medicine in the treatment of HCC. This view holds the promise of providing new targets， new perspectives， and new therapies for HCC treatment and advancing the modernization and development of Chinese medicine.

Objective To investigate the amplitude-integrated electroencephalography(aEEG)monitoring results of hospitalized neonates in plateau areas.Methods A retrospective analysis was conducted on 5 945 neonates who were admitted to the Department of Neonatology,Kunming Children's Hospital,and received aEEG monitoring from January 2020 to December 2022.According to the aEEG monitoring results,they were divided into a normal aEEG group and an abnormal aEEG group.The incidence rate of aEEG abnormalities was analyzed in neonates with various systemic diseases,as well as the manifestations of aEEG abnormalities and the consistency between aEEG abnormalities and clinical abnormalities.Results Among the 5 945 neonates,the aEEG abnormality rate was 19.28%(1 146/5 945),with an abnormality rate of 29.58%(906/3 063)in critically ill neonates and 8.33%(240/2 882)in non-critically ill neonates(P<0.05).The children with inherited metabolic diseases showed the highest aEEG abnormality rate of 60.77%(79/130),followed by those with central nervous system disorders[42.22%(76/180)]and preterm infants[35.53%(108/304)].Compared with the normal aEEG group,the abnormal aEEG group had significantly lower age and gestational age,as well as a significantly lower birth weight of preterm infants(P<0.05).Among the 1 146 neonates with aEEG abnormalities,the main types of aEEG abnormalities were sleep cycle disorders in 597 neonates(52.09%),background activity abnormalities in 294 neonates(25.65%),and epileptiform activity in 255 neonates(22.25%),and there were 902 neonates(78.71%)with abnormal clinical manifestations.The sensitivity and specificity of aEEG monitoring for brain function abnormalities were 33.51%and 92.50%,respectively.Conclusions In plateau areas,there is a relatively high rate of aEEG abnormalities among hospitalized neonates,particularly in critically ill neonates and those with smaller gestational ages and younger ages,suggesting a high risk of brain injury.Therefore,routine aEEG monitoring for the hospitalized neonates can help with the early detection of brain function abnormalities,the decision-making in treatment,and the formulation of brain protection strategies.

A 5-year-old girl was admitted due to one episode of melena and one episode of hematemesis.Upon admission,gastroscopy revealed esophageal and gastric varices.Abdominal CT scan,MRI,and color Doppler ultrasound suggested cirrhosis,intrahepatic bile duct dilation,and bilateral kidney enlargement.Genetic testing identified compound heterozygous mutations in the PKHD1 gene:c.2264C>T(p.Pro755Leu)and c.1886T>C(p.Val629Ala).The c.2264C>T(p.Pro755Leu)mutation is a known pathogenic variant with previous reports,while c.1886T>C(p.Val629Ala)is a novel mutation predicted to have pathogenic potential according to Mutation Taster and PolyPhen2.The child was diagnosed with autosomal recessive polycystic kidney disease.In children presenting with gastrointestinal bleeding without obvious causes,particularly those with liver or kidney disease,consideration should be given to the possibility of autosomal recessive polycystic kidney disease,and genetic testing should be conducted for definitive diagnosis when necessary.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.