Remimazolam Dosing for Gastroscopy: A Randomized Noninferiority Trial.

BACKGROUND: Remimazolam, an ultra-short-acting benzodiazepine, may provide adequate sedation for endoscopy while causing less cardiovascular or respiratory disturbance than propofol. Although fixed-dose administration is suggested, body weight affects the volume of the central chamber and thus affects the sedation depth that can be achieved by the first dose. This study aimed to compare the efficacy and safety of different doses of remimazolam and propofol by body weight for sedation during gastroscopy. METHODS: This multicenter, randomized, single-blind, parallel-controlled noninferiority trial recruited patients from five centers between March 2021 and July 2022. A total of 1,883 patients scheduled to undergo gastroscopy were randomized to groups receiving 0.15 mg/kg remimazolam, 0.2 mg/kg remimazolam, or 1.5 mg/kg propofol. The noninferiority margin was set to 5%. The primary outcome was the success rate of sedation. Adverse events were recorded to evaluate safety. RESULTS: The sedation success rate of the 0.2 mg/kg remimazolam group was not inferior to that of the 1.5 mg/kg propofol group (98.7% vs. 99.4%; risk difference, -0.64%; 97.5% CI, -2.2 to 0.7%, meeting criteria for noninferiority). However, the sedation success rate of the 0.15 mg/kg remimazolam group was 88.5%, and that of the 1.5 mg/kg propofol group was 99.4% (risk difference, -10.8%; 97.5% CI, -14.0% to -8.0%), demonstrating inferiority. Simultaneously, the overall adverse events rate of remimazolam was lower than that of propofol, and the incidence of bradycardia, hypotension, subclinical respiratory depression, and hypoxia in the remimazolam groups was significantly lower than that in the propofol group. CONCLUSIONS: This trial established the noninferior sedation success rate of remimazolam (0.2 mg/kg but not 0.15 mg/kg) compared with propofol (1.5 mg/kg), with a superior safety profile.

Analyzing the photoassociation spectrum of ultracold 85Rb 133Cs molecule in (3)3Σ+ state.

We establish a theoretical model to analyze the photoassociative spectroscopy of 85Rb 133Cs molecules in the (3)3Σ+ state. The vibrational energy, spin-spin coupling constant, and hyperfine interaction constant of the (3)3Σ+ state are determined based on nine observed vibrational levels. Consequently, the Rydberg-Klein-Rees potential energy curve of the (3)3Σ+ state is obtained and compared with the ab initial potential energy curve. Our model can be adopted to analyze the photoassociative spectroscopy of other heteronuclear alkali-metal diatomic molecules in the (3)3Σ+ state.

Narrow laser linewidth measurement with the optimal demodulated Lorentzian spectrum.

A method called the optimal demodulated Lorentzian spectrum is employed to precisely quantify the narrowness of a laser's linewidth. This technique relies on the coherent envelope demodulation of a spectrum obtained through short delayed self-heterodyne interferometry. Specifically, we exploit the periodic features within the coherence envelope spectrum to ascertain the delay time of the optical fiber. Furthermore, the disparity in contrast within the coherence envelope spectrum serves as a basis for estimating the laser's linewidth. By creating a plot of the coefficient of determination for the demodulated Lorentzian spectrum fitting in relation to the estimated linewidth values, we identify the existence of an optimal Lorentzian spectrum. The corresponding laser linewidth found closest to the true value is deemed optimal. This method holds particular significance for accurately measuring the linewidth of lasers characterized as narrow or ultranarrow.

Supraglottic jet oxygenation and ventilation improves oxygenation during endoscopic retrograde cholangiopancreatography: a randomized controlled clinical trial.

PURPOSE: Hypoxia is one of the most frequent adverse events under deep sedation in the semiprone position. We hypothesized that supraglottic jet oxygenation and ventilation (SJOV) via Wei nasal jet tube (WNJ) can reduce the incidence of hypoxia in patients under deep sedation during endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A total of 171 patients were divided into three groups: N group, supplementary oxygen via a nasopharyngeal airway (4-6 L/min); W group, supplementary oxygen via WNJ (4-6 L/min); WS group, SJOV via WNJ. The primary outcome was the incidence of adverse events, including sedation-related adverse events [SRAEs, hypoxemia (SpO2 = 75-89% lasted less than 60 s); severe hypoxemia (SpO2 < 75% at any time or SpO2 < 90% lasted more than 60 s] and subclinical respiratory depression (SpO2 = 90-95%). Other intraoperative and post-operative adverse events were also recorded as secondary outcomes. RESULTS: Compared with the N group, the incidence of hypoxemia and subclinical respiratory depression in the WS group was significantly lower (21% vs. 4%, P = 0.005; 27% vs. 6%, P = 0.002). Compared with Group W, the incidence of hypoxemia and subclinical respiratory depression in Group WS was also significantly less frequent (20% vs. 4%, P = 0.009; 21% vs. 6%, P = 0.014). No severe hypoxia occurred in the group WS, while four and one instances were observed in the group N and group W respectively. There were no significant differences in other adverse events among the three groups. CONCLUSION: SJOV can effectively improve oxygenation during ERCP in deeply sedated semiprone patients.

Co-Administration of nalbuphine to improve morphine tolerance in mice with bone cancer pain.

BACKGROUND: Kappa-opioid receptor (KOR) agonists are known for having opposite and/or different effects compared with Mu-opioid receptor (MOR) agonists. This study is aimed at clarifying the analgesic effect and tolerance of nalbuphine combined with morphine, and quantifying the mRNA and protein expression of spinal MOR and KOR in a mouse bone cancer pain (BCP) model treated with nalbuphine and morphine. METHOD: BCP model was prepared in C3H/HeNCrlVr Mice by implanting the sarcoma cells into the intramedullary space of the femur. The paw withdrawal thermal latency (PWL) measured by thermal radiometer was used to assess thermal hyperalgesia. PWL testing was performed after implantation and drug administration according to the protocol. Hematoxylin-eosin staining in the spinal cord and x-ray in the femoral intramedullary canal was detected. Real-time PCR and western blot analysis played a role in detecting spinal MOR and KOR expression changes. RESULTS: In tumor-implanted mice, the spinal MOR and KOR protein and mRNA expression was down-regulated when compared to that in sham-implanted mice (p < 0.05). Morphine therapy can lead to a decrease in spinal µ receptor expression. Similarly, the nalbuphine therapy can lead to a decrease in the expression of κ receptor protein and mRNA at the spinal cord level (p < 0.05). Morphine, nalbuphine, or nalbuphine co-administration with morphine all can extend the paw withdrawal thermal latency (PWL) to radiant thermal stimulation in tumor-implanted mice (p < 0.05). Compared with the morphine treatment group, nalbuphine co-administration with morphine delayed the reduction of PWL value again (p < 0.05). DISCUSSION: BCP itself may induce down-regulation of the spinal MOR and KOR expression. A low dose of nalbuphine co-administration with morphine led to the delayed emergence of morphine tolerance. The part of the mechanism may be due to the regulation of spinal opioid receptors expression.

LncRNA LINC01871 sponging miR-142-3p to modulate ZYG11B promotes the chemoresistance of colorectal cancer cells by inducing autophagy.

BACKGROUND: Colorectal cancer (CRC) is a malignant tumor in the digestive tract. Increasing evidence indicated that chemoresistance leads to a poor prognosis of CRC. Herein, we aimed to uncover the potential mechanism by which long intergenic noncoding RNA-1871 (LINC01871) affects the chemoresistance of CRC cells. METHODS: Relative level of LINC01871 in CRC tissues was assessed by reverse transcription quantitative PCR (RT-qPCR). Kaplan-Meier analysis was conducted to determine the relevance of LINC01871 and the prognosis of CRC patients. Cell Counting Kit-8 (CCK-8) and colony formation assay were used to evaluate the proliferation of SW480 cells. Expression levels of proteins and their genes were assessed by western blot, immunofluorescence staining and RT-qPCR. In addition, the interaction of LINC01871, miR-142-3p and protein zyg-11 homolog B (ZYG11B) were analyzed via dual-luciferase reporter assays. RESULTS: LINC01871 was low-expressed in CRC tissues and cell lines. Patients with a low level of LINC01871 showed significantly lower survival rate. pcDNA-LINC01871 significantly reduced the viability of SW480 cells ( P < 0.01), elevated SW480 cells sensitivity to 5-FU ( P < 0.01), reduced LC3 punctate aggregates ( P < 0.01) and downregulated the relative mRNA expression level of autophagy related protein 9A, autophagy related protein 4B and high mobility group box 1 ( P < 0.01) in SW480 cells. Moreover, LINC01871 was found to sponge miR-142-3p, and ZYG11B was the target of miR-142-3p. MiR-142-3p mimic significantly recovered the effect of pcDNA-LINC001871, whereas pcDNA-ZYG11B reversed the recovery effect of the miR-142-3p mimic. CONCLUSION: LINC01871/miR-142-3p/ ZYG11B axis regulates the chemoresistance of CRCs by inducing autophagy.

Simple, low-cost, and well-performing optical phase-locked loop for frequency and phase locking of semiconductor lasers.

We demonstrate a simple, low-cost, and well-performing optical phase-locked loop (OPLL) circuit with ADF4007 as the phase frequency detector chip to achieve frequency and phase locking of two semiconductor lasers in both short and long terms. The measured short term performances, determined by fast feedback, show that the spectral width of the beat signal is low, around 1 Hz, and the residual phasing error is 0.04r a d 2. The measured long term performances, determined by slow feedback, show that the drift of the central frequency of the beat signal is within 1.1(1) Hz in 2 h, and the derived Allan deviation is less than 0.4 Hz within all integration times of up to 1000 s. The phase noise measurement shows a suppression of phase noise of the beat signal from free running to closed-loop OPLLs in a Fourier frequency of 10 Hz-20 kHz. These measurements show that the OPLL circuit we modified can fit most scientific experiments requiring a fixed frequency difference and phase coherence.

Dissolving Microneedle Arrays as a Hepatitis B Vaccine Delivery System Adjuvanted by APC-Targeted Poly (Lactic-co-Glycolic Acid) (PLGA) Nanoparticles.

The objective of this study is to develop a new hepatitis B surface antigen (HBsAg) delivery system by coating soluble microneedle arrays with mannose-modified PLGA nanoparticles (MNPs). MNPs of different sizes were synthesized. The effects these nanoparticles on the maturation of dendritic cells were studied by flow cytometry. HBsAg-containing MNPs (HBsAg/MNPs) of the appropriate sizes were coated into water-soluble microneedle arrays. The in vitro characteristics of microneedles arrays and the immune responses after subcutaneous administration in mice were studied. The results showed that PLGA nanoparticles with an average size of about 800 nm showed the most significant effects in stimulating the maturation of dendritic cells. In the water-soluble microneedle array, the targeted PLGA nanoparticles containing HBsAg were distributed discretely with a maximum distribution height of about 280 µm with a drug load of 0.98 ± 0.05 µg/mg. The drug-containing microneedle arrays exhibited excellent mechanical properties and improved biosafety. The results of immune responses in vivo showed that the subcutaneous administration of the microneedle arrays induced the proliferation of splenocyte, secreted specific IL-12 and IFN-γ, and promote the production of IgG in mice. This study verifies the feasibility of soluble composited microneedles administration in hepatitis B immunization, and provides new ideas for the development and application of non-injectable vaccine delivery systems.

Tunable laser frequency lock based on a temperature-dependent Fabry-Perot etalon.

A simple method for laser frequency stabilizing by a temperature-tuned Fabry-Perot etalon is reported. The etalon is a plano-convex lens that permits tuning the length and refractive index via controlling the temperature for shifting wavelengths in the region of 852 nm, with a transmission spectral linewidth of ∼72.5MHz and free spectral region of ∼16GHz. Using this scheme, arbitrary frequency locking of a laser with an adjustable frequency resolution of 2.34GHz/∘C is realized, and MHz-level long-term stability is demonstrated.

Measurement of the permanent electric dipole moment of ultracold ground state 85Rb133Cs molecules by microwave coherent spectroscopy.

We demonstrate measurement of the permanent electric dipole moment (EDM) of 85Rb133Cs molecules in the absolute vibrational ground state by microwave (MW) coherent spectroscopy. The rotational states of the considered molecules, which are formed from short-range photoassociation of mixed cold atoms, are nondegenerated under external electric field. To measure the EDM based on electric-field-induced shifts of the sublevels of X1Σ+(v = 0, J = 1) rotational state, we utilized a MW coherent spectroscopy, which has a higher resolution than depletion spectroscopy and one-photon MW spectroscopy and can also eliminate the influence from Stark shift of the excited state existing in both spectroscopies above. In order to acquire accurate electric intensity, electromagnetic induced transparency spectroscopy of 85Rb Rydberg atoms is used to implement the calibration. The permanent EDM of 85Rb133Cs molecules is finally determined to be 1.266(15) D, which agrees with the theoretical calculations and is comparable with the value of its isotopic molecule.

Distinction of electromagnetically induced transparency and Autler-Towners splitting in a Rydberg-involved ladder-type cold atom system.

Electromagnetically induced transparency (EIT) and Autler-Townes splitting (ATS) are two similar quantum coherent phenomena but have different mechanisms and applications. Akaike information criteria (AIC), an objective method to discriminate EIT and ATS from an experimental viewpoint, has been employed in a variety of systems. Here we use AIC method to quantitively discriminate a series of spectra of cold atoms in a Rydberg-involved upper-driving ladder-type. The derived weights of EIT and ATS reflect that our spectra change from EIT-ATS intermediate region to ATS-dominated region along Rabi frequency of coupling field increases. We find that there are two factors affecting EIT-ATS weights in a Rydberg-involved three-level system: dephasing rate, induced by the interactions among Rydberg atoms, makes the EIT-ATS crossover move to the direction of low Rabi frequency of coupling field and the experimental noise makes the difference between EIT and ATS weights reduce at elsewhere. Our investigation could provide a meaningful reference for the observations and applications of Rydberg-involved quantum coherent spectroscopy.

Microwave-assisted coherent control of ultracold polar molecules in a ladder-type configuration of rotational states.

We demonstrate microwave-assisted coherent control of ultracold 85Rb133Cs molecules in a ladder-type configuration of rotational states. Specifically, we use a probe and a control MW field to address the transitions between the J = 1 → 2 and J = 2 → 3 rotational states of the X1Σ+(v = 0) vibrational level, respectively, and use the control field to modify the response of the probe MW transition by coherently reducing the population of the intermediate J = 2 state. We observe that an increased Rabi frequency of the control field leads to broadening of the probe spectrum splitting and a shift of the central frequency. We apply Akaike's information criterion (AIC) to conclude that the observed coherent spectral response appears across the crossover regime between electromagnetically induced transparency and Aulter-Townes splitting. Our work is a significant development in microwave-assisted quantum control of ultracold polar molecules with multilevel configuration.

Radiative lifetime measurement of ultracold cesium Rydberg states by a simplified optical pumping method.

We demonstrate one simplified all-optical method to measure the radiative lifetime of ultracold cesium (Cs) Rydberg atoms. This method is based on photodetection of one ground state atomic absorption in a ladder-type electromagnetic induced transparency (EIT), which contains one ground state, one intermediate state, and one Rydberg state. In the presence and absence of optical pumping between the Rydberg state and the intermediate state, the absorption difference with varying delay time can reconstruct the population evolution of target Rydberg atoms. By using this method, the radiative lifetimes of 50S1/2 and 50D5/2 of Cs atoms are measured to be 53(9)µs and 42(9)µs, respectively, which are consistent with theoretical calculations. The agreements show the reliability of our presented method, which can provide a route for researching light-matter interaction behavior without the need to quantify absorption characteristic.

The mechanisms of immune-chemotherapy with nanocomplex codelivery of pTRP-2 and adjuvant of paclitaxel against melanoma.

Melanoma accounts for the highest proportion of all skin cancer deaths. Immune-chemotherapy has transformed anti-melanoma therapy and is a preferred first-line combination strategy for melanoma. We previously prepared dendritic cells (DCs) targeting the nanocomplex paclitaxel (PTX)-encapsulated sulfobutylether-ß-cyclodextrin (SBE)/mannosylated N,N,N-trimethyl chitosan (mTMC)/DNA (PTX/SBE-DNA/Man-TMC) for the co-delivery of pTRP-2 DNA and adjuvant PTX. The nanocomplex PTX/SBE-DNA/Man-TMC promoted DC maturation and antigen presentation and spur potent anti-melanoma immunity. However, the mechanism by which PTX/SBE-DNA/Man-TMC regulates the biological functions of DCs and T lymphocytes is unknown. Therefore, we explored the underlying signaling pathways and mixed leukocyte reactions, resulting in enhanced T cell-mediated anti-tumor immunity. Interleukin-12 secretion from nanocomplex-pulsed mouse bone marrow-derived DCs was inhibited by treatment with Toll-like receptor 4 (TLR-4), nuclear factor kappa-B (NF-κB), and a specific blocker of p38 mitogen-activated protein kinase (MAPK). The results revealed that TLR-4, NF-κB, and MAPK signaling pathways were essential anti-tumor immune responses regulation factors. Furthermore, mixed leukocytes pulsed with PTX/SBE-DNA/Man-TMC induced tumor cell apoptosis and arrested the cell cycle in G0/G1, significantly promoting the synergy. Thus, we concluded that the mechanism driving the PTX/SBE-DNA/Man-TMC immune-chemotherapy synergistic effect was multifactorial.

Microwave coherent control of ultracold ground-state molecules formed by short-range photoassociation.

We report the observation of microwave coherent control of rotational states of ultracold 85Rb133Cs molecules formed in their vibronic ground state by short-range photoassociation. Molecules are formed in the single rotational state X(v = 0, J = 1) by exciting pairs of atoms to the short-range state (2)3Π0-(v = 11, J = 0), followed by spontaneous decay. We use depletion spectroscopy to record the dynamic evolution of the population distribution and observe clear Rabi oscillations while irradiating on a microwave transition between coupled neighbouring rotational levels. A density-matrix formalism that accounts for longitudinal and transverse decay times reproduces both the dynamic evolution during the coherent process and the equilibrium population. The coherent control reported here is valuable both for investigating coherent quantum effects and for applications of cold polar molecules produced by continuous short-range photoassociation.

Production of ultracold 85Rb133Cs molecules in the lowest ground state via the B1Π1 short-range state.

We investigate the production of cold 85Rb133Cs molecules in the lowest vibronic level of the ground electronic state via the B1Π1 short-range state. The photoassociation (PA) spectra of the B1Π1 state, including newly observed transition to 2 vibronic levels, are obtained by high sensitivity time-of-flight mass spectrometry. Based on these PA spectra, the harmonic and anharmonic constants of vibronic states are obtained, resulting in predicted vibronic energies with an uncertainty of 1-2 cm-1. The B1Π1 (v = 3) state is found to have the maximum production rate for ground-state molecules with a value of 3(1) × 104 s-1, which is 3 times larger than the value via the previously studied 23Π0+ (v = 10, J = 0) state with two-photon cascade decay. The populations of J = 0, 1, and 2 rotational levels of X1Σ+ (v = 0) state molecules formed via the B1Π1 (v = 3, J = 1) state are measured to be around 20%, 40%, and 20%. To quantify the coupling strength between the B1Π1 (v = 3) state and X1Σ+ (v = 0) state, the transition dipole moment between them is measured to be 7.2(2) × 10-3ea0, which is also 3 times larger than the value between the 23Π0+ (v=10) state and X1Σ+ (v = 0) state, meaning the B1Π1 (v = 3) state has a stronger coupling with the X1Σ+ (v = 0) state. Our detailed measurements provide relevant parameters for investigation on direct stimulated Raman adiabatic passage transfer between the atomic scattering state and molecular bound state for 85Rb133Cs molecules.

Mannose-Modified PLGA Nanoparticles for Sustained and Targeted Delivery in Hepatitis B Virus Immunoprophylaxis.

The launched hepatitis B vaccine could induce powerful antibodies, whereas it failed to improve potent cellular immune responses due to that the Th2-type response-induced aluminum adjuvant was adopted. Here, to target antigen-presenting cells under the epidermis and induce potent cellular and humoral immune responses, mannose-modified poly D,L-lactide-co-glycolic acid (PLGA) was synthesized and nanoparticle (MNP)-loaded hepatitis B surface antigen (HBsAg) protein was prepared. HBsAg could be slowly released and highly presented to lymphocytes which facilitated to produce long-lasting immunity based on characters of PLGA. In vitro uptake test results showed that MNPs could enhance internalization in bone marrow-derived dendritic cells (BMDCs) and RAW 264.7 cells. Subcutaneous delivery of MNPs into mice kept humoral immune and strengthened cellular immune responses. Experimental results indicated that MNPs showed significantly modified properties compared with parental PLGA nanoparticles. Thus, the obtained MNPs could be a promising vehicle for hepatitis B vaccine delivery.

Microwave spectroscopy measurement of ultracold ground state molecules produced via short-range photoassociation.

The high-resolution microwave (MW) spectroscopy is employed to measure the rotational structures of ultracold 85Rb133Cs molecules prepared in the X1Σ+ (v = 0) ground state. These ground-state molecules are created using short-range photoassociation (PA) followed by the spontaneous emission. Using a combination of continuous-wave (CW) depletion spectroscopy and photoionization (PI) technique, we obtain the MW spectroscopy by coupling the neighboring rotational levels of ground-state molecules. Based on the frequency spacing obtained from the MW spectroscopy, the rotational constant of X1Σ+ (v = 0) can be accurately determined with the rigid rotor model. The precision of the measurement by MW spectroscopy is found to be 3 orders of magnitude higher than the CW depletion spectroscopy. Our scheme provides a simple and highly accurate method for the measurement of molecular structure.

A dynamical process of optically trapped singlet ground state 85Rb133Cs molecules produced via short-range photoassociation.

We investigate the dynamical process of optically trapped X1Σ+ (v'' = 0) state 85Rb133Cs molecules distributed in J'' = 1 and J'' = 3 rotational states. The considered molecules, formed from short-range photoassociation of mixed cold atoms, are subsequently confined in a crossed optical dipole trap. Based on a phenomenological rate equation, we provide a detailed study of the dynamics of 85Rb133Cs molecules during the loading and holding processes. The inelastic collisions of 85Rb133Cs molecules in the X1Σ+ (v'' = 0, J'' = 1 and J'' = 3) states with ultracold 85Rb (or 133Cs) atoms are measured to be 1.0 (2) × 10-10 cm3 s-1 (1.2 (3) × 10-10 cm3 s-1). Our work provides a simple and generic procedure for studying the dynamical process of trapped cold molecules in the singlet ground states.

Diphenyleneiodonium Mitigates Bupivacaine-Induced Sciatic Nerve Damage in a Diabetic Neuropathy Rat Model by Attenuating Oxidative Stress.

BACKGROUND: Increased oxidative stress has been linked to local anesthetic-induced nerve injury in a diabetic neuropathy (DN) rat model. The current study explores the effects of diphenyleneiodonium (DPI) chloride, an NADPH oxidase (NOX) inhibitor, on bupivacaine-induced sciatic nerve injury in DN rats. METHODS: A rat DN model was established through high-fat diet feeding and streptozotocin injection. The model was confirmed via testing (i) blood glucose, (ii) hindpaw allodynia responses to von Frey (VF) monofilaments, (iii) paw withdrawal thermal latency (PWTL), and (iv) nerve conduction velocity (NCV). Bupivacaine (Bup, 0.2 mL, 5 mg/mL) was used to block the right sciatic nerve. DPI (1 mg/kg) was injected subcutaneously 24 hours and 30 minutes before the sciatic block. At 24 hours after the block, NCV, various reactive oxygen species, and Caspase-3 were evaluated to determine the extent of sciatic nerve injury. RESULTS: The DN rat model was successfully established. Compared with the DN control group, the postblock values of VF responses (DN-Con, 16.5 ± 1.3 g; DN + Bup, 19.1 ± 1.5 g, P < .001) and PWTL significantly increased (DN-Con, 13.3 ± 1.1 seconds; DN + Bup, 14.6 ± 1.1 seconds, P = .028); the NCV of sciatic nerve was significantly reduced (DN-Con, 38.8 ± 2.4 m/s, DN + Bup, 30.5 ± 2.0 m/s, P = .003), and sciatic nerve injury (as indicated by axonal area) was more severe in the bupivacaine-treated DN group (DN-Con, 11.6 ± 0.3 µm, DN + Bup, 7.5 ± 0.3 µm, P < .001). In addition, DPI treatment significantly improved nerve function (VF responses, 17.3 ± 1.3 g; PWTL, 13.4 ± 1.1 seconds; NCV, 35.6 ± 3.1 m/s) and mitigated loss of axonal area (9.6 ± 0.3 µm). Compared to the DN + Bup group (without DPI), the levels of lipid peroxides and hydroperoxides, as well as the protein expression of NOX2, NOX4, and Caspase-3, were significantly reduced in the DN + Bup + DPI group (P < .05). CONCLUSIONS: Subcutaneous injection of DPI appears to protect against the functional and neurohistological damage of bupivacaine-blocked sciatic nerves in a high-fat diet/streptozotocin-induced DN model.