Background During pregnancy, negative emotions such as anxiety and depression may induce cortisol disruption. Cortisol can be transmitted to the fetus through the placental barrier, thereby affecting the neurodevelopment of the offspring. Objective To investigate the relationship between placental cortisol, maternal depression during pregnancy, and neurodevelopment of 3-month-old infants. Methods From September 2022 to September 2023, 171 pregnant women ordered routine prenatal checks at the obstetrics outpatient department of a tertiary hospital in Ningxia were selected using a prospective cohort design. After providing informed consent, these women participated in a questionnaire survey that covered general individual characteristics, prenatal depression, and sleep quality. At birth, placental samples were collected to measure cortisol levels using ELISA kits. Follow-up assessments on the neurodevelopmental of 3-month-old infants were conducted using the Warning Sign for Children Mental and Behavioral Development. LASSO regression analysis was conducted to screen the influencing factors of depression during pregnancy. Huber regression analysis was then applied to assess potential linear relationship between depression during pregnancy and placental cortisol levels. Log-binomial regression was used to analyze the linear relationships between cortisol levels and neurodevelopmental delay in 3-month-old infants. Additionally, a mediation effect model was fitted using R 4.3.3 to assess possible mediating role of cortisol in the association between prenatal depression and neurodevelopmental delay in 3-month-old infants. Results The positive rate of prenatal depression was 33.33%. Nine factors affecting prenatal depression were identified by LASSO regression, including rural residence, high school education or above, extroverted personality characteristics, moderate early pregnancy reactions, baby sex expectation, prenatal anxiety, family dysfunction, exposure to stressful life events during pregnancy, and moderate prenatal sleep quality. The Huber regression model showed a positive linear correlation between prenatal depression and placental cortisol (P<0.05). With or without controlling confounding factors, the results of log-binomial regression modeling showed that cortisol levels were associated with a reduced risk of neurodevelopmental delay in 3-month-old infants (crude model: RR=0.988, 95%CI: 0.9768, 0.9996, P＜0.05; adjusted model: RR=0.988, 95%CI: 0.9764, 0.9993, P＜0.05). A mediating effect of placental cortisol between prenatal depression and the risk of neurodevelopmental delay in 3-month-old offspring was found statistically significant (P=0.045), accounting for 67.0% of the total effect. Conclusion Prenatal depression is associated with elevated placental cortisol levels, and higher cortisol levels are found to be related to a lower risk of neurodevelopmental delay in infants. Placental cortisol mediates the relationship between prenatal depression and infant neurodevelopment.

By consulting the ancient and modern literature， the name， origin， quality evaluation， harvesting and processing methods of Curculiginis Rhizoma（CR） were systematically combed and verified， in order to provide a basis for the development and utilization of famous classical formulas containing CR. The results of herbal textual research showed that the name Xianmao was first recorded in Leigong Paozhilun， the name of CR was used in all dynasties and this name came from its efficacy and morphological characteristics， the mainstream source for CR of the past dynasties was the rhizome of Curculigo orchioides or C. capitulata， since modern times， C. orchioides has been the main source of commodities. In ancient times， most of the places of origin of the description were the western regions and southwest China， while in modern times， Sichuan and Guizhou were regarded as genuine places. Since modern times， its quality has been summarized as the best with thick roots， firm texture and black-brown surface， the harvesting and processing methods recorded in the past dynasties are mainly sun drying after harvest in the second， eighth and ninth months of the lunar calendar， and most of them are harvested in autumn and winter in modern times. In ancient times， there were many processing methods of CR， mainly in processing with rice swill， while in modern times， stir-frying with wine was the main processing method. The nature， taste， meridian tropism， functions and indications of CR are basically consistent from ancient to modern times， the taboos for taking are to avoid iron， cow's milk， and beef. Although there are some differences in the understanding of the toxicity of CR in the past dynasties， most of the materia medica are clear that it has a certain toxicity. Based on the research conclusion， it is suggested that the rhizome of C. orchioides of Lycoris family should be used as its source in the famous classical formulas， and the corresponding processing method should be selected according to the processing requirements in the formulas， while the raw products is recommended to be selected as medicine if the processing requirement is not specified.

OBJECTIVE To identify, synthesize and analyze the structure of unknown impurities unique to bromhexine hydrochloride injection and set the impurities as known impurity to control. METHODS The structure of unknown impurities was derived through two-dimensional liquid chromatography tandem mass spectrometry(2DLC-HRMS/MS), and the source of impurities was derived based on the product's prescription process. The mechanism of impurities generation was analyzed, and impurity monomers were obtained through directional synthesis. The structure of impurities was confirmed using techniques such as 2DLC-HRMS/MS and nuclear magnetic resonance. Finally, HPLC was used to verify the analysis method of impurities. RESULTS It was confirmed that such impurities were produced in a reaction between bromhexine and the excipient glucose. The correction factor of the two impurities were 2.2 and 2.4, the analytical method was specific and reproducible. CONCLUSION Name the two injection specific impurities as impurity 1 and impurity 2 respectively, and use them as known impurities to be included in the standard, calculate the impurity content using the self control and correction factor method. This study is of great significance in guiding the impurity control of bromhexine hydrochloride injection and the screening of excipient glucose.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To investigate the incidence and treatment of gastric cancer in 16 medical centers in Tianjin from 2020 to 2021.Methods:The retrospective and descriptive study was conducted. The clinical data of 3 122 gastric cancer patients who underwent surgery in 16 medical centers, including Tianjin Medical University Cancer Institute & Hospital, et al, in Tianjin from 2020 to 2021 were collected. There were 2 112 males and 1 010 females, aged (64±11)years. Observation indicators: (1) general data of patients; (2) treatment situations; (3) postoperative complications. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were descri-bed as absolute numbers or percentages, and comparison between groups was conducted by the chi-square test. Results:(1) General data of patients. From 2020 to 2021, a total of 3 122 gastric cancer patients received surgeries in 16 medical centers in Tianjin, including 2 112 males and 1 010 females. There were 1 443 cases in 2020, including 976 males and 467 females, aged (63±11) years. There were 1 679 cases in 2021, including 1 136 males and 543 females, aged (65±11) years. Of the 3 122 pati-ents, cases in stage Ⅰ, Ⅱ, Ⅲ, Ⅳ were 696, 667, 1 466, 293, accounting for 22.293%(696/3 122), 21.365%(667/3 122), 46.957%(1 466/3 122), 9.385%(293/3 122), respectively. Cases with early gastric cancer, locally advanced gastric cancer, advanced gastric cancer account for 17.265%(539/3 122), 73.350%(2 290/3 122), 9.385%(293/3 122). There were 2 829 patients without distant metastasis and 293 patients with distant metastasis. For the 2 829 patients without distant metas-tasis, cases in stage T1, T2, T3, T4a, T4b accounted for 19.053%(539/2 829), 12.089%(342/2 829), 20.148%(570/2 829), 41.499%(1 174/2 829), 7.211%(204/2 829)respectively, cases in stage N0, N1, N2, N3 account for 37.328%(1 056/2 829), 16.331%(462/2 829), 15.836%(448/2 829), 30.505%(863/2 829). For the 293 advanced gastric cancer patients with distant metastasis, 190 cases had peri-toneal metastasis, 47 cases had lymph node metastasis, 27 cases had ovarian metastasis, 37 cases had liver metastasis, 14 cases had other metastasis (some patients had ≥2 distant metastases). (2) Treatment situations. ① For the 539 with early gastric cancer, cases undergoing endoscopic submu-cosal dissection, laparoscopic surgery, open surgery were 22, 150, 86 in 2020, versus 19, 212, 50 in 2021, showing a significant difference between them ( χ2=19.42, P<0.05). For the 498 patients with early gastric cancer who underwent laparoscopic or open surgery, cases undergoing open surgery including total gastrectomy, distal gastrectomy, proximal gastrectomy were 25, 81, 30, and cases undergoing laparoscopic surgery including total gastrectomy, distal gastrectomy, proximal gastrec-tomy were 18, 309, 35, respectively, showing a significant difference between them ( χ2=40.62, P<0.05). For the 2 290 patients with locally advanced gastric cancer, cases undergoing open surgery and laparoscopic surgery were 446 and 617 in 2020, versus 410 and 817 in 2021, showing a significant difference between them ( χ2=17.75, P<0.05). For the 2 290 patients with locally advanced gastric cancer, cases undergoing open surgery including total gastrectomy, distal gastrectomy, proxi-mal gastrectomy were 336, 377, 143, and cases undergoing laparoscopic surgery including total gastrectomy, distal gastrectomy, proximal gastrectomy were 377, 920, 137, respectively, showing a significant difference between them ( χ2=89.64, P<0.05). Of the 293 patients with advanced gastric cancer, 175 cases underwent surgeries due to hemorrhage, stenosis, perforation, 76 cases under-went surgery after chemotherapy, 42 cases underwent surgery directly. ② For 756 cases of 3 122 pati-ents undergoing total gastrectomy, 357 and 4 cases received open digestive tract reconstruction including Roux-en-Y and other anastomosis, versus 380 and 15 cases with laparoscopic digestive tract reconstruction including Roux-en-Y and other anastomosis, showing a significant difference between them ( χ2=5.57, P<0.05). For 1 687 cases undergoing distal gastrectomy, 84, 160, 158, 55 cases received open digestive tract reconstruction including Billroth Ⅰ anastomosis, Billroth Ⅱ + Braun anastomosis, Roux-en-Y anastomosis, uncut Roux-en-Y anastomosis, versus 154, 489, 417, 170 cases with laparoscopic digestive tract reconstruction including Billroth Ⅰ anastomosis, Billroth Ⅱ + Braun anastomosis, Roux-en-Y anastomosis, uncut Roux-en-Y anastomosis, showing a significant difference between them ( χ2=10.90, P<0.05) . Of the 539 patients with early gastric cancer, 65 cases had lymph node metastasis, in which 18 of 306 stage T1a cases had lymph node metastasis and 47 of 233 stage T1b cases had lymph node metastasis. The number of detected lymph nodes for the 2 290 patients with advanced gastric cancer was 31±15, including ≥16 for 2 059 cases and ≥30 for 1 276 cases. Of the 3 122 patients, cases with neoadjuvant therapy, complete response and incomplete response was 128, 13 and 115 in 2020, versus 250, 49 and 201 in 2021, showing a significant difference between them ( χ2=5.51, P<0.05). (3) Postoperative complications. Of the 3 122 patients, 746 cases had postoperative complications, with an incidence of 23.895%(746/3 122). There were 62 patients with grade 3 or more complications. Reoperation was conducted in 34 patients. There were 14 cases of postoperative death. The duration of postoperative hospital stay and hospital expense were (11±5)days and (98 114±46 598)yuan for the 3 122 patients, (26±14)days and (122 066±68 317)yuan for cases with complications, (40±21)days and (196 926±12 747)yuan for cases with grade 3 or more complications. Conclusion:Compared with 2020, cases undergoing laparoscopic surgery and distal gastrectomy for gastric cancer in Tianjin increases in 2021, and the digestive tract reconstruction also differs. The number of patients with neoadjuvant chemotherapy and complete response rate for advanced gastric cancer increases.

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

OBJECTIVE: To explore the correlation of mitochondrial DNA (mtDNA) variants and coronary heart disease (CHD) in a Chinese pedigree and the possible molecular mechanisms. METHODS: A Chinese pedigree featuring matrilineal inheritance of CHD who visited Hangzhou First People's Hospital in May 2022 was selected as the study subject. Clinical data of the proband and her affected relatives was collected. By sequencing the mtDNA of the proband and her pedigree members, candidate variants were identified through comparison with wild type mitochondrial genes. Conservative analysis among various species was conducted, and bioinformatics software was used to predict the impact of variants on the secondary structure of tRNA. Real-time PCR was carried out to determine the copy number of mtDNA, and a transmitochondrial cell line was established for analyzing the mitochondrial functions, including membrane potential and ATP level. RESULTS: This pedigree had contained thirty-two members from four generations. Among ten maternal members, four had CHD, which yielded a penetrance rate of 40%. Sequence analysis of proband and her matrilineal relatives revealed the presence of a novel m.4420A>T variant and a m.10463T>C variant, both of which were highly conserved among various species. Structurally, the m.4420A>T variant had occurred at position 22 in the D-arm of tRNAMet, which disrupted the 13T-22A base-pairing, while the m.10463T>C variant was located at position 67 in the acceptor arm of tRNAArg, a position critical for steady-state level of the tRNA. Functional analysis revealed that patients with the m.4420A>T and m.10463T>C variants exhibited much fewer copy number of mtDNA and lower mitochondrial membrane potential (MMP) and ATP contents (P < 0.05), which were decreased by approximately 50.47%, 39.6% and 47.4%, respectively. CONCLUSION Mitochondrial tRNAMet 4420A>T and tRNAArg 10463T>C variants may underlay the maternally transmitted CHD in this pedigree, which had shown variation in mtDNA homogeneity, age of onset, clinical phenotype and other differences, suggesting that nuclear genes, environmental factors and mitochondrial genetic background have certain influence on the pathogenesis of CHD.
Humans ; Female ; Mutation ; Pedigree ; RNA, Transfer, Met ; East Asian People ; RNA, Transfer, Arg ; DNA, Mitochondrial/genetics* ; Coronary Disease/genetics* ; Adenosine Triphosphate

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

In order to explore the effect of peptidoglycan hydrolase on the viable cell counts of Bacillus amyloliquefaciens and the yield of alkaline protease, five peptidoglycan hydrolase genes (lytC, lytD, lytE, lytF and lytG) of B. amyloliquefaciens TCCC111018 were knocked out individually. The viable cell counts of the bacteria and their alkaline protease activities before and after gene deletion were determined. The viable cell counts of the knockout mutants BA ΔlytC and BA ΔlytE achieved 1.67×10⁶ CFU/mL and 1.44×10⁶ CFU/mL respectively after cultivation for 60 h, which were 32.5% and 14.3% higher than that of the control strain BA Δupp. Their alkaline protease activities reached 20 264 U/mL and 17 265 U/mL, respectively, which were 43.1% and 27.3% higher than that of the control strain. The results showed that deleting some of the peptidoglycan hydrolase genes effectively maintained the viable cell counts of bacteria and increased the activity of extracellular enzymes, which may provide a new idea for optimization of the microbial host for production of industrial enzymes.
Bacillus amyloliquefaciens/genetics* ; Bacterial Proteins ; Cell Count ; Endopeptidases/genetics* ; N-Acetylmuramoyl-L-alanine Amidase/genetics*

Background The optimal model method for estimation of benchmark dose (BMD) does not consider the uncertainty of model selection. There is a lack of studies on using Bayesian model averaging (BMA) to estimate BMD. Objective To apply BMA to the exposure assessment of cadmium pollution in China, discuss the role of BMA in estimating BMD based on dose-response models, and to provide methodological support for health risk assessment of hazardous substances. Methods The parameters of five dose-response models (Gamma, Log-logistic, Log-probit, Two-stage, and Weibull models) estimated from the data from a cadmium-contaminated area in Baiyin City of Gansu Province and the urinary cadmium ranges in five cadmium-contaminated areas in China were used to simulate the data of varied correct models with different numbers of dosage groups (5 and 8) and different sample sizes (50, 100, and 200), then the performance of BMA and traditional optimal model were compared. The case analysis used the cadmium exposure data in Baiyin, Gansu Province. All analyses set urinary cadmium as the indicator of cadmium exposure, the abnormal rate of β₂-microglobulin as the effect indicator, and the benchmark response to 10%. The correct model (the model used when simulating data), optimal model [the model with smallest Akaike information criterion (AIC)], and BMA were used to estimate BMD and lower confidence limit of benchmark dose (BMDL); the BMDs, BMDLs, and relative deviations from different methods were compared. Results In the simulation study, with increasing sample size or the number of dosage groups, the intervals of the 5th percentile and the 90th percentile of BMD tended to be narrower; when the correct model was a single model, the relative deviation of BMD estimation by BMA was greater than that of the traditional optimal model; when the correct model was an equal weight mixed model, the relative deviation of BMD estimation by BMA was less than that by the traditional optimal model. For the data of cadmium-contaminated areas, the optimal model was a Log-probit model (AIC=1814.46), followed by a Log-logistic model (AIC=1814.57); the BMDs (BMDLs) estimated by the Log-probit model, the Log-logistic model, and BMA were 3.46 (2.68), 3.16 (2.33), and 2.92 (2.07) μg·g⁻¹, respectively. Conclusion The traditional optimal model is still recommended when the correct model is known. However, when the dose-response relationship of a hazardous substance is uncertain or with different sources or exposure grouping, compared with the traditional optimal model, BMA theoretically provides more stable estimation of BMD and BMDL by considering multiple possible alternative models.