Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Objective: To explore the epidemiological characteristic of a COVID-19 outbreak caused by 2019-nCoV Omicron variant BF.7 and other provinces imported in Shenzhen and analyze transmission chains and characteristics. Methods: Field epidemiological survey was conducted to identify the transmission chain, analyze the generation relationship among the cases. The 2019-nCoV nucleic acid positive samples were used for gene sequencing. Results: From 8 to 23 October, 2022, a total of 196 cases of COVID-19 were reported in Shenzhen, all the cases had epidemiological links. In the cases, 100 were men and 96 were women, with a median of age, M (Q₁, Q₃) was 33(25, 46) years. The outbreak was caused by traverlers initial cases infected with 2019-nCoV who returned to Shenzhen after traveling outside of Guangdong Province.There were four transmission chains, including the transmission in place of residence and neighbourhood, affecting 8 persons, transmission in social activity in the evening on 7 October, affecting 65 persons, transmission in work place on 8 October, affecting 48 persons, and transmission in a building near the work place, affecting 74 persons. The median of the incubation period of the infection, M (Q₁, Q₃) was 1.44 (1.11, 2.17) days. The incubation period of indoor exposure less than that of the outdoor exposure, M (Q₁, Q₃) was 1.38 (1.06, 1.84) and 1.95 (1.22, 2.99) days, respcetively (Wald χ²=10.27, P=0.001). With the increase of case generation, the number and probability of gene mutation increased. In the same transmission chain, the proportion of having 1-3 mutation sites was high in the cases in the first generation. Conclusions: The transmission chains were clear in this epidemic. The incubation period of Omicron variant BF.7 infection was shorter, the transmission speed was faster, and the gene mutation rate was higher. It is necessary to conduct prompt response and strict disease control when epidemic occurs.
Male ; Humans ; Female ; SARS-CoV-2 ; COVID-19/epidemiology* ; Disease Outbreaks ; Epidemics ; China/epidemiology*

Aim To investigate the regulatory effect of glucagon on gluconeogenesis in liver, kidney and intes¬tine during different fasting periods and the underlying mechanism. Methods The 8-week-old male C57BIV 6J mice were randomly divided into six groups ( n = 6) :control group, control + glucagon group, fasting 18 h group, fasting 18 h + glucagon group, fasting 36 h group, and fasting 36 h + glucagon group. Glucose, triglyceride ( TG) and free fatty acids ( FFAs ) kits were used to detect their serum contents in mouse in-traperitoneal injection of glucagon at different fasting time points. Besides, liver/muscle glycogen assay kit and PAS staining were used to detect the glycogen con¬tents in liver tissue. RT-PCR method was used to observe the effects of glucagon on the gene expressions of peroxisome proliferators-activated receptor y coactivator la (PGC-1α), glucose-6-phosphatase (G6Pase) and phosphoenol pyruvate carboxykinase 1 (PEPCK) in liver, kidney and intestine of mice at different fasting time. Western blot was employed to detect the protein expressions of PGC-1α, G6Pase, PEPCK, phosphoryl-ase protein kinase A ( p-PKA) , protlein kinase A (PKA) , phosphorylase cAMp-response element binding protein (p-CREB) and cAMp-response element binding protein (CREB) in liver, kidney and intestine of mice were. Results (1) Glucagon increased the serum glucose level, reduced serum TG and FFAs levels, and reduced the hepatic glycogen content. (2) Glucagon promoted gluconeogenesis via upregulation of PGC-1α. On the stimulation of glucagon, PGC-1α gene and protein expressions in liver were significantly raised by glucagon when the mice were fasted 18 h and 36 h, while the gene and protein expressions of PGC-1α in kidney were obviously up-regulated by glucagon after fasting 18 h. However, PGC-1α gene and protein expressions in intestine were significantly elevated by glucagon at 36 h after fasting. (3 ) Glucagon induced gene and protein expressions of gluconeogenesis-related enzymes G6Pase and PEPCK in liver, kidney and intestine after fasting. (4 ) Glucagon upregulated p-PKA/PKA and p-CREB/CREB in liver. Conclusions Glucagon shows temporal difference in the gluconeo-genic response of liver, kidney and intestine in mice. Glucagon promotes the gene and protein expressions of key gluconeogenic enzymes G6Pase and PEPCK by increasing PGC-1α gene and protein expression, and thus increasing fasting blood glucose. Besides, glucagon promotes hepatic gluconeogenesis via PKA/CREB signaling pathway.

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.
Humans ; Middle Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemoradiotherapy ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoadjuvant Therapy ; Prospective Studies ; Rectal Neoplasms/pathology* ; Thrombocytopenia/drug therapy* ; Treatment Outcome ; Adult ; Aged

OBJECTIVE: To investigate the gene mutation and genotype distribution of thalassemia in the population of childbearing age in Chongzuo area of Guangxi. METHODS: Six α-thalassemia and 17 β-thalassemia gene mutations common in Chinese were detected by gap-polymerase chain reaction (gap-PCR) combined with agarose gel eletrophoresis and reserve dot bolt hybridization in 29 266 cases of child-bearing age suspected of thalassemia. RESULTS: A total of 19 128 (65.36%) cases were identified with thalassemia. The detection rate of α-thalassemia, β-thalassemia and α-combining β-thalassemia was 45.25% (13 242/29 266), 15.47% (4 526/29 266) and 4.65% (1 360/29 266), respectively. A total carrying rate of 8 kinds of α-thalassemia gene mutations was 26.74% (15 649/58 532), including 12.51% for --^SEA, followed by 5.70% for -α^3.7, and 0.24% for --^Thai. Among 32 α-thalassemia genotypes, the most common five were --^SEA/αα, -α^3.7/αα, α^CSα/αα, -α^4.2/αα and α^WSα/αα, accounting for 47.27%, 18.31%, 8.56%, 8.52% and 7.91%, respectively, as well as 0.97% for --^Thai/αα. A total carrying rate of 13 kinds of β-thalassemia gene mutations was 10.07% (5 897/58 532), including 3.63% for CD41-42, followed by 2.55% for CD17, and 0.003% for -50 (G>A). Among 17 β-thalassemia genotypes, the most common six were CD41-42/N, CD17/N, CD71-72/N, CD26/N, 28/N and IVSI-1/N, accounting for 36.15%, 25.81%, 9.43%, 8.18%, 8.09% and 7.75%. The homozygous genotype CD26/CD26 [hemoglobin (Hb): 121 g/L] and -28/-28 (Hb: 56 g/L) were respectively detected in one case, and double heterozygous genotype were detected in 5 cases, including 3 cases of CD41-42/CD26 (Hb: 41 g/L, 51 g/L, 63 g/L, respectively), 1 case of -28/IVSI-1 (Hb: 53 g/L), and 1 case of CD71-72/CD26 (Hb: 89 g/L), in which patients with moderate or severe anemia had a history of blood transfusion. Among 104 α-combining β-thalassemia genotypes, the most common were --^SEA/αα, -α^3.7/αα combining CD41-42/N and --^SEA/αα combining CD17/N, accounting for 12.13%, 9.63% and 9.26%, respectively. In addition, 1 case of --^SEA/-α^3.7 combining -28/IVSI-1 (Hb: 83 g/L) and 1 case of -α^3.7/αα combining CD41-42/ CD41-42 (Hb: 110 g/L) were detected without history of blood transfusion, while 1 case of α^WSα/αα combining CD41-42/CD17 (Hb: 79 g/L) and 1 case of --^SEA/αα combining CD17/-28 (Hb: 46 g/L) were detected with history. CONCLUSIONS The detection rate of thalassemia genes is high and the mutations are diverse in the population of childbearing age in Chongzuo area of Guangxi. The common deletion genotype is --^SEA/αα in α-thalassemia and CD41-42/N in β-thalassemia, and deletion genotype --^Thai is not rare. There is a certain incidence of intermediate and severe β-thalassemia, and most patients require transfusion therapy. The results are beneficial for genetic consultation and intervention of thalassemia.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Dipeptidyl Peptidase 4/genetics* ; China/epidemiology* ; Genotype ; Mutation

Objective:To evaluate the residual risk (RR) of transfusion transmitted HIV (TT-HIV) after the implementation of nucleic acid amplification test (NAT) in blood screening test among blood centers in China.Methods:The data of blood donors and HIV infection markers from 2017 to 2020 were collected from 28 blood centers via the Platform of Comparison of blood establishments Practice in Chinese Mainland. The new infection rate/window period mathematical model was used for two types of blood screening strategies, namely, two rounds ELISA plus individual NAT take turn with pooling NAT (2ELISA+ ID-NAT/MP-NAT) and two ELISA plus one round pooling NAT (2ELISA+ MP-NAT), and the RR of HIV infection was estimated also based on first donors (FDs) and repeated donors (RDs) in different blood donation years. T-test analyses were conducted for comparing TT HIV RR among FDs and RDs in different blood donation years with two blood screening strategies, and the variation trend of RR in HIV test was observed.Results:From 2017 to 2020, the RR of FDs in 2ELISA+ ID-NAT/MP-NAT blood screening strategy was 2.869/10 6 person-year, 3.795/10 6 persons-year, 3.879/10 6 person-year, and 2.890/10 6 person-year respectively. The RR of RDs was 1.797/10 6 person-year, 1.502/10 6 person-year, 1.857/10 6 person-year, and 1.483/10 6 person-year respectively. Significant difference exists between RR of FDs and RDs, with F=9.898 and p<0.05. In 2ELISA+ MP-NAT strategy, the RR of FDs was 3.508/10 6 person-year, 1.868/10 6 person-year, 2.204/10 6 person-year, and 1.765/10 6 person-year respectively. The RR of RDs was 0.948/10 6 person-year, 0.926/10 6 person-year, 0.748/10 6 person-year, and 0.682/10 6 person-year respectively. Statistical difference existed between RR of FDs and RDs, with F=17.126 and P<0.05. There was no significant difference between the RR of FDs in these two strategies with F=3.493 and P>0.05, while there was a difference between the RR of RDs in these two strategies with F=24.516 and P<0.05, and a difference between the RR of total donors (TDs) in these two strategies F=20.216 and P<0.05. Conclusions:The RR of TT HIV significantly decreased after the introduction of NAT into blood test among blood centers in China. There were some differences in the RR of HIV testing among different blood screening strategies. There could be significant differences in the RR of HIV testing among different groups of blood donors. Compared with FDs, RDs is the low risk group for HIV.

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.
Rats ; Mice ; Animals ; Chronic Pain/metabolism* ; Rats, Sprague-Dawley ; Ganglia, Spinal/metabolism* ; Ligands ; Signal Transduction ; Hyperalgesia/metabolism* ; Drugs, Chinese Herbal

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Homeodomain Proteins/genetics* ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Nuclear Pore Complex Proteins ; Oncogene Proteins, Fusion/genetics* ; Translocation, Genetic