AIM To evaluate the quality of Yanyangke Mixture.METHODS The HPLC fingerprints were established,after which cluster analysis,principal component analysis and partial least squares discriminant analysis were performed.The contents of liquiritin,rosmarinic acid,sheganoside,irisgenin,honokiol,monoammonium glycyrrhizinate,irisflorentin,isoliquiritin and magnolol were determined,the analysis was performed on a 35 ℃ thermostatic Agilent ZORBAX SB-C18 column(5 μm,250 mmx4.6 mm),with the mobile phase comprising of 0.1％phosphoric acid-acetonitrile flowing at 1 mL/min in a gradient elution manner,and multi-wavelength detection was adopted.RESULTS There were ten common peaks in the fingerprints for twelve batches of samples with the similarities of more than 0.9.Various batches of samples were clustered into three types,three principal components displayed the acumulative variance contribution rate of 87.448％,peaks 5、14(honokiol),3(liquiritin),11(monoammonium glycyrrhizinate)and 15(asarinin)were quality markers.Nine constituents showed good linear relationships within their own ranges(r＞0.999 0),whose average recoveries were 98.5％-103.6％with the RSDs of 0.92％-1.7％.CONCLUSION This stable and reliable method can provide a basis for the quality control of Yanyangke Mixture.

Objective To evaluate the intraoperative identification of ectopic parathyroid tissue in the central neck region using autofluorescence point-spectral analysis(AFPSA)combined with immune colloidal gold technique(ICGT),for guiding total parathyroidectomy(TPTX)or clean parathyroidectomy(CPTX)in the management of secondary hyperparathyroidism(SHPT).Methods Retrospectively collected and compared the clinical data of 64 patients with SHPT from October 2019 to June 2023.In the observation group,TPTX was performed as the initial procedure in 36 cases,followed by sampling of suspicious targets using AFPSA in the central neck area and subsequent detection through ICGT.CPTX was then conducted if a positive result was obtained.On the other hand,the control group consisted of 28 cases where only TPTX was performed without any additional tests during surgery.The surgical data,parathyroid hormone(PTH)levels,blood calcium levels,blood phosphorus levels,alkaline phosphatase(ALP)levels,regression of clinical symptoms,changes in parathyroid function and occurrence of hypocalcemia were compared between these two groups.Results In the observation group,there were 9 cases of AFPSA-ICGT positivity,including 2 left-sided cases,4 right-sided cases,and 3 thymic cases;among these posi-tive cases,there were a total of 10 locations with mildly hyperplastic or nonhyperplastic microscopic parathyroid tissue.The difference in the number of total parathyroid glands removed(including ectopic)between the two groups was statistically significant(P<0.05).At both 3 and 6 months postoperatively,ALP levels in the observation group were significantly lower than those in the control group(P<0.01 and P<0.001 respectively);at 6 months postoperatively,differences in PTH and blood phosphorus levels between the two groups were also statistically significant(P<0.05 and P<0.001 respectively).Joint bone pain and skin itching recurred in some patients within the control group at six months after surgery(P<0.05),whereas recurrence of SHPT was less frequent within the observation group compared to controls(P<0.05);however,no statistically significant differences were observed regarding postoperative hypoparathyroidism or hyperparathyroidism as well as hypocalcemia between either groups.Conclusion The AFPSA-ICGT intraoperative test can be utilized to guide surgery for SHPT,enabling accurate and efficient identification as well as safe targeting of parathyroid tissues that may not exhibit obvious hyperplasia in the central cervical region.

Here,5 important pathogens carried by ticks in Maanshan City,Anhui Province,China were identified.In to-tal,642 ticks were collected from 13 villages around Maanshan City and identified by morphological and mitochondrial COI genes.The 16S rRNA gene of Francisella tularensis,ssrA gene of Bartonella,16S rRNA,ompA and ompB genes of Rickett-sia,16S rRNA and gltA genes of Anaplasma,and groEL and rpoB genes of Coxiella were sequenced.Reference sequences were retrieved from a public database.Phylogenetic trees were constructed with MEG A1 1.0 software.In total,36 Rickettsiae isolates were detected in 640 Haemaphysalis longicornis ticks,which included 20 isolates of Rickettsia heilongjian-gensis,16 of Candidatus Rickettsia jingxinensis,2 of Ana-plasma bovis,and 186 of Coxiella-like endosymbiont.R.hei-longjiangensis HY2 detected in this study and Anhui B8 strain,Ca.R.jingxinensis QL3 and those from Shanxi Prov-ince and Jiangsu Province,A.bovis JX4 and those from Shanxi Province were clustered on the same branch.Overall,17 ticks had combined infections and none of the 5 bacteria were detected in two Amblyomma testudinarium ticks.This is the first report of Ca.R.jingxinensis detected in H.longicornis ticks from Anhui Province.It is recommended that the two types of Rickettsia that cause spotted fever and A.bovis should be reported to local health authorities to initiate appropriate prevention and control measures.

Recent studies revealed the relationship among homologous recombination repair (HRR), androgen receptor (AR), and poly(adenosine diphosphate-ribose) polymerase (PARP); however, the synergy between anti-androgen enzalutamide (ENZ) and PARP inhibitor olaparib (OLA) remains unclear. Here, we showed that the synergistic effect of ENZ and OLA significantly reduced proliferation and induced apoptosis in AR-positive prostate cancer cell lines. Next-generation sequencing followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed the significant effects of ENZ plus OLA on nonhomologous end joining (NHEJ) and apoptosis pathways. ENZ combined with OLA synergistically inhibited the NHEJ pathway by repressing DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and X-ray repair cross complementing 4 (XRCC4). Moreover, our data showed that ENZ could enhance the response of prostate cancer cells to the combination therapy by reversing the anti-apoptotic effect of OLA through the downregulation of anti-apoptotic gene insulin-like growth factor 1 receptor ( IGF1R ) and the upregulation of pro-apoptotic gene death-associated protein kinase 1 ( DAPK1 ). Collectively, our results suggested that ENZ combined with OLA can promote prostate cancer cell apoptosis by multiple pathways other than inducing HRR defects, providing evidence for the combined use of ENZ and OLA in prostate cancer regardless of HRR gene mutation status.
Male ; Humans ; Prostatic Neoplasms, Castration-Resistant/genetics* ; Drug Resistance, Neoplasm/genetics* ; Cell Line, Tumor ; Receptors, Androgen/genetics* ; Nitriles ; Apoptosis

This study aims to explore the auditory response characteristics of the thalamic reticular nucleus (TRN) in awake mice during auditory information processing, so as to deepen the understanding of TRN and explore its role in the auditory system. By in vivo electrophysiological single cell attached recording of TRN neurons in 18 SPF C57BL/6J mice, we observed the responses of 314 recorded neurons to two kinds of auditory stimuli, noise and tone, applied to mice. The results showed that TRN received projections from layer six of the primary auditory cortex (A1). Among 314 TRN neurons, 56.05% responded silently, 21.02% responded only to noise and 22.93% responded to both noise and tone. The neurons with noise response can be divided into three patterns according to their response time: onset, sustain and long-lasting, accounting for 73.19%, 14.49% and 12.32%, respectively. The response threshold of the sustain pattern neurons was lower than those of the other two types. Under noise stimulation, compared with A1 layer six, TRN neurons showed unstable auditory response (P < 0.001), higher spontaneous firing rate (P < 0.001), and longer response latency (P < 0.001). Under tone stimulation, TRN's response continuity was poor, and the frequency tuning was greatly different from that of A1 layer six (P < 0.001), but their sensitivity to tone was similar (P > 0.05), and TRN's tone response threshold was much higher than that of A1 layer six (P < 0.001). The above results demonstrate that TRN mainly undertakes the task of information transmission in the auditory system. The noise response of TRN is more extensive than the tone response. Generally, TRN prefers high-intensity acoustic stimulation.
Rats ; Mice ; Animals ; Wakefulness ; Auditory Pathways/physiology* ; Rats, Wistar ; Mice, Inbred C57BL ; Thalamus/physiology*

The pharmaceutical manufacturing model is gradually changing from intermittent manufacturing to continuous manufacturing and intelligent manufacturing. This paper briefly reviewed the supervision and research progress in continuous pharmaceutical manufacturing in China and abroad and described the definition and advantages of continuous pharmaceutical manufacturing. The continuous manufacturing of traditional Chinese medicine(TCM) at the current stage was summarized in the following three terms: the enhancement of the continuity of intermittent manufacturing operations, the integration of continuous equipment to improve physical continuity between units, and the application of advanced process control strategies to improve process continuity. To achieve continuous manufacturing of TCM, the corresponding key technologies, such as material property characterization, process modeling and simulation, process analysis technology, and system integration, were analyzed from the process and equipment, respectively. It was proposed that the continuous manufacturing equipment system should have the characteristics of high speed, high response, and high reliability, "three high(H~3)" for short. Considering the characteristics and current situation of TCM manufacturing, based on the two dimensions of product quality control and production efficiency, a maturity assessment model for continuous manufacturing of TCM, consisting of operation continuity, equipment continuity, process continuity, and quality control continuity, was proposed to provide references for the application of continuous manufacturing technology for TCM. The implementation of continuous manufacturing or the application of key continuous manufacturing technologies in TCM can help to systematically integrate advanced pharmaceutical technology elements and promote the uniformity of TCM quality and the improvement of production efficiency.
Medicine, Chinese Traditional ; Reproducibility of Results ; China ; Quality Control ; Pharmaceutical Preparations

Objective:To compare the surgical safety and postoperative quality of life between proximal gastrectomy with double tract reconstruction (PG-DT) and proximal gastrectomy with gastric tube reconstruction (PG-GT) for proximal gastric cancer.Methods:This was a retrospective cohort study of clinical and follow-up data of 99 patients with proximal gastric cancer who had undergone double tract or gastric tube surgery in Nanjing Drum Tower Hospital from January 2016 to September 2021. We allocated them to two groups according to surgical procedure, namely a double tract group (PG-DT, 50 patients) and gastric tube group (PG-GT, 49 patients). Proximal gastrectomy with double tract reconstruction entails constructing a Roux-en-Y esophagojejunostomy after severing the proximal stomach, and then constructing a side-to-side anastomosis between the residual stomach and the jejunum to establish an anti-reflux barrier and thus minimize postoperative gastroesophageal reflux. Proximal gastrectomy with gastric tube reconstruction entails severing the proximal gastric stomach, constructing a tubular shaped gastric remnant, and then using a linear stapler to directly anastomose the posterior wall of the esophagus to the anterior wall of the resultant gastric tube. The primary end point was the quality of life of the two groups 1 year postoperatively (post-gastrectomy syndrome assessment scale: the higher the scores for change in body mass, food intake per meal, meal quality subscale, total physical health measurement, and total mental health measurement, the better the quality-of-life, and the higher the scores for other indicators, the worse the quality-of-life). The secondary end points were intraoperative and postoperative status, changes in nutritional status 1, 3, 6, and 12 months postoperatively, and long-term postoperative complications (gastroesophageal reflux, anastomotic stenosis, intestinal obstruction, and gastric emptying disorder 1 year postoperatively).Results:In the PG-DT group, there were 35 (70%) men and 15 (30%) women, 33 (66.0%) patients were aged <65 years, and 37 (74.0%) of them had a body mass index of 18–25 kg/m 2; whereas in the PG-GT group, there were 41 (83.7%) men and eight (16.3%) women, 21 (42.9%) patients aged <65 years, and 34 (69.4%) patients with a body mass index of 18–25 kg/m 2. There were no significant differences in baseline data between the two groups except for age ( P=0.021). There were no significant differences in intraoperative blood loss, number of lymph node dissected, length of hospital stay, and incidence of perioperative complications between the two groups (all P>0.05). Compared with the PG-GT group, the incidence and severity of postoperative reflux esophagitis were significantly lower in the PG-DT group (4.0% [2/50] vs. 26.5% [13/49], χ 2=13.507, P=0.009). The incidences of postoperative anastomotic stenosis, intestinal obstruction, and gastric retention did not differ significantly between the two groups (all P>0.05). Patients in the PG-DT group had better quality-of-life scores for esophageal reflux (2.8 [2.3,4.0] vs. 4.8 [3.8,5.0], Z=3.489, P<0.001), eating discomfort (2.7 [1.7,3.0] vs. 3.3 [2.7,4.0 ], Z=3.393, P=0.001), and total symptoms (2.3 [1.7,2.7] vs. 2.5 [2.2,2.9], Z=2.243, P=0.025) than those in the gastric tube group; The scores for postoperative symptoms (2.0 [1.0,3.0] vs. 2.0 [2.0, 3.0], Z=2.127, P=0.033), meals consumed (2.0 [1.0, 2.0] vs. 2.0 [2.0, 3.0], Z=3.976, P<0.001), work (1.0 [1.0, 2.0] vs. 2.0 [1.0, 2.0], Z=2.279, P=0.023] and daily life (1.7 [1.3, 2.0] vs. 2.0 [2.0, 2.3], Z=3.950, P<0.001) were better in the PG-DT than the PG-GT group. Patients in the PG-GT group scored better than those in the PG-DT group for somatic symptoms, such as anal evacuation (3.0 [2.0, 4.0] vs. 3.5 [2.0, 5.0], Z=2.345, P=0.019). There were no significant differences in hemoglobin, serum albumin, serum total protein, or weight loss 1 year postoperatively between the two groups (all P>0.05). Conclusions:The safety of double tract anastomosis for proximal gastric cancer is comparable to that of gastric tube surgery. Compared with gastric tube surgery, double tract anastomosis achieves less esophageal reflux and better quality of life, making it a preferable surgical procedure for proximal gastric cancer.

Objective:To compare the surgical safety and postoperative quality of life between proximal gastrectomy with double tract reconstruction (PG-DT) and proximal gastrectomy with gastric tube reconstruction (PG-GT) for proximal gastric cancer.Methods:This was a retrospective cohort study of clinical and follow-up data of 99 patients with proximal gastric cancer who had undergone double tract or gastric tube surgery in Nanjing Drum Tower Hospital from January 2016 to September 2021. We allocated them to two groups according to surgical procedure, namely a double tract group (PG-DT, 50 patients) and gastric tube group (PG-GT, 49 patients). Proximal gastrectomy with double tract reconstruction entails constructing a Roux-en-Y esophagojejunostomy after severing the proximal stomach, and then constructing a side-to-side anastomosis between the residual stomach and the jejunum to establish an anti-reflux barrier and thus minimize postoperative gastroesophageal reflux. Proximal gastrectomy with gastric tube reconstruction entails severing the proximal gastric stomach, constructing a tubular shaped gastric remnant, and then using a linear stapler to directly anastomose the posterior wall of the esophagus to the anterior wall of the resultant gastric tube. The primary end point was the quality of life of the two groups 1 year postoperatively (post-gastrectomy syndrome assessment scale: the higher the scores for change in body mass, food intake per meal, meal quality subscale, total physical health measurement, and total mental health measurement, the better the quality-of-life, and the higher the scores for other indicators, the worse the quality-of-life). The secondary end points were intraoperative and postoperative status, changes in nutritional status 1, 3, 6, and 12 months postoperatively, and long-term postoperative complications (gastroesophageal reflux, anastomotic stenosis, intestinal obstruction, and gastric emptying disorder 1 year postoperatively).Results:In the PG-DT group, there were 35 (70%) men and 15 (30%) women, 33 (66.0%) patients were aged <65 years, and 37 (74.0%) of them had a body mass index of 18–25 kg/m 2; whereas in the PG-GT group, there were 41 (83.7%) men and eight (16.3%) women, 21 (42.9%) patients aged <65 years, and 34 (69.4%) patients with a body mass index of 18–25 kg/m 2. There were no significant differences in baseline data between the two groups except for age ( P=0.021). There were no significant differences in intraoperative blood loss, number of lymph node dissected, length of hospital stay, and incidence of perioperative complications between the two groups (all P>0.05). Compared with the PG-GT group, the incidence and severity of postoperative reflux esophagitis were significantly lower in the PG-DT group (4.0% [2/50] vs. 26.5% [13/49], χ 2=13.507, P=0.009). The incidences of postoperative anastomotic stenosis, intestinal obstruction, and gastric retention did not differ significantly between the two groups (all P>0.05). Patients in the PG-DT group had better quality-of-life scores for esophageal reflux (2.8 [2.3,4.0] vs. 4.8 [3.8,5.0], Z=3.489, P<0.001), eating discomfort (2.7 [1.7,3.0] vs. 3.3 [2.7,4.0 ], Z=3.393, P=0.001), and total symptoms (2.3 [1.7,2.7] vs. 2.5 [2.2,2.9], Z=2.243, P=0.025) than those in the gastric tube group; The scores for postoperative symptoms (2.0 [1.0,3.0] vs. 2.0 [2.0, 3.0], Z=2.127, P=0.033), meals consumed (2.0 [1.0, 2.0] vs. 2.0 [2.0, 3.0], Z=3.976, P<0.001), work (1.0 [1.0, 2.0] vs. 2.0 [1.0, 2.0], Z=2.279, P=0.023] and daily life (1.7 [1.3, 2.0] vs. 2.0 [2.0, 2.3], Z=3.950, P<0.001) were better in the PG-DT than the PG-GT group. Patients in the PG-GT group scored better than those in the PG-DT group for somatic symptoms, such as anal evacuation (3.0 [2.0, 4.0] vs. 3.5 [2.0, 5.0], Z=2.345, P=0.019). There were no significant differences in hemoglobin, serum albumin, serum total protein, or weight loss 1 year postoperatively between the two groups (all P>0.05). Conclusions:The safety of double tract anastomosis for proximal gastric cancer is comparable to that of gastric tube surgery. Compared with gastric tube surgery, double tract anastomosis achieves less esophageal reflux and better quality of life, making it a preferable surgical procedure for proximal gastric cancer.

OBJECTIVE: To investigate the auditory response patterns of mouse primary auditory cortex (A1) neurons. METHODS: In vivo cell-attached recordings and neural network modeling were performed to detect the changes in response patterns of A1 neurons of awake C57BL/6J mice to sound stimulation with varying lengths. A1 neuron signals were recorded for 216 neurons in 20 awake mice using a target sound stimulation sequence, and the classification and response characteristics of A1 neuron response patterns were examined using post-stimulus spike time histograms. To simulate the diversity of the A1 neuron response patterns, an A1 neuron model was established based on the Wilson-Cowan model and integral-firing model. The neuron connection weight parameters in the model were calculated by examining the micro loop structure of the pyramidal neurons, parvalbumin neurons, and somatostatin neurons in the A1 region, and the A1 neural network information coding model was constructed. RESULTS: The Onset response neurons only had fast spike response within 10 to 40 ms after the beginning of noise stimulation (122 neurons). The Sustained response neurons had spike response continuously during the noise stimulation (26 neurons). The On-off response neurons had fast spike response after the beginning and the end of noise stimulation (40 neurons). The Offset response neurons only had fast spike response within 10 to 40 ms after the end of noise stimulation (22 neurons). In the neural network model, the Onset peak neural activities of A1 pyramidal neurons, parvalbumin neurons, and somatostatin neurons were 0.7483, 0.5236 and 0.9427, respectively, and their response half peak widths were 18.5 ms, 12 ms and 31 ms during the 100 ms noise stimulation, respectively. By changing the feedforward excitation and synaptic inhibition time constants in the model, the neurons generated numerous different types of spike train. CONCLUSION The auditory response of mouse A1 neurons to sound stimuli shows mainly the Onset, Sustained, On-off, and Offset response patterns.
Acoustic Stimulation ; Animals ; Auditory Cortex/physiology* ; Mice ; Mice, Inbred C57BL ; Parvalbumins ; Somatostatin

Sterol-regulatory element binding proteins (SREBPs) are the key transcriptional regulators of lipid metabolism. The activation of SREBP requires translocation of the SREBP precursor from the endoplasmic reticulum to the Golgi, where it is sequentially cleaved by site-1 protease (S1P) and site-2 protease and releases a nuclear form to modulate gene expression. To search for new genes regulating cholesterol metabolism, we perform a genome-wide CRISPR/Cas9 knockout screen and find that partner of site-1 protease (POST1), encoded by C12ORF49, is critically involved in the SREBP signaling. Ablation of POST1 decreases the generation of nuclear SREBP and reduces the expression of SREBP target genes. POST1 binds S1P, which is synthesized as an inactive protease (form A) and becomes fully mature via a two-step autocatalytic process involving forms B'/B and C'/C. POST1 promotes the generation of the functional S1P-C'/C from S1P-B'/B (canonical cleavage) and, notably, from S1P-A directly (non-canonical cleavage) as well. This POST1-mediated S1P activation is also essential for the cleavages of other S1P substrates including ATF6, CREB3 family members and the α/β-subunit precursor of N-acetylglucosamine-1-phosphotransferase. Together, we demonstrate that POST1 is a cofactor controlling S1P maturation and plays important roles in lipid homeostasis, unfolded protein response, lipoprotein metabolism and lysosome biogenesis.