Expression profiling and function analysis identified new genes regulating cumulus expansion and apoptosis.

Studies on the mechanisms behind cumulus expansion and cumulus cell (CC) apoptosis are essential for understanding the mechanisms for oocyte maturation. Genes expressed in CCs might be used as markers for competent oocytes and/or embryos. In this study, both in vitro (IVT) and in vivo (IVO) mouse oocyte models with significant difference in cumulus expansion and CC apoptosis were used to identify and validate new genes regulating cumulus expansion and CC apoptosis of mouse oocytes. We first performed mRNA sequencing and bioinformatic analysis using the IVT oocyte model to identify candidate genes. We then analyzed functions of the candidate genes by RNAi or gene overexpression to select the candidate cumulus expansion and CC apoptosis-regulating genes. Finally, we validated the cumulus expansion and CC apoptosis-regulating genes using the IVO oocyte model. The results showed that while Spp1, Sdc1, Ldlr, Ezr and Mmp2 promoted, Bmp2, Angpt2, Edn1, Itgb8, Cxcl10 and Agt inhibited cumulus expansion. Furthermore, Spp1, Sdc1 and Ldlr inhibited CC apoptosis. In conclusion, by using both IVT and IVO oocyte models, we have identified and validated a new group of cumulus expansion and/or apoptosis-regulating genes, which may be used for selection of quality oocytes/embryos and for elucidating the molecular mechanisms behind oocyte maturation.

Role and action mechanisms of tPA in CRH-induced apoptosis of mouse oviductal epithelial and mural granulosa cells.

Understanding how stress hormones induce apoptosis in oviductal epithelial cells (OECs) and mural granulosa cells (MGCs) can reveal the mechanisms by which female stress impairs embryonic development and oocyte competence. A recent study showed that tissue plasminogen activator (tPA) ameliorates corticosterone-induced apoptosis in MGCs and OECs by acting on its receptors low-density lipoprotein receptor-related protein 1 (LRP1) and Annexin A2 (ANXA2), respectively. However, whether tPA is involved in corticotropin-releasing hormone (CRH)-induced apoptosis and whether it uses the same or different receptors to inhibit apoptosis induced by different hormones in the same cell type remains unknown. This study showed that CRH triggered apoptosis in both OECs and MGCs and significantly downregulated tPA expression. Moreover, tPA inhibits CRH-induced apoptosis by acting on ANXA2 in both OECs and MGCs. While ANXA2 inhibits apoptosis via phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling, LRP1 reduces apoptosis via mitogen-activated protein kinase (MAPK) signaling. Thus, tPA used the same receptor to inhibit CRH-induced apoptosis in both OECs and MGCs, however used different receptors to inhibit corticosterone-induced apoptosis in MGCs and OECs. These data helps understand the mechanism by which female stress impairs embryo/oocyte competence and proapoptotic factors trigger apoptosis in different cell types.

Channel-Blind Joint Source-Channel Coding for Wireless Image Transmission.

Joint source-channel coding (JSCC) based on deep learning has shown significant advancements in image transmission tasks. However, previous channel-adaptive JSCC methods often rely on the signal-to-noise ratio (SNR) of the current channel for encoding, which overlooks the neural network's self-adaptive capability across varying SNRs. This paper investigates the self-adaptive capability of deep learning-based JSCC models to dynamically changing channels and introduces a novel method named Channel-Blind JSCC (CBJSCC). CBJSCC leverages the intrinsic learning capability of neural networks to self-adapt to dynamic channels and diverse SNRs without relying on external SNR information. This approach is advantageous, as it is not affected by channel estimation errors and can be applied to one-to-many wireless communication scenarios. To enhance the performance of JSCC tasks, the CBJSCC model employs a specially designed encoder-decoder. Experimental results show that CBJSCC outperforms existing channel-adaptive JSCC methods that depend on SNR estimation and feedback, both in additive white Gaussian noise environments and under slow Rayleigh fading channel conditions. Through a comprehensive analysis of the model's performance, we further validate the robustness and adaptability of this strategy across different application scenarios, with the experimental results providing strong evidence to support this claim.

Postovulatory Aging of Mouse Oocytes Impairs Offspring Behavior by Causing Oxidative Stress and Damaging Mitochondria.

Information on long-term effects of postovulatory oocyte aging (POA) on offspring is limited. Whether POA affects offspring by causing oxidative stress (OS) and mitochondrial damage is unknown. Here, in vivo-aged (IVA) mouse oocytes were collected 9 h after ovulation, while in vitro-aged (ITA) oocytes were obtained by culturing freshly ovulated oocytes for 9 h in media with low, moderate, or high antioxidant potential. Oocytes were fertilized in vitro and blastocysts transferred to produce F1 offspring. F1 mice were mated with naturally bred mice to generate F2 offspring. Both IVA and the ITA groups in low antioxidant medium showed significantly increased anxiety-like behavior and impaired spatial and fear learning/memory and hippocampal expression of anxiolytic and learning/memory-beneficial genes in both male and female F1 offspring. Furthermore, the aging in both groups increased OS and impaired mitochondrial function in oocytes, blastocysts, and hippocampus of F1 offspring; however, it did not affect the behavior of F2 offspring. It is concluded that POA caused OS and damaged mitochondria in aged oocytes, leading to defects in anxiety-like behavior and learning/memory of F1 offspring. Thus, POA is a crucial factor that causes psychological problems in offspring, and antioxidant measures may be taken to ameliorate the detrimental effects of POA on offspring.

Distances from ligands as main predictive features for pathogenicity and functional effect of variants in NMDA receptors.

Genetic variants in genes GRIN1 , GRIN2A , GRIN2B , and GRIN2D , which encode subunits of the N-methyl-D-aspartate receptor (NMDAR), have been associated with severe and heterogeneous neurologic diseases. Missense variants in these genes can result in gain or loss of the NMDAR function, requiring opposite therapeutic treatments. Computational methods that predict pathogenicity and molecular functional effects are therefore crucial for accurate diagnosis and therapeutic applications. We assembled missense variants: 201 from patients, 631 from general population, and 159 characterized by electrophysiological readouts showing whether they can enhance or reduce the receptor function. This includes new functional data from 47 variants reported here, for the first time. We found that pathogenic/benign variants and variants that increase/decrease the channel function were distributed unevenly on the protein structure, with spatial proximity to ligands bound to the agonist and antagonist binding sites being key predictive features. Leveraging distances from ligands, we developed two independent machine learning-based predictors for NMDAR missense variants: a pathogenicity predictor which outperforms currently available predictors (AUC=0.945, MCC=0.726), and the first binary predictor of molecular function (increase or decrease) (AUC=0.809, MCC=0.523). Using these, we reclassified variants of uncertain significance in the ClinVar database and refined a previous genome-informed epidemiological model to estimate the birth incidence of molecular mechanism-defined GRIN disorders. Our findings demonstrate that distance from ligands is an important feature in NMDARs that can enhance variant pathogenicity prediction and enable functional prediction. Further studies with larger numbers of phenotypically and functionally characterized variants will enhance the potential clinical utility of this method.

De novo GRIN variants in M3 helix associated with neurological disorders control channel gating of NMDA receptor.

N-methyl-D-aspartate receptors (NMDARs) are members of the glutamate receptor family and participate in excitatory postsynaptic transmission throughout the central nervous system. Genetic variants in GRIN genes encoding NMDAR subunits are associated with a spectrum of neurological disorders. The M3 transmembrane helices of the NMDAR couple directly to the agonist-binding domains and form a helical bundle crossing in the closed receptors that occludes the pore. The M3 functions as a transduction element whose conformational change couples ligand binding to opening of an ion conducting pore. In this study, we report the functional consequences of 48 de novo missense variants in GRIN1, GRIN2A, and GRIN2B that alter residues in the M3 transmembrane helix. These de novo variants were identified in children with neurological and neuropsychiatric disorders including epilepsy, developmental delay, intellectual disability, hypotonia and attention deficit hyperactivity disorder. All 48 variants in M3 for which comprehensive testing was completed produce a gain-of-function (28/48) compared to loss-of-function (9/48); 11 variants had an indeterminant phenotype. This supports the idea that a key structural feature of the M3 gate exists to stabilize the closed state so that agonist binding can drive channel opening. Given that most M3 variants enhance channel gating, we assessed the potency of FDA-approved NMDAR channel blockers on these variant receptors. These data provide new insight into the structure-function relationship of the NMDAR gate, and suggest that variants within the M3 transmembrane helix produce a gain-of-function.

Preclinical Evaluation of Azabenzimidazole-Based PET Radioligands for γ-8 Dependent Transmembrane AMPA Receptor Regulatory Protein Imaging.

AMPA glutamate receptors (AMPARs) play a pivotal role in excitatory neurotransmission, particularly in the hippocampus where the TARP γ-8 subunit is enriched and serves as a target for emerging anti-epileptic drugs. To enable in vivo visualization of TARP γ-8 distribution and expression by positron emission tomography (PET), this study focuses on the development of novel 18 F-labeled TARP γ-8 inhibitors and their corresponding precursors, stemming from the azabenzimidazole scaffold. The resulting radioligands [18 F]TARP-2204 and [18 F]TARP-2205 were successfully synthesized with acceptable radiochemical yield, high molar activity, and excellent radiochemical purity. In vitro autoradiography demonstrates high level of specific binding of [18 F]TARP-2205 to TARP γ-8 in both rat and nonhuman primate brain tissues. However, unexpected radiodefluorination in PET imaging studies of rodents emphasizes the need for further structural refinement. This work serves as an excellent starting point for the development of future 18 F-labeled TARP γ-8 PET tracers, offering valuable insights into medicinal chemistry design, radiosynthesis and subsequent PET evaluation.

Interface Charge Distribution Engineering of Pd-CeO2 /C for Efficient Carbohydrazide Oxidation Reaction.

Carbohydrazide electrooxidation reaction (COR) is a potential alternative to oxygen evolution reaction in water splitting process. However, the sluggish kinetics process impels to develop efficient catalysts with the aim of the widespread use of such catalytic system. Since COR concerns the adsorption/desorption of reactive species on catalysts, the electronic structure of electrocatalyst can affect the catalytic activity. Interface charge distribution engineering can be considered to be an efficient strategy for improving catalytic performance, which facilitates the cleavage of chemical bond. Herein, highly dispersed Pd nanoparticles on CeO2 /C catalyst are prepared and the COR catalytic performance is investigated. The self-driven charge transfer between Pd and CeO2 can form the local nucleophilic and electrophilic region, promoting to the adsorption of electron-withdrawing and electron-donating group in carbohydrazide molecule, which facilitates the cleavage of C-N bond and the carbohydrazide oxidation. Due to the local charge distribution, the Pd-CeO2 /C exhibits superior COR catalytic activity with a potential of 0.27 V to attain 10 mA cm-2 . When this catalyst is used for energy-efficient electrolytic hydrogen production, the carbohydrazide electrolysis configuration exhibits a low cell voltage (0.6 V at 10 mA cm-2 ). This interface charge distribution engineering can provide a novel strategy for improving COR catalytic activity.

Clinical features, functional consequences, and rescue pharmacology of missense GRID1 and GRID2 human variants.

GRID1 and GRID2 encode the enigmatic GluD1 and GluD2 proteins, which form tetrameric receptors that play important roles in synapse organization and development of the central nervous system. Variation in these genes has been implicated in neurodevelopmental phenotypes. We evaluated GRID1 and GRID2 human variants from the literature, ClinVar, and clinical laboratories and found that many of these variants reside in intolerant domains, including the amino terminal domain of both GRID1 and GRID2. Other conserved regions, such as the M3 transmembrane domain, show different intolerance between GRID1 and GRID2. We introduced these variants into GluD1 and GluD2 cDNA and performed electrophysiological and biochemical assays to investigate the mechanisms of dysfunction of GRID1/2 variants. One variant in the GRID1 distal amino terminal domain resides at a position predicted to interact with Cbln2/Cbln4, and the variant disrupts complex formation between GluD1 and Cbln2, which could perturb its role in synapse organization. We also discovered that, like the lurcher mutation (GluD2-A654T), other rare variants in the GRID2 M3 domain create constitutively active receptors that share similar pathogenic phenotypes. We also found that the SCHEMA schizophrenia M3 variant GluD1-A650T produced constitutively active receptors. We tested a variety of compounds for their ability to inhibit constitutive currents of GluD receptor variants and found that pentamidine potently inhibited GluD2-T649A constitutive channels (IC50 50 nM). These results identify regions of intolerance to variation in the GRID genes, illustrate the functional consequences of GRID1 and GRID2 variants, and suggest how these receptors function normally and in disease.

Therapeutic potential of N-methyl-D-aspartate receptor modulators in psychiatry.

N-methyl-D-aspartate (NMDA) receptors mediate a slow component of excitatory synaptic transmission, are widely distributed throughout the central nervous system, and regulate synaptic plasticity. NMDA receptor modulators have long been considered as potential treatments for psychiatric disorders including depression and schizophrenia, neurodevelopmental disorders such as Rett Syndrome, and neurodegenerative conditions such as Alzheimer's disease. New interest in NMDA receptors as therapeutic targets has been spurred by the findings that certain inhibitors of NMDA receptors produce surprisingly rapid and robust antidepressant activity by a novel mechanism, the induction of changes in the brain that well outlast the presence of drug in the body. These findings are driving research into an entirely new paradigm for using NMDA receptor antagonists in a host of related conditions. At the same time positive allosteric modulators of NMDA receptors are being pursued for enhancing synaptic function in diseases that feature NMDA receptor hypofunction. While there is great promise, developing the therapeutic potential of NMDA receptor modulators must also navigate the potential significant risks posed by the use of such agents. We review here the emerging pharmacology of agents that target different NMDA receptor subtypes, offering new avenues for capturing the therapeutic potential of targeting this important receptor class.

Clinical and functional consequences of GRIA variants in patients with neurological diseases.

AMPA receptors are members of the glutamate receptor family and mediate a fast component of excitatory synaptic transmission at virtually all central synapses. Thus, their functional characteristics are a critical determinant of brain function. We evaluate intolerance of each GRIA gene to genetic variation using 3DMTR and report here the functional consequences of 52 missense variants in GRIA1-4 identified in patients with various neurological disorders. These variants produce changes in agonist EC50, response time course, desensitization, and/or receptor surface expression. We predict that these functional and localization changes will have important consequences for circuit function, and therefore likely contribute to the patients' clinical phenotype. We evaluated the sensitivity of variant receptors to AMPAR-selective modulators including FDA-approved drugs to explore potential targeted therapeutic options.

Lumbar Spinal Stenosis and Minimally Invasive Lumbar Decompression: A Narrative Review.

Background: Lumbar spinal stenosis (LSS) is a common pain condition that causes lumbar back pain, radiating leg pain, and possible functional impairment. MILD is an emerging minimally invasive treatment for LSS. It is an image-guided percutaneous procedure designed to debulk hypertrophied ligamentum flavum. However, the exact short- and long-term efficacy, safety profile, indication criteria, and certain procedure details reported in medical literature vary. Objective: This narrative review was to elucidate efficacy, safety profile, certain procedure details, advantages, and limitations of MILD. Study Design: This is a narrative review. Setting: All included articles are clinic trials including analytic studies and descriptive studies. Methods: PubMed, Cochrane Library, and Scopus were searched. Only clinical trials of MILD procedure were included. Information of indications, contraindications, VAS scores, ODI scores, effective rate, efficacy durations, and certain procedure details was focused on. Results: According to the literature, for the MILD procedure, the VAS score could be reduced from a pre-treatment level of 6.3-9.6 to a post-treatment level of 2.3-5.8. The ODI score could be reduced from a pre-treatment level of 38.8-55.3 to a post-treatment level of 27.4-39.8. The effective rate of the MILD procedure was reported to be 57.1%-88%. A 2-year postoperative stability of efficacy was also supported. One RCT study testified superior efficacy of MILD over epidural steroid injection. Limitations: There is few high-quality literature in the review. Moreover, the long-term efficacy of MILD cannot be revealed according to the current literature. Conclusion: Based on the reviewed literature, MILD is an effective and safe procedure. MILD can reduce pain intensity and improve functional status significantly. Therefore, it is a preferable option for LSS patients who failed conservative treatments, but not for those who require immediate invasive decompression surgery.

How does adoption of electric vehicles reduce carbon emissions? Evidence from China.

We investigate the effect of the adoption of electric vehicles (EVs) on CO2 emissions using spatial econometric models and have three findings. First, there are spatial spillover effects of EV adoption on CO2 emissions, implying that the CO2 mitigation of a city depends on local sales of EVs and sales of EVs in neighboring cities. A 1% increase in the sale of EVs in a city can reduce CO2 emissions locally by 0.096% and by 0.087% in a nearby city. Second, EVs indirectly impact CO2 emissions through the substitution effect, energy consumption effect, and technological effect. The overall impact of EV adoption on CO2 emissions is negative. Finally, we demonstrate the moderating effect of urban energy structure on EVs' CO2 emissions mitigation. A 1% increase in the proportion of renewable energy generation increases the decarbonization of EVs by 0.036%. These findings provide policy implications for the coordinated development of EV market and energy system.

Loss of Grin2a causes a transient delay in the electrophysiological maturation of hippocampal parvalbumin interneurons.

N-methyl-D-aspartate receptors (NMDARs) are ligand-gated ionotropic glutamate receptors that mediate a calcium-permeable component to fast excitatory neurotransmission. NMDARs are heterotetrameric assemblies of two obligate GluN1 subunits (GRIN1) and two GluN2 subunits (GRIN2A-GRIN2D). Sequencing data shows that 43% (297/679) of all currently known NMDAR disease-associated genetic variants are within the GRIN2A gene, which encodes the GluN2A subunit. Here, we show that unlike missense GRIN2A variants, individuals affected with disease-associated null GRIN2A variants demonstrate a transient period of seizure susceptibility that begins during infancy and diminishes near adolescence. We show increased circuit excitability and CA1 pyramidal cell output in juvenile mice of both Grin2a+/- and Grin2a-/- mice. These alterations in somatic spiking are not due to global upregulation of most Grin genes (including Grin2b). Deeper evaluation of the developing CA1 circuit led us to uncover age- and Grin2a gene dosing-dependent transient delays in the electrophysiological maturation programs of parvalbumin (PV) interneurons. We report that Grin2a+/+ mice reach PV cell electrophysiological maturation between the neonatal and juvenile neurodevelopmental timepoints, with Grin2a+/- mice not reaching PV cell electrophysiological maturation until preadolescence, and Grin2a-/- mice not reaching PV cell electrophysiological maturation until adulthood. Overall, these data may represent a molecular mechanism describing the transient nature of seizure susceptibility in disease-associated null GRIN2A patients.

Compulsory schooling system and equity in education: An analysis on intergenerational transmission of education.

This paper uses the China Family Panel Studies' micro-level data and the ordered logit model to study intergenerational transmission of education and examines whether the nine-year compulsory schooling system affects equity in education. The results show that when parents have higher educational attainments, their children will have higher educational attainments. Full-sample results show that when the mother has higher education, the probability that her children have higher education increases by 7.97%, whereas for the sub-sample after the compulsory schooling policy carried out, the probability increases by 22.42%. We find that the compulsory schooling system strengthens intergenerational transmission of education in the level of higher education. An implication is that the compulsory schooling system may promote equity in compulsory education but does not promote equity in higher education.

Differential responses of disease-related GRIN variants located in pore-forming M2 domain of N-methyl-D-aspartate receptor to FDA-approved inhibitors.

N-methyl-D-aspartate receptors (NMDAR), ionotropic glutamate receptors, mediate a slow component of excitatory synaptic transmission in the central nervous system and play a key role in normal brain function and development. Genetic variations in GRIN genes encoding NMDAR subunits that alter the receptor's functional characteristics are associated with a wide range of neurological and neuropsychiatric conditions. Pathological GRIN variants located in the M2 re-entrant loop lining the channel pore cause significant functional changes, the most consequential alteration being a reduction in voltage-dependent Mg2+ inhibition. Voltage-dependent Mg2+ block is a unique feature of NMDAR biology whereby channel activation requires both ligand binding and postsynaptic membrane depolarization. Thus, loss of NMDAR Mg2+ block will have a profound impact on synaptic function and plasticity. Here, we choose 11 missense variants within the GRIN1, GRIN2A, and GRIN2B genes that alter residues located in the M2 loop and significantly reduce Mg2+ inhibition. Each variant was evaluated for tolerance to genetic variation using the 3-dimensional structure and assessed for functional rescue pharmacology via electrophysiological recordings. Three FDA-approved NMDAR drugs-memantine, dextromethorphan, and ketamine-were chosen based on their ability to bind near the M2 re-entrant loop, potentially rectifying dysregulated NMDAR function by supplementing the reduced voltage-dependent Mg2+ block. These results provide insight of structural determinants of FDA-approved NMDAR drugs at their binding sites in the channel pore and may further define conditions necessary for the use of such agents as potential rescue pharmacology.

Development of a Dihydroquinoline-Pyrazoline GluN2C/2D-Selective Negative Allosteric Modulator of the N-Methyl-d-aspartate Receptor.

Subunit-selective inhibition of N-methyl-d-aspartate receptors (NMDARs) is a promising therapeutic strategy for several neurological disorders, including epilepsy, Alzheimer's and Parkinson's disease, depression, and acute brain injury. We previously described the dihydroquinoline-pyrazoline (DQP) analogue 2a (DQP-26) as a potent NMDAR negative allosteric modulator with selectivity for GluN2C/D over GluN2A/B. However, moderate (<100-fold) subunit selectivity, inadequate cell-membrane permeability, and poor brain penetration complicated the use of 2a as an in vivo probe. In an effort to improve selectivity and the pharmacokinetic profile of the series, we performed additional structure-activity relationship studies of the succinate side chain and investigated the use of prodrugs to mask the pendant carboxylic acid. These efforts led to discovery of the analogue (S)-(-)-2i, also referred to as (S)-(-)-DQP-997-74, which exhibits >100- and >300-fold selectivity for GluN2C- and GluN2D-containing NMDARs (IC50 0.069 and 0.035 µM, respectively) compared to GluN2A- and GluN2B-containing receptors (IC50 5.2 and 16 µM, respectively) and has no effects on AMPA, kainate, or GluN1/GluN3 receptors. Compound (S)-(-)-2i is 5-fold more potent than (S)-2a. In addition, compound 2i shows a time-dependent enhancement of inhibitory actions at GluN2C- and GluN2D-containing NMDARs in the presence of the agonist glutamate, which could attenuate hypersynchronous activity driven by high-frequency excitatory synaptic transmission. Consistent with this finding, compound 2i significantly reduced the number of epileptic events in a murine model of tuberous sclerosis complex (TSC)-induced epilepsy that is associated with upregulation of the GluN2C subunit. Thus, 2i represents a robust tool for the GluN2C/D target validation. Esterification of the succinate carboxylate improved brain penetration, suggesting a strategy for therapeutic development of this series for NMDAR-associated neurological conditions.

De novo CLPTM1 variants with reduced GABAA R current response in patients with epilepsy.

OBJECTIVE: To investigate the clinical features and potential pathogenesis mechanism of de novo CLPTM1 variants associated with epilepsy. METHODS: Identify de novo genetic variants associated with epilepsy by reanalyzing trio-based whole-exome sequencing data. We analyzed the clinical characteristics of patients with these variants and performed functional in vitro studies in cells expressing mutant complementary DNA for these variants using whole-cell voltage-clamp current recordings and outside-out patch-clamp recordings from transiently transfected human embryonic kidney (HEK) cells. RESULTS: Two de novo missense variants related to epilepsy were identified in the CLPTM1 gene. Functional studies indicated that CLPTM1-p.R454H and CLPTM1-p.R568Q variants reduced the γ-aminobutyric acid A receptor (GABAA R) current response amplitude recorded under voltage clamp compared to the wild-type receptors. These variants also reduced the charge transfer and altered the time course of desensitization and deactivation following rapid removal of GABA. The surface expression of the GABAA R γ2 subunit from the CLPTM1-p.R568Q group was significantly reduced compared to CLPTM1-WT. SIGNIFICANCE: This is the first report of functionally relevant variants within the CLPTM1 gene. Patch-clamp recordings showed that these de novo CLPTM1 variants reduce GABAA R currents and charge transfer, which should promote excitation and hypersynchronous activity. This study may provide insights into the molecular mechanisms of the CLPTM1 variants underlying the patients' phenotypes, as well as for exploring potential therapeutic targets for epilepsy.

Alive but not well: The neglected cost of air pollution.

Besides medical expenses, hospitalizations associated with air pollution will incur the welfare loss due to activity restrictions and the wage loss due to inability to work. We fill in the gap in the literature by examining the impact of air pollution on volume and intensity of hospitalizations, which allows us to incorporate the welfare loss and the wage loss. Using a data set that covers most of the inpatients in a major Chinese city during 2015-16, we find that worse air quality causes more hospital admissions, more total inpatient days, and higher total inpatient expenditure for various diseases, particularly diseases of the respiratory and circulatory systems. We also find that there would be an underestimate of the loss from air pollution if we had ignored the loss associated with activity restrictions and the wage loss during hospitalization.

Coaxial radiography guided puncture technique for percutaneous transforaminal endoscopic lumbar discectomy: A randomized control trial.

BACKGROUND: The coaxial radiography-guided puncture technique (CR-PT) is a novel technique for endoscopic lumbar discectomy. As the X-ray beam and the puncturing needle are maintained in a parallel and coaxial direction, the X-ray beam can be used to guide the trajectory angle, facilitating the choice of the puncture site and providing real-time guidance. This puncture technique offers numerous advantages over the conventional anterior-posterior and lateral radiography-guided puncture technique (AP-PT), especially in cases of herniated lumbar discs with a hypertrophied transverse process or articular process, high iliac crest, and narrowed intervertebral foramen. AIM: To confirm whether CR-PT is a superior approach to percutaneous transforaminal endoscopic lumbar discectomy compared to AP-PT. METHODS: In this parallel, controlled, randomized clinical trial, herniated lumbar disc patients appointed to receive percutaneous endoscopic lumbar discectomy treatment were recruited from the Pain Management Department of the Affiliated Hospital of Xuzhou Medical University and Nantong Hospital of Traditional Chinese Medicine. Sixty-five participants were enrolled and divided into either a CR-PT group or an AP-PT group. The CR-PT group underwent CR-PT, and the AP-PT group underwent AP-PT. The number of fluoroscopies during puncturing, puncture duration (min), surgery duration (min), VAS score during puncturing, and puncture success rate were recorded. RESULTS: Sixty-five participants were included, with 31 participants in the CR-PT group and 34 in the AP-PT group. One participant in the AP-PT group dropped out due to unsuccessful puncturing. The number of fluoroscopies [median (P25, P75)] was 12 (11, 14) in the CR-PT group vs 16 (12, 23) in the AP-PT group, while the puncture duration (mean ± SD) was 20.42 ± 5.78 vs 25.06 ± 5.46, respectively. The VAS score was 3 (2, 4) in the CR-PT group vs 3 (3, 4) in the AP-PT group. Further subgroup analysis was performed, considering only the participants with L5/S1 segment herniation: 9 patients underwent CR-PT, and 9 underwent AP-PT. The number of fluoroscopies was 11.56 ± 0.88 vs 25.22 ± 5.33; the puncture duration was 13.89 ± 1.45 vs 28.89 ± 3.76; the surgery duration was 105 (99.5, 120) vs 149 (125, 157.5); and the VAS score was 2.11 ± 0.93 vs 3.89 ± 0.6, respectively. All the above outcomes demonstrated statistical significance (P < 0.05), favoring the CR-PT treatment. CONCLUSION: CR-PT is a novel and effective technique. As opposed to conventional AP-PT, this technique significantly improves puncture accuracy, shortens puncture time and operation time, and reduces pain intensity during puncturing.