Clinical spectrum, over 12-year follow-up and experience of SGLT2 inhibitors treatment on patients with glycogen storage disease type Ib: a single-center retrospective study.

BACKGROUND: Glycogen storage disease type Ib (GSD Ib) is a rare disorder characterized by impaired glucose homeostasis caused by mutations in the SLC37A4 gene. It is a severe inherited metabolic disease associated with hypoglycemia, hyperlipidemia, lactic acidosis, hepatomegaly, and neutropenia. Traditional treatment consists of feeding raw cornstarch which can help to adjust energy metabolism but has no positive effect on neutropenia, which is fatal for these patients. Recently, the pathophysiologic mechanism of the neutrophil dysfunction and neutropenia in GSD Ib has been found, and the treatment with the SGLT2 inhibitor empaglifozin is now well established. In 2020, SGLT2 inhibitor empagliflozin started to be used as a promising efficient remover of 1,5AG6P in neutrophil of GSD Ib patients worldwide. However, it is necessary to consider long-term utility and safety of a novel treatment. RESULTS: In this study, we retrospectively examined the clinical manifestations, biochemical examination results, genotypes, long-term outcomes and follow-up of thirty-five GSD Ib children who visited our department since 2009. Fourteen patients among them underwent empagliflozin treatment since 2020. This study is the largest cohort of pediatric GSD Ib patients in China as well as the largest cohort of pediatric GSD Ib patients treated with empagliflozin in a single center to date. The study also discussed the experience of long-term management on pediatric GSD Ib patients. CONCLUSION: Empagliflozin treatment for pediatric GSD Ib patients is efficient and safe. Increase of urine glucose is a signal for pharmaceutical effect, however attention to urinary infection and hypoglycemia is suggested.

[Effect of internal heat-type acupuncture needle on the expression of osteoprotegerin, receptor activator of NF-κB ligand and receptor activator of NF-κB of subchondral bone in knee osteoarthritis rabbits].

OBJECTIVE: To investigate the effect of internal heat-type acupuncture needle on the expression of osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL), and receptor activator of NF-κB (RANK) in knee osteoarthritis (KOA) rabbits, so as to explore its mechanisms in relieving KOA. METHODS: Thirty New Zealand rabbits were randomly divided into control, model and treatment groups, with 10 rabbits in each group. The KOA model was established by using Hulth method. The rabbits of the treatment group received internal heat-type acupuncture needles (42 ℃) on the left hind limb 20 min, once a week for 4 weeks. The behavioral scores were assessed according to the pain severity, gait, joint motion range and articular swelling severity in reference to the modified Lequesne's methods. Toluidine Blue staining was performed to observe the structure of the subchondral bone and to analyze the difference of morphometric parameters. The protein and mRNA expressions of OPG, RANKL and RANK were detected by Western blot and real-time PCR, respectively. RESULTS: Compared with the control group, the Lequesne total score, the separation degree of trabecular bone, the protein and mRNA expressions of RANKL and RANK in subchondral bone tissues were significantly increased in the model group, while the percentage of trabecular bone area, number of trabecular bone, the expression of OPG protein and mRNA were decreased (P<0.05, P<0.01). The above indexes were all reversed in the treatment group relevant to those of the model group (P<0.05). CONCLUSION: The internal heat-type acupuncture needle therapy can improve the motor function of rabbits with KOA, which may be related to its effects in up-regulating the expression of OPG and down-regulating the RANKL and RANK in subchondral bone tissue.

[Electrophysiological Characteristics of Sensitized Acupoints after Acute Intestinal Mucosal Injury in Rats].

OBJECTIVE: To observe the dynamic distribution of the extravasated Evans Blue (EB) dye points at the skin after acute colorectal mucosal injury (AIMI) so as to reveal characteristics of acupoint sensitization. METHODS: Forty adult male SD rats were randomly divided into control (n= 10), AIMI (n=20) and AIMI-recovery (n= 10) groups. According to the reaction state (EB-dye extravasation), each group was further divided into resting state (control), sensitized state (appearance of extravasated EB points), recovery state (disappearance of the extravasated EB points), non-sensitization (NS, no extravasated EB points) state and NS recovery state. The AIMI model was induced by perfusion of 2. 5% mustard oil into the colorectum via a thin tube. Evans blue dye was injected into the caudal vein 4 h after AIMI modeling. The distribution of plasma extravasated EB dye points at the skin of the lower limbs was observed. The C-fiber discharge of the separated ipsilateral sciatic nerve was induced by electrical stimulation of the EB-extravasated acupoints and non-acupoint at the threshold and double-fold threshold using an electric stimulator and recorded using a bicelectric amplifier-computer system. RESULTS: In AIMI rats, the extravasated EB-dye points were found to overlap the "Xiqian" and "Zusanli" (ST 36)-"Shangjuxu"(ST 37) regions. Moreover, the thresholds of C-fiber discharges induced by electrical stimulation of "Xiqian" and "Zusanli" (ST 36)-"Shangluxu"(ST 37) regions were significantly lower than those of the regions without extravasated EB dye acupoint and non-acupoint(P<0. 01, P<0. 05). The numbers of C-fiber discharges evoked by 2-fold threshold electro-stimulation at the "Xiqian" and "Zusanli" (ST 36)-"Shangjuxu" (ST 37) regions were obviously more than those of stimulation of non-acupoint which were experiencing sensitized state(P<0. 01, P<0. 05). CONCLUSION: In rats with acute colorectal mucosal injury, electrical stimulation of the acupoints where the extravasated EB-dye points appear may produce an obvious increase of C-fiber discharges under lower electro-stimulation threshold, suggesting a larger action of the sensitized acupoint.

Clinical, biochemical, neuroimaging and molecular findings of X-linked Adrenoleukodystrophy patients in South China.

X-linked adrenoleukodystrophy is a common X-linked recessive peroxisomal disorder caused by the mutations in the ABCD1 gene. In this study, we analyzed 19 male patients and 9 female carriers with X-linked adrenoleukodystrophy in South China. By sequencing the ABCD1 gene, 13 different mutations were identified, including 7 novel mutations, and 6 known mutations, and 1 reported polymorphism. Mutation c.1180delG was demonstrated to be de novo mutation. 26.3 % (5/19) patients carried the deletion c.1415_16delAG, which may be the mutational hot spot in South China population. In addition, 73.7 % (14/19) patients were type of childhood cerebral adrenoleukodystrophy, 26.3 %(5/19) were in Addison only. Half of the childhood cerebral adrenoleukodystrophy patients had the adrenocortical insufficiency preceded the onset of neurological symptoms. Furthermore, 5 of 19 cases underwent hematopoietic stem cell transplantation. Our data showed that hematopoietic stem cell transplantation performed at an advanced stage of the cerebral X- linked adrenoleukodystrophy would accelerate the progression of the disease. Good clinical outcome achieved when hematopoietic stem cell transplantation performed at the very early stage of the disease.

Observation of CARS signal via maximal atomic coherence prepared by F-STIRAP in a three-level atomic system.

We control the atomic coherence and the population transfer among Rb hyperfine atomic levels by the fractional stimulated Raman adiabatic passage (F-STIRAP) in a L-type configuration, and verify the theoretical predictions. Applying this technique, we are able to prepare the atoms with maximal coherence to enhance coherent anti-Stokes Raman scattering (CARS) signal. In our experiment by scanning the frequency of one laser from 794.9839 nm to 794.9844 nm with the 794.9698 nm laser frequency fixed to generate a maximum of the CARS signal we are able to obtain the energy level diagram of the sample.