[This corrects the article DOI: 10.11909/j.issn.1671-5411.2017.08.005.].

G protein-coupled receptors (GPCRs) are the largest family of membrane proteins in eukaryotes, with nearly 800 genes coding for these proteins. They are involved in many physiological processes, such as light perception, taste and smell, neurotransmitter, metabolism, endocrine and exocrine, cell growth and migration. Importantly, GPCRs and their ligands are the targets of approximately one third of all marketed drugs. GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane. However, emerging evidence suggests that GPCRs are also localized on mitochondria, where they play critical roles in modulating mitochondrial functions. These mitochondrial GPCRs (mGPCRs) can influence processes such as mitochondrial respiration, apoptosis, and reactive oxygen species (ROS) production. By interacting with mitochondrial signaling pathways, mGPCRs contribute to the regulation of energy metabolism and cell survival. Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling, highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction. This expanding understanding of mGPCR function on mitochondria opens new avenues for research, particularly in the context of diseases where mitochondrial dysfunction plays a key role. Abnormalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease, diabetes, obesity and Alzheimer's disease. In this review, we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases. We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease, and to underscore their potential as therapeutic targets in the treatment of these conditions.

BACKGROUND: China is seeing a growing demand for rehabilitation treatments for post-stroke upper limb spastic paresis (PSSP-UL). Although acupuncture is known to be effective for PSSP-UL, there is room to enhance its efficacy. OBJECTIVE: This study explored a semi-personalized acupuncture approach for PSSP-UL that used three-dimensional kinematic analysis (3DKA) results to select additional acupoints, and investigated the feasibility, efficacy and safety of this approach. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This single-blind, single-center, randomized, controlled trial involved 74 participants who experienced a first-ever ischemic or hemorrhagic stroke with spastic upper limb paresis. The participants were then randomly assigned to the intervention group or the control group in a 1:1 ratio. Both groups received conventional treatments and acupuncture treatment 5 days a week for 4 weeks. The main acupoints in both groups were the same, while participants in the intervention group received additional acupoints selected on the basis of 3DKA results. Follow-up assessments were conducted for 8 weeks after the treatment. MAIN OUTCOME MEASURES: The primary outcome was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) response rate (≥ 6-point change) at week 4. Secondary outcomes included changes in motor function (FMA-UE), Brunnstrom recovery stage (BRS), manual muscle test (MMT), spasticity (Modified Ashworth Scale, MAS), and activities of daily life (Modified Barthel Index, MBI) at week 4 and week 12. RESULTS: Sixty-four participants completed the trial and underwent analyses. Compared with control group, the intervention group exhibited a significantly higher FMA-UE response rate at week 4 (χ² = 5.479, P = 0.019) and greater improvements in FMA-UE at both week 4 and week 12 (both P < 0.001). The intervention group also showed bigger improvements from baseline in the MMT grades for shoulder adduction and elbow flexion at weeks 4 and 12 as well as thumb adduction at week 4 (P = 0.007, P = 0.049, P = 0.019, P = 0.008, P = 0.029, respectively). The intervention group showed a better change in the MBI at both week 4 and week 12 (P = 0.004 and P = 0.010, respectively). Although the intervention group had a higher BRS for the hand at week 12 (P = 0.041), no intergroup differences were observed at week 4 (all P > 0.05). The two groups showed no differences in MAS grades as well as in BRS for the arm at weeks 4 and 12 (all P > 0.05). CONCLUSION: Semi-personalized acupuncture prescription based on 3DKA results significantly improved motor function, muscle strength, and activities of daily living in patients with PSSP-UL. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR2200056216. Please cite this article as: Huang XY, Liao OP, Jiang SY, Tao JM, Li Y, Lu XY, Li YY, Wang C, Li J, Ma XP. Three-dimensional kinematic analysis can improve the efficacy of acupoint selection for post-stroke patients with upper limb spastic paresis: A randomized controlled trial. J Integr Med. 2025; 23(1): 15-24.
Humans ; Male ; Female ; Middle Aged ; Acupuncture Points ; Upper Extremity/physiopathology* ; Biomechanical Phenomena ; Single-Blind Method ; Aged ; Stroke/therapy* ; Acupuncture Therapy/methods* ; Stroke Rehabilitation/methods* ; Adult ; Muscle Spasticity/therapy* ; Paresis/physiopathology* ; Treatment Outcome

Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

Purpose::Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation.Methods::C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. Results::Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol.Conclusions::Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

【Objective】 To explore the diagnosis, treatment, prognosis and long-term follow-up of urogenital solitary fibrous tumor (SFT) and to differentiate the characteristics between benign and malignant SFT. 【Methods】 Clinical data of 20 patients with urogenital SFT treated in our hospital during Jan.2004 and Aug.2021 were respectively analyzed, including the general characteristics, clinical symptoms, imaging results, treatment methods, pathological results, and long-term follow-up results. 【Results】 Of the 20 cases, 9 cases had tumor in kidney, 7 in pelvic cavity, 3 in bladder and 1 in prostate.Six patients showed non-specific clinical symptoms, including lower extremity weakness, urodynia, dysuria, frequent urination with changes in stool habits, low back pain, and abdominal wall mass with abdominal pain, and the other 14 cases were asymptomatic.The median diameter of SFT was 5.2 cm (range:1.7-15.0 cm).All patients received surgical treatment, including robotic-assisted surgery in 8 cases, open surgery in 5 cases, laparoscopic surgery in 5 cases, and transurethral resection of tumor in 2 cases.CT plain scan showed high, low and mixed density soft tissue masses, and enhanced CT showed enhanced results.Pathology results revealed frequent nuclear divisions, morphological variations and necrosis in malignant SFT, which had higher expression of Ki-67 than benign SFT.The results of the modified Demicco prognostic risk stratification model showed that all malignant SFT cases were at intermediate risk. The DFS of the SFT radical tumor resection group was slightly longer than that of the simple tumor resection group but the difference was not statistically significant (P=0.203). 【Conclusion】 Markers such as CD34, Bcl2, STAT6 and CD99 are used to diagnose SFT, while Ki-67 and tumor necrosis are used to differentiate benign and malignant SFT.The modified Demicco prognostic risk stratification model plays an important role in predicting the prognosis of SFT.Surgical resection is the most common treatment with excellent prognosis.In addition, benign SFT has much better prognosis than malignant case.

Aim To explore the effects of sirolimus on the growth and development of motor,vascular,nerv-ous,and immune systems through zebrafish models.Methods After 3 hours of fertilization of zebrafish embryos,different concentrations of sirolimus were add-ed to the growth environment,and the growth and de-velopment of the embryos was recorded.Transgenic ze-brafish models labeled with blood vessels,nerves or im-mune cells were used to compare the drug effects on the growth and development of those systems.Results At the concentration of 0.5 μmol·L-1,the hatching rate and the body length(P＜0.01)were significantly smaller than those of the control group,and movement was also significantly slowed down.Meanwhile,the length of axons of the nervous system,the development of intersegmental vessels,and the growth of immune cells were significantly delayed by drug treatment.But when the concentration was below 0.1 μmol·L-1,there was no statistically difference between the control group and the sirolimus group.Conclusions When the concentration of sirolimus exceeds a certain level,it can significantly slow down the growth and development of movement,blood vessels,nervous system and im-mune system of zebrafish.Therefore,in clinical prac-tice,it is important to monitor the blood concentration of sirolimus in children on time.

Objective:To investigate the biomechanical stabilities of different internal screw fixations for Sanders type ⅡB calcaneal fractures using finite element analysis.Methods:Based on the CT scan data of a male volunteer's calcaneus (26 years old, 173 cm tall, weighing 70 kg), a three-dimensional finite element model of the calcaneus was established using digital medical software such as Mimics 22.0, Geomagic 12.0, Solidworks 2019, and ANSYS Workbench 2022. A three-dimensional finite element model of Sanders type ⅡB calcaneal fracture was also established. The following 3 kinds of screws were used: ① longitudinal screws: from the calcaneal tuberosity to the anterior part; ② transverse screws: from the lateral wall of the calcaneus to the sustentaculum tali; ③ vertical screws: from the base of the calcaneus to the talar dome, perpendicular to the posterior articular surface. The scheme of screw configuration was as follows: the longitudinal screws were divided into the upper, middle, and lower groups based on their entry points from the upper, middle, and lower parts of the calcaneal tuberosity. Based on different configurations (double transverse screws + single vertical screw, single transverse screw + single vertical screw, double transverse screws without a vertical screw, and single transverse screw without a vertical screw) 4 subgroups were further subdivided, resulting in a total of 12 models (a, b, c, d, e, f, g, h, i, j, k, l). Forces of 420 N and 200 N were applied to the posterior and middle subtalar joints, respectively, to simulate the load on the calcaneus during single-leg standing in adults. In each model, total deformation displacement, relative displacement of the sustentaculum tali fracture gap, relative displacement of the anterior fracture gap, relative displacement of the articular surface fracture gap, peak stress at the fracture ends and peak screw stress were analyzed.Results:The total deformation displacement was the lowest in models i and j, while models k and l exhibited the highest deformation displacement. The maximum deformation values in the remaining models varied only slightly. The average relative displacement of the sustentaculum tali fracture gap was the lowest in the upper group (0.27 mm) and relatively higher in the lower group, with the greatest variation seen in models k and l. The average relative displacement of the anterior fracture gap was the smallest in the lower group (0.16 mm), with models i and k performing the best. The relative displacement of the articular surface fracture gap remained at a low level across all models. The upper group had the lowest average peak stress at the fracture ends (60.20 MPa), while the middle and lower groups had similar values (103.88 MPa and 99.76 MPa, respectively). The upper group had the lowest average screw stress peak value (222.77 MPa), whereas models k and l in the lower group had the highest stress peaks, reaching 331.48 MPa and 349.82 MPa, respectively.Conclusions:Model i (inferior longitudinal screw + double transverse screws + single vertical screw) can be recommended in clinic because it demonstrates balanced performance in displacement and stress and a notable advantage in reducing overall deformation displacement and anterior fracture gap displacement. As longitudinal, vertical, and transverse screws each play their distinct role in calcaneal fracture fixation, surgeons should select an appropriate screw configuration based on the patient's needs.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Candida albicans as a pathogen of great clinical significance can widely colonize in many ecological niches of human body, especially in the immunocompromised population. Currently, antifungal drugs that can be used in clinical treatment are very limited. However, the genome of Candida albicans has a high rate of mutation, which can help it quickly develop resistance to antifungal drugs. Therefore, drug resistance in Candida albicans remains a great threat to clinical practice. This article focused on the frequent loss of heterozygosity (LOH) events in Candida albicans, summarized the association between LOH and other genomic variants and discussed the relationship of the frequency of de novo mutations, heterozygous status of key drug resistance genes and reproductive pattern with antifungal drug resistance.