OBJECTIVE To provide a reference for the pharmaceutical care of a patient with type 2 diabetes mellitus （T2DM） and limb-girdle muscular dystrophy （LGMD） who developed euglycemic diabetic ketoacidosis （euDKA） after taking empagliflozin. METHODS Clinical pharmacists provided pharmaceutical care for a patient with T2DM and LGMD who developed euDKA after taking empagliflozin. According to the patient’s recent use of medications and his conditions， clinical pharmacists assessed the correlation between euDKA and empagliflozin as “very likely”. As to euDKA， clinical pharmacists suggested discontinuing empagliflozin and metformin， and giving intravenous infusion of 10% Glucose injection instead of 5% Glucose injection for fluid resuscitation. Clinical pharmacists monitored the patient’s laboratory indicators such as arterial blood gas analysis， blood/urine ketones and electrolytes. They assisted physicians to decide when to stop intravenous supplements of liquid and insulin. Clinical pharmacists also assisted physicians to adjust the antidiabetic drugs and educated the patient to avoid empagliflozin or other sodium- glucose linked transporter 2 inhibitors （SGLT2i）. RESULTS Physicians adopted the suggestions of clinical pharmacists. After treatment， the patient’s condition improved， and he was allowed to be discharged with medication. CONCLUSIONS euDKA is a relatively rare and serious adverse reaction associated with SGLT2i， and the patients with LGMD are susceptible to euDKA. Clinical pharmacists assist physicians in developing personalized medication plans by evaluating the association between euDKA and empagliflozin， adjusting medication regimens，conducting pharmaceutical monitoring，and other pharmaceutical services. Meanwhile， they provide medication education to patients to ensure their medication safety.

OBJECTIVE To provide a reference for the pharmaceutical care of a patient with type 2 diabetes mellitus （T2DM） and limb-girdle muscular dystrophy （LGMD） who developed euglycemic diabetic ketoacidosis （euDKA） after taking empagliflozin. METHODS Clinical pharmacists provided pharmaceutical care for a patient with T2DM and LGMD who developed euDKA after taking empagliflozin. According to the patient’s recent use of medications and his conditions， clinical pharmacists assessed the correlation between euDKA and empagliflozin as “very likely”. As to euDKA， clinical pharmacists suggested discontinuing empagliflozin and metformin， and giving intravenous infusion of 10% Glucose injection instead of 5% Glucose injection for fluid resuscitation. Clinical pharmacists monitored the patient’s laboratory indicators such as arterial blood gas analysis， blood/urine ketones and electrolytes. They assisted physicians to decide when to stop intravenous supplements of liquid and insulin. Clinical pharmacists also assisted physicians to adjust the antidiabetic drugs and educated the patient to avoid empagliflozin or other sodium- glucose linked transporter 2 inhibitors （SGLT2i）. RESULTS Physicians adopted the suggestions of clinical pharmacists. After treatment， the patient’s condition improved， and he was allowed to be discharged with medication. CONCLUSIONS euDKA is a relatively rare and serious adverse reaction associated with SGLT2i， and the patients with LGMD are susceptible to euDKA. Clinical pharmacists assist physicians in developing personalized medication plans by evaluating the association between euDKA and empagliflozin， adjusting medication regimens，conducting pharmaceutical monitoring，and other pharmaceutical services. Meanwhile， they provide medication education to patients to ensure their medication safety.

Objective To explore the dilution conditions and standards in detecting the semen samples with high sperm concentration using computer-aided sperm analysis(CASA)systems.Methods CASA systems with 10 μm depth disposable counting chambers were used for the examination.The samples were divided into undiluted group(Group 1∶sperm concentration＜50×106/mL)and diluted groups(Group 2∶50×106/mL≤ sperm concentration＜100× 106/mL;Group 3∶sperm concentration≥100× 106/mL).When sperm concentration＜50×106/mL,no dilution was performed.When sperm concentration≥50× 106/mL,the samples were diluted with saline at 1∶n/(50×106)ratio(n=sperm concentration,n/[50×106]rounded down)to＜50×106/mL of sperm concentration.The sperm concentration,progressive motility(PR),non-progressive motility(NP),total motility(PR+NP)and immotile sperm percent-age(IM)were analyzed before and after dilution.The consistency of results pre-and post-dilution was compared.ROC curve was used to analyze the optimal dilution threshold.Results The differences in the parameters pre-and post-dilution gradually rosed with the increased sperm concentration.ROC curve analysis showed optimal dilution thresholds were 133.05 × 106/mL,101.75 × 106/mL,118.60×106/mL,90.90×106/mL,111.83×106/mL for the sperm concentration,PR+NP,PR,NP and IM respectively.Considering sperm concentration and NP were most affected the undiluted high concentration samples,the optimal comprehensive dilution threshold was determined as 125.08× 106/mL.Conclusion When sperm concentration exceeds 125×106/mL,it is recommended to dilute semen sample with normal saline.

Objective:To observe the rehabilitation effect of balance training relying on tilted table on diaphragmatic function of patients with prolonged disorder of consciousness (pDoC).Methods:A prospective study was performed. Thirty patients with pDoC were enrolled from Department of Hyperbaric Oxygen Medicine and Rehabilitation, General Hospital of Southern Theater Command of PLA from May to December 2023. The pateints were divided into study group ( n=15) and control group ( n=15) according to different rehabilitation. Patients from the control group received conventional rehabilitation, while those in the study group received passive balance training relying on tilted table in addition to conventional rehabilitation. Diaphragmatic ultrasound examination was performed before treatment, and 4 and 8 weeks after treatment to measure diaphragm excursion (DE), diaphragm thickening inspiration (DTei), diaphragm thickening expiration (DTee) and diaphragm thickening fraction (DTF) so as to assess the diaphragmatic functions of patients with pDoC. Results:During treatment, 2 patients dropped out from the study group resulting from the willing of the family members, ultimately including 13 and 15 patients in the study and control groups, respectively. (1) Between-group comparison: no significant difference in DE, DTei, DTee or DTF was noted between the study group and control group 4 weeks after treatment ( P>0.05). However, 8 weeks after treatment, the study group had statistically increased DE, DTei and DTF compared with the control group ([1.65±0.32] cm vs. [1.21±0.22] cm; [2.07±0.26] cm vs. [1.83±0.26] cm; and [24.39±3.19]% vs. [18.93±2.50]%). (2) Within-group comparison: both group had significantly increased DE 4 and 8 weeks after treatment compared with those before treatment ( P<0.05); in the study group, DE 8 weeks after treatment was significantly increased compared with that 4 weeks after treatment ( P<0.05). No significant difference in DTei, DTee or DTF was noted in both groups between 4 weeks after treatment and before treatment ( P>0.05). In the study group, DTei, DTee and DTF 8 weeks after treatment were significantly higher than those before treatment and 4 weeks after treatment ( P<0.05). Conclusion:Balance training relying on tilted table is feasible and effective in improving diaphragmatic function in patients with pDoC, and the effect is positively correlated with treatment time within a certain time.

Background: and Purpose X-linked Charcot-Marie-Tooth disease type 1 (CMTX1) is characterized by peripheral neuropathy with or without episodic neurological dysfunction. We performed clinical, neuropathological, and genetic investigations of a series of patients with mutations of the gap-junction beta-1 gene (GJB1) to extend the phenotypic and genetic description of CMTX1. Methods: Detailed clinical evaluations, sural nerve biopsy, and genetic analysis were applied to patients with CMTX1. Results: We collected 27 patients with CMTX1 with GJB1 mutations from 14 unrelated families. The age at onset (AAO) was 20.9±12.2 years (mean±standard deviation; range, 2–45 years). Walking difficulties, weakness in the legs, and pes cavus were common initial symptoms. Compared with female patients, males tended to have a younger AAO (males vs. females=15.4±9.6 vs. 32.0±8.8 years, p=0.002), a longer disease course (16.8±16.1 vs. 5.5±3.8 years, p=0.034), and more-severe electrophysiological results. Besides peripheral neuropathy, six of the patients had special episodic central nervous system (CNS) evidence from symptoms, signs, and/or reversible white-matter lesions. Neuropathology revealed the loss of large myelinated fibers, increased number of regenerated axon clusters with abnormally thin myelin sheaths, and excessively folded myelin. Genetic analysis identified 14 GJB1 variants, 6 of which were novel. Conclusions These findings expand the phenotypic and genetic spectrum of CMTX1. Although CMTX1 was found to have high phenotypic and CNS involvement variabilities, detailed neurological examinations and nerve conduction studies will provide critical clues for accurate diagnoses. Further exploration of the underlying mechanisms of connexin 32 involvement in neuropathy or CNS dysfunction is warranted to develop promising therapies.

The purpose of this study was to clone and characterize the ZFP36L1 (zinc finger protein 36-like 1) gene, clarify its expression characteristics, and elucidate its expression patterns in different tissues of goats. Samples of 15 tissues from Jianzhou big-eared goats, including heart, liver, spleen, lung and kidney were collected. Goat ZFP36L1 gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR), then the gene and protein sequence were analyzed by online tools. Quantitative real-time polymerase chain reaction (qPCR) was used to detect the expression level of ZFP36L1 in intramuscular preadipocytes in different tissues and adipocytes of goat at different differentiation stages. The results showed that the length of ZFR36L1 gene was 1 224 bp, and the coding sequence (CDS) region was 1 017 bp, encoding 338 amino acids, which was a non-secretory unstable protein mainly located in nucleus and cytoplasm. Tissue expression profile showed that ZFP36L1 gene was expressed in all selected tissues. In visceral tissues, the small intestine showed the highest expression level (P < 0.01). In muscle tissue, the highest expression level was presented in longissimus dorsi muscle (P < 0.01), whereas the expression level in subcutaneous adipose tissue was significantly higher than that in other tissues (P < 0.01). The results of induced differentiation showed that the expression of this gene was up-regulated during adipogenic differentiation of intramuscular precursor adipocytes (P < 0.01). These data may help to clarify the biological function of the ZFP36L1 gene in goat.
Animals ; Goats/genetics* ; Amino Acid Sequence ; Liver ; Cloning, Molecular

OBJECTIVE: The research progress of new multifunctional bone cement in bone tumor therapy in recent years was reviewed, in order to provide help for the future research of anti-tumor bone cement. METHODS: The related literature on the treatment of bone tumors with new multifunctional bone cement at home and abroad in recent years was extensively reviewed and summarized. RESULTS: The new multifunctional bone cements include those with the functions of photothermotherapy, magnetic thermotherapy, chemoradiotherapy, and antibacterial after operation, which are discussed from the aspects of anti-tumor, drug controlled release, and cytotoxicity. Controlled drug release has been achieved in multifunctional bone cements by adjusting heat and pH or incorporating particles such as chitosan oligosaccharides and γ-cyclodextrin. At present, multifunctional bone cement with hyperthermia, radiotherapy, and chemotherapy has effectively inhibited the local recurrence and distant metastasis of bone tumors. Broadening the application of bone cement for photothermal and magnetic thermal therapy to deeper bone tumors, investigating more precise controlled release of drug-loaded bone cement, and introducing nanoparticles with both thermal conversion and intrinsic enzymatic activities into bone cement for synergistic anti-tumor therapy are promising research directions. CONCLUSION The new multifunctional bone cement inhibits bone tumor cells, promotes new bone formation in bone defects, and prevents incision infection after tumor resection. Certain progress has been made in anti-tumor, antibacterial, drug-controlled release, and reduction of cytotoxicity. Expanding the deeper application range of the new multifunctional bone cement, verifying the safety in clinical application, and focusing on the individualized treatment of the new multifunctional bone cement are the problems that need to be solved in the future.
Humans ; Bone Cements/therapeutic use* ; Delayed-Action Preparations ; Bone Neoplasms/therapy* ; Anti-Bacterial Agents/therapeutic use* ; Nanoparticles/therapeutic use*

Objective:To summarize and analyze the clinical and genetic characteristics of Chinese patients with adrenomyeloneuropathy (AMN).Methods:Clinical data were collected and analyzed retrospectively on AMN patients who were diagnosed by genetic testing in Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University School of Medicine from May 2008 to August 2022. Clinical characteristics of AMN patients with different types of gene mutations were compared. Loe score was used to evaluate the severity of white matter demyelinating, and the serum levels of very long-chain fatty acids (VLCFA) in patients with or without white matter demyelinating were compared. The motor function of the AMN patients was assessed using the Expanded Disability Status Scale (EDSS), and the association between EDSS scores and the course of disease was analyzed.Results:A total of 23 male patients with onset age of (29.52±9.91) years were included in this study. The first symptom of all patients was abnormal lower extremities, of which 17 patients showed stiffness and weakness in their lower limbs (73.9%, 17/23), and 6 patients showed numbness and pain in both lower limbs (26.1%, 6/23). The occurrence of symptoms was not related to the type of gene mutation. White matter demyelination occurred in 33.3% (7/21) of patients over a disease duration of (7.67±4.46) years. There was no statistically significant difference in serum VLCFA level between the white-matter demyelination group and the non-demyelination group. The EDSS score was positively correlated with the disease duration ( r=0.57, P=0.006). Sixteen ABCD1 gene mutations were found in this study, among which c.5_19delinsTCTCCAGG (p.P2Lfs *12) was reported for the first time. Four probands belonging to different families carried the c.1415_1416del (p.Q472Rfs *83) variant. Conclusions:Lower limb movement disorders and sensory dysfunction are the prominent clinical manifestations in AMN patients, with deterioration of motor function associated with the course of disease. AMN may be converted to cerebral type and VLCFA concentration is not associated with the phenotypic changes. The c.1415_1416del (p.Q472Rfs *83) mutation is a hot spot mutation of the disease.

In this study, we cloned the complete sequence coding for aminoacids in protein (CDS) of goat ST13 gene, analyzed the bioinformation of it, and explored the expression pattern in different goat tissues and goat subcutaneous preadipocytes at different differentiation stages. To be specific, ST13 gene was cloned by reverse transcription PCR (RT-PCR), and the bioinformation was analyzed by online tools or software. The expression in various goat tissues and subcutaneous preadipocytes at different differentiation stages was detected by quantitative reverse transcription PCR (qRT-PCR). The results showed that the cloned goat ST13 gene was 1 380 bp, with CDS of 1 101 bp, encoding 366 amino acids. Protein prediction results showed that ST13 had 26 phosphorylation sites and that some sequences were highly hydrophilic and unstable. Moreover, ST13 was a non-transmembrane and non-secretory protein. Subcellular localization demonstrated that ST13 was mostly distributed in the nucleus (69.6%). Phylogeny analysis suggested that goat ST13 had the highest identity to sheep ST13. Tissue expression pattern showed that ST13 gene expressed in all of the collected 13 tissues of goat, including heart, liver, spleen, lung and kidney, especially in triceps brachii and subcutaneous fat (P < 0.01) and that the expression among heart, liver, spleen, lung, kidney, large intestine, small intestine and pancreas was insignificantly different (P > 0.05). In addition, according to the temporal expression pattern in adipocytes, the expression of ST13 was up-regulated in differentiated adipocytes, and the expression was the highest at the 108th hour of induction, significantly higher than that at other time points (P < 0.01). In conclusion, this gene expresses in various tissues of goat and regulates the differentiation of goat subcutaneous adipocytes.
Adipocytes ; Animals ; Cloning, Molecular ; Goats/genetics* ; Liver ; Phylogeny ; Real-Time Polymerase Chain Reaction ; Sheep

Objective To investigate the radioprotective function and its mechanism of miR-223 in acute radiation-induced lung injury in mice.Methods Forty female C57BL/6 J mice were randomly divided into healthy control group,irradiation group,irradiation plus miR-223 group and irradiation plus NC group.Radiation groups were exposed with a single dose of 15 Gy of 6 MV X-rays delivered by a linear accelerator.The mice in drug group were administered by tail vein injection with miR-223 agomir or agomirNC every other day from 1 d before irradiation to 14 d after irradiation.The lung tissue samples of mice were taken at 14 d post-irradiation.The pathological changes were observed by HE staining.The localization and expressions of IL-1β and IL-18 were observed by immunohistochemistry (IHC).Real-time PCR was used to detect miR-223,but NLRP3 mRNA expression in lung tissue.Western blot was used to detect the protein expressions of NLRP3 and Caspase-1,and ELISA assay was used to detect the expressions of IL-1β and IL-18 in lung homogenate.Results Radiation decreased the expression of miR-223,but increased the expression of NLRP3 in lung tissue.Administration of miR-223 agomir inhibited the expression of NLRP3 and attenuated lung inflammation.HE and IHC staining showed that miR-223 reduced the acute inflammatory response and the expressions of IL-1β and IL-18 in lung tissue compared with irradiation group (t=10.16,6.00,P＜0.05).The expressions of NLRP3 and Caspase-1 protein in lung tissue of irradiated plus miR-223 group was lower than that in the irradiation alone group (t =12.47,4.95,P＜ 0.05).ELISA assay also showed a decrease of inflammatory factors IL-1β and IL-18 in lung tissue homogenate of the irradiation plus miR-223 group (t =8.22,8.47,P＜0.05).Conclusions MiR-223 effectively reduces the secretion of radiation-induced inflammatory factors IL-1β and IL-18 by inhibiting the expression of NLRP3 in lung tissue of mice,and thus has protective effect on radiation-induced lung injury.