Clinical efficacy and safety of adjuvant immunotherapy (Tislelizumab) plus chemotherapy vs. adjuvant chemotherapy alone in lymph node-positive patients with gastric cancer after D2 radical resection: a prospective, 2-arm, phase II study.

OBJECTIVE: This study aims to investigate the effectiveness and safety of adjuvant Tislelizumab (BeiGene China Co., Ltd, Changping District, Beijing, China) in combination with chemotherapy for patients with localized lymph node-positive disease following D2 (extended lymphadenectomy) radical gastrectomy for gastric cancer. PATIENTS AND METHODS: Patients with lymph node-positive gastric cancer who underwent D2 radical gastrectomy at Yixing People's Hospital between April 2021 and June 2022 were selected and enrolled in the study. They were divided into the study group, which received immunotherapy (Tislelizumab) in combination with chemotherapy (XELOX regimen: Xeloda plus Oxaliplatin), or the control group, which received chemotherapy alone (XELOX regimen). Adverse events, disease-free survival (DFS), and overall survival (OS) were observed. This study was registered on ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT05844371). RESULTS: The one-year disease-free survival (DFS) rate was 81.82% in the study group compared to 71.43% in the control group. Although the DFS rate tended to be higher in the study group, the difference did not reach statistical significance (p=0.388, HR=0.573, 95% CI: 0.161-2.032). Patients in both groups tolerated the treatment well. Both groups exhibited similar rates of neutropenia, hemoglobin depletion, gastrointestinal reactions, abnormal liver function, and peripheral neuritis. The majority of adverse events in both groups were grade 1-2, with only hypothyroidism showing a significant difference (p=0.021). The only statistically significant difference in grade 3-4 adverse events was thrombocytopenia (p=0.048). All adverse reactions were effectively managed with symptomatic treatment. CONCLUSIONS: The addition of adjuvant PD-1 inhibitor (Tislelizumab) to XELOX therapy showed a favorable impact on the one-year disease-free survival (DFS) rate when compared to adjuvant XELOX chemotherapy alone in patients with regional lymph node-positive disease after D2 radical gastrectomy. Moreover, patients were able to tolerate the accompanying adverse effects, which were deemed safe.

Application of Trace Biological Evidence Collection Kit in DNA Examination of Trace Bloodstain Samples from the Scene.

ABSTRACT: Objective To evaluate the effects of DNA examination of trace bloodstain samples from the scene collected with Trace Biological Evidence Collection kit. Methods Venous blood was made into bloodstains on the ground. The trace bloodstain samples were collected with Trace Biological Evidence Collection kit and common methods, respectively. DNA examination of trace bloodstain samples （50 from each group） was conducted on the constant temperature shaker for 2, 24, 48, 72, and 96 h, respectively, and the examination results of every group were compared. Results When the trace bloodstain samples were placed on the constant temperature shaker for 24, 48, 72, and 96 h, the DNA detection rates in the group which used Trace Biological Evidence Collection kit （100.00%, 100.00%, 100.00%, 96.00%） were significantly higher than those in the group using common methods （62.00%, 26.00%, 10.00%, 0）, the differences had statistical significance （P<0.05）. When the trace bloodstain samples were placed on the constant temperature shaker for 2 h, the differences of DNA detection rates between the two groups had no statistical significance （ P>0.05）. Conclusion The Trace Biological Evidence Collection kit can effectively improve DNA detection rate and extend detection time limit for trace bloodstain samples from the scene that have been stored for a relatively long time.

[The problems and countermeasures in the training of public health talents in colleges and universities in China].

Colleges and universities are the cradle for public health talents training. Under the epidemic situation, the new requirements for the construction of public health service system and the promotion of population health, urged us to rethink how to reform the training of public health talents in colleges and universities. This research focused on key problems of the construction and distribution, scale, orientation, and contents of training for various public health talents in colleges and universities. It was suggested to reinforce the balanced development of public health in colleges and universities in various areas in China, to refine interdisciplinary training, to intensively cultivate technical and research-oriented talents, to expand talents within and outside the colleges and universities, as well as to introduce and cultivate public health teachers simultaneously, so as to better play the role of colleges and universities in the training of the public health talents.

Standardized out-patient diagnosis and treatment process for osteoporosis clinics during the COVID-19 pandemic.

Since the end of 2019, China and other regions around the world have been facing a pandemic of novel coronavirus pneumonia (COVID-19). The virus is highly transmissible, and the human population is generally susceptible. Most patients with osteoporosis are postmenopausal women or elderly people with hypoimmunity, so the osteoporosis clinic has become a new hotspot for corona virus infection. During the COVID-19 pandemic, it is necessary to establish standardized out-patient protocols to provide safe and effective treatment for osteoporosis patients and medical staff. In an osteoporosis clinic, we advocate the following suggestions to prevent and control osteoporosis during the pandemic period: (1) specialized diagnosis and treatment techniques for osteoporosis patients in the outpatient care, including enhancing the prevention for outpatient medical staff, strengthening awareness of COVID-19 prevention, strictly screening outpatients with COVID-19 infection, and insistent administration of anti-osteoporosis drugs during outbreaks; (2) home prevention for osteoporosis patients including keeping windows open, exposing them to sunlight, supplementing them with enough protein, exercising regularly, and administrating calcium supplements; and (3) simplifying the follow-up and evaluation of osteoporosis using online platforms.

[Effect of Benzidine Test on DNA Analysis of Bloodstain].

OBJECTIVES: To explore the effect of benzidine test and related reagents on DNA analysis of bloodstain. METHODS: A total of 970 bloodstain filter paper samples with 1 µL venous blood were collected, and 10 of them acted as control samples. After benzidine test and related reagent processing, DNA of 960 samples was extracted by Chelex-100 and silica bead methods and then multiplex amplified by AmpFℓSTR™ Identifiler™ Plus PCR kits. The results of STR typing were compared between different groups. RESULTS: DNA were extracted immediately after benzidine test. Totally STR loci （3.80±1.34） were detected by silica bead method, while no STR loci were obtained by Chelex-100 method. Thirteen samples （21.7%） with whole STR typing results were obtained by drying after benzidine test, and the STR locus number （12.90±1.49） which obtained by silica bead method was much higher than by Chelex-100 method （4.70±1.96） （P<0.05）. When DNA was extracted immediately after the addition of glacial acetic acid, the STR locus number was （9.40±2.09） by silica bead method, but no STR typing result was obtained by Chelex-100 method. All 15 STR loci could be obtained by only adding glacial acetic acid after drying and only adding tetramethylbenzidine alcoholization liquid or 3% hydrogen peroxide liquid. CONCLUSIONS: Benzidine test has significant influence on DNA analysis of bloodstain. The Chelex-100 method is not suitable for the DNA extraction of bloodstain after benzidine test. Drying after benzidine test and silica bead methods can effectively enhance the STR locus number of bloodstain.

Anti-waveguiding vertical-cavity surface-emitting laser at 850 nm: From concept to advances in high-speed data transmission.

Oxide-confined vertical cavity surface emitting lasers (VCSELs) with anti-waveguiding AlAs-rich core presently attract a lot of attention. Anti-waveguiding cavity enables the maximum possible optical confinement of the VCSEL mode ("λ/2 design"), increases its oscillator strength and reduces dramatically the optical power accumulated in the VCSEL mesa regions outside the aperture. VCSEL designs are suggested that favor single transverse mode operation. Modeling including current-induced and absorption-induced overheating shows that the preference for the transverse fundamental mode persists up to 10 mA current at 5 µm aperture diameter. Error-free data transmission is realized up to 160 Gb/s in digital-multitone (DMT) format using single-mode anti-waveguiding VCSELs. The approach to single-mode anti-waveguiding VCSELs is extended over a broad spectral range realizing error-free high-speed data transmission at both 850 nm and 910 nm.

Immunological function and antibacterial activity of two ferritin proteins from the freshwater pearl mussel Hyriopsis schlegelii.

Ferritin is a conserved iron-binding protein involved in host defense and cellular iron metabolism in most organisms. We investigated the expression profiles of two ferritin genes (designated HsFer-1 and HsFer-2) in the hemocytes, gonad, and hepatopancreas of Hyriopsis schlegelii, when challenged with bacteria and metal ions. HsFer gene transcription increased 1.8-7.7- and 1.9-6.1-fold in these tissues after stimulation with Staphylococcus aureus and Vibrio anguillarum, respectively. In addition, following exposure to Fe3+, expression of HsFer-1 and HsFer-2 was elevated by 1.5-6.1- and 3.6-10.1-fold, respectively. Levels of HsFer-1 and -2 mRNA also increased significantly after treatment with Cu2+ and Pb2+ at certain concentrations. Moreover, recombinant HsFer-1 and -2 were able to inhibit the growth of two strains of bacteria, and the former efficiently chelated Fe3+. From these results, we conclude that HsFer-1 and -2 may be involved in iron metabolism and immune defense by inhibiting the growth of bacteria.

Coding for stable transmission of W-band radio-over-fiber system using direct-beating of two independent lasers.

We demonstrate experimentally Manchester (MC) coding based W-band (75 - 110 GHz) radio-over-fiber (ROF) system to reduce the low-frequency-components (LFCs) signal distortion generated by two independent low-cost lasers using spectral shaping. Hence, a low-cost and higher performance W-band ROF system is achieved. In this system, direct-beating of two independent low-cost CW lasers without frequency tracking circuit (FTC) is used to generate the millimeter-wave. Approaches, such as delayed self-heterodyne interferometer and heterodyne beating are performed to characterize the optical-beating-interference sub-terahertz signal (OBIS). Furthermore, W-band ROF systems using MC coding and NRZ-OOK are compared and discussed.

Expression pattern of the zona pellucida 3 (ZP3) gene during ovarian development and the location of ZP3 protein in oocytes in a natural, wild triploid crucian carp mutant, Carassius auratus var. Pingxiangnensis.

Carassius auratus var. Pingxiangnensis (designated CaP), distributed in the Pingxiang region of Jiangxi Province, China, is a natural, wild triploid crucian carp mutant that has two reproductive development modes: gynogenesis and bisexual reproduction. Little information is available about the expression pattern of the zona pellucida 3 (ZP3) gene during ovarian development and the location of the ZP3 protein in oocytes of this fish. In this study, we obtained the full-length cDNA of ZP3 (CaP_ZP3). CaP_ZP3 contains an open reading frame of 1305 bp that encodes 435 amino acid residues. Real-time polymerase chain reaction (PCR) was used to determine the CaP_ZP3 mRNA expression levels in the ovary at different stages of maturation. Results revealed high levels of CaP_ZP3 expression in 4- to 8-month-old ovaries (stage II-stage III), with a significant decline in 9- to 12-month-old ovaries (stages IV-stage V). The high levels of CaP_ ZP3 transcripts during the early growth period suggest an important role for CaP_ZP3 in early oocyte development. In addition, a polyclonal antibody was prepared against CaP_ZP3, and the immunofluorescence localization was determined. CaP_ZP3 protein was detected close to the oocyte plasma membrane. The results also showed that no fluorescent signal was detected in stage I and II oocytes. CaP_ZP3 protein is primarily detected in stage III oocytes, and the protein accumulates as oocytes develop into stage IV oocytes. These results suggested that the transcription and translation of the CaP_ZP3 gene is asynchronous and that the transcription of the CaP_ZP3 protein occurs prior to its translation in this triploid fish.

100 GHz ultra-wideband (UWB) fiber-to-the-antenna (FTTA) system for in-building and in-home networks.

Fiber-to-the-antenna (FTTA) system can be a cost-effective technique for distributing high frequency signals from the head-end office to a number of remote antenna units via passive optical splitter and propagating through low-loss and low-cost optical fibers. Here, we experimentally demonstrate an optical ultra-wideband (UWB) - impulse radio (IR) FTTA system for in-building and in-home applications. The optical UWB-IR wireless link is operated in the W-band (75 GHz - 110 GHz) using our developed near-ballistic unitraveling-carrier photodiode based photonic transmitter (PT) and a 10 GHz mode-locked laser. 2.5 Gb/s UWB-IR FTTA systems with 1,024 high split-ratio and transmission over 300 m optical fiber are demonstrated using direct PT modulation.

Temporal changes of preproenkephalin mRNA and leu-enkephalin-like immunoreactivity in the neurons of the caudal spinal trigeminal nucleus and upper cervical cord after noxious stimuli.

The changing levels of preproenkephalin (PPE) mRNA expression and leu-enkephalin-like immunoreactivity (L-ENK-LI) in the caudal spinal trigeminal nucleus (Vc) and the upper cervical cord subsequent to subcutaneous injection of formalin into orofacial region were examined using in situ hybridization histochemistry and immunohistochemistry. Formalin injection resulted in a significant increase in the number of neurons expressing PPE mRNA in the superficial (laminae I-II) and deep (lamina V) layers of the ipsilateral Vc and the first cervical cord (C1). The expression of PPE mRNA increased 2 h and 4 h after formalin injection in the neurons of deep layer and superficial layers of the Vc, respectively. An increased expression of PPE gene could still be observed 48 h after formalin injection. The PPE mRNA expression in the neurons of the C1 had similar temporal changes as in the Vc. In parallel, the L-ENK-LI did not show any significant changes in the Vc and C1. These results indicate that peripheral noxious stimulation trans-synapticaly activates the expression of PPE gene in the neurons of the Vc and C1 and suggest that enkephallin (ENK) plays an important role in the processing and modulation of the oroficial noxious stimulation.

[Co-existence of glutamate and substance P in electrophysiologically identified dorsal root ganglion neurons of rats].

Electrophysiological properties, reaction to substance P (SP) receptor agonist, and co-existence of glutamate (Glu) and SP in neurons of the spinal dorsal root ganglion (DRG) of the rat were investigated in vitro. The main results were: (1) According to the fiber conduction velocity, totally 135 intracellularly recorded DRG neurons were divided into A alpha/beta type (> 12 m/s) and C type (< 1.3 m/s). There were remarkable differences between the fast after hyperpolarization (fAHP) of action potential between the two types: fAHP of C type neurons had smaller amplititude and longer duration, whereas the fAHP of A alpha/beta type neurons had larger amplititude and shorter duration. (2) Among 22 DRG neurons of which overshoots of action potential appeared, specific SP receptor agonist Sar-SP induced depolorization in 42% (5/12) of the A alpha/beta type neurons and 80% (8/10) of the C type neurons. (3) Biocytin was intracellularly injected into the 22 Sar-SP administrated DRG neurons. After fixation and section, employing the immunofluorescent histochemical multi-staining technique for phosphate-activated glutaminase (PAG, a specific marker for glutamatergic neurons), SP and biocytin, 25% (3/12) of the A alpha/beta type neurons and 80% (8/10) of the C type neurons showed both PAG- and SP-like immunoreactivities. There was a great difference between the percentages of the PAG/SP co-existing A alpha/beta type neurons and C type neurons (P < 0.05). The present results indicated that there were some differences in chemicoanatomical and electrophysiological properties between A alpha/beta type and C type neurons, and SP might facilitate the discharge of DRG neurons through activating SP autoreceptors on their membrane.

[Peripheral substance P receptor mediating c-fos gene expression in the spinal dorsal horn induced by peripheral noxious stimulation].

Employing immunohistochemical staining for FOS protein, which is the expression product of c-fos proto-oncogene, the role of substance P receptor (SPR) in noxious information transmission at peripheral terminals of the dorsal root ganglion cells was investigated by means of a selective SPR antagonist L668, 169 and agonist Sar-SP. Unilateral injection of L668, 169 (10(-4) mol/L) into the plantar of hindpaw 10 min before injection of 4% formalin, the number of FOS-like immunoreactive (LI) neurons in the superficial laminae of dorsal horn was significantly decreased, but the changes were not obvious in the deeper laminae. Smaller doses of L668, 169 (10(-5), 10(-6) mol/L) were almost ineffective on FOS-LI neurons in both the superficial and the deeper laminae. However, Sar-SP (10(-4) mol/L) or formalin did result in the expression of c-fos gene in the superficial laminae of the dorsal horn. These results indicated that SP might contribute to the transmission of nociceptive information and induce noxious sensation, at least in part by activating SPR in peripheral terminals of the dorsal root ganglion cells.

Evidence of gamma-aminobutyric acidergic control over the catecholaminergic projection from the medulla oblongata to the central nucleus of the amygdala.

It is known that the nucleus of the solitary tract (NTS) and the ventrolateral medulla (VLM) project to the central nucleus of the amygdala (Ce), conveying visceral information. Conversely, the Ce sends projections to the NTS and the VLM. To understand better the role of catecholamine and gamma-aminobutyric acid (GABA) in these reciprocal connections, experiments were performed by combining lectin-conjugated horseradish peroxidase (WGA-HRP) anterograde and retrograde transport with preembedding immunocytochemistry to detect tyrosine hydroxylase (TH), and postembedding immunocytochemistry to detect GABA. The light microscopic study suggested that the majority of neurons in the NTS and the VLM projecting to the Ce were TH immunoreactive (TH-IR). Most of them were located at the level of the obex. Under the electron microscope, the GABAergic and non-GABAergic terminals were found to form synaptic contacts with the TH-(IR) or Ce-projecting or TH-IR/Ce-projecting double-labelled neurons of the NTS and VLM. The GABAergic terminals mostly formed symmetrical synaptic contacts with the postsynaptic structure in which perikarya (14-19%), dendrites (79-84%), and spines (2%) were observed. Approximately 94% of the axon terminals in the NTS and 90% of those in the VLM arising from the Ce were GABAergic and appeared not to form synaptic contacts with the TH-IR or Ce-projecting neurons in these regions. The present results demonstrated that the catecholaminergic neurons of the NTS and VLM projecting to the Ce receive an extensive GABAergic innervation and that the amygdala projection to the medulla is mostly GABAergic.

Fos expression in catecholaminergic medullary neurons induced by chemical stimulation of stomach projecting to the paraventricular nucleus of the hypothalamus in rats.

AIM: To determine whether medullary catecholaminergic neurons expressing Fos induced by chemical stimulation of the stomach project to the paraventricular nucleus of hypothalamus (PVH) in rats. METHODS: Horseradish peroxidase (HRP) was introduced stereotaxically into the PVH of rats. Histochemical analysis of coronal sections through the medulla were analyzed using triple-label immunohistochemistry to identify cells that were retrogradely labeled with HRP, Fos (ABC method), and tyrosin hydroxylase (TH) (PAP method). RESULTS: Seven kinds of labeled neurons were found in the nucleus tractus solitarii (NTS), the ventrolateral medulla (VLM) and the reticular formation (RF) of the medulla: Fos-like immunoreactive (FosLI) neurons, TH-like immunoreactive (TH-LI) neurons and HRP retrogradely single-labeled neurons, FosLI/HRP, FosLI/TH-LI and HRP/TH-LI double-labeled neurons, and FosLI/HRP/TH-LI triple-labeled neurons. CONCLUSION: Ascending projections from the NTS, VLM and RF to the PVH might be involved in the transmitting process of visceral noxious stimulation.

GABAergic synapses upon neurons expressing substance P receptors in the nucleus of the solitary tract: an immunocytochemical electron microscope study in the rat.

Morphological substrates for interactions between gamma-aminobutyric acid (GABA) and substance P upon neurons expressing substance P receptor (SPR) in the nucleus of the solitary tract (NST) were investigated by immunocytochemical electron microscopy. In the NST of the rat, many GABA-like immunoreactive axon terminals were in symmetric synaptic contacts with dendritic profiles; they were observed on nearly a half of the SPR-like immunoreactive dendritic profiles in the medial part of the caudal half of the NST.

Central origins of substance P-like immunoreactive fibers and terminals in the spinal trigeminal caudal subnucleus in the rat.

After trigeminal rhizotomy, some substance P-like immunoreactive (SP-LI) fibers and terminals in the spinal trigeminal caudal subnucleus (Vc), specially in its superficial laminae (laminae I and II), still remained in the rat. Employing a combination of Fluoro-Gold retrograde tracing and immunofluorescence histochemical staining for SP, we found that the main central origins of these SP-LI fibers and terminals were midbrain periaqueductal gray (PAG), nucleus raphe magnus (NRM) and other raphe nuclei, and nucleus reticularis gigantocellularis pars alpha; all of them are important structures of the endogenous pain control system. The present results provided morphological evidence for PAG or NRM stimulation could inhibit neuronal activities in the Vc evoked by orofacial nociceptive stimulation and also suggested that SP might be an important neurotransmitter or neuromodulator for endogenous pain control system.

Catecholaminergic neurons in the nucleus tractus solitarii which send their axons to the midbrain periaqueductal gray express Fos protein after noxious stimulation of the stomach: a triple labeling study in the rat.

In rats which were injected with horseradish peroxidase (HRP) into the midbrain periaqueductal gray (PAG) and then administered with formaldehyde into the stomach, Fos-like immunoreactivity was found in tyrosine hydroxylase-like immunoreactive neurons in the nucleus tractus solitarii (NTS) which were retrogradely labeled with HRP. The results indicate that catecholaminergic NTS neurons may mediate nociceptive visceral information to the PAG.

An indirect projection from the nucleus of the solitary tract to the central nucleus of the amygdala via the parabrachial nucleus in the rat: a light and electron microscopic study.

The morphological basis of how visceral information from the nucleus of the solitary tract (NTS) is relayed from the parabrachial nucleus (PBN) to the central nucleus of the amygdala (Ce) was studied at the light and electron microscopic levels using the anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHA-L), kainic acid degeneration, and retrograde tracing with horseradish peroxidase (HRP). After injection of PHA-L into the caudal NTS, anterogradely labeled fibers and terminals were predominantly distributed in the external lateral (el) and central lateral (cl) subnuclei of the PBN. After injection of HRP into the Ce, retrogradely labeled neurons in PBN were mainly distributed in the same areas. In double-labeling experiments, there was a clear overlap between neuronal elements labeled with HRP and PHA-L in the el and cl. At the electron microscopic level, the PHA-L-labeled axon terminals from the NTS mainly contained spherical agranular synaptic vesicles and formed asymmetric contacts with the postsynaptic dendrites or dendritic spines in PBN. After the lesioning agent kainic acid was injected into the NTS and HRP deposited in the Ce, it was found the afferent fibers from the NTS made direct synaptic contact with the lateral PBN neurons which in turn projected to Ce. Such evidence adds to our growing knowledge of regulation of visceral function in central nervous system and would be likely helpful for understanding the important roles of the NTS, PBN and Ce in the central control of cardiovascular, respiratory and gastrointestinal functions.