Metastatic vascular calcification and calcinosis universalis, as severe complications of parathyroid hyperfunction and hyperparathyroidism, have attracted more attention in patients with renal secondary hyperparathyroidism and primary hyperparathyroidism. But, they are of little concern in patients with long-term negative calcium balance related parathyroid hyperfunction or hyperparathyroidism caused by calcium and/or vitamin D insufficiency (CVI). CVI is common in the population. Relatively low level of serum calcium and negative calcium balance caused by long-term CVI result in parathyroid hyperfunction or hyperparathyroidism, which may cause secretion of PTH beyond the physiological level, leading to bone absorption and release of a large amount of bone calcium into the blood. It may not only cause bone loss and osteoporosis, but also form metastatic vascular calcification or calcinosis universalis presented by cardiovascular diseases and other multi-organ lesions. Early calcium deposition can gradually fade after reasonable treatment, but middle arterial calcification is not easy to fade once it occurs. Therefore, vascular calcification and calcium deposition should be actively prevented and early screened and diagnosed. The early prevention, diagnosis and treatment of parathyroid hyperfunction or hyperparathyroidism can prevent, delay, or even reverse the occurrence and development of metastatic vascular calcification and calcinosis universalis, which is significant for disease prevention and protecting the patients' health influenced by these diseases.

The lifetime prevalence of nephrolithiasis is 15% for men, with a 5-year recurrence rate of 35% to 50% after an initial event. Although it was initially recommended to limit calcium intake in these patients, a number of studies have reported association between lower total dietary calcium intake and increased risk of incident kidney stones, and that increased calcium intake might reduce the risk of incident kidney stones. We report a 35-year-old male who presented recurrent 8-years of nephrolithiasis and urine crystal with calcium intake restriction, and had no recurrence after 5 years of follow-up after intensive calcium and vitamin D supplementation.

Objective:To study the phenotype and genotype distribution of Yersinia pestis ( Y. pestis) in different natural foci of plague in China, so as to provide scientific basis for plague prevention and control. Methods:A total of 2 184 strains of Y. pestis isolated from different time periods, regions, hosts and vectors in 11 plague natural foci of China since 1943 were selected for biochemical type identification, glycolysis test, virulence factor test [capsule antigen (F1), pesticin Ⅰ (Pst Ⅰ), virulence antigen factor (VWa), pigmentation factor (Pgm)], different region (DFR) typing and clustered regularly interspaced short palindromic repeats (CRISPR) typing. Results:There were 16 biochemical types of Y. pestis in the natural foci of plague in China, and each biochemical type showed obvious regional distribution in each foci. Most strains were positive for ass hide glue glycolysis (89.79%, 1 961/2 184), maltose (80.13%, 1 750/2 184), glycerol (94.23%, 2 058/2 184), and denitrification (82.78%, 1 808/2 184), and negative for rhamnose (88.78%, 1 939/2 184) and melibiose (85.62%, 1 870/2 184). Virulence factor test results showed that 99.95% (2 183/2 184) of Y. pestis were F1 positive; 99.73% (2 178/2 184) of Y. pestis can produce Pst Ⅰ; 73.31% (1 601/2 184) of Y. pestis were VWa positive and 26.69% (583/2 184) were VWa negative; Pgm positive strains accounted for 72.62% (1 586/2 184), Pgm negative strains accounted for 21.52% (470/2 184), and Pgm mixed type strains accounted for 5.86% (128/2 184). According to DFR typing results, there were 52 genotypes in 2 184 strains of Y. pestis, of which 19 were major genotypes and 33 were minor genotypes. CRISPR typing revealed 16 major genotypes, of which 7 were newly discovered. Conclusion:The phenotypes and genotypes of Y. pestis in various natural foci of plague in China are diverse and have geographical distribution characteristics.

Objective:To evaluate the effect of esmketamine for labor analgesia on the occurrence of postpartum depression (PPD).Methods:Two hundred and forty-two cases of nulliparous parturients who selected natural labor and agreed to receive labor analgesia were selected and divided into conventional labor analgesia group (C-LA group, n=119) and esmketamine-based labor analgesia group (E-LA group, n=123). The epidural labor analgesia solution contained ropivacaine 100 mg and sufentanil 30 μg in 100 ml of normal saline in C-LA group. The epidural labor analgesia solution contained ropivacaine 100 mg, sufentanil 30 μg and esketamine 50 mg in 100 ml of normal saline in E-LA group. The Edinburgh Postnatal Depression Scale (EPDS) was used to screen parturients for depression on admission to the predelivery room and at 2 h and 1, 7 and 42 days after delivery, and EPDS scores were recorded. The patients were diagnosed as having PPD when EPDS score ≥ 9 at 7-42 days after delivery. Peripheral venous blood samples were collected on admission to the predelivery room and at 1 day after delivery to determine the concentrations of serum estrogen, progesterone, 5-hydroxytryptamine and cortisol by enzyme linked inmunosorbent assay. Results:Compared with group C-LA, the EPDS scores were significantly decreased on the 1 and 42 days after delivery( P<0.01), no significant change was found in the incidence of PPD (1.7%/0.8%, P>0.05), no significant change was found in the concentrations of serum estrogen, progesterone, 5-hydroxytryptamine and cortisol on admission to the delivery room ( P>0.05), and the concentrations of serum progesterone and cortisol were significantly increased on 1 day after delivery in group E-LA ( P<0.05). Conclusions:Combination of esketamine is helpful in reducing the risk of postpartum depression when used for epidural labor analgesia, and the mechanism is related to slowing the declines in blood levels of sex hormones and stress hormones after delivery.

Objective:To observe the effect of combination of esketamine and sufentanil on postoperative analgesia and postpartum depression after cesarean section.Methods:A total of 150 primiparous women who underwent lower segment cesarean section under spinal anesthesia and postoperative analgesia at Changsha Maternal and Child Health Hospital from February to October 2021 were selected and randomly divided into three groups: A, B, and C, with 50 cases in each group. All three groups underwent combined spinal epidural anesthesia and received patient-controlled intravenous analgesia (PCIA) after surgery. The group A received low-dose esketamine via intravenous pump after fetal delivery, with PCIA formula esketamine combined with sufentanil; After the delivery of fetuses in the group B and the group C, an equal dose of physiological saline was pumped into the vein. The PCIA formula of esketamine combined with sufentanil for the group B and Sufentanil for the group C. We compared the pain Visual Analogue Scale (VAS) and Edinburgh Postpartum Depression Scale (EPDS) scores of three groups of patients at different time points after surgery, as well as the postoperative pain relief rate and incidence of adverse reactions.Resultsl:There was a statistically significant difference in VAS between the group A and the group B within 48 hours after surgery compared to the group C (all P<0.05), while there was a statistically significant difference in VAS between the group A and the group B within 24 hours after surgery (all P<0.05). The postoperative pain relief rate in the group A and group B was significantly lower than that in the group C, and the incidence of postpartum depression within 7 days after surgery was significantly lower than that in the group C. Moreover, the incidence of postpartum depression in the group A was lower than that in the group B within 3 days after surgery, and the differences were statistically significant (all P<0.05). There was no statistically significant difference in the incidence of postpartum depression among the three groups 42 days after surgery (all P>0.05), and there was no statistically significant difference in the incidence of adverse reactions among the three groups ( P>0.05). Conclusions:Esketamine combined with sufentanil can synergistically enhance the analgesic effect after cesarean section and reduce the incidence of early postpartum depression after surgery.

Ventilators are currently the most commonly used auxiliary mechanical ventilation equipment in clinical practice, and play an important role in the treatment of hypoxemia. Ventilator-associated pneumonia (VAP) is a special type of pulmonary parenchymal inflammation of nosocomial infection in patients with mechanical ventilation, which leads the increase of mortality and affects the prognosis of patients. The non-standard management of ventilator pipeline joints and the aerosol formed by bacterial condensate splashed from ventilator pipeline pollute the air, resulting in cross infection, which are the important reasons for VAP. The existing ventilator pipeline joint cap can achieve the effect of preventing pollution, but the clinical application compliance is not high. Based on the above factors, teachers, students and medical staff of the School of Public Health and Management, Guangxi University of Chinese Medicine and other units have designed a device for preventing pollution and air pollution of the ventilator pipeline joint, and obtained the national utility model patent of China (ZL 2020 2 1361981.X). The device is composed of a model lung, a mask body, a suspension part and a beam mouth part, etc. The use method is simple, and can be applied to the pollution avoidance of invasive ventilator and non-invasive ventilator pipeline joints, to reduce the occurrence of VAP in patients and the occupational exposure of medical staff.

Objective:To explore the association of DNA methylation with immune response to hepatitis B (HepB) vaccine in Han nationality children from Guangxi province.Methods:A total of 263 children aged 8-9 months who had completed HepB immunization program were recruited from three hospitals in Guangxi province by using unmatched case-control method. Children with the HepB surface antibody concentration(Anti -HBs)<100 mIU/ml was set as the case group and ≥100 mIU/ml as the control group. Multiplex PCR and heavy sulfite sequencing were used to treat the samples. Illumina platform was used for high-throughput DNA methylation sequencing of IFNG gene target regions and CpG sites. Unconditional logistic regression was used to analyze the association between cytosine-phospho-guanosine DNA methylation at 18 loci of IFNG gene and HepB immune response level. Results:There were 104 children in the case group and 159 in the control group. The median ( Q1, Q3) level of anti -HBs in two groups were 62.34 (30.06, 98.88) mIU/ml and 1 089.10 (710.35, 1 233.45) mIU/ml. The methylation levels of IFNG_1 gene 44 and 93 locus in the case group were higher than those in the control group ( P<0.05). The unconditional logistic regression model showed that the DNA methylation level of IFNG_1 gene at 44 ( OR=1.18, 95% CI: 1.03-1.35) and 93 ( OR=1.21, 95% CI: 1.07-1.38) locus was associated with the HepB response level. Conclusion:The changes of DNA methylation at locus 44 and 93 of IFNG_1 gene may be relevant factors affecting the response level of HepB in Han nationality children from Guangxi province.

Objective:To explore the association of DNA methylation with immune response to hepatitis B (HepB) vaccine in Han nationality children from Guangxi province.Methods:A total of 263 children aged 8-9 months who had completed HepB immunization program were recruited from three hospitals in Guangxi province by using unmatched case-control method. Children with the HepB surface antibody concentration(Anti -HBs)<100 mIU/ml was set as the case group and ≥100 mIU/ml as the control group. Multiplex PCR and heavy sulfite sequencing were used to treat the samples. Illumina platform was used for high-throughput DNA methylation sequencing of IFNG gene target regions and CpG sites. Unconditional logistic regression was used to analyze the association between cytosine-phospho-guanosine DNA methylation at 18 loci of IFNG gene and HepB immune response level. Results:There were 104 children in the case group and 159 in the control group. The median ( Q1, Q3) level of anti -HBs in two groups were 62.34 (30.06, 98.88) mIU/ml and 1 089.10 (710.35, 1 233.45) mIU/ml. The methylation levels of IFNG_1 gene 44 and 93 locus in the case group were higher than those in the control group ( P<0.05). The unconditional logistic regression model showed that the DNA methylation level of IFNG_1 gene at 44 ( OR=1.18, 95% CI: 1.03-1.35) and 93 ( OR=1.21, 95% CI: 1.07-1.38) locus was associated with the HepB response level. Conclusion:The changes of DNA methylation at locus 44 and 93 of IFNG_1 gene may be relevant factors affecting the response level of HepB in Han nationality children from Guangxi province.

Objective:To understand whether there are drug resistant and disinfectant resistant Yersinia pestis strains in China, and to provide accurate information for clinical treatment of plague. Methods:A total of 2 753 Yersinia pestis strains isolated from 10 natural plague foci in China from 1943 to 2016 were collected. According to National Center for Biotechnology Information (NCBI) released sequences of aminoglycoside streptomycin resistant genes strA, strB, β-lactam antibiotics resistant genes TEM, SHV and CTX-M, sulfamilamide resistant genes sul1, sul2 and sul3, and disinfectant resistant gene qacE△1-sul1, a pair of primers of each gene was designed for above-mentioned genes. Genomic DNA of 2 753 strains of Yersinia pestis was extracted, and the 9 target genes of all DNA samples were amplified by PCR. Results:Negative and positive controls of PCR detection were established. No corresponding target bands of aminoglycoside streptomycin resistant genes strA, strB, β-lactam antibiotics resistant genes TEM, SHV and CTX-M, sulfamilamide resistant genes sul1, sul2 and sul3, and disinfectant resistant gene qacE△1-sul1 were found in the DNA samples of 2 753 strains of Yersinia pestis.Conclusion:The above-mentioned genes of drug resistance and disinfectant resistance have not been detected in Yersinia pestis of China, but the monitoring of drug resistance of Yersinia pestis still needs to be carried out continuously.

Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers, including lung cancer; however, targeting the lipogenetic pathways for cancer therapy remains an unmet clinical need. In this study, we tested the anticancer activity of orlistat, an FDA-approved anti-obesity drug, in human and mouse cancer cells in vitro and in vivo, and we found that orlistat, as a single agent, inhibited the proliferation and viabilities of lung cancer cells and induced ferroptosis-like cell death in vitro. Mechanistically, we found that orlistat reduced the expression of GPX4, a central ferroptosis regulator, and induced lipid peroxidation. In addition, we systemically analyzed the genome-wide gene expression changes affected by orlistat treatment using RNA-seq and identified FAF2, a molecule regulating the lipid droplet homeostasis, as a novel target of orlistat. Moreover, in a mouse xenograft model, orlistat significantly inhibited tumor growth and reduced the tumor volumes compared with vehicle control (P < 0.05). Our study showed a novel mechanism of the anticancer activity of orlistat and provided the rationale for repurposing this drug for the treatment of lung cancer and other types of cancer.
Animals ; Cell Death ; Cell Line, Tumor ; Ferroptosis ; Lung Neoplasms/drug therapy* ; Mice ; Orlistat